OA19159A - Pesticidal Compositions and Processes Related Thereto - Google Patents

Pesticidal Compositions and Processes Related Thereto Download PDF

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OA19159A
OA19159A OA1201400481 OA19159A OA 19159 A OA19159 A OA 19159A OA 1201400481 OA1201400481 OA 1201400481 OA 19159 A OA19159 A OA 19159A
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alkyl
haloalkyl
cycloalkyl
alkenyl
phenyl
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OA1201400481
Inventor
Ricky Hunter
Akshay PATNY
Paul Renee Leplae
Daniel Knueppel
Noormohamed M. Niyaz
Tony K. Trullinger
Carl Deamicis
Frank Wessels
Asako KUBOTA
Christian T. Lowe
David A. Demeter
Ann M. Buysse
Martin J. Walsh
Peter BORROMEO
Negar Garizi
Ronald Ross
Yu Zhang
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Dow Agrosciences Llc
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Publication of OA19159A publication Critical patent/OA19159A/en

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Abstract

This document discloses molecules having the following formulas ("Formula One" & ''Formula Two'' and ''Formula Three'' ). The Ar1, Het, Ar2, R1 , R2 , R3 , R4 , and R5 are further described herein.

Description

PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO CROSS-REFERENCE TO RELATED APPLICATIONS
This Application claims priority from U.S. provisional application 61/594,107 filed on February 2, 2012. The entire content of this provisional application is hereby incorporated by reference into this Application.
FIELD OF THE INVENTION
The invention disclosed in this document is related to the field of processes to produce molécules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molécules, and processes of using such molécules to control pests.
BACKGROUND OF THE INVENTION
Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.
Termites cause damage to ail kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.
Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.
There is an acute need for new pesticides. Certain pests are developing résistance to pesticides in current use. Hundreds of pest species are résistant to one or more pesticides. The development of résistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known, but résistance has even developed to some of the newer pesticides.
Therefore, for many reasons, including the above reasons, a need exists for new pesticides.
DEFINITIONS
The examples given in the définitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molécule to which it is attached.
“Acaricide Group” is defined under the heading “ACARICIDES”.
“AI Group” is defined after the place in this document where the “Herbicide Group” is defined.
“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.
“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
“Alkoxy” means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.
“Alkyl” means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl.
“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.
“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.
“Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at least one carboncarbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbomenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
“Cycloalkenyloxy” means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbomenyloxy, and bicyclo [2.2.2] octenyloxy.
“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbomyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbomyloxy, and bicyclo [2.2.2] octyloxy.
“Fungicide Group” is defined under the heading “FUNGICIDES.” “Halo” means fluoro, chloro, bromo, and iodo.
“Haloalkoxy” means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2tetrafluoroethoxy, and pentafluoroethoxy.
“Haloalkyl” means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.
“Herbicide Group” is defined under the heading “HERBICIDES.” “Heterocyclyl” means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-lH-pyrazolyl,
4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]-oxadiazolyl.
“Insecticide Group” is defined under the heading “INSECTICIDES.” “Nematicide Group” is defined under the heading “NEMATICIDES” “Synergist Group” is defined under the heading “SYNERGISTIC MIXTURES AND SYNERGISTS”
DETAILED DESCRIPTION OF THE INVENTION
This document discloses molécules having the following formulas (“Formula One” &“Formula Two” and “Formula Three”): (In the following formulas the nitrogens are numbered 1, 2, and 3, solely for the purpose of identifying them and being able to refer to them throughout this document for clarity purposes)
RI R2 xHet\ ,N2 .S.u_
Αη Ar2 NI Y R3
N3 'R4
Formula 1
RI xHet\ .N2 .S
Aei Ar2 NI Y \
N3-R5 /
R4
Formula 2
RI R5 xHet\ ^N2 k
Aq Ar2 NI Y
Formula 3 wherein:
(a) Ari is (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, ΝΟ2, Ci-Ce alkyl, Ci-Cg haloalkyl, C3-C6 cycloalkyl, C3-Ce halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-C6 alkoxy, CrC6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(C1-C6 alkyl), (CrC6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, C]-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C2-Ce alkenyl, C2-Ce alkynyl, S(=O)n(C]C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(CrC6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(CrC6 alkyl), (Ci-C6 alkyl)S(Ci-Ce alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl) phenyl, and phenoxy;
(b) Het is a 5 or 6 membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and where Arj and Ar2 are not ortho to each other (but may be meta or para, such as, for a five membered ring they are 1,3 and for a 6 membered ring they are either 1,3 or 1,4), and where said heterocyclic ring may also be substituted with one or more substituents independently selected from H, F, Cl, Br, I, CN, ΝΟ2, oxo, C|-Cô alkyl, C|-Cg haloalkyl, C3Cô cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, Cj-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Cr Cf, alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, Ci-Cô haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CrC6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, and phenoxy;
(c) Ar2 is ( 1 ) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, C|-Cf) alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cf, alkoxy, C,-Cô haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(—O)n(Cj
C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-Cô alkyl)C(=O)O(Ci-Cg alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-Cô halocycloalkyl, C3-Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cô alkoxy, Ci-C6 haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(CrC6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(Ci-C6 haloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Cr C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, and phenoxy;
(d) RI is selected from H, CN, F, Cl, Br, I, Ci-Cô alkyl, C3-Cô cycloalkyl, C3-Cô cycloalkoxy, Ci-Cô alkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), OSO2(Ci-C6 alkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, or phenoxy, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, and phenoxy, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, oxo, Ci-C6 alkyl, Ci-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cô alkoxy, Ci-Cô haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-Cô alkyl), S(=O)n(Ci-Cô haloalkyl), OSO2(Ci-Cô alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CiCô alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyWQ-Cô alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, and phenoxy;
(e) R2 is H, Cj-Cô alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(Cj-C6 alkyl), C(=O)O(Cj-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Cj-C6 alkyl)O(Cj-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, CrC6 alkylphenyl, Cj-Cô alkyl-O-phenyl, C(=O)Het-l, Het-1, Cj-Cô alkylHet-1, or Cj-Cô alkyl-OHet-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, Cj-Cô alkyl, Cj-Cô haloalkyl, C3-Cô cycloalkyl, C3-C6 halocycloalkyl, C3Ce cycloalkoxy, C3-Cô halocycloalkoxy, Cj-Cô alkoxy, Cj-Cô haloalkoxy, C2-C6 alkenyl, C3Cô cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-Cô alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Cj-C6 alkyl), C(=O)(Cj-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3Cô cycloalkyl), C(=O)O(C3-Cô cycloalkyl), C(=O)(C2-Cô alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Cj-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, and Het-1 ;
(f) R3 is Cj-Cô alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CrC6 alkyl)O(Cj-C6 alkyl), (Cj-Cô alkyl)S(Ci-C6 alkyl), C(=O)(Cj-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, Ci-C6 alkylphenyl, Cj-Cô alkyl-O-phenyl, C(=O)Het-l, Het-1, Cj-Cô alkylHet-1, Cj-Cô alkyl-OC(=O)Ci-C6 alkyl-O-Ci-Cô alkyl, Cj-C6 alkyl-O-C(=O)Ci-C6 alkyl-O-Cj-C6 alkyl-O- Cj-C6 alkyl, Ci-C6 alkyl-O-C(=O)Cj-C6 alkyl-O-Cj-C6 haloalkyl, Cj-C6 alkyl-O-C(=O)Cj-C6 alkylN(Rx)C(=O)-O-phenyl, Cj-Cô alkyl-O-C(=O)Cj-Cô alkyl-N(Rx)C(=O)-O-Cj-Cô alkylphenyl, Ci-C6 alkylC(=O)N(Rx)C1-C6 alkyl, Cj-Cô alkylC(=O)N(Rx)Ci-C6 alkylHet-lC(=O)-O-Cj-C6 alkyl, Ci-C6alkylC(=O)N(Rx)Cj-C6 alkylHet-1, Cj-C6alkylC(=O)Het-l, Cj-C6 alkylC(=O)N(Rx)Ci-C6 alkyl(N(Rx)(Ry))(C(=O)OH), Cj-C6 alkylC(=O)N(Rx)Cj-C6 alkylN(Rx)(Ry), Cj-C6alkylC(=O)N(Rx)Cj-C6 alkylN(Rx)C(=O)-O-Cj-C6 alkyl, Cj-C6 alkylC(=O)N(Rx)Ci-C6 alkyl(N(Rx)C(=O)-O-Cj-C6 alkyl)(C(=O)OH), Cj-C6 alkylC(=O)Het1C(=O)-O-C1-C6 alkyl, Ci-C6 alkyl-O-C(=O)-O-Ci-C6 alkyl, Cj-C6alkyl-O-C(=O)Ci-C6 alkyl, Cj-C6 alkyl-O-C(=O)C3-C6 cycloalkyl, Cj-C6alkyl-O-C(=O)Het-l, Cj-C6 alkyl-OC(=O)Ci-C6 alkyl-N(Rx)C(=O)-O-Cj-Cô alkyl, Cj-C6 alkyl-NRxRy, or Cj-C6 alkyl-O-Het-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-Cô halocycloalkyl, C3Cé cycloalkoxy, C3-C6 halocycloalkoxy, Cj-Cô alkoxy, C|-Cô haloalkoxy, C2-C6 alkenyl, C3Cô cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(C]-Cô alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(CrC6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(CiCô alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, Si(C|-C6 alkyl)3, S(=O)nNRxRy, and Het-1;
(g) R4 is H, Ci-Cô alkyl, C3-Cô cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-Cô alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-Cô alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, Ci-C6 alkylphenyl, Ci-Cô alkyl-O-phenyl, C(=O)Het-l, Het-1, Ci-Cô alkylHet-1, or Ci-Cô alkyl-OHet-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, Ci-C6 alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cg alkoxy, Ci-Cô haloalkoxy, C2-C6 alkenyl, C3Cô cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-Cô alkyl), S(=O)n(Ci-Cô haloalkyl), OSO2(Ci-Cô alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3C6 cycloalkyl), C(-O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-Cô alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, and Het-1;
(h) R5 is a 2 to 4 membered saturated or unsaturated hydrocarbyl linkage where said linkage may also be substituted with at least one OH and optionally one or more substituents selected from F, Cl, Br, I, CN, NO2, oxo, NRxRy, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRxRy, (Ci-Cô alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl),
C(=O)(C1-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(C]-C6 alkyl), (Ci-Cô alkyl)S(Ci-Cô alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-Cô alkyl), phenyl, phenoxy, and Het-1, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and Het-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, oxo, NRxRy, Ci-C6 alkyl, Ci-C6 haloalkyl, C3-C6 cycloalkyl, C3-Cg halocycloalkyl, C3-Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cô alkoxy, Ci-Cô haloalkoxy, C2-Ce alkenyl, C3-Cé cycloalkenyl, C2-Cg alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, halophenyl, phenoxy, and Het-1;
(i) n= 0,1, or 2;
(j) Rx and Ry are independently selected from H, Ci-Cô alkyl, Ci-Cg haloalkyl, C3-C6 cycloalkyl, C3-Cô halocycloalkyl, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(CrC6 haloalkyl), C(=O)H, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Cl-C6 alkyl), (Cj-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), and phenyl, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and Het-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, oxo, Ci-Cô alkyl, Ci-Cè haloalkyl, C3-Ce cycloalkyl, C3Cô halocycloalkyl, C3-Cg cycloalkoxy, C3-Cg halocycloalkoxy, Ci-Cg alkoxy, C|-C6 haloalkoxy, C2-Cô alkenyl, C3-Cô cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (CrC6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci
Cô alkyl)C(=O)O(Ci-C6 alkyl), phenyl, halophenyl, phenoxy, and Het-1, or Rx and Ry together can optionally form a 5- to 7-membered saturated or unsaturated cyclic group which may contain one or more heteroatoms selected from nitrogen, sulfur, and oxygen, and where said cyclic group can contain >C=O or >C=S, and where said cyclic group may be substituted with F, Cl, Br, I, CN, Ci-Cô alkyl, Cj-Cf, haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cé alkoxy, Ci-Cô haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Cr C6 alkyl)O(Ci-C6 alkyl), (CrC6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, substituted phenyl, phenoxy, and Het-1 ; and (k) Het-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen.
It is understood that in Formula 1, when R2 is H, the compounds may exist in more than one tautomeric or isomeric form, wherein the hydrogen is attached to either of the nitrogen atoms; further, both E and Z isomers may exist. Any and ail isomeric forms of the compounds of this invention are claimed.
In another embodiment An is a substituted phenyl, wherein said substituted phenyl has one or more substituents independently selected from Ci-Cô haloalkyl and Ci-Cé haloalkoxy.
In another embodiment An is a substituted phenyl, wherein said substituted phenyl has one or more substituents independently selected from CF3, OCF3, and OCF2CF3.
In another embodiment Het is selected from triazolyl, imidazolyl, or pyrazolyl, which can be substituted or unsubstituted.
In another embodiment Het is a 1,2,4-triazolyl
In another embodiment Het is 1,4-imidazolyl
In another embodiment Het is 1,3-pyrazolyl
In another embodiment Het is a substituted 1,3-pyrazolyl.
In another embodiment Het is 1,4-pyrazolyl
Ar1
N
ΑΓ2
In another embodiment Ar2 is a phenyl.
In another embodiment RI is H or Cj-Cô alkyl.
In another embodiment RI is H or CH3.
In another embodiment R2 is H.
In another embodiment R3 is selected from Ci-Cô alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Cô alkylphenyl, Ci-Cô alkylHet-1, Ci-C6alkyl-O-C(=O)Ci-C6 alkyl-O-Ci-Ce alkyl, Ci-Cé alkyl-O-C(=O)Ci-C6 alkyl-O-Ci-C6 alkyl-O- Ci-C6 alkyl, Ci-C6alkyl-O-C(=O)Ci-C6 alkylO-Ci-C6 haloalkyl, Ci-C6 alkyl-O-C(=O)Ci-C6 alkyl-N(Rx)C(=O)-O-phenyl, CrC6 alkyl-OC(=O)Ci-C6 alkyl-N(Rx)C(=O)-O-Ci-C6 alkylphenyl, Ci-C6 alkylC(=O)N(Rx)Ci-C6 alkyl, Ci-C6 alkylC(=O)N(Rx)Ci-C6 alkylHet-lC(=O)-O-Ci-C6 alkyl, Ci-C6alkylC(=O)N(Rx)Ci-C6 alkylHet-1, Ci-C6 alkylC(=O)Het-l, Ci-C6 alkylC(=O)N(Rx)Ci-C6 alkyl(N(Rx)(Ry))(C(=O)OH), Ci-C6 alkylC(=O)N(Rx)Ci-C6 alkylN(Rx)(Ry), Ci-C6 alkylC(=O)N(Rx)Ci-C6 alkylN(Rx)C(=O)-O-Ci-C6 alkyl, Ci-C6alkylC(=O)N(Rx)Ci-C6 alkyl(N(Rx)C(=O)-O-Ci-C6 alkyl)(C(=O)OH), Ci-C6alkylC(=O)Het-lC(=O)-O-Ci-C6 alkyl, Ci-C6alkyl-O-C(=O)-O-Ci-C6 alkyl, Ci-C6alkyl-O-C(=O)Ci-C6 alkyl, CrC6 alkyl-OC(=O)C3-C6 cycloalkyl, Ci-C6 alkyl-O-C(=O)Het-l, or Ci-C6 alkyl-O-C(=O)Ci-C6 alkylN(Rx)C(=O)-O-Ci-C6 alkyl, wherein each alkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, Ci-Cô alkyl, Ci-Cg haloalkyl, Ci-Cg haloalkoxy, S(=O)n(Ci-C6 alkyl), C(=O)OH, C(=O)O(CiCô alkyl), phenyl, Si(Ci-Cô alkyl)3, and S(=O)nNRxRy.
In another embodiment R4 is phenyl, C|-C6 alkylphenyl, Het-1, or Ci-Cf) alkyl-Ophenyl, wherein each alkyl, Het-1, and phenyl are optionally substituted with one or more substituents independently selected from F, Cl, NRxRy, Cj-Cg alkyl, C3-Cg cycloalkyl, C|-Cg haloalkoxy, C(=O)O Ci-Cg alkyl, or C]-Cg alkoxy.
In another embodiment R5 is substituted with oxo, C(=O)OH, phenyl, and Het-1, wherein each phenyl and Het-1, may be optionally substituted with one or more substituents independently selected from oxo, C]-Cg haloalkyl, Cj-Cg haloalkoxy, C(=O)OH, and halophenyl.
In another embodiment Rx and Ry are independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F and Cl.
In another embodiment:
Ari is a substituted phenyl wherein said substituted phenyl, has one or more C,-Cg haloalkoxy;
Het is a triazolyl;
Ar2 is a phenyl;
RI is H;
R2 is H;
R3 is Ci-Cé alkylHet-1 wherein said alkyl and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, Ci-C6 alkyl, Ci-Cô haloalkyl, CrC6 haloalkoxy, S(=O)n(Ci-C6 alkyl), C(=O)OH, C(=O)O(Ci-C6 alkyl), phenyl, Si(Ci-C6 alkyl)3, and S(=O)nNRxRy;
R4 is phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from F, Cl, NRxRy, Ci-Cg alkyl, or Ci-Cô alkoxy; and n= 0, 1, or 2;
Rx and Ry are independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F and Cl; and
Het-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen.
In another embodiment Het-1 is selected from benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydrooxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]oxadiazolyl.
In another embodiment Het is selected benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl,
4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[ 1,3,4]-oxadiazolyl.
In another embodiment Het-1 is selected from benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzothiadizolyl, cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, thienylpyrazolyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3dihydro-[ 1,3,4]-oxadiazolyl.
In another embodiment Het-1 is selected from benzothiadizolyl, furanyl, oxazolyl, and thienylpyrazolyl.
While these embodiments hâve been expressed, other embodiments and combinations of these expressed embodiments and other embodiments are possible.
The Molécules of Formulae One, Two and Three will generally hâve a molecular mass of about 100 Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally preferred if the molecular mass is from about 400 Daltons to about 800 Daltons.
PREPARATION OF TRIARYL-INTERMEDIATES
Compounds of this invention can be prepared by making a triaryl intermediate, AjjHet-Ar2, and then linking it to the desired intermediate to form the desired compound. A wide variety of triaryl intermediates can be used to préparé compounds of this invention, provided that such triaryl intermediates contain a suitable functional group on Ar2 to which the rest of the desired intermediate can be attached. Suitable functional groups include an oxoalkyl or a formyl group. These triaryl intermediates can be prepared by methods previously described in the chemical literature, including Crouse et al. PCT Int. Appl. Publ. W02009/102736 Al.
PREPARATION OF HYDRAZONE-LINKED COMPOUNDS
Hydrazone-linked compounds can be prepared from the corresponding aryl aldéhydes or ketones by one of three methods: (1) by reaction with a hydrazine, followed by reaction with an aryl isothiocyanate in tetrahydrofuran (THF), at températures between 0 and 100 °C (Reaction A); (2) by reaction with methyi hydrazinecarbodithioate, followed by reaction with an aniline in a polar aprotic solvent such as ΛζΑ-dimethylformamide (DMF), at températures between 25 and 150 °C (Reaction B); or (3) by reaction with an aryl thiosemicarbazide, that is either commercially available or can be prepared by one who is skilled in the art, in a polar 5 protic solvent such as ethyl alcohol (EtOH), at températures between 0 and 100 °C (Reaction
Q.
1. NH2NH-R2
2. R4-NCS,
THF, 0 - 100 °C
S (A)
RI
2. R4-NH2, DMF,
- 150 °C
H2N,
(C)
i
R3
EtOH, 0 - 100 °C
PREPARATION OF ALKYLATED HYDRAZONE-LINKED COMPOUNDS
Alkylated hydrazone-linked compounds can be prepared from the corresponding hydrazone-linked compounds by one of two methods: (1) by reaction with an alkylating agent in EtOH or acetone, at températures between 0 and 100 °C for from 1 to 24 h or (2) by reaction with an alkylating agent in chloroform (CHCI3), dichloromethane (CH2CI2), or other 15 halocarbon solvent, with or without a base such as sodium bicarbonate, at from 20 to 60 °C.
Alkylating agent, EtOH (D)
0-100 °C,
1-24 h
RI R2
RI R2 R3
I ι ι „Het Xxt.N2 »N3 Αη 'Ar2 N! 2f 3'R4
S xHet A N
Αη Ar2 N(
R4
Alkylating agent, CH2C12 or CHC13
R5
- 60 °C,
1-24 h
Compounds of Formula Two, wherein R5 forms a ring with N3 (see Scheme below) or of Formula Three, wherein R5 forms a ring with N2, can be prepared from a suitable acyclic precursor by using α-halo acids, acid halides, esters, or ketones (F or G or H). For example, treatment of the thiosemicarbazone with a slight excess of an α-halo ester, in a protic solvent such as EtOH or methyl alcohol (CH3OH) results in S-alkylation and subséquent ring closure exclusively onto N3 (Reaction F; see for example, J. Indian Chemical Society 1966, 43, 275-276, or J.Heterocycl. Chem. 1978,15, 335-336). When an aprotic solvent such as CH2C12 or dichloroethane (C1CH2CH2C1) is used at températures from 30 °C to 80 °C, the orientation of addition of α-halo ketones also favors closure onto N3, with subséquent déhydration to form an imino thiazole (Reaction G). With α-halo acids or acid halides or esters in a halocarbon solvent such as CH2C12 or C1CH2CH2C1, ring closure onto both N2 (Reaction H) and N3 is observed. Though these reactions often proceed in the absence of added base, a base such as sodium bicarbonate, sodium carbonate or sodium acetate, or an amine base such as pyridine or triethylamine, can be added.
R1 R2
R3
I
Νλ
Br^CO2H
Br^CO2CH3
EtOH or MeOH
O Br\J\
Br^CO2CH3
CH2C12 or
C1CH2CH2C1
(F) (θ) (H)
R4
H H
N. N
I R4
S
Alternatively, 3-arylidineimino-2-aryliminothiazolin-4-ones can be prepared by treating an aldéhyde or ketone, wherein RI is as previously described, with a 3-amino- 25 (arylimino)thiazolidin-4-one in acetic acid at from 30 to 70 °C as shown in the following scheme (I). The intermediate l-amino-2-aryliminothiazolin-5-one, wherein R4 is phenyl, has been described (see for example, J. Org. Chem. 1962, 27, 2878); it was prepared in 80% yield by treatment of 4-phenyl thiosemicarbazide with ethyl 2-chloroacetate and sodium acetate in hot EtOH.
Οχ
Br^CO2CH3 )—\
------- H2NNys N-R4 Ari >r2
Het y (i) O θχ ri
Het X ,N >S Αη Ar2 N Ύ NL R4
Alternatively, compounds of Formula 2 and Formula 3 may be formed by heating a thiosemicarbazone precursor with a di-halo group Hall-R5-Hal2 such as 1 -bromo-2-chloro ethane, in acetone or 2-butanone or other suitable solvent, using a base such as potassium carbonate or triethylamine, at températures between ambient and 100 °C for from 1 to 72 hours. The S-alkylated intermediate undergoes cyclization at N2 or N3 to generate compounds of Formula Two or Formula Three (Reaction J). In some cases, addition of Kl may be required to accelerate the cyclization of the intermediate S-alkylated dérivatives to 5 the ring-closed products.
S
Ha\ Hal Ri
RI
Q /Hal
R4
Kl (J)
RI
R4
An alternative method of preparing compounds of this invention is by treatment of a thiosemicarbazone precursor with an unsaturated ester or acid chloride (Reaction L).
Compounds of Formula Two, wherein R5 forms a hydroxyl-containing ring with N3, or of Formula Three, wherein R5 forms a hydroxyl-containing ring with N2 (see Scheme 15 below), can be prepared from a suitable acyclic precursor by using an cc-halo ketone (Reaction M). This procedure is similar to Reaction G; under milder conditions (usually ambient température to 90 °C), the intermediate hydroxy thiazoline can be isolated prior to déhydration. This procedure is conveniently conducted in an aprotic solvent such as acetone,
2-butanone or dichloroethane, with or without a base such as triethylamine or sodium bicarbonate. The direction of cyclization often favors reaction at N3, although when highly hindered R4 groups are used, products resuiting from cyclization at N2 may be formed.
Substituted hydrazinecarbothioamide intermediates, such as those utilized in Method C above, can be prepared by a number methods known in the chemical literature. Alternatively, compounds wherein Ra, Rb, and Rc are not derived from a commercially available aniline can be prepared according to the scheme below. For example, a 2-halo nitrobenzene, such as 2-chloronitrobenzene, substituted with one or multiple Rc substituents, wherein Rc can be H, alkyl, alkoxy, or halo, such as fiuoro, can be reacted with a boronic acid or boronate ester, such as the substituted 4,4,5,5-tetramethyl-l,3,2-dioxaborolane, wherein Ra and Rb are H, in the presence of a base, for example sodium carbonate, and a palladium catalyst, such as bis(triphenylphosphine)palladium(II)chloride, in an aqueous solvent system, such as 4:1 dioxane/water, at an elevated température, for example 80 °C, affords the alkenyl substituted nitrobenzene compounds. Alternatively, Ra and Rb can be taken together to form a ring, such as a cyclopentene, to give the corresponding 2-(cyclopent-1 -en-l-yl)-4,4,5,5tetramethyl-l,3,2-dioxaborolane, which under the conditions described above affords the cyclic alkene substituted nitrobenzene. Treatment of a solution of the olefinic nitrobenzenes in an aprotic solvent, such as ethyl acetate, wherein Ra, Rb, and Rc are as defined above, with hydrogen gas in the presence of a catalyst, for example palladium on carbon (Pd / C), affords the corresponding alkyl or cycloalkyl substituted anilines. Treating a biphasic solution of the anilines, wherein Ra, Rb, and Rc are as defined, in a mixture of halogenated solvent and water, such as 2:1 dichloromethane / water, with a base, such as sodium hydrogencarbonate, followed by thiophosgene affords the intermediate isothiocyanatobenzenes. Séparation and removal ofthe aqueous phase, followed by drying and évaporation ofthe organic solvent affords the crude intermediate, which is immediately dissolved in an alcohol, such as éthanol, and treated with hydrazine hydrate to give the hydrazinecarbothioamide intermediates, wherein Ra, Rb, and Rc are as defined.
EXAMPLES
The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.
Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molécules are given their known names, named according to naming programs within MDL ISIS™/Draw 2.5, ChemBioDraw Ultra 12.0 or ACD Name Pro. If such programs are unable to name a molécule, the molécule is named using conventional naming rules. *H NMR spectral data are in ppm (δ) and were recorded at 300, 400 or 600 MHz, and 13C NMR spectral data are in ppm (δ) and were recorded at 75, 100 or 150 MHz, unless otherwise stated.
Example 1: Préparation of (/f)-A-(4-dimethylamino)phenyl)-2-(4-(l-(4(triiluoromethoxy)phenyl)-l//-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 1-1) [Synthesis Method A].
Step 1. (£)-3-(4-(Hydi azonomethyl)phenyl)-l-(4-(tritluoromethoxy)phenvl)-lH-
1,2,4-triazole. To a 250 milliliter (mL) round-bottomed flask containing hydrazine hydrate (64% aqueous (aq) solution; 7.27 mL, 15.0 millimoles (mmol)) in EtOH (100 mL) at 80 °C was added 4-[l-(4-trifluoromethoxyphenyl)-l//-[l,2,4]triazol-3-yl]-benzaldehyde (5.00 grams (g), 1.50 mmol) portionwise over 5 minutes (min). The solution was stirred at reflux for an additional 3 hours (h) before being diluted with water (H2O; 300 mL) and cooled to 0 °C. The precipitated product was collected by vacuum filtration as a white solid (4.89 g, 93%): mp 222 - 226 °C; Ή NMR (400 MHz, DMSO-J6) δ 8.59 (s, 1H), 8.22 (d, J= 8.2 Hz, 2H), 7.84-7.79 (m, 3H), 7.66 (d, J= 8.3 Hz, 2H), 7.41 (d, J= 8.2 Hz, 2H), 7.29 (s, 1H), 5.63 (br s, 2H); ESIMS m/z 348 (M+H).
Step 2. To a 25 mL round-bottomed flask containing (£)-3-(4-(hydrazonomethyl)phenyl)-l-(4-(trifluoromethoxy)phenyl)-\H- 1,2,4-triazole (250 mg, 0.720 mmol) in THF (10 mL) was added 4-isothiocyanato-Ar,/V-dimethylaniline (385 mg, 2.16 mmol). The contents were heated at 65 °C with stirring for 2 h before the solvent was removed under reduced pressure. The residue was slurried in CH2C12 (10 mL) resulting in précipitation of product material. The desired product was obtained as a yellow solid via vacuum filtration (350 mg, 93%): mp 205 - 208 °C; Ή NMR (400 MHz, DMSO-J6) δ 11.78 (s, 1H), 10.02 (s, 1H), 9.42 (s, 1H), 8.19-7.99 (m, 6H), 7.64 (d, J= 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 7.73 (d, J= 8.3 Hz, 2H), 2.92 (s, 6H); ESIMS m/z 526 (M+H).
Example 2: Préparation of A-(3-(dimethylamino)pheny 1)-2-(4-(1-(4(trifluoromethoxy)phenyl)-lfi-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 1-2) [Synthesis Method B].
Step 1. (E)-Methyl 2-(4-(l-(4-(trifluoromethoxy)phenyl)-l//-l,2,4-triazol-3yl)benzylidene)hydrazinecarbodithioate. To a 250 mL round-bottom flask containing hydrazinecarbodithioic acid methyl ester (2.38 g, 1.95 mmol) in EtOH (100 mL) was added
4-[l-(4-trifluoromethoxyphenyl)-l/Z-[l,2,4]triazol-3-yl]-benzaldehyde (5.00 g, 1.50 mmol). The vessel was heated at 80 °C for 3 h before being diluted with H2O (300 mL) and cooled to 0 °C. The precipitated product was collected by vacuum filtration as an off-white solid (6.13 g, 93%): mp 204 - 206 °C; ’H NMR (400 MHz, DMSO-î/6) δ 13.39 (s, 1H), 9.43 (s, 1H),
8.38 (s, 1H), 8.21 (d, J= 8.3 Hz, 2H), 8.09 (d, J= 8.4 Hz, 2H), 7.88 (d, J= 8.4 Hz, 2H), 7.62 (d, J= 8.3 Hz, 2H), 2.57 (s, 3H); ESIMS m/z 438 (M+H).
Step 2. To a 50 mL round-bottomed flask containing (E)-methyl 2-(4-(1-(4(trifluoromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbodithioate (250 mg, 0.571 mmol) in DMF (3 mL) was added -dimethylbenzene-1,3-diamine (195 mg,
1.43 mmol). The contents were heated at 150 °C with stirring for 5 h before the solution was allowed to cool ovemight. The mixture was filtered, and the filtrate was purified via RPHPLC to afford the desired material (235 mg, 78%) as an off-white solid: mp 192-194 °C; 'HNMR (400 MHz, DMSO-J6) δ 11.82 (s, 1H), 10.04 (s, 1H), 9.41 (s, 1H), 8.19 (s, 1H), 8.16-7.99 (m, 6H), 7.61 (d, J= 8.3 Hz, 2H), 7.16 (t, J= 7.2 Hz, 1H), 7.01 (m, 1H), 6.87 (m, 1H), 6.58 (m, 1H), 2.88 (s, 6H); ESIMS m/z 526 ([M+H]+).
Example 3: Préparation of A-benzyl-2-(4-(l-(4-(trifluoromethoxy)phenyl)-117-l,2,4triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 1-3) [Synthesis Method C].
To a 50 mL round-bottomed flask containing 4-[l-[4-(trifluoromethoxy)phenyl]- l,2,4-triazol-3-yl]benzaldehyde (500 mg, 1.5 mmol) in EtOH (3 mL) was added 4benzylthiosemicarbazide (650 mg, 3.6 mmol). The reaction mixture was heated at 80 °C ovemight. H2O was added upon completion of the reaction, and the crude product material was isolated by vacuum filtration. The title compound was isolated via RP-HPLC as a white solid (390 mg, 52%): mp 220 - 224 °C; 'H NMR (400 MHz, CDCI3) δ 9.29 (s, 1H), 8.59 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 7.85-7.79 (m, 3H), 7.71 (d, J= 8.4 Hz, 2H), 7.46-7.30 (m, 8H), 5.01 (d, J= 5.8 Hz, 2H); ESIMS m/z 497.2 (M+H).
Compounds 1-4 through 1-31 in Table 1 were synthesized in accordance with the examples above. Other intermediates used in the préparation of compounds of this invention were prepared in accordance with the procedures described in Brown, et al, WO 2011017504 Al, or by other known routes.
Example 4: Préparation of .V-(4-dimethylaminophenyl)-S-methyl-2-{4-|l-(4trifluoromethoxyplienyl)-l//-| 1,2,4 ]-triazol-3-yl]-benzylidene}-hydrazinecarbothioamide (Compound IC) (Synthesis Method D)
A solution containing (£)-A-(4-(dimethylamino)phenyl)-2-(4-(l-(4(trifluoromethoxy)phenyl)-l/Z-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (150 mg, 0.285 mmol) and iodomethane (0.054 mL, 0.856 mmol) in EtOH (5 mL) was heated at 80 °C for 3 h before the solvent was removed under reduced pressure. The residue was purified via normal phase flash chromatography (gradient elution with hexanes/EtOAc) to afford the title compound as an orange foam (93 milligrams (mg), 60%): ’H NMR (400 MHz, DMSO-6/6) δ 8.61 (s, 1H), 8.48 (s, 1H), 8.22 (d, J= 8.24 Hz, 2H), 8.17 (s, 1H), 7.89 (d, J= 8.24 Hz, 2H), 7.80 (d, J= 8.28 Hz, 2H), 7.41 (d, J= 8.28 Hz, 2H), 7.19 (d, J= 8.24 Hz, 2H), 6.71 (d, J= 8.24 Hz, 2H), 2.99 (s, 6H), 2.42 (s, 3H); EIMS m/z 540 (M+).
Example 5: General procedure for S-alkylation of triaryl thiosemicarbazones (Synthesis Method E)
A stirred solution of the thiosemicarbazone and alkylating reagent in CH2CI2 or chloroform (CHCI3) was heated at from 35 to 50 °C for from 10 to 24 h. The cooled solution was concentrated under reduced pressure. The residue was generally purified via chromatography using a chloroform/methanol (CHCI3/CH3OH) or EtOAc-hexane solution as the eluent to afford the S-alkylated products.
Example 6: Préparation of (X)-/VH-butyl 3-((2-((Z)-(2,6-dimethylphenylimino)-((£)-2-(4(l-(4-(trifluoromethoxy)phenyl)-lÆ-l,2,4-triazol-3-yl)benzylidene)hydrazinyl)23 methylthio)acetamido)methyl)piperidine-l-carboxylate (Compound 56C) (Synthesis Method E)
To a solution of bromoacetyl bromide (26 microliters (pL), 0.299 mmol) in dichloroethane (3 mL) was added dropwise a solution of (S)-terkbutyl 3(aminomethyl)piperidine-l-carboxylate (63.9 mg, 0.298 mmol) in dichloromethane (1 mL), followed by /V-ethyl-7V-isopropylpropan-2-amine (76 mg, 0.588 mmol). This mixture was stirred at room température for 30 min, then (E)-N-(2,6-dimethylphenyl)-2-(4-(l-(4(trifluoromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzylidene)hydrazine-carbothioamide (100 mg, 0.196 mmol) was added as a solid and the mixture was heated to 40 °C for 90 min. It was then allowed to cool to room température and evaporated under reduced pressure, giving a light yellow glass, which was dissolved in acetonitrile (2 mL) and allowed to stand at room température. The resulting precipitate was isolated by centrifuge and decanting, washing with ffesh acetonitrile. The solid was dried under a nitrogen stream and then under high vacuum. The crude product was recrystallized from acetone-isopropyl alcohol. The title compound was isolated as a white solid (36.5 mg, 24%): mp 148 - 151 °C; H NMR (400 MHz, methanol-iZ4) δ 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J= 8.1 Hz, 2H), 8.12 (m, 2H), 8.07 - 8.00 (m, 2H), 7.58 - 7.43 (m, 2H), 7.33 (dd, J= 8.6, 6.5 Hz, 1H), 7.25 (d, J= 7.6 Hz, 2H), 4.02 (m, 2H), 3.97 - 3.75 (m, 2H), 3.21 (d, J= 6.9 Hz, 2H), 2.90 (m, 1H), 2.59 (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 - 1.63 (m, 2H), 1.44 (s, 9H), 1.29 (m, 3H); ESIMS m/z 765 (M+H).
Example 7: Préparation of (lZ,2£)-2-oxo-2-(((7î)-piperidin-3-ylmethyl)ainino)ethyl N(2,6-dimethylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-LH-l,2,4-triazol-3yl)benzylidene)hydrazinecarbimidothioate trifluoroacetic acid (Compound 62C) (Synthesis Method K)
A solution of (5)-ierZ-butyl 3-((2-((Z)-(2,6-dimethylphenylimino)-((£)-2-(4-(l-(4(trifluoromethoxy)phenyl)-177-1,2,4-tri azol-3-yl)benzylidene)hydrazinyl)methylthio)acetamido)methyl)piperidine-l-carboxylate (32.0 mg, 0.042 mmol) in TFA (250 pL, 3.24 mmol) was stirred at room température for 10 min. Et2O (10 mL) was then added giving a white precipitate, which was isolated by centrifuge and decanting, then rinsing with fresh Et2O (5 mL). The solid was dried under nitrogen stream and then under high vacuum giving the title compound as a white solid (19.8 mg, 60%): mp 110 - 120 °C; 'H NMR (400 MHz, methanol-<Z4) δ 9.18 (s, 1H), 8.56 (m, 1H), 8.26 (m, 2H), 8.16 - 7.84 (m, 4H), 7.52 (m, 2H), 7.27 (m, 1H), 7.22 (m, 2H), 4.00 (s, 2H), 3.28 (m, 3H), 3.06 - 2.83 (m, 1H), 2.75 (t, J= 12.2 Hz, 1H), 2.34 (s, 6H), 2.21 - 1.83 (m, 4H), 1.72 (m, 1H), 1.47 - 1.19 (m, 2H); ESIMS m/z 665 (M+H).
Example 8: Préparation of 2-(((Z)-((4-methoxy-2,6-dimethylphenyl)imino)((E)-2-(4-(l(4-(tr i fin o roniethoxy)pheny 1)-177-1,2,4-triazoI-3-yl)benzylidene)hydrazinyl) methyl)thio)acetic acid sodium sait (Compound 68C)
To a solution of 2-((Z)-(4-methoxy-2,6-dimethylphenylimino)((£')-2-(4-(l-(4(trifluoromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzylidene)hydrazinyl)methylthio)acetic acid (77.7 mg, 0.130 mmol) in THF (10 mL) was added slowly sodium methanolate (0.5 M in methanol; 260 pL, 0.130 mmol) at room température. The mixture immediately tumed a darker yellow and was then evaporated at room température under vacuum giving a light orange solid. This material was triturated with Et2O (2X) and isolated by decanting using a centrifuge and drying under a nitrogen stream and then under high vacuum. The title compound was isolated as a light orange solid (32 mg, 39%): mp 146-154 °C; *H NMR (400 MHz, methanol-J4) δ 9.11 (s, 1H), 8.64 - 7.68 (m, 7H), 7.51 (m, 2H), 6.70 (s, 2H), 3.85 - 3.70 (m, 4H), 3.61 (m, 1H), 2.29 (s, 6H); ESIMS m/z 599 (M+H).
Example 9: Préparation of (Z)-3-(4-methoxy-2,6-dimethylphenyI)-2-((jE)-(4-(l-(4(trifluoromethoxy)ph envi)-1/7-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4one (Compound 69C) (Synthesis Method F)
To a solution of (£)-N-(4-methoxy-2,6-dimethylphenyl)-2-(4-(l-(4(trifhioromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzylidene)hydrazine-carbothioamide (250 mg, 0.462 mmol) in EtOH (5 mL) was added methyl bromoacetate (100 mg, 0.65 mmol), and the mixture was heated to 70 °C for 4 h. The mixture was allowed to cool to room température and diluted with water (1 mL). The precipitate was vacuum filtered, giving the title compound as a white solid (204 mg, 76%): mp 188 - 190 °C; 'H NMR (400 MHz, CDC13) δ 8.56 (s, 1H), 8.33 (s, 1H), 8.22 (d, J= 8.1 Hz, 2H), 7.90-7.70 (m, 4H), 7.39 (d, J= 8.7 Hz, 2H), 6.72 (s, 2H), 4.01 (s, 2H), 3.87 - 3.73 (s, 3H), 2.18 (s, 6H); ESIMS m/z 581 (M+H).
Example 10: Préparation of 4-((2Z)-3-(2,6-dimethylphenyl)-2-((4-(l-(4(trifluoromethoxy)phenyl)-lZ7-l,2,4-triazol-3-yI)benzylidene)hydrazono)-2,3dihydrothiazol-4-yl)-7V,/V-diethylaniline (Compound 74C) (Synthesis Method G)
To a solution of (E)-N-(2,6-dimethylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)lH-l,2,4-triazol-3-yl)benzylidene)hydrazine-carbothioamide (74.7 mg, 0.144 mmol) in dichloroethane (5 mL), was added a-bromo-4-diethylamino)acetophenone (53.9 mg, 0.199 mmol), and the mixture was heated to 40 °C for 4 h. The mixture was then cooled to room température and evaporated under vacuum. The crude material was triturated with acetonitrile and decanted (2X). The resulting solid was dried under a stream of nitrogen, giving the title compound as a pale yellow solid (25 mg, 25%): mp 190 - 193 °C dec; lH NMR (400 MHz, methanol-iZ4) δ 9.20 (s, 1H), 8.38 (s, 1H), 8.31 - 8.24 (m, 2H), 8.08 - 8.00 (m, 2H), 7.95 7.88 (m, 2H), 7.55 - 7.48 (m, 3H), 7.48 - 7.36 (m, 5H), 7.31 (d, J= 7.7 Hz, 2H), 3.60 (q, J=
7.2 Hz, 4H), 2.20 (s, 6H), 1.07 (t, 7.2 Hz, 6H); ESIMS m/z 682 (M+H).
Example 11: Préparation of (Z)-2-(2,6-dimethylphenylimino)-3-((jE)-4-(l-(4(trifluoromethoxy)phenyl)-ljHr-l,2,4-triazol-3-yl)benzylideneamino)thiazolidin-4-one (Compound 81C) (Synthesis Method I)
To a solution of 1 -(2,6-dimethylphenyl)thiourea (1.0 g, 5.55 mmol) in EtOH (10 mL) was added methyl 2-bromoacetate (1.0 g, 6.5 mmol) and sodium acetate (1.0 g, 12.2 mmol). The solution was stirred and heated to reflux for 1 h, then it was cooled and the liquid was decanted from a small amount of solid material and the liquid was then diluted with water (10 ml,). The precipitate was isolatedby filtration to give (1.1 g, 83%) of (Z)-3-amino-2-(2,6dimethylphenylimino)thiazolidin-4-one: mp 149- 152 °C; !H NMR (400 MHz, CDCfi) δ
7.06 (d, J= 7.2 Hz, 2H), 6.98 (m, 1H), 4.75 (s, 2H), 3.80 (s, 2H), 2.12 (s, 6H); ESIMS m/z 236 (M+H).
A portion of this material (0.07 g, 0.3 mmol) was dissolved in glacial acetic acid (3 mL) and treated with 4-(l-(4-(trifluoromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzaldehyde (0.10 g, 0.30 mmol), and the solution was heated to 60 °C for 2 h. The solution was then cooled and diluted with water (1 mL), and the resulting solid was filtered and air-dried to give the title compound (0.12 g, 67%): mp 209 - 213 °C; ’H NMR (400 MHz, CDCfi) δ 9.42 (s, 1H), 8.59 (s, 1H), 8.28 (d, J= 8.4 Hz, 2H), 8.01 (d, J= 8.3 Hz, 2H), 7.80 - 7.77 (m, 2H),
7.43 - 7.34 (m, 2H), 7.07 (d, J= 7.5 Hz, 2H), 6.98 (dd, J= 8.2, 6.7 Hz, 1H), 3.90 (s, 2H),
2.17 (s, 6H); ESIMS m/z 551 (M+H).
Example 12: Préparation of (2Z,A£')-2-((2-isopiopylphenyl)imino)-N-(4-(l-(4(trifluoromethyl)phenyl)- 1H-1,2,4-triazol-3-yl)benzylidene)-1,3-thiazinan-3-amine and (Z)-3-(2-isopropylphenyl)-2-((E)-(4-(l-(4-(trifluoromethyl)phenyl)-LH-l,2,4-triazol-3yl)benzylidene)hydrazono)-l,3-thiazinane (Compound 87C and 179C) (Synthesis Method J)
To (E)-/V-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethyl)phenyl)-lH-l,2,4-triazol-3yl)benzylidene)hydrazinecarbothioamide (200 mg, 0.393 mmol) and potassium carbonate (217 mg, 1.57 mmol) in butanone (10 ml) in a 25 mL vial equipped with a stirbar and vigruex column was added l-bromo-3-chloropropane (0.047 ml, 0.472 mmol). The reaction was heated to 60 °C ovemight. The reaction was determined to be complété by LCMS. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided two compounds. The minor compound was dried ovemight under house vacuum providing the title compound 87C (2Z^VE)-2-((2-isopropylphenyl)imino)-7V-(4-(l-(4-(trifluoromethyl)phenyl)-l//-l,2,4-triazol-
3-yl)benzylidene)-l,3-thiazinan-3-amine (28.5 mg, 13%) as a yellow solid: mp 187-189 °C;
’H NMR (400 MHz, CDC13) δ 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J= 8.3 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.81 (t, J= 10.2 Hz, 4H), 7.30 - 7.26 (m, 2H), 7.17 - 7.04 (m, 1H), 6.83 (d, J = 6.4 Hz, 1H), 3.96 (t, J = 6.1 Hz, 2H), 3.13 (heptet, J = 6.9 Hz, 1H), 2.97 - 2.90 (m, 2H),
2.47 - 2.38 (m, 2H), 1.25 (d, J= 7.5 Hz, 6H); ESIMS m/z 550 (M+H). The major compound was recrystallized with MeOH. The solid was filtered, washed with MeOH and dried at 50°C under vacuum. The solid was then azeotroped with acetone (3x) and the résultant solid was dried at 50°C under vacuum providing the title compound 179C (Z)-3-(2-isopropylphenyl)-2((£)-(4-(1 -(4-(trifluoromethyl)phenyl)-\H-1,2,4-triazol-3 -yl)benzylidene)hydrazono)-1,3thiazinane as a yellow solid (92.3 mg, 0.168 mmol, 43%): mp 212-213 °C; Y NMR (400 MHz, CDC13) δ 8.64 (s, 1H), 8.15 (d, 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J= 8.5 Hz, 2H),
7.79 (d, J= 8.6 Hz, 2H), 7.75 (d, 8.4 Hz, 2H), 7.38 (dd, J= 7.8, 1.6 Hz, 1H), 7.33 (td, J =
7.5, 1.4 Hz, 1H), 7.29-7.23 (m, 1H), 7.18 (dd, J= 7.8, 1.4 Hz, 1H), 3.78 - 3.72 (m, 1H), 3.59 - 3.48 (m, 1H), 3.18 - 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, 6H); ESIMS m/z 550 (M+H).
Example 13: Préparation of (Z)-3-(2-cyclopropylphenyl)-5-methyl-2-((£)-(4-(l-(4(trifluoromethoxy)phenyl)-l//-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4one (Compound 127C) (Synthesis Method F)
To (£)-N-(2-cyclopropylphenyl)-2-(4-(l-(4-(trifluoromethoxyjphenyl)-1/7-1,2,4triazol-3-yl)benzylidene)hydrazinecarbothioamide (100 mg, 0.191 mmol) and sodium acetate (63.0 mg, 0.765 mmol) in EtOH (4 mL) was added methyl 2-bromopropanoate (0.026 mL, 0.230 mmol). The reaction was heated to 60 °C ovemight. The reaction was then heated to 85 °C for 72 hours. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided the title compound as a white solid (32.5 mg, 0.056 mmol, 30%): mp 112-115 °C; 'H NMR (400 MHz, CDCI3) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.43
- 7.32 (m, 4H), 7.26 - 7.24 (m, 2H), 4.23 (q, J= 7.3 Hz, 1H), 1.85 - 1.78 (m, 4H), 0.90 0.78 (m, 2H), 0.78 - 0.69 (m, 1H), 0.65 - 0.55 (m, 1H); ESIMS m/z 578 (M+H).
Example 14: Préparation of (Z)-3-(2-isopropylphenyl)-2-((£)-(4-(l-(4(trifluoromethoxy)phenyl)-lH-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidine (Compound 132C) (Synthesis Method J)
To (£)-A-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-17/-l,2,4-triazol-
3-yl)benzylidene)hydrazinecarbothioamide (214 mg, 0.407 mmol) and potassium carbonate (225 mg, 1.63 mmol) in butanone (4 ml) was added 1-bromo-2-chloroethane (70.0 mg, 0.489 mmol). The reaction was heated to 90 °C ovemight. The reaction was determined to be complété by LCMS. The reaction mixture was cooled, diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were filtered through a phase separator and concentrated. Séparation by flash column chromatography and drying the recovered solid at 55 °C under vacuum provided the title compound as a white solid (137 mg, 0.249 mmol, 61%): mp 193 - 196 °C; ‘H NMR (400 MHz, CDC13) δ 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.80 (ddd, J= 9.5, 6.9, 4.9 Hz, 4H), 7.43 - 7.33 (m, 4H), 7.31 - 7.21 (m, 2H), 4.05 (td, J= 9.4, 7.1 Hz, 1H), 3.97 - 3.87 (m, 1H), 3.42 - 3.33 (m, 1H), 3.33-3.24 (m, 1H), 3.12 (heptet, J= 6.8 Hz, 1H), 1.27 (d, J= 6.8 Hz, 3H), 1.22 (d, J =6.9 Hz, 3H); ESIMS m/z 552 (M+H).
Example 15: Préparation of (Z)-3-(2-isopropylphenyl)-4-methyl-2-((E)-(4-(l-(4(trifluoromethoxy)phenyI)-117-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidine (Compound 155C) (Synthesis Method J)
To (£)-7V-(2-isopropylphenyl)-2-(4-(l -(4-(trifluoromethoxy)phenyl)-177-1 ,2,4-triazol3-yl)benzylidene)hydrazinecarbothioamide (300 mg, 0.572 mmol) and potassium carbonate (316 mg, 2.29 mmol) in butanone (4 ml) was added 1,2-dibromopropane (0.072 ml, 0.686 mmol). The reaction was heated to 85 °C overnight. The reaction was determined to be complété by LCMS. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow solid. The solid was recrystallized from MeOH. The solid was filtered, washed with MeOH, and dried to provide the title compound as a yellow solid which was dissolved in acetone and concentrated (3x). The light yellow solid was collected and dried under to provide the title compound as a 1:1 mixture of rotational diastereoisomers (75.1 mg, 0.133 mmol, 23%): mp 201 - 204 °C; ’H NMR of mixture (400 MHz, CDC13) δ 8.56 (s, 2H), 8.18 (dd, J= 10.8, 7.4 Hz, 6H), 7.84 - 7.73 (m, 8H), 7.45 - 7.30 (m, 8H), 7.30 - 7.23 (m, 2H), 7.20 (d, J= 6.7 Hz, 1H), 7.12 (dd, J= 7.8, 1.2 Hz, 1H), 4.43 - 4.33 (m, 1H), 4.16 (dd, J= 12.6, 6.3 Hz, 1H), 3.48 (dt, J= 13.3,6.7 Hz, 1H), 3.37 (dd, 10.8, 6.2 Hz, 1 H), 3.24 (dt, J= 13.7, 6.9 Hz, 1H), 3.08 - 2.92 (m, 3H), 1.33 - 1.16 (m, 18H); ESIMS m/z 566 (M+H).
Example 16: Préparation of (Z)-3-(2,6-dimethylphenyl)-4-methyl-2-((4E)-(4-(l-(4(trifluoromethoxy)phenyl)-ljff-l,2,4-triazol-3-yl)benzylidene)hydrazono)-2,3dihydrothiazole (Compound 173C) (Synthesis Method G)
To a solution of (£)-N-(o-tolyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-\H-1,2,4triazol-3-yl)benzylidene)hydrazinecarbothioamide (257 mg, 0.520 mmol) in butanone (5 mL) was added triethylamine (0.14 mL, 1.0 mmol) and chloroacetone (0.06 mL, 0.73 mmol) and refluxed at 75 °C for 15 h. The mixture was allowed to cool to room température and then transferred to a separatory tunnel containing water (5 mL) and extracted twice with dichloromethane. The organic layers were filtered through a phase separator, adsorbed onto silica gel, and purified by flash column chromatography to afford the title compound as a yellow solid (229 mg, 83%): mp 87 °C (dec); ’H NMR (400 MHz, CDC13) δ 8.56 (s, 1H), 8.19-8.15 (m, 3H), 7.82 - 7.75 (m, 4H), 7.43 - 7.30 (m, 5H), 7.24 (d, J= 7.3 Hz, 1H), 5.88 (d, J= 1.3 Hz, 1H), 2.21 (s, 3H), 1.80 (d, J= 1.2 Hz, 3H); ESIMS m/z 536 (M+H).
Example 17: Préparation of (Z)-3-(2-isopropylphenyl)-5-methyl-2-((E)-(4-(l-(4(trifluoromethoxy)pheny 1)-1//-1,2,4-triazol-3-yl)benzylidene)hydrazono)-l,3-thiazinane (Compound 178C) (Synthesis Method J)
To (£')-#-(2-isopropylphenyl)-2-(4-( 1 -(4-(trifluoromethoxy)phenyl)-1/7-1,2,4-triazol3-yl)benzylidene)hydrazinecarbothioamide (100 mg, 0.191 mmol) and potassium carbonate (105 mg, 0.763 mmol) in butanone (4 ml) was added l-bromo-3-chloro-2-methylpropane (39.0 mg, 0.229 mmol). The reaction was heated to 80 °C overnight. The reaction mixture was then diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided the title compound as a light yellow solid as a mixture of rotational diastereoisomers: mp 186— 190 °C; !H NMR (400 MHz, CDC13) δ 8.55 (d, J= 3.6 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.84-7.77 (m, 2H), 7.74 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 9.0 Hz, 3H), 7.32 (td, J= 7.5, 1.4 Hz, 1H), 7.26 (s, 1H),
7.17 (t, J= 7.1 Hz, 1H), 3.69 - 3.26 (m, 1H), 3.55 - 3.37 (m, 1H), 3.18 - 2.98 (m, 2H), 2.93 -
2.80 (m, 1H), 2.47 (d, 7 = 35.9 Hz, 1H), 1.31 - 1.12 (m, 9H); ESIMS m/z 580 (M+H).
Example 18: Préparation of (Z)-3-(2,6-dimethylphenyl)-2-((E)-(4-(l-(4(tri lluoro met hoxy)pheny 1)-1//-1,2,4-triazol-3-y l)benzyliden e)hydrazono)-l ,3-thiazepane (Compound 211C) (Synthesis Method J)
To (E)-/V-(2,6-dimethylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-177-l,2,4triazol-3-yl)benzylidene)hydrazinecarbothioamide (500 mg, 0.979 mmol) and potassium carbonate (541 mg, 3.92 mmol) in acetone (4 ml) was added 1 -bromo-4-chlorobutane (0.135 ml, 1.18 mmol). The reaction was heated to 60 °C ovemight. The alkylation was determined to be complété by ultra performance liquid chromatography (“UPLC”). The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided (lZ,7V'E)-4-chlorobutyl /V-(2,6-dimethylphenyl)-2V’(4-( 1 -(4-(trifluoromethoxy)phenyl)-177-1,2,4-triazol-3 yl)benzylidene)carbamohydrazonothioate (427 mg, 0.710 mmol, 73%) as a yellow gum which was used without further purification. To (lZ,7V'7T)-4-chlorobutyl N-(2,6dimethylphenyl)-TV-(4-(l-(4-(trifluoromethoxy)phenyl)-177-1,2,4-triazol-3-yl)benzylidene)carbamohydrazonothioate (427 mg, 0.710 mmol), potassium iodide (236 mg, 1.42 mmol) and potassium carbonate (393 mg, 2.84 mmol) was added acetone (7 ml). The reaction was heated to 65°C for 72 h. The reaction was cooled to room température, diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow oil. The yellow oil was recrystallized from MeOH, filtered, washed with MeOH and dried to provide the title compound as a yellow solid (100 mg, 0.177 mmol, 25%); mp 100 - 106 °C; 'H NMR (400 MHz, CDC13) δ 8.55 (s, IH), 8.15 (d, J= 8.4 Hz, 2H), 8.10 (s, IH), 7.79 (dt, J= 10.4, 5.8 Hz, 4H), 7.38 (d, J = 8.3 Hz, 2H),
7.11 (s, 3H), 3.85 - 3.78 (m, 2H), 3.20 - 3.12 (m, 2H), 2.30 (s, 6H), 2.13 - 2.07 (m, 2H), 1.87 - 1.82 (m, 2H); ESIMS m/z 566 (M+H).
Example 19: Préparation of (Z)-3-(2-isopropylphenyl)-2-((E)-(4-(l-(4(trifluoromethoxy)phenyl)-177-l,2,4-triazol-3-yl)benzylidene)hydrazono)-l,3-thiazinan-
4-one (Compound 224C) (Synthesis Method L)
To (£)-/V-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-177-l,2,4-triazol3-yl)benzylidene)hydrazinecarbothioamide (500 mg, 0.953 mmol) in butanone (9.5 ml) was added acryloyl chloride (0.077 ml, 0.953 mmol). The reaction was stirred at ambient température for 10 min followed by 50 °C for 2 h. The reaction was cooled to 40 °C overnight. The reaction was determined to be complété by LCMS. The reaction mixture was diluted with DCM and washed with saturated sodium bicarbonate. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow oil. The oil was recrystallized with diethyl ether/hexanes to provide the title compound as a light yellow solid (125 mg, 0.217 mmol, 23%): mp 118 °C (dec); *H NMR (400 MHz, CDC13) δ 8.57 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 - 7.75 (m, 4H), 7.46 - 7.36 (m, 4H), 7.33 7.26 (m, 1H), 7.10 (d, J= 7.6 Hz, 1H), 3.26 - 3.14 (m, 4H), 2.81 (heptet, J= 6.9 Hz, 1H),
1.21 (t, J= 7.2 Hz, 6H); ESIMS m/z 580 (M+H).
Example 20: Séparation of rotationally stable atropisomers from racemic mixtures
Séparation of constituent isomers from racemic mixtures can be carried out utilizing one of the following chiral HPLC methods.
Séparation Method A: The column used for séparation was a Chiral Technologies INC Chiral Pak 1A 5 μιη, 4.6 X 250 mm column (Part number 80325). The method consists of a 1.0 ml,/min flow rate from 0 to 30 min with an isocratic hold at 25% B for the duration of the run. The A eluent is n-hexane, the B eluent is Z5o-propyl alcohol.
Séparation Method B: The column used for séparation was a Chiral Technologies INC Chiral Pak IB 5 pm, 4.6 X 250 mm column (Part number 81325). The method consists of a 1.0 ml,/min flow rate from 0 to 30 min with an isocratichold at 15% B for the duration of the run. The A eluent is n-pentane, the B eluent is π-butyl alcohol.
Example 21: Préparation of (Z)-3-(2,6-difluorophenyl)-4-methyl-2-((E)-(4-(l-(4(trifluoroniethoxy)phenyl)-l//-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4-ol (Compound 240C; Synthesis Method M).
To a solution of (£)-7V-(2,6-difluorophenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-lÆ-
I, 2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (253 mg, 0.49 mmol) inbutanone (4.9 mL) was added triethylamine (0.14 mL, 0.98 mmol) and chloroacetone (0.055 mL, 0.68 mmol), and the reaction was stirred at 80 °C for 15 hours. The mixture was allowed to cool to room température, transferred to a separatory funnel containing water (5 mL), and extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0 - 20% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes) to afford the title compound as a yellow solid (248 mg, 88%); mp 105 °C (dec); *H NMR (400 MHz, CDC13) δ 8.57 (s, 1H), 8.25 - 8.12 (m, 3H), 7.88 - 7.72 (m, 4H), 7.39 (d, 8.5 Hz, 3H), 7.06 (td, J= 8.9, 4.4 Hz, 2H), 3.58 (d, J =
II. 5 Hz, 1H), 3.37 (d, J= 11.5 Hz, 1 H), 3.24 (d, J=2.7 Hz, 1H), 1.59 (s, 3H); 19F NMR (376 MHz, CDCI3) δ -58.02, -113.71, -115.83, -115.84; ESIMS m/z 576 (M+H)+.
Example 22: Préparation of (Z)-2-((2-chloro-6-(trifluoromethyl)phenyl)imino)-4methyl-3-((E)-(4-(l-(4-(trifluoromethoxy)phenyl)-lH-l,2,4-triazol-3yl)benzylidene)amino)thiazolidin-4-ol (Compound 241C; Synthesis Method M).
To a solution of (E)-7V-(2-chloro-6-(trifluoromethyl)phenyl)-2-(4-(l-(4(trifluoromethoxy)-phenyl)-lH-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (111 mg, 0.19 mmol) in butanone (2 mL) was added chloroacetone (0.02 mL, 0.27 mmol) and triethylamine (0.05 mL, 0.38 mmol), and the reaction was stirred at 75 °C for 16 hours. The mixture was allowed to cool to room température, transferred to a separatory funnel containing water (5 mL), and was extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0 - 20% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes). The title compound was isolated as a yellow solid (60.5 mg, 50%): mp 97 °C (dec); *H NMR (400 MHz, CDC13) δ 9.72 - 9.57 (m, IH), 8.58 (s, IH), 8.24 (d, J= 8.4 Hz, 2H), 7.88 - 7.72 (m, 4H), 7.56 (dt, J= 18.3, 5.8 Hz, 2H), 7.40 (d, J= 8.3 Hz, 2H), 7.09 (t, J= 8.0 Hz, IH), 3.49 (d, J= 13.3 Hz, IH), 3.35 (m, 2H), 1.86 (d, J= 14.0 Hz, 3H); 19F NMR (376 MHz, CDCI3) δ -58.01, -62.05, -62.22; ESIMS m/z 642 (M+H).
Example 23: Préparation of (Z)-3-(2-isopropylphenyl)-4-methyl-2-((jE)(4-(l-(4(trifluoromethoxy)phenyl)-ljfiT-l,2,4-triazol-3-yI)benzylidene)hydrazono)thiazolidm-4-ol (Compound 242C; Synthesis Method M).
To a solution of (E)-N-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)- 1H- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (134 mg, 0.26 mmol) in butanone (1.9 mL) was added chloroacetone (0.03 mL, 0.33 mmol) and triethylamine (0.04 mL, 0.28 mmol), and the reaction was stirred at room température for 16 hours. The mixture was transferred to a separatory funnel containing water (5 mL) and extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0 - 25% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes) to provide the title compound as a yellow solid (117 mg, 79%) : mp 114 - 116 °C; rH NMR (400 MHz, CDCI3) δ 8.57 (s, IH), 8.19 (dd, J= 10.1, 6.2 Hz, 3H), 7.79 (dd, J= 11.5, 4.7 Hz, 4H), 7.50 - 7.44 (m, IH), 7.44 - 7.36 (m, 4H), 7.29 - 7.25 (m, 1H), 3.55 (d, J = 11.5 Hz, 1H), 3.45 (s, 1H), 3.34 (d, J= 11.5 Hz, 1H), 2.98 (dt, J = 13.8,
6.9 Hz, 1H), 1.43 (s, 3H), 1.27 - 1.16 (m, 6H); 19F NMR (376 MHz, CDC13) δ -58.02; ESIMS m/z 582 (M+H)+.
Example 24: Préparation of (Z)-3-(2-(xec-butyl)phenyl)-4-methyl-2-((E)-(4-(l-(4(trifhi or omethoxy)pheny 1)-1//-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4-ol (Compound 243C; Synthesis Method M).
Starting from (Æ)-JV-(2-5ec-butylphenyl)-2-(4-( 1 -(4-(trifluoromethoxy)phenyl)-1H- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide, and using conditions described in Example 23, the title compound was isolated as a yellow solid (122 mg, 89%): mp 112 °C (dec); !H NMR (400 MHz, CDC13) δ 8.57 (s, 1H), 8.23 - 8.13 (m, 3H), 7.84 - 7.74 (m, 4H), 7.55 - 7.44 (m, 1H), 7.43 - 7.32 (m, 4H), 7.28 - 7.24 (m, 1H), 3.55 - 3.51 (m, 2H), 3.32 (dd, J= 11.5, 1.0 Hz, lH),2.69(td, J= 13.9, 7.0 Hz, 1H), 1.63- 1.56 (m, 2H), 1.45 (d, J =4.9 Hz, 3H), 1.26 - 1.16 (m, 3H), 0.83 (dt, J= 10.2, 7.4 Hz, 3H); 19F NMR (376 MHz, CDC13) δ -58.02; ESIMS m/z 596 (M+H)+.
Example 25: Préparation of (Z)-3-(2-chloro-6-methylphenyl)-4-methyl-2-((£)-(4-(l-(4(trifluoromethoxy)phenyl)-1//-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4-ol (Compound 244C; Synthesis Method M).
Starting from (£)-7V-(2-chloro-6-methylphenyl)-2-(4-(l -(4-(trifluoromethoxy)phenyl)l//-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide, and using conditions described in Example 23, the title compound was isolated as a yellow solid (107 mg, 91%): mp 103 °C (dec); ’H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.22 (s, 1H), 8.18 (d, J= 8.4 Hz, 2H), 7.83 - 7.76 (m, 4H), 7.41 - 7.32 (m, 3H), 7.25 - 7.21 (m, 2H), 3.70 - 3.61 (m, 1H), 3.53 (s, 1H), 3.30 (d, J= 11.2 Hz, 1H), 2.49 (s, 3H), 1.51 (s, 3H); 19F NMR (376 MHz, CDC13) δ -58.02; ESIMS m/z 588 (M+H)+.
Example 26: Préparation of (Z)-3-(4-methoxy-2-methylphenyl)-4-methyl-2-((£)-(4-(l(4-(trifluoromethoxy)phenyl)-17ïr-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-
4-ol (Compound 245C; Synthesis Method M).
O
Starting from (£)-7V-(2-methyl-4-methoxyphenyl)-2-(4-( 1 -(4-(trifluoromethoxy)phenyl)-17f-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide, and using conditions described in Example 23, the title compound was isolated as a yellow solid (88 mg, 76%) : mp 129 °C (dec); Ή NMR (400 MHz, CDCI3) δ 8.57 (s, 1H), 8.25 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.82 - 7.75 (m, 4H), 7.39 (t, J= 8.8 Hz, 3H), 6.86 - 6.76 (m, 2H), 3.83 (s, 3H), 3.52 (d, J= 11.5 Hz, 1H), 3.43 (s, 1H), 3.31 (d, J= 11.6 Hz, 1H), 2.19 (s, 2H), 1.43 (s, 3H); 19F NMR (376 MHz, CDC13) δ -58.02; ESIMS m/z 584 (M+H)+.
Example 27: Préparation of (Z)-3-(2-isopropylphenyl)-2-((£)-(4-(l-(4(trifluoromethoxy)phenyl)-17Z-l,2,4-triazol-3-yl)benzylidene)hydrazono)-4(trifluoromethyl)thiazolidin-4-ol (Compound 246C; Synthesis Method M).
To a solution of (£)--^-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-U/- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (351 mg, 0.67 mmol) inbutanone (6.7 mL) was added 3-bromo-l,l,l-trifluoroacetone (0.14 mL, 1.34 mmol) and triethylamine (0.19 mL, 1.34 mmol), and the reaction was stirred at 85 °C for 21 hours. The mixture was allowed to cool to room température, transferred to a separatory funnel containing water (5 mL), and the aqueous mixture extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0 - 20% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes) to provide a diastereomeric mixture (2:1) of the title compound as an orange solid (189 mg, 45%): mp 185 - 187 °C; *H NMR (400 MHz, CDC13, both diastereomers) δ 8.56 (m, 2H),
8.22 - 8.14 (m, 6H), 7.83 - 7.75 (m, 8H), 7.49 - 7.34 (m, 10H), 7.32 - 7.23 (m, 2H), 4.22 (s, 1H), 3.82 (dd, J= 12.5, 4.8 Hz, 2H), 3.51 (d, J= 13.2 Hz, 1H), 3.40 (d, J= 12.3 Hz, 1H), 3.31 (s, 1H), 3.09 (tt, J= 13.9, 7.0 Hz, 2H), 1.31 - 1.13 (m, 12H); 19F NMR (376 MHz, CDC13) δ -58.02, -78.33, -78.77; ESIMS m/z 636 (M+H)+.
Example 28: Préparation of (Z)-3-(2-(sec-butyl)phenyl)-2-((£)-(4-(l-(4(trifluoromethoxy)phenyl)-ljHr-l,2,4-triazol-3-yl)benzylidene)hydrazono)-4(trifluoromethyl)thiazolidin-4-ol (Compound 247C; Synthesis Method M).
To a solution of (E)-#-(2-(s<?c-butyl)phenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)177-l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (203 mg, 0.38 mmol) in butanone (3.8 mL) was added triethylamine (0.07 mL, 0.49 mmol) and 3-bromo-l,l,ltrifluoroacetone (0.05 mL, 0.49 mmol), and the reaction was stirred at 85 °C for 20 hours, after which LC/MS analysis showed minimal conversion. Additional triethylamine (0.03 mL, 0.21 mmoL) and 3-bromo-l,l,l-trifluoroacetone (0.1 mL, 0.98 mmol) were added to the reaction mixture and the reaction was stirred at 90 °C for an additional 20 hours. The mixture was allowed to cool to room température, transferred to a separatory funnel containing water (5 mL), and extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0 - 20% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes). Further purification by reversephase flash chromatography (0 - 100% acetonitrile/water) provided the title compound as an orange solid (16 mg, 7%): *Η NMR (400 MHz, CDC13) δ 8.59 - 8.54 (m, 1H), 8.30 - 8.13 (m, 3H), 7.79 (dd, J= 8.6, 6.7 Hz, 4H), 7.45 - 7.34 (m, 5H), 7.32 - 7.21 (m, 1H), 3.99 (s, 1H), 3.83 (d, J= 12.2 Hz, 1H), 3.52 - 3.38 (m, 1H), 2.82 - 2.75 (m, 1H), 1.27 - 1.26 (m, 1H),
1.21 - 1.12 (m, 3H), 0.97 - 0.75 (m, 4H); 19F NMR (376 MHz, CDC13) δ -58.03, -78.23, 78.32, -78.76, -78.84; ESIMS m/z 650 (M+H)+.
Compounds 248-256, 258-262, and 264, shown in Table 3, were prepared according to the method described in Example 23 from the appropriately substituted intermediates disclosed in Table 1. Characterization data for these compounds is reported in Table 4.
Example 29: Préparation of (Z)-3-(2-isopropylphenyl)-4,5-dimethyI-2-((Ê)-(4-(l-(4(trifluoromethoxy)phenyl)-ljHr-l,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4-ol (Compound 257C).
To a solution of (E)-A-(2-isopropylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-l//- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (114 mg, 0.22 mmol) in butanone (2.2 mL) was added 3-bromo-2-butanone (0.03 mL, 0.28 mmol) and triethylamine (0.06 mL, 0.44 mmol), and the reaction was stirred at room température overnight. The reaction mixture was directly applied to a silica gel cartridge and purified by flash chromatography (0 - 30% ethyl acetate/B, where B = 1:1 dichloromethane/hexanes) to provide the title compound as a yellow solid (108 mg, 84% yield): mp 140 °C (dec); NMR (400 MHz, CDC13) δ 8.57 (s, 1H), 8.22 - 8.16 (m, 3H), 7.82 - 7.74 (m, 4H), 7.55 - 7.47 (m, 1H), 7.42 - 7.35 (m, 4H), 7.29 -7.24 (m, 1H), 3.92-2.96 (m, 3H), 1.57 (s, 1H), 1.57- 1.50 (m, 3H), 1.35-1.17 (m, 9H); 19F NMR (376 MHz, CDC13) Ô -58.02; ESIMS m/z 595 ([M+H]+).
Example 30: Préparation of (Z)-3-(2-isopropyl pheny 1)-2-((/7)-(4-(1-(4(trifluoromethoxy)pheny 1)-1/7-1,2,4-triazol-3-y!)benzylidene)hydrazono)-4-(2(trifluoromethyl)phenyl)thiazolidin-4-ol (Compound 263C).
A solution of (E)-N-(2-isopropylphenyl)-2-(4-( 1 -(4-(trifluoromethoxy)phenyl)-1 /7- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (0.30 g, 0.57 mmol) and 2(trifluoromethyl)phenacyl bromide (0.22 g, 0.85 mmol) in DCE (30 mL) was heated to reflux and stirred overnight. The reaction mixture was cooled to room température, diluted with ethyl acetate (100 mL), washed with water (2 x 50 mL), washed with brine solution (1 x 25 mL), and dried over anhydrous sodium sulfate. The solution was filtered, the filtrate concentrated, and the residue purified by flash chromatography (0 - 100% ethyl acetate/hexanes) to provide (Z)-3-(2-isopropylphenyl)-2-((£)-(4-(l-(4-(trifluoromethoxy)phenyl)-117-l,2,4-triazol-3-yl)benzylidene)hydrazono)-4-(2-(trifluoromethyl)phenyl)thiazolidin-4-ol as a yellow solid (0.15 g, 38% yield): mp 115 — 117.5 °C; H NMR (400 MHz, CDCI3) δ 8.59 (s, 1H), 8.33 (s, 1H), 8.24 (d, J= 8.4 Hz, 2H), 8.13 (s, 1H), 7.86 -
7.77 (m, 5H), 7.73 (d, J= 7.2 Hz, 1H), 7.62 (dt, J = 21.6, 7.2 Hz, 2H), 7.40 (d, J= 8.2 Hz, 2H), 7.37 - 7.28 (m, 3H), 7.24 - 7.17 (m, 1H), 4.34 (s, 2H), 3.20 (dt, J= 13.7, 6.8 Hz, 2H),
1.25 (d, J= 6.9 Hz, 6H); 19F NMR (376 MHz, CDCI3) δ -57.99, -58.02; ESIMS m/z 711 ([M+H]+).
Example 31 : (7f)-A-(2-cyclopentylphenyl)-2-(4-(l-(4-(trifluoromethoxy)phenyl)-1 /7- l,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 1-35; Synthesis Methods N and C)
Step 1: Préparation of l-(cyclopent-l-en-l-yl)-2-nitrobenzene (1-32, Method N).
To a mixture of l-chloro-2-nitrobenzene (0.5 g, 3.2 mmol) and sodium carbonate (0.34 g, 3.2 mmol) in a 100 mL roundbottom flask equipped with a magnetic stir bar and nitrogen inlet were added water (3.2 mL), dioxane (13 mL) and 2-(cyclopent-l-en-l-yl)-4,4,5,5tetramethyl-l,3,2-dioxaborolane (0.77 mL, 3.8 mmol). The reaction flask was evacuated and purged with nitrogen (2 x) prior to the addition of bis(triphenylphosphine)palladium(II) chloride (0.18 g, 0.25 mmol), and then evacuated and purged (3 x) following the addition of the catalyst. The reaction was heated to 80 °C and stirred overnight. The reaction was cooled and filtered through a pad of Celite® which was subsequently washed with water and ethyl acetate. The phases were separated and the organic phase was dried by passing it through a phase separator cartridge and concentrated. The residue was purified by flash column chromatography providing the title compound (0.56 g, 3.0 mmol, 93 % yield) as a yellow oil:
NMR (400 MHz, CDC13) δ 7.78 - 7.71 (m, 1H), 7.54 - 7.47 (m, 1H), 7.40 - 7.32 (m, 2H),
5.86 - 5.82 (m, 1H), 2.63 - 2.55 (m, 2H), 2.55 - 2.47 (m, 2H), 2.09 - 1.98 (m, 2H); 13C NMR (101 MHz, CDC13) δ 148.77, 139.96, 133.58, 132.08, 130.87, 130.52, 127.55, 123.70, 35.31, 33.49, 24.05; ESIMS m/z 190 ([M+H]+).
Step 2: Préparation of 2-cyclopentylaniline (1-33, Method N). To a solution of 120 (cyclopent-l-en-l-yl)-2-nitrobenzene (0.58 g, 3.0 mmol) in ethyl acetate (30 mL) in a 200 mL roundbottom flask equipped with a magnetic stir bar and nitrogen inlet was added palladium on carbon (0.63 g, 0.30 mmol, 5 %). The flask was evacuated and purged with nitrogen (3 x), and then evacuated and placed under hydrogen (1 atmosphère (atm)). The mixture was stirred at room température overnight, filtered through a pad of Celite®, and the filter cake washed with ethyl acetate. The filtrate was concentrated to provide the title compound (0.46 g, 2.9 mmol, 98 % yield) as a clear and slightly red oil: *H NMR (400 MHz, CDC13) δ 7.14 (dd, J= 7.7, 1.3 Hz, 1H), 7.02 (td, J= 7.6, 1.5 Hz, 1H), 6.76 (td, J= 7.4, 1.1 Hz, 1H), 6.68 (dd, J= 7.8, 1.2 Hz, 1H), 3.66 (bs, 2H), 3.04-2.92 (m, 1 H), 2.13 - 1.98 (m, 2H), 1.88 - 1.58 (m, 6H); 13C NMR (101 MHz, CDC13) δ 144.12, 130.34, 126.51, 125.95, 118.78, 115.70, 39.89, 32.17, 25.21; ESIMS m/z 162 ([M+H]+).
Step 3: Préparation of A-(2-cyclopentylphenyI)hydrazinecarbothioamide (1-34, Method N). To a biphasic solution of 2-cyclopentylaniline (0.46 g, 2.9 mmol) in dichloromethane (10 mL) and water (4.8 mL) in a 100 mL roundbottom flask equipped with a magnetic stir bar and nitrogen inlet was added sodium hydrogencarbonate (0.73 g, 8.6 mmol) followed by thiophosgene (0.21 mL, 2.8 mmol). The reaction was stirred at room température for 1 hour, filtered through a phase separator cartridge, and concentrated providing the 1 -cyclopentyl-2-isothiocyanatobenzene as a red oil which was used without further purification. To a solution of the isothiocyanate in éthanol (5.5 mL) in a 100 mL roundbottom flask was added hydrazine hydrate (0.15 mL, 3.1 mmol), and the reaction was stirred at room température ovemight. The reaction mixture was diluted with hexanes and the resulting solid was collected by filtration, washed with hexanes, and dried under house vacuum to provide the title compound (0.41 g, 1.7 mmol, 63 % yield) as a white solid: JH NMR (400 MHz, CDC13) δ 9.02 (bs, 1H), 7.52 (bs, 1H), 7.41 - 7.18 (m, 4H), 4.06 (bs, 2H),
3.21 - 3.06 (m, 1H), 2.04 (s, 2H), 1.90 - 1.74 (m, 2H), 1.74 - 1.58 (m, 4H); ESIMS m/z 236 ([M+H]+).
Step 4: Préparation of (£)-A-(2-cyclopentylphenyl)-2-(4-(l-(4-(trifluoromethoxy)pheny 1)-1//-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (1-35, Method C). To a mixture of 4-(l-(4-(trifluoromethoxy)phenyl)-lH-l,2,4-triazol-3yl)benzaldehyde (0.58 g, 1.7 mmol) and W-(2-cyclopentylphenyl)hydrazinecarbothioamide (0.41 g, 1.7 mmol) in a 100 mL roundbottom flask equipped with a magnetic stir bar and reflux condenser was added methanol (17 mL), and the reaction was heated to 50 °C and stirred ovemight. The reaction was cooled to room température and the resulting solid was filtered, washed with methanol and dried under vacuum (25 in Hg) at 55 °C to give the title compound (795 mg, 1.44 mmol, 83 % yield) as a yellow solid: mp 213-216 °C; ’H NMR (400 MHz, CDCI3) δ 9.45 (s, 1H), 9.11 (s, 1H), 8.60 (s, 1H), 8.26 (d, J= 8.4 Hz, 2H), 7.91 (s, 1H), 7.86 - 7.71 (m, 5H), 7.40 (dd, J= 8.8, 6.4 Hz, 3H), 7.35 - 7.27 (m, 2H), 3.22 (t, J= 8.0 Hz, 1H), 2.13 (d, J= 2.5 Hz, 2H), 1.90 - 1.59 (m, 6H); ESIMS m/z 551 ([M+H]+).
Intermediate compounds 1-36 —1-55 and 1-61 —1-62, shown in Table 1, were prepared according to the methods outlined in Example 29, Steps 1-4. Characterization data for these intermediates is shown in Table 2.
Example 32: Bioassays on Beet Armyworm (“BAW”) and Corn Earworm (“CEW”)
BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In varions places, it is of économie concem upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be résistant to certain insecticides. Consequently, because ofthe above factors control of these pests is important. Furthermore, molécules that control these pests are useful in controlling other pests.
Certain molécules disclosed in this document were tested against BAW and CEW using procedures described in the following examples. In the reporting of the results, the “BAW & CEW Rating Table” was used (See Table Section).
Bioassays on BAW (Spodoptera exigud)
Bioassays on BAW were conducted using a 128-well diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 pg/cm2 of the test compound (dissolved in 50 pL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 °C, 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
Bioassays on CEW (Helicoverpa zea)
Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 pg/cm2 ofthe test compound (dissolved in 50 pL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 °C, 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
Example 33: Bioassays ON Green Peach Aphid (“GPA”) (Myzuspersicaë).
GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many omamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed résistance to many pesticides.
Certain molécules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting ofthe results, the “GPA Rating Table” was used (See Table Section).
Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in H2O to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott’s correction formula (W.S. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp.265-267) as follows.
Corrected % Control = 100 * (X - Y) / X where
X = No. of live aphids on solvent check plants and
Y = No. of live aphids on treated plants
The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND RADIONUCLIDES
Molécules of Formulas One, Two and Three may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnésium.
Molécules of Formulas One, Two and Three may be formulated into sait dérivatives. By way of a non-limiting example, a sait dérivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a sait. A free base may be regenerated by treating the sait with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine sait..
Molécules of Formulas One, Two and Three may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as solvatés.” However, it is particularly désirable to form stable hydrates with water as the solvent.
Molécules of Formulas One, Two and Three may be made into ester dérivatives. These ester dérivatives can then be applied in the same manner as the invention disclosed in this document is applied.
Molécules of Formulas One, Two and Three may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molécule can hâve vastly different physical properties and biological performances.
Molécules of Formulas One, Two and Three may be made with different isotopes. Of particular importance are molécules having 2H (also known as deuterium) in place of ’h.
Molécules of Formulas One, Two and Three may be made with different radionuclides. Of particular importance are molécules having 14C.
STEREOISOMERS
Molécules of Formulas One, Two and Three may exist as one or more stereoisomers. Thus, certain molécules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known sélective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures.
INSECTICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following insecticides - 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, a/jj/za-cypermethrin, a/p/m-ecdysone, α/ρ/ζα-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-Omethyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, dlimonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, flonicamid, flubendiamide (additionally resolved isomers thereof), flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, flufiprole, flupyradifurone, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, fufenozide, fürathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvénile hormone I, juvénile hormone II, juvénile hormone III, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methothrin, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxirn, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp'-DDT, prallethrin, precocene I, precocene II, precocene III, primidophos, profenofos, profluralin, profluthrin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pymetrozine, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, i/zeta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, and zolaprofos (collectively these commonly named insecticides are defined as the “Insecticide Group”).
ACARICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following acaricides - acequinocyl, amidoflumet, arsenous oxide, azobenzene, azocyclotin, benomyl, benoxafos, benzoximate, benzyl benzoate, bifenazate, binapacryl, bromopropylate, chinomethionat, chlorbenside, chlorfenethol, chlorfenson, chlorfensulphide, chlorobenzilate, chloromebuform, chloromethiuron, chloropropylate, clofentezine, cyenopyrafen, cyflumetofen, cyhexatin, dichlofluanid, dicofol, dienochlor, diflovidazin, 49 dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenyl sulfone, disulfiram, dofenapyn, etoxazole, fenazaquin, fenbutatin oxide, fenothiocarb, fenpyroximate, fenson, fentrifanil, fluacrypyrim, fluazuron, flubenzimine, fluenetil, flumethrin, fluorbenside, hexythiazox, mesulfen, MNAF, nikkomycins, proclonol, propargite, quintiofos, spirodiclofen, sulfiram, sulfur, tetradifon, tetranactin, tetrasul, and thioquinox (collectively these commonly named acaricides are defined as the “Acaricide Group”).
NEMATICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following nematicides — 1,3-dichloropropene, benclothiaz, dazomet, dazomet-sodium, DBCP, DCIP, diamidafos, fluensulfone, fosthiazate, furfural, imicyafos, isamidofos, isazofos, metam, metam-ammonium, metam-potassium, metam-sodium, phosphocarb, and thionazin (collectively these commonly named nematicides are defined as the “Nematicide Group”)
FUNGICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following fungicides - (3-ethoxypropyl)mercury bromide, 2-methoxyethylmercury chloride, 2-phenylphenol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, acibenzolar, acibenzolar-S-methyl, acypetacs, acypetacs-copper, acypetacs-zinc, aldimorph, allyl alcohol, ametoctradin, amisulbrom, ampropylfos, anilazine, aureofungin, azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiavalicarb-isopropyl, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzohydroxamic acid, bethoxazin, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, Bordeaux mixture, boscalid, bromuconazole, bupirimate, Burgundy mixture, buthiobate, butylamine, calcium polysulfide, captafol, captan, carbamorph, carbendazim, carboxin, carpropamid, carvone, Cheshunt mixture, chinomethionat, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chlorodinitronaphthalene, chloroneb, chloropicrin, chlorothalonil, chlorquinox, chlozolinate, climbazole, clotrimazole, copper acetate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, dazomet-sodium, DBCP, debacarb, decafentin, dehydroacetic acid, dichlofluanid, dichlone, dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomezine, diclomezine-sodium, dicloran, diethofencarb, diethyl pyrocarbonate, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, dinocap4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, DNOC, DNOC-ammonium, DNOC-potassium, DNOCsodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin-sodium, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldéhyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furconazole-cis, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexachlorobenzene, hexachlorobutadiene, hexaconazole, hexylthiofos, hydrargaphen, hymexazol, imazalil, imazalil nitrate, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, iodomethane, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, isovaledione, kasugamycin, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mepanipyrim, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl isothiocyanate, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, metiram, metominostrobin, metrafenone, metsulfovax, milneb, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, natamycin, nitrostyrene, nitrothal-isopropyl, nuarimol, OCH, octhilinone, ofurace, orysastrobin, oxadixyl, oxine-copper, oxpoconazole, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury dérivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phosdiphen, phthalide, picoxystrobin, piperalin, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, potassium azide, potassium polysulfide, potassium thiocyanate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothiocarb, prothiocarb hydrochloride, prothioconazole, pyracarbolid, pyraclostrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, quinacetol, quinacetol sulfate, quinazamid, quinconazole, quinoxyfen, quintozene, rabenzazole, salicylanilide, sedaxane, silthiofam, simeconazole, sodium azide, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, spiroxamine, streptomycin, sulfur, sultropen, TCMTB, tebuconazole, tebufloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, thiochlorfenphim, thiomersal, thiophanate, thiophanate-methyl, thioquinox, thiram, tiadinil, tioxymid, tolclofosmethyl, tolylfhianid, tolylmercury acetate, triadimefon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tributyltin oxide, trichlamide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, uniconazole, uniconazole-P, validamycin, valifenalate, vinclozolin, zarilamid, zinc naphthenate, zineb, ziram, zoxamide (collectively these commonly named fongicides are defined as the “Fungicide Group”).
HERBICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more ofthe following herbicides — 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBAsodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl,
2.4.5- TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl,
2.4.5- T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-Ttriethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,
2.4- DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-Ddiethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium,
2.4- DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-Doctyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-teforyl, 2,4-Dtetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4D-trolamine, 3,4-DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP, acetochlor, acifhiorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrolein, alachlor, allidochlor, alloxydim, alloxydim-sodium, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlorpotassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2hydroxypropyl)ammonium, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, asulam-potassium, asulam-sodium, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, benazolindimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone, bentazone-sodium, benzadox, benzadox-ammonium, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzoylprop-ethyl, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bilanafos-sodium, bispyribac, bispyribac-sodium, borax, bromacil, bromacillithium, bromacil-sodium, bromobonil, bromobutide, bromofenoxim, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole, carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chlorambensodium, chloranocryl, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenac-sodium, chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuronethyl, chlomitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorprocarb, chlorpropham, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clodinafop-propargyl, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloransulam, cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanamide, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyhalofop-butyl, cyperquat, cyperquat chloride, cyprazine, cyprazole, cypromid, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, dazomet, dazomet-sodium, delachlor, desmedipham, desmetryn, di-allate, dicamba, dicamba-dimethylammonium, dicamba-diolamine, dicambaisopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba sodium, dicamba-trolamine, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorpropethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-Pdimethylammonium, dichlorprop-potassium, dichlorprop-sodium, diclofop, diclofop-methyl, diclosulam, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinosebdiolamine, dinoseb-sodium, dinoseb-trolamine, dinoterb, dinoterb acetate, diphacinonesodium, diphenamid, dipropetryn, diquat, diquat dibromide, disul, disul-sodium, dithiopyr, diuron, DMP A, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, DSMA, EBEP, eglinazine, eglinazine-ethyl, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxyfen-ethyl, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoprop-3butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenteracol, fenthiaprop, fenthiaprop-ethyl, fentrazamide, fenuron, fenuron TCA, ferrous sulfate, flamprop, flamprop-isopropyl, flamprop-M, flampropmethyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfaron, florasulam, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazolate, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fhioroglycofen-ethyl, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupropanate-sodium, flupyrsulfuron, flupyrsulfuron-methyl-sodium, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesafen-sodium, foramsulfuron, fosamine, fosamine-ammonium, furyloxyfen, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-Psodium, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosateisopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosatesesquisodium, glyphosate-trimesium, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquinammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iodosulfuronmethyl-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, ΜΑΜΑ, MCP A, MCPA-2ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPAolamine, MCP A-potassium, MCP A-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mecoprop, mecoprop-2-ethylhexyl, mecopropdimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecopropmethyl, mecoprop-P, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoproppotassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medinoterb, medinoterb acetate, mefenacet, mefluidide, mefluidide-diolamine, mefluidide-potassium, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsulfùron-methyl, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, monuron TCA, morfamquat, morfamquat dichloride, MSMA, naproanilide, napropamide, naptalam, naptalam-sodium, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2hydroxypropyl)ammonium, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, proglinazineethyl, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, proxan-sodium, prynachlor, pydanon, pyraclonil, pyraflufen, pyraflufen-ethyl, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, rhodethanil, rimsulfuron, saflufenacil, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCAmagnesium, TCA-sodium, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, tri-allate, triasulfuron, triaziflam, tribenuron, tribenuron-methyl, tricamba, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tridiphane, trietazine, trifloxysulfuron, trifloxysulfuron-sodium, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vemolate, xylachlor, (collectively these commonly named herbicides are defined as the “Herbicide Group”).
BIOPESTICIDES
Molécules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The terni “biopesticide” is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents hâve also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of
Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:
1. entomopathogenic fungi (e.g. Metarhizium anisopliae)'.
2. entomopathogenic nematodes (e.g. Steinernema feltiae)', and
3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).
Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolérant or résistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect résistant property to the genetically modified organism. In one embodiment, the Molécules of Formula One, Two or Three may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.
OTHER ACTIVE COMPOUNDS
Molécules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more of the following:
1. 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec-3-en-2-one;
2. 3-(4’-chloro-2,4-dimethyl[l,l’-biphenyl]-3-yl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec3-en-2-one;
· 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(577)-furanone;
4. 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5/7)-furanone;
5. 3-chloro-A2-[(lS)-l-methyl-2-(methylsulfonyl)ethyl]-M-[2-methyl-4-[l,2,2,2tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl] -1,2-benzenedicarboxamide;
6. 2-cyano-7V-ethyl-4-fluoro-3-methoxy-benenesulfonamide;
7. 2-cyano-jV-ethyl-3-methoxy-benzenesulfonamide;
8. 2-cyano-3 -difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;
9. 2-cyano-3 -fluoromethoxy-A-ethyl-benzenesulfonamide;
10. 2-cyano-6-fluoro-3 -methoxy-TV, 7V-dimethyl-benzenesulfonamide;
11. 2-cyano-7V-ethyl-6-fluoro-3 -methoxy-A-methyl-benzenesulfonamide;
12. 2-cyano-3 -difluoromethoxy-Λζ A-dimethylbenzenesulfon-amide;
13. 3-(difluoromethyl)-V-[2-(3,3-dimethylbutyl )phenyl] -1 -methyl-1 H-pyrazole-4carboxamide;
14. 7V-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-p-tolyl) hydrazone;
15. A-ethyl-2,2-dichloro-1 -methyl cyclopropane-carboxamide-2-(2,6-dichloro-a, a, atrifluoro-p-tolyl) hydrazone nicotine;
16. O- {(E-)-[2-(4-chloro-phenyl)-2-cyano-1 -(2-trifluoromethylphenyl)-vinyl]} S-methyl thiocarbonate;
17. (E)-N 1 -[(2-chloro-1,3 -thiazol-5-ylmethyl)]-N2-cyano-N 1 -methylacetamidine;
18. l-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-l,2,3,5,6,7-hexahydro-imidazo[l,2a]pyridin-5-ol;
19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and
20. N-Ethyl-2,2-dichloro-1 -methylcyclopropanecarboxamide-2-(2,6-dichloroalpha, alpha, a/p/za-trifluoro-p-tolyl)hydrazone.
Molécules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more compounds in the following groups: algicides, antifeedants, avicides, bactéricides, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, molluscicides, plant activators, plant growth regulators, rodenticides, and/or virucides (collectively these commonly named groups are defined as the “AI Group”). It should be noted that compounds falling within the AI Group, Insecticide Group, Fungicide Group, Herbicide Group, Acaricide Group, or Nematicide Group might be in more than one group, because of multiple activities the compound has. For more information consult the “Compendium of Pesticide Common Names” located at http://www.alanwood.net/pesticides/index.html. Also consult “The Pesticide Manual” 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent éditions.
SYNERGISTIC MIXTURES AND SYNERGISTS
Molécules of Formulas One, Two and Three may be used with the compounds in the Insecticide Group to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the Molécules of Formula One and Two are the same, similar, or different. Examples of modes of action include, but are not limited to.
acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acétylcholine receptor agonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acétylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Additionally, Molécules of Formula One and Two may be used with compounds in the Fungicide Group, Acaricide Group, Herbicide Group, or Nematicide Group to form synergistic mixtures. Furthermore, Molécules of Formulas One, Two and Three may be used with other active compounds, such as the compounds under the heading “OTHER ACTIVE COMPOUNDS”, algicides, avicides, bactéricides, molluscicides, rodenticides, virucides, herbicide safeners, adjuvants, and/or surfactants to form synergistic mixtures. Generally, weight ratios of the Molécules of Formulas One, Two and Three in a synergistic mixture with another compound are from about 10:1 to about 1:10, preferably from about 5:1 to about 1:5, and more preferably from about 3:1, and even more preferably about 1:1. Additionally, the following compounds are known as synergists and may be used with the molécules disclosed in Formula One: piperonyl butoxide, piprotal, propyl isome, sesamex, sesamolin, sulfoxide, and tribufos (collectively these synergists are defined as the “Synergists Group”).
FORMULATIONS
A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated émulsions, dusts, emulsifiable concentrâtes, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrâtes, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions. For further information on formulation types see “Catalogue of Pesticide Formulation Types and International Coding System” Technical Monograph n°2, 5th Edition by CropLife International (2002).
Pesticides are applied most often as aqueous suspensions or émulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrâtes, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually chosen from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phénols.
Emulsifiable concentrâtes of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin dérivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrâtes are chosen from conventional anionic and non-ionic surfactants.
Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingrédients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, bail mill, or piston-type homogenizer.
Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.
Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcamc rock, and the like. Dusts can suitably contain from about 1% to about 10% ofthe pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.
It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
Pesticides can also be applied in the form of an aérosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressuregenerating propellant mixture. The aérosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the hait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.
Fumigants are pesticides that hâve a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest’s respiratory system or being absorbed through the pest’s cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in spécial chambers.
Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of varions types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of varions sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govem the speed with which the active ingrédient within is released, which in tum, affects the residual performance, speed of action, and odor of the product.
Oil solution concentrâtes are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better pénétration of crevices, and better adhesion to greasy surfaces.
Another embodiment is an oil-in-water émulsion, wherein the émulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilie surface-active agent, (2) at least one nonionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published February 1, 2007, having Patent Application serial number 11/495,228. For ease of use, this embodiment will be referred to as “OIWE”.
For further information consult “Insect Pest Management” 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult “Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
OTHER FORMULATION COMPONENTS
Generally, when the molécules disclosed in Formulas One, Two and Three are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, pénétrants, buffers, sequestering agents, drift réduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
A wetting agent is a substance that when added to a liquid increases the spreading or pénétration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrâtes for soluble liquids or suspension concentrâtes; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the pénétration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phénol ethoxylates; and aliphatic alcohol ethoxylates.
A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrâtes and water-dispersible granules. Surfactants that are used as dispersing agents hâve the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrâtes, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldéhyde condensâtes. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensâtes and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrâtes. In recent years, new types of very high molecular weight polymeric surfactants hâve been developed as dispersing agents. These hâve very long hydrophobie ‘backbones’ and a large number of ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrâtes because the hydrophobie backbones hâve many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldéhyde condensâtes; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifïer blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oilsoluble calcium sait of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable émulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.
A solubilizing agent is a surfactant which will form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobie part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.
Surfactants are sometimes used, either alone or with other additives such as minerai or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement dépend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.
A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and waterdispersible granules.
Organic solvents are used mainly in the formulation of emulsifiable concentrâtes, oilin-water émulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffmic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and CIO aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.
Thickeners or gelling agents are used mainly in the formulation of suspension concentrâtes, émulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent séparation and settling of the dispersed particles or droplets. Thickening, gelling, and anti-settling agents generally fall into two categories, namely waterinsoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnésium aluminum silicate, and attapulgite. Water-soluble polysaccharides hâve been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic dérivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.
Microorganisms can cause spoilage of formulated products. Therefore préservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium sait; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium sait; j?-hydroxybenzoic acid sodium sait; methyl phydroxybenzoate; and l,2-benzisothiazolin-3-one (BIT).
The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones are usually aqueous émulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.
“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodégradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Spécifie examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.
For further information, see “Chemistry and Technology of Agrochemical Formulations” edited by D.A. Knowles, copyright 1998 by Kluwer Academie Publishers. Also see “Insecticides in Agriculture and Environment — Retrospects and Prospects” by A.S. Perry, L Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.
PESTS
In general, the Molécules of Formula Formulas One, Two and Three may be used to control pests e.g. beetles, earwigs, cockroaches, Aies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests in the Phyla Nematoda and/or Arthropoda.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests ofthe Order Anoplura. A non-exhaustive list of particular généra includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus,
Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular généra includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nénuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinocéros, Oryzaephilus mercator, Oryzaephilus surinamensis, Ouléma melanopus, Ouléma oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Dermaptera.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Diptera. A non-exhaustive list of particular généra includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Délia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Délia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular généra includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvégiens, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus héros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxéra vitifoliae,
Physokermes piceae,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular généra includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Isoptera. A non-exhaustive list of particular généra includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procorniterm.es spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular généra includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria,
Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Dama diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodopterafrugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Aeuzera coffeae, and Aeuzera pyrina.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular généra includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular généra includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,
Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests ofthe Order Thysanoptera. A non-exhaustive list ofparticular généra includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests ofthe Order Thysanura. A non-exhaustive list of particular généra includes, but is not limited to, Lepisma spp. and Thermobia spp.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests ofthe Order Acarina. A non-exhaustive list of particular généra includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pest ofthe Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.
In another embodiment, the Molécules of Formulas One, Two and Three may be used to control pests ofthe Phylum Nematoda. A non-exhaustive list of particular généra includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp.,
Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognito, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis.
For additional information consult “Handbook of Pest Control — The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
APPLICATIONS
Molécules of Formulas One, Two and Three are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.
The area to which a molécule of Formulas One, Two and Three is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and omamental plants, are growing; where domesticated animais are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molécule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use aluminum sulfate with a molécule of Formula One when growing varions plants.
Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can corne about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.
The Molécules of Formulas One, Two and Three may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP).
The Molécules of Formulas One, Two and Three can be applied to the foliar and fruiting portions of plants to control pests. The molécules will either corne in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The Molécules of Formulas One, Two and Three can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molécule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
Generally, with baits, the baits are placed in the ground where, for example, termites can corne into contact with, and/or be attracted to, the hait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can corne into contact with, and/or be attracted to, the hait. Baits can comprise a molécule of Formula One, Two or Three.
The Molécules of Formulas One, Two and Three can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).
Because ofthe unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the Formula One, Two or Three may be désirable to control newly emerged larvae.
Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the Molécules of Formula One, Two or Three to a different portion of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.
Seed treatment can be applied to ail types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Représentative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide résistance, such as “Roundup Ready” seed, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide résistance, nutrition-enhancement, drought résistance, or any other bénéficiai traits.
Furthermore, such seed treatments with the Molécules of Formula One, Two or Three may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the Molécules of Formula One, Two or Three to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.
It should be readily apparent that the Molécules of Formulas One, Two and Three may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide résistance, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide résistance, nutrition-enhancement, or any other bénéficiai traits.
The Molécules of Formulas One, Two and Three may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The Molécules of Formulas One, Two and Three are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parentéral administration in the form of, for example, an injection.
The Molécules of Formulas One, Two and Three may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animais. Suitable formulations are administered orally to the animais with the drinking water or feed. The dosages and formulations that are suitable dépend on the species.
The Molécules of Formulas One, Two and Three may also be used for controlling parasitic worms, especially of the intestine, in the animais listed above.
The Molécules of Formula One, Two, and Three may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
Pests around the world hâve been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The Molécules of Formula One and Two may also be used on such new invasive species to control them in such new environment.
The Molécules of Formula One, Two, and Three may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molécules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingrédients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingrédients), and improving the tolérance to abiotic and/or biotic stress of the plant.
Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy évaluation processes by varions govemmental authorities (local, régional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data génération and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These govemmental authorities then review such data and if a détermination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.
A molécule according to Formula One, Two, and Three can be tested to détermine its efficacy against pests. Furthermore, mode of action studies can be conducted to détermine if said molécule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.
The headings in this document are for convenience only and must not be used to interpret any portion hereof.
TABLE SECTION
BAW & CEW Rating Table
% Control (or Mortality) Rating
50-100 A
More than 0 - Less than 50 B
Not Tested C
No activity noticed in this bioassay D
GPA Rating Table
% Control (or Mortality) Rating
80-100 A
More than 0 - Less than 80 B
Not Tested C
No activity noticed in this bioassay D
Table 1: Structures for Compounds
ID Structure
136 °N*0' ,
1-37 NH2 I
1-38 sFy^ h 2n.nAnXJ H H JL
1-39 F F P Y /=\ s fyy UYn.nanXj H H JL
1-40 °^Ν+θ , ¢0
1-41
1-42 s fX h2n.nAnAA H H JL
1-43 F F f-X χ\ X 0 vX nX\ s [X l JL n X -LJL H H LL
1-44 o.+ .o”
8l
Table 2: Analytical Data for Compounds in Table 1.
ID Synthesis Method MS mp (°C) ‘H, 13C, or ”F NMR (δ)1
1-4 A 551 (M+1) 209-211 (DMSO-rtô) 12.06 (s, 1 H), 10.19 (s, 1H), 9.42 (s, 1H), 8.22 (s, 1H), 8.17-8.03 (m, 5H), 7.66-7.57 (m, 4H), 7.42-7.38 (m, 2H)
1-5 C 511 (M+1) 220-225 (CDC13) 9.30 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H), 8.26 (d, J= 8.4 Hz, 2H), 7.89 (s, 1H), 7.81 (m, 4H), 7.41 (d, J= 8.4 Hz, 2H), 7.19 (m, 3H), 2.35 (s, 6H)
1-6 C 555 (M+H) 206-209 (CDCI3) 8.90 (s, 1H), 8.80 (s, 1H), 8.6 (s, 1H), 8.28 (d, J= 8.4 Hz, 2H), 8.9-8.7 (m, 4H), 7.4 (d, J= 8.6 Hz, 2H), 6.7 (s, 2H), 3.80 (s, 3H), 2.39 (s, 3H), 2.32 (s, 6H)
1-7 C 541 (M+H) 202-210 (CDCI3) 9.88 (s, 1H), 8.61 (s, 1H), 8.60 (s, 1H), 8.27 (d, J= 8.4 Hz, 2H), 7.9 (s, 1H), 7.9-7.7 (m, 4H), 7.4 (d, J= 8.6 Hz, 2H), 6.7 (s, 2H), 3.81 (s, 3H), 2.33 (s, 6H)
1-8 B 581 195-199 (CDCI3) 10.2 (s, 1H), 8.7 (s, 1H), 8.6 (s, 1H), 8.25 (d, J= 8.4 Hz, 2H), 8.0 (s, 1H), 7.82 (m, 4H), 7.4 (d, J= 8.4 Hz, 2H), 7.0 (s, 2H), 3.82 (s, 3H)
1-9 C 591 (M+H) 233-236 (CDCI3) 9.89 (s, 1H), 8.60 (s, 2H), 8.25 (d, J= 8.5 Hz, 2H), 7.95 (s, 1H), 7.88- 7.70 (m, 4H), 7.41 (d, J= 9.0 Hz, 2H), 6.70 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H)
ID Synthesis Method MS mp (°C) ‘H, 13C, or ”F NMR (δ)1
1-10 C 525 (M+H) 230-240 (CDC13) 9.93 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.93 (d, J= 9.5 Hz, 2H), 7.95 (s, 1H), 7.86-7.75 (m, 4H), 6.69 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H)
1-11 C 561 (M+H) 234-238 (CDC13) 9.62 (s, 1H), 8.70 (s, 1H), 8.60 (s, 1H), 8.26 (d, J= 8.4 Hz, 2H), 7.92 (s, 1H), 7.86-7.75 (m, 4H), 7.41 (d, J= 9.0 Hz, 2H), 7.18 (m, 3H), 2.35 (s, 6H)
1-12 C 577 (M+H) 197-200 (CDCI3) 10.2 (s, 1H), 8.90 (s, 1H), 8.62 (s, 1H), 8.25 (d, J= 8.4 Hz, 2H), 7.98 (s, 1H), 7.9-7.7 (m, 4H), 7.4 (m, 3H), 6.8 (m, 2H), 3.82 (s, 3H), 2.37 (s, 3H)
1-13 B 541 (M+H) 180-186 (CDCI3) 9.9 (s, 1H), 8.6 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.9 (s, 1H), 7.8 (d, J = 8.6 Hz, 2H), 7.75 (d, J= 8.4 Hz, 2H), 7.7 (d, J= 7 Hz, 1H), 7.45-7.35 (m, 4H), 6.91 (d, J= 8 Hz, 2H), 5.73 (m, 1H), 3.80 (s, 3H), 1.65 (d, .7=7.2 Hz, 3H)
1-14 B 559 (M+H) 196-203 (CDCI3) 9.32 (s, 1H), 8.6 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.85-7.7 (m, 5H), 7.6 (d, J = 6 Hz, 1H), 7.4 (d, J= 8.5 Hz, 2H), 7.25-7.15 (m, 2H), 6.93 (m, 1H), 5.7 (m, 1H), 3.89 (s, 3H), 1.67 (d, J= 6 Hz, 3H)
1-15 B 511 (M+H) 201-206 (CDCI3) 9.32 (s, 1H), 8.61 (s, 1H), 8.27 (d, J= 8.4 Hz, 2H), 7.9-7.7 (m, 6H), 7.5- 7.3 (m, 7H), 5.76 (m, 1H), 1.67 (d, J= 7 Hz, 3H)
1-16 C 525 (M+1) 218-225 (CDCI3) 9.37 (s, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.85-7.76 (m, 4H), 7.41 (d, J= 8.4 Hz, 2H), 6.97 (s, 2H), 2.32 (s, 3H), 2.30 (s, 6H)
1-17 C 525 (M+H) 168-180 (CDCI3) 10.2 (s, 1H), 9.07 (s, 1H), 8.63 (s, 1H), 8.25 (d, J= 8.4 Hz, 2H), 8.0 (s, 1H), 7.9-7.7 (m, 4H), 7.65 (d, J= 8 Hz, 1H), 7.4-7.25 (m, 5H), 3.25 (heptet, J= 7 Hz, 1H), 1.35 (d, J= 7 Hz, 6H)
ID Synthesis Method MS mp (°C) 13C, or 19F NMR (5)‘
1-18 C 539 (M+1) 216-221 (CDC13) δ 9.29 (s, 1H), 8.87 (s, 1H), 8.59 (s, 1H), 8.31 - 8.19 (m, 2H), 7.90 - 7.84 (m, 2H), 7.85 - 7.79 (m, 2H), 7.73 (dd, J = 7.5, 1.7 Hz, 1H), 7.39 (dd, 7= 12.6, 5.1 Hz, 3H), 7.35 - 7.27 (m, 2H), 3.37 - 3.04 (m, 1H), 2.40 (s, 3H), 1.29 (d, J= 7.5 Hz, 6H)
1-19 C 509 (M+1) 223-225 (CDC13) δ 9.74 (s, 1H), 9.06 (s, 1H), 8.69 (s, 1H), 8.31 - 8.20 (m, 2H), 7.98 - 7.84 (m, 3H), 7.80 (m, 4H), 7.65 (d, 7= 1.4 Hz, 1H), 7.43 - 7.28 (m, 3H), 3.19 (heptet, 7= 6.9 Hz, 1H), 1.32 (d, 7= 6.9 Hz, 6H)
1-20 C 538 (M+H) 220 (dec) (CDC13) δ 9.52 (s, 1H), 9.31 (s, 1H), 8.66 (d, 7= 8.2 Hz, 1H), 8.60 (s, 1H), 8.25 (d, 7= 8.4 Hz, 2H), 7.87 (s, 1H), 7.86 - 7.80 (m, 2H), 7.77 (d, 7= 8.4 Hz, 2H), 7.41 (d, 7= 8.3 Hz, 2H), 7.32 (ddd, 7= 13.9, 7.2, 4.3 Hz, 1H), 7.24 - 7.15 (m, 2H), 6.27 (s, 1H), 2.03 (d,7= 1.3 Hz, 3H), 1.73 (d,7= 1.1 Hz, 3H)
1-21 C 540 (M+H) 207- 210; 215-218 (CDC13) δ 9.48 (s, 1H), 9.14 (s, 1H), 8.60 (s, 1H), 8.26 (d, 7= 8.4 Hz, 2H), 7.92 (s, 1H), 7.87 (d, 7= 7.7 Hz, 1H), 7.84 - 7.76 (m, 4H), 7.40 (d, 7= 8.3 Hz, 2H), 7.30 (dt, 7= 8.2, 3.7 Hz, 1H), 7.28 - 7.23 (m, 2H), 2.57 (d, 7= 7.2 Hz, 2H), 1.93 (dq, J = 13.6, 6.7 Hz, 1H), 0.98 (d,7= 6.6 Hz, 6H)
1-22 C 540 (M+H) 210-215 (CDC13) δ 9.46 (s, 1H), 9.05 (s, 1H), 8.60 (s, 1H), 8.26 (d, 7= 8.4 Hz, 2H), 7.91 (s, 1H), 7.84 - 7.74 (m, 4H), 7.69 (d, 7= 7.4 Hz, 1H), 7.40 (d, 7= 8.3 Hz, 2H), 7.36 7.27 (m, 3H), 2.91 (dt, 7= 13.9, 6.9 Hz, 1H), 1.75- 1.58 (m, 2H), 1.30 (d, 7= 6.9 Hz, 3H), 0.92 (t, 7 = 7.4 Hz, 3H)
1-23 C 560 (M+H) 213-216 (CDC13) δ 9.41 (s, 1H), 9.01 (s, 1H), 8.74 (d, 7= 7.7 Hz, 1H), 8.60 (s, 1H), 8.15 (d, 7= 8.4 Hz, 2H), 7.86 - 7.78 (m, 2H), 7.69 (s, 1H), 7.57 - 7.44 (m, 6H), 7.42 (d, 7= 9.1 Hz, 2H), 7.37 - 7.27 (m, 4H)
ID Synthesis Method MS mp (°C) ‘H, 1jC, or ”F NMR (δ)1
1-24 C 524 (M+H) 200- 206; 210-211 (CDC13) δ 9.65 (d, J= 17.9 Hz, 1H), 9.20 (s, 1H), 8.60 (s, 1H), 8.27 (dd, J= 8.0, 4.5 Hz, 3H), 7.89 (s, 1H), 7.86 - 7.75 (m, 4H), 7.41 (d, J= 8.3 Hz, 2H), 7.30 - 7.27 (m, 1H), 7.18 (q, J= 7.8 Hz, 2H), 2.00 1.90 (m, 1H), 1.09 - 1.01 (m, 2H), 0.81 0.73 (m, 2H)
1-25 C 550 (M+H) 221-223 (DMSO-î76) δ 12.13 (s, 1H), 10.07 (s, 1H), 9.44 (s, 1H), 8.23 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 8.13 - 8.06 (m, 2H), 8.01 - 7.98 (m, 3H), 7.63 (d, J= 8.4 Hz, 2H), 7.38 - 7.26 (m, 3H), 7.23 (t, JHF= 74.1 Hz, 1H)
1-26 C 590 (M+H) 230-231 (CDC13) δ 9.37 (s, 1H), 8.60 (s, 1H), 8.57 (s, 1H), 8.27 (d, J= 8.4 Hz, 2H), 7.90 (s, 1H), 7.81 (dt, J= 8.5, 4.8 Hz, 4H), 7.41 (d, J= 8.3 Hz, 2H), 7.31 (s, 2H), 2.31 (s, 6H)
1-27 C 556 (M+H) 190-192 (CDCI3) δ 9.39 (s, 1H), 9.15 (s, 1H), 8.61 (s, 1H), 8.29 (d, J= 8.4 Hz, 2H), 8.16 8.05 (m, 2H), 7.95 - 7.85 (m, 3H), 7.85 7.76 (m, 4H), 7.41 (d, J = 8.3 Hz, 2H), 4.39 (q, J =7.1 Hz, 2H), 1.41 (t, J =7.1 Hz, 3H)
1-28 C 528 (M+H) 219-221 (300 MHz, CDCI3) δ 10.17 (s, 1H), 9.09 (s, 1H), 9.03 (t, J= 5.4 Hz, 1H), 8.60 (s, 1H), 8.23 (t, J= 8.9 Hz, 2H), 7.89 - 7.76 (m, 5H), 7.39 (t, J = 7.2 Hz, 2H), 7.17 7.07 (m, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.94 (d, J=6.9 Hz, 1H), 4.18 (q, J= 7.1 Hz, 2H), 1.61 (t, J = 7.0 Hz, 3H)
1-29 C 499 (M+1) 195-200 (DMSO-îZô) δ 9.44 (s, 1H), 8.49 (s, 1H), 8.42 (d, J= 5.2 Hz, 1H), 8.29 - 8.21 (m, 2H), 8.16 (d, J = 8.5 Hz, 2H), 8.10 (d, J = 2.3 Hz, 1H), 8.08 (d, J = 3.0 Hz, 1H), 8.04 (t, J= 6.5 Hz, 2H), 7.63 (d, J= 8.3 Hz, 3H), 2.29 (s, 3H)
ID Synthesis Method MS mp (°C) ‘H, 13C, or 19F NMR (δ)1
1-30 C 499 (M+1) 114-118 (CDC13) δ 8.60 (s, 1H), 8.31 (s, 1H), 8.24 (d, J= 8.4 Hz, 2H), 8.16 (d, J = 3.9 Hz, 1H), 7.95 (d, 7 = 8.4 Hz, 2H), 7.82 (d, J = 9.0 Hz, 2H), 7.55 (d, 7 = 6.7 Hz, 1H), 7.41 (s, 2H), 6.99 (dd, J= 7.4, 5.1 Hz, 1H), 2.35 (s, 3H).
1-31 C 513 (M+1) 122-125 (CDC13) δ 8.60 (s, 1H), 8.32 (s, 1H), 8.25 (d, J= 8.4 Hz, 2H), 8.19 - 8.16 (m, 1H), 7.97 (d, J= 8.4 Hz, 2H), 7.84 - 7.81 (m, 2H), 7.58 (d, J= 7.5 Hz, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.03 (dd, J= 7.5, 5.1 Hz, 1H), 2.67 (s, 2H), 1.35 (t, J= 7.5 Hz, 3H)
1-32 N 190 ([M+H]+) — (CDCI3) δ 7.78 - 7.71 (m, 1H), 7.54 - 7.47 (m, 1H), 7.40 - 7.32 (m, 2H), 5.86 5.82 (m, 1H), 2.63 - 2.55 (m, 2H), 2.55 - 2.47 (m, 2H), 2.09 - 1.98 (m, 2H); 13C NMR (101 MHz, CDC13) δ 148.77, 139.96, 133.58, 132.08, 130.87, 130.52, 127.55, 123.70, 35.31, 33.49, 24.05
1-33 N 162 ([M+H]+) — (CDC13) δ 7.14 (dd, J= 7.7, 1.3 Hz, 1H), 7.02 (td, 7= 7.6, 1.5 Hz, 1H), 6.76 (td, J = 7.4, 1.1 Hz, 1H), 6.68 (dd, 7=7.8, 1.2 Hz, 1H), 3.66 (bs, 2H), 3.04 - 2.92 (m, 1H), 2.13 - 1.98 (m, 2H), 1.88 - 1.58 (m, 6H);
13C NMR (101 MHz, CDC13) δ 144.12, 130.34, 126.51, 125.95, 118.78, 115.70, 39.89, 32.17, 25.21
1-34 N 236 ([M+H]+) CDC13) δ 9.02 (bs, 1H), 7.52 (bs, 1H), 7.41-7.18 (m, 4H), 4.06 (bs, 2H), 3.21 -3.06(m, 1H), 2.04 (s, 2H), 1.90-1.74 (m, 2H), 1.74- 1.58 (m, 4H);
ID Synthesis Method MS mp(°C) ‘h, l3C, or ”f NMR (δ)1
1-35 C 551 ([M+H]+) 213-216 (CDC13) δ 9.45 (s, IH), 9.11 (s, IH), 8.60 (s, IH), 8.26 (d, J= 8.4 Hz, 2H), 7.91 (s, IH), 7.86 - 7.71 (m, 5H), 7.40 (dd, J= 8.8, 6.4 Hz, 3H), 7.35 - 7.27 (m, 2H), 3.22 (t, J = 8.0 Hz, IH), 2.13 (d, J= 2.5 Hz, 2H), 1.90-1.59 (m, 6H)
1-36 N — — (CDC13) δ 7.48 - 7.36 (m, IH), 7.21 7.06 (m, 2H), 5.23 (p, J = 1.5 Hz, IH), 5.05 (q, J= 1.1 Hz, IH), 2.09 (s, 3H); 13C NMR (101 MHz, CDCI3) δ 153.56 (A,Jcf= 257.5 Hz), 139.62,139.60 , 138.83 , 131.48 (d, JCf=8.6 Hz), 124.47 (d, JCF= 3.6 Hz), 117.60,115.51 (d, JCF = 19.1 Hz), 23.18
1-37 N — — (CDCI3) δ 6.92 (dt, J= 7.7, 1.2 Hz, IH), 6.86 (ddd, J= 10.8, 8.1, 1.4 Hz, IH), 6.69 (td, J = 8.0, 5.6 Hz, IH), 3.71 (bs, 2H), 2.92 (hept, J = 6.8 Hz, IH), 1.26 (d, J =6.8 Hz, 6H); 13CNMR(101 MHz, CDCI3) δ 151.91 (d, J = 237.6 Hz), 135.10 (d, J= 2.3 Hz), 131.60 (d, J= 11.8 Hz), 120.52 (d, J= 3.0 Hz), 117.99 (d, J =8.0 Hz), 112.28 (d, J = 19.6 Hz), 27.77 (d, J= 2.9 Hz), 22.22
1-38 N 229 ([M+H]+) 122-124 (CDCI3) δ 8.56 (bs, IH), 7.54 (bs, IH), 7.32 (td, J = 8.1, 5.6 Hz, IH), 7.17 - 7.09 (m, IH), 7.00 (ddd, J= 9.5, 8.2, 1.4 Hz, IH), 4.07 (bs, 2H), 3.15 (hept, J = 7.0 Hz, IH), 1.24 (d, J= 6.9 Hz, 6H), 7.78 7.39 (m, IH)
1-39 C 544 ([M+H]+) 210-212 (CDCI3) δ 9.54 (s, IH), 8.60 (s, IH), 8.56 (s, IH), 8.30 - 8.22 (m, 2H), 7.92 (s, IH), 7.86 - 7.76 (m, 4H), 7.44 - 7.38 (m, 2H), 7.35 (dd, J= 8.1, 5.6 Hz, IH), 7.18 (d, J= 7.9 Hz, IH), 7.04 (ddd, J= 9.4, 8.2, 1.3 Hz, IH), 3.22 (p, J =6.9 Hz, IH), 1.29 (d, J =6.9 Hz, 6H)
ID Synthesis Method MS mp(°C) 13C, or 19F NMR (δ)'
1-40 N — — (CDC13) δ 7.60 (dd, J= 8.2, 2.5 Hz, IH), 7.37 - 7.21 (m, 2H), 5.19 (p, J= 1.5 Hz, IH), 4.97 - 4.89 (m, IH), 2.11 - 2.04 (m, 3H); 13C NMR (101 MHz, CDC13) δ 160.96 (d, J =250.8 Hz), 148.46,141.88, 135.18 (d, J= 4.1 Hz), 132.09 (d, J= 7.8 Hz), 119.98 (d, 7=20.9 Hz), 115.99, 111.63 (d, 7=26.4 Hz), 23.35
1-41 N — -- (CDC13) δ 7.05 (dd, 7= 8.5, 6.4 Hz, IH), 6.45 (td, 7= 8.5, 2.6 Hz, IH), 6.37 (dd, 7 = 10.6, 2.6 Hz, IH), 3.74 (bs, 2H), 2.83 (hept, 7= 6.8 Hz, IH), 1.24 (d, 7= 6.8 Hz, 6H); 13CNMR(101 MHz, CDC13) δ 161.75 (d, 7= 241.3 Hz), 144.76 (d, 7= 10.3 Hz), 128.11 (d, 7= 2.8 Hz), 126.53 (d,7 = 9.6 Hz), 105.06 (d, 7= 20.7 Hz), 102.26 (d, 7= 24.2 Hz), 27.27,22.35
1-42 N 226 ([M-H]+) 133-135 (CDC13) δ 9.11 (bs, IH), 7.44 (bs, 2H), 7.35 - 7.27 (m, IH), 6.99 (s, IH), 4.03 (bs, 2H), 3.05 (hept, 7= 6.9 Hz, IH), 1.23 (d, 7=6.9 Hz, 6H)
1-43 C 537 ([M-H]') 219-222 (CDC13) δ 9.52 (s, IH), 9.09 (s, IH), 8.59 (s, IH), 8.26 (d, 7= 8.2 Hz, 2H), 7.92 (s, IH), 7.85 - 7.71 (m, 4H), 7.47 (d, 7= 7.5 Hz, IH), 7.40 (d, 7= 8.7 Hz, 2H), 7.21 7.08 (m, 2H), 3.52 - 3.34 (m, IH), 2.42 (s, 3H), 1.39 (d, 7 = 7.2 Hz, 6H)
ID Synthesis Method MS mp (°C) 'h, 13C, or”FNMR (δ)1
1-44 N — — (CDC13) δ 7.67 (d, J= 0.8 Hz, 1H), 7.34 (ddd, J =7.8, 1.6, 0.5 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 5.15 (pentet, J= 1.4 Hz, 1H), 4.93 - 4.89 (m, 1H), 2.42 (s, 3H), 2.06 (dd, J= 1.4, 1.0 Hz, 3H); 13C NMR (101 MHz, CDC13) δ 148.17, 142.71, 138.30, 136.16, 133.37, 130.33, 124.29, 115.18, 23.32, 20.81
1-45 N — — (CDC13) δ 7.03 (d, J= 7.8 Hz, 1H), 6.65 - 6.56 (m, 1H), 6.52 (d, J= 0.9 Hz, 1H), 3.58 (bs, 2H), 2.87 (hept, J= 6.8 Hz, 1H), 1.24 (d, J =6.8 Hz, 6H); 13C NMR (101 MHz, CDC13) δ 143.15, 136.16, 129.82, 125.33, 119.79, 116.55, 27.37, 22.41,20.96
1-46 N 224 ([M+H]+) 167-169 (CDC13) δ 8.95 (bs, 1H), 7.53 - 6.93 (m, 4H), 4.08 (bs, 2H), 3.06 (heptet, J= 6.8 Hz, 1H), 2.33 (s, 3 H), 1.19 (d, J= 6.8 Hz, 6H)
1-47 C 540 ([M+H]+) 194-196 (CDC13) δ 9.50 (s, 1H), 9.00 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.91 (s, 1H), 7.86 - 7.72 (m, 4H), 7.49 - 7.36 (m, 3H), 7.27 (d, J= 9.2 Hz, 1H), 7.15 (d, J = 6.7 Hz, 1H), 3.14 (heptet, J= 6.8 Hz, 1H), 2.37 (s, 3H), 1.29 (d, J= 6.9 Hz, 6H)
1-48 N _ (CDC13) δ 7.96 (dd, J= 9.0, 5.1 Hz, 1H), 7.08 (ddd, J= 9.0, 7.4, 2.8 Hz, 1H), 7.02 (dd, .7=8.7, 2.8 Hz, 1 H), 5.20 (p, .7=1.5 Hz, 1H), 4.96 (p, J= 1.0 Hz, 1H), 2.11 2.06 (m, 3H)
ID Synthesis Method MS mp (°C) ’H, 13C, or 19F NMR (δ)1
1-49 N — — (CDC13) δ 6.85 (dd, J= 10.3, 2.9 Hz, 1H), 6.72 (td, J= 8.3, 2.9 Hz, 1H), 6.60 (dd, J= 8.6, 5.1 Hz, 1H), 3.49 (bs, 2H), 2.88 (hept, J =6.8 1H), 1.24 (d, J =6.8 Hz, 6H); 13C NMR (101 MHz, CDC13) δ 156.92 (d, Jcf = 235.0 Hz), 139.17 (d, Jcf = 2.1 Hz), 134.61 (d, JCf= 6.2 Hz), 116.55 (d, Jcf = 7.5 Hz), 112.69 (d, JCF = 22.5 Hz), 112.17 (d, JCF = 22.4 Hz), 27.90,22.11
1-50 N 228 ([M+H]+) 163-167 (CDC13) δ 8.88 (bs, 1H) 7.42 (bs, 1H), 7.03 (dd, J= 10.0, 2.9 Hz, 1H), 6.93 (ddd, J= 8.7, 7.7, 3.0 Hz, 1H), 4.03 (bs, 2H), 3.14-3.00 (m, 1H), 1.23 (d, J =6.9 Hz, 6H)
1-51 C 544 ([M+H]+) 219-221 (CDC13) δ 9.55 (s, 1H), 8.90 (s, 1H), 8.59 (s, 1H), 8.30 - 8.21 (m, 2H), 7.92 (s, 1H), 7.85 - 7.74 (m, 4H), 7.54 (dd, J= 8.8, 5.5 Hz, 1H), 7.40 (d, J= 8.6 Hz, 2H), 7.07 (dd, J= 10.0, 2.9 Hz, 1H), 6.97 (td, J= 8.2, 2.9 Hz, 1H), 3.24 - 3.08 (m, 1H), 1.29 (d,J=6.9 Hz, 6H)
1-52 N — — (CDC13) δ 7.87 - 7.78 (m, 1H), 7.19 7.09 (m, 1H), 5.20 (q, J= 1.5 Hz, 1H), 4.94 (q, J= 1.2 Hz, 1H), 2.07 (t, J= 1.3 Hz, 3H); 13C NMR (101 MHz, CDC13) δ 152.53 (dd, JCF= 259.5, 12.5 Hz), 148.52 (dd, JCF = 253.7, 13.8 Hz), 143.22,141.38 , 137.23 (dd, Jcf =7.1,4.2 Hz), 119.27 (d, Jcf = 18.9 Hz), 116.39,114.49 (dd, JCf = 21.9, 2.1 Hz), 23.12
ID Synthesis Method MS mp(°C) ’H, 13C, or 19F NMR (δ)1
1-53 N — — (CDC13) δ 6.97 - 6.84 (m, 1H), 6.45 (dd, J= 12.1, 7.2 Hz, 1H), 3.57 (bs, 2H), 2.89 - 2.72 (m, 1H), 1.22 (d, J= 6.8 Hz, 6H); 13C NMR (101 MHz, CDC13) δ 148.36 (dd, = 243.1, 13.4 Hz), 143.71 (dd, Jcf= 236.4, 12.4 Hz), 139.79 - 139.13 (m), 128.70 (t, JCF = 3.7 Hz), 114.07 (d, Jcf= 18.1 Hz), 104.18 (d, JCF= 19.8 Hz), 27.44, 22.20
1-54 N 246 ([M+H]+) 169-170 (CDC13) δ 8.95 (s, 1H), 7.82 - 7.34 (m, 2H), 7.10 (dd, J = 11.7,8.5 Hz, 1H), 4.01 (s, 2H), 3.13 - 2.94 (m, 1H), 1.22 (d, J = 6.9 Hz, 6H)
1-55 C 561 ([M+H]+) 217-221 (CDC13) δ 9.46 (s, 1H), 8.96 (s, 1H), 8.60 (s, 1H), 8.31 - 8.22 (m, 2H), 7.92 (s, 1H), 7.84 - 7.75 (m, 4H), 7.60 (dd, J= 11.2, 7.7 Hz, 1H), 7.44 - 7.36 (m, 2H), 7.14 (dd, J= 11.7, 8.5 Hz, 1H), 3.19 3.04 (m, 1H), 1.29 (d, J= 6.9 Hz, 6H)
1-56 p* 402 [M-H]-) — (CDC13) δ 8.64 (d, J = 1.1 Hz, 1H), 8.09 (m, 3H), 7.93 (m, 3H), 7.78 (d, J = 8.5 Hz, 3H), 7.30 (d, J = 7.9 Hz, 3H), 2.42 (s, 4H); 19F NMR (376 MHz, CDC13) δ -75.61, -75.63, -75.63, -182.14, -182.17, -182.18
1-57 p* 418 ([M+H]+) — (CDC13) δ 10.09 (s, 1H), 8.71 (s, 1H), 8.39 (d, J = 8.3 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.95 (m, 2H), 7.82 (d, J = 8.6 Hz, 2H); 19F NMR (376 MHz, CDC13) δ -75.57, -75.59, -182.14, -182.16, -182.18
1-58 N 210 ([M+H]+) — (CDC13) δ 8.97 (bs, 1H), 7.74 - 7.11 (m, 5H), 4.06 (bs, 2H), 3.11 (hept, J= 6.9 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H)
ID Synthesis Method MS mp(°C) Ή, 13C, or 19F NMR (δ)1
1-59 C 609 ([M+H]+) — (CDC13) δ 9.59 (s, 1H), 9.05 (s, 1H), 8.69 (s, 1H), 8.31 - 8.24 (m, 2H), 7.94 (d, 7 = 8.8 Hz, 3H), 7.85 - 7.74 (m, 4H), 7.66 (dd, 7= 7.7, 1.5 Hz, 1H), 7.39 (dd, J= 7.7, 1.8 Hz, 1H), 7.37 - 7.27 (m, 2H), 3.19 (hept, J =6.9 Hz, 1H), 1.32 (d, J= 6.8 Hz, 6H);
19F NMR (376 MHz, CDC13) δ -75.58 , -182.16
1-60- C 575 ([M+H]+) 214-216 (DMSO-76) δ 11.87 (s, 1H), 10.08 (s, 1H), 9.44 (s, 1H), 8.20 (s, 1H), 8.17 8.02 (m, 6H), 7.63 (d, J= 9.0 Hz, 2H), 7.39 - 7.35 (m, 1H), 7.35 - 7.28 (m, 1H), 7.27 - 7.18 (m, 2H), 3.19 - 3.05 (m, 1H), 1.20 (d, 7=6.9 Hz, 6H);
19F NMR (376 MHz, DMSO-76) δ -85.20, -86.94
1-61 N 227 ([M+2H]+) — (DMSO-4) δ 9.20 (brs, 1H), 8.89 (s, 1H), 7.20 (d, J = 8.32 Hz, 1H), 6.71-6.77 (m, 2H), 4.71 (brs, 2H), 3.74 (s, 3H), 2.52-2.46 (m, 2H), 1.11 (t, J = 7.56 Hz, 3H)
1-62 C 591 ([M+H]+) — (DMSO-76) δ 11.83 (s, 1H), 9.94 (s, 1H), 9.44 (s, 1H), 8.19 (s, 1H), 8.16 - 8.08 (m, 4H), 8.05 (d, J= 8.3 Hz, 2H), 7.63 (d, J= 9.0 Hz, 2H), 7.14 (d, J = 8.5 Hz, 1H), 6.85 (d, J= 2.9 Hz, 1H), 6.80 (dd, J = 8.5, 2.9 Hz, 1H), 3.78 (s, 3H), 2.57 (q, 7=7.5 Hz, 2H), 1.16 (t, 7= 7.6 Hz, 3H);
19F NMR (376 MHz, DMSO-76) δ -85.18, -86.92
NMR spectral data were acquired using a 400 MHz instrument unless otherwise noted.
P* - Prepared according to methods described in Crouse et al. PCT Int. Appl. Publ. W02009/102736 Al and Brown, et al, WO 2011017504 Al.
Table 3: Structures for Compounds
ID Structure
IC o-O'NDn s ηΛ
2C ,ΓΛ. O-/ / N X CF y N iXn 1Ώ F F \Z\Y N Cl
3C / VN. A CF y N uln i n F F N Cl
4C /=N BrK_ / y n \ x P \=/ y V> fcA II JL m JL JL J F F N
5C cyp /=n yz ρ^ο^Νν\Υ n 1X) F F νΥγΑπΥζ
6C OH ° /X? ζτ-Λ /^N L II α J Vn. \ x . îX N ULn\ X) f f YYyyy
7C R_^ (X—F Λ=Ν V-Z Y<Yy^j\ xq F F
8C T? F FS-O-^v F i] f^ N lX n 1X) F F \Υ^χ+Ν·Ν Ν^γ
ID Structure
9C CJ yN a ' γ x p+ N iQ n W
10C oYvyaYY y N uCui Ό F F U+U^ N N^Y
11C AVF oxyuuA-A v N uAi Y F F N N^Y
12C O ΓΛ °ΧΧί NΊΧν 1X) F F N N^Y
13C 0 H2N-S^\ Λ-Ν 0 L L Ωγ y-N. j ^Υχ x y Y N Un 1 X) F F \U^1N n N^Y
14C N-S YyN >r-^ ^N i J fy N lX N 11) F F YU^’fiY'Y
15C ojVI/Jh f-^ N lX°n 1X) F F \Ζ\ΥΝΑΥ^
100
ID Structure
52C 0- o °Y X Y N
53C F 0/^N ΗΟγθ VY (J VN. \ k < / P n^v\ xs W F F F XJN'N^N J
54C ,».N ΗΟ-γΟ ΓΆ / yN i k < / P s y fff υ^Ν·Ν\Υ
55C ° X /^N Λ-’Ν'χ / VN. \ < P Ύ n pXp s y=\ F F F JJN-N\aJ
56C ) ογΧΧ o ° N-S \ p F _ /=N S VY rY CVN. Y-YY y x J o-Αγ N tyYN'N N [
57C -^-o O^NJNY° fY YV'J f TJ
58C J-o O^N / n /^N N-^0 / y n. \ P \ . j N iXn i X)
ΙΟΙ
102
103
104
105
106
ID Structure
94C O / /-N ' / Y rN A YY.æn F OÂY AZ
95C J3 Cl /=N V/) F F V'nX V F fW
96C ° Q /=Y syn U Fx J^Vn'n'ki)X^n''n F (MA
97C r\ NY. /=N M XVn'n \TVn'n F ΟΑΥ
98C V ΓΆ r~f OM F ° A=Y ΝΝ^γΧ Sy-NxJ^ LX\^N-N T J
99C V Br lXn-Y Xj
100C F\/F Ω fX/F zr-\ /=N f—/ . F °O'nnjys sVn>A UUn-Y Xj
101C F F /^N X F °Υ_Υν·νΎ s?n i .>Ύλι·ν J.,
102C Β\χΒ j-—s /—>N ,—/ ci fX°X_Z ΝΥγ> M'A LJ\^n-n L J Cl
107
ID Structure
103C F F __ zP LONA sÇi 1 LXn-L A
104C F F __ /P ’MAA ÇU LAn-n JO
105C FF A TA A A
106C FF /^N zP fM2>'VO'I Çvj
107C p p O 0 SZ r~A /^N r-/ Lo -w-..v, ςίJΊ oA^n-n LJ
108C V r-x \^ pX° ν^ΝΝ^Ο O_A lAn-Z o
109C oA3- A rvn A « °A_7 CaTx lAn-Z x)
HOC o=^°~ FF A, F 0 \Lv N'n’A/A An-T\ AAajO
me V zr-N /-N r-P / F «A\O (A UA A
112C F F /^N A V? F Αλα (A UA u
108
ID Structure
113C FF __ P ρΧο-Ον νΛ^ sU IXn-n U
114C UF /-A /-N Y , F ojj NnYa·, sÇnxJ\ lXn-/ U ^O
115C F F _ _P FkQ'N NJvx
116C V ΓΆ '-N r~?° F θΆ/Α^υυ suJ\ lXn-Z u
117C FF __ /^N S> fXo-On nX^ sÇt 1 uUn u
118C V ΓΛ '-N rJ ! F °H/’nn+y^% s ,-nJ, IXm Un
119C FF /^N P A FXHu (U IXn-nX U
120C F ΓΆ r~f A f+-O'NnU> syNU F W-N U
121C V ΓΛ Y A F HHu eu Ύ Ί Y r Ί
122C FVF ΓΆ Y y y-N. À ς <T / ΤΑγΝ-Ν JJ
109
ID Structure
123C F fa /—/° X J J VLn'N XJ)
124C F F F P θ FX ΓΧν^ γ~Λ °Λρ 0 'N^yy ΧΝγΛ UUn-X X)
125C P Y ΓΛ F'XnA y-N À sXo NAp, i ΙΧ^Ν-Ν >=X\ o
126C F. ,F A /=N FXny y-N Λ sXo F O-W N'A \Ay~N \_X~< w F
127C F F /^N \γΡ V> Fsfi Γ UX U
128C FyF ΓΑ V_/° A- fXJ Y-n. χ JJ [ υ \=/ VnyS
129C FyF r-p Z^N y_/° C1 f%_X y-N x r υ\=Χ N'A'X X/XpL T Χ\/Ν-Ν ~X J
130C FVF X° Cl fX0-ONn'V^ G JL LXn-n<X)
131C V i-A C-.N X° F F N / y-N. X J}, 1 °Ά/ n-Ax νΝ>Α \A/zN-N J
132C FyF f—, \A a-AAnA^ Ç»A ‘../...ri-N fol
110
ID Structure
133C F F λ—\ /N F o-O'N-V'x. ÇN f X.J .N-X ITj
134C F-\—/ Vn \ r~\ T F « T 1 XAX'N
135C FVF ζτ-χ /==N .—. FCA UA u
136C FVF zr-\ ( 7 F O77SCAX UA X)
137C FyF ζτ-χ /=N ,—. . F O-V/ Νν\λ SÇnZx TXn-Z ul \
138C F ®X/NnXs \aA lXnZ xi \
139C F F __ F °\_7 nn”%^ UUn-Z xx
140C FyF /—, o- XXXNX^, sXN î IXnX Xj
141C FVF Γ-χ /=N ,—. . F °svnyJ JXn-n JJ)
142C F%ΧΧΝΝ·χ^ sPA TX^N-N JCJ
143C FyF zr-N /=Ν r—, ci FXQ^X sXN f lXnV X)
111
ID Structure
144C V f-A /-N O Wv sçN r
145C FyF /^N F o-θ' NN! r-' l C\A LXn-/ ίΟ
146C FyF t OX f VN- Λ /a Ym Y x U \=/ N VN, SVNA\ XXYn-n ΥΥ
147C FVF /-A r— F sa/na^\A> Tl Γ lT x WN~N yyi
148C FVF ΓΛ r~\ F F θΌΛΜ O I UV o
149C FyF rx /-N Fy_F F F°Όλ\λ <?nJz XXn-TXj
150C FVF ΓΛ F ° V_7 NnYaA S\^nYYX Tl \ Il
151C FyF ''N r~\ r==4 F o'Va NnYa sCnYT Tl r il VYN'N kv
152C F V ΓΆ „ <V fMXa <?Ύ IAa^n-n
153C F V ΓΆ '-N „ (A f y-N. \ Y F °aa V VNrS W^n-n vj
112
ID Structure
154C FyF r-χ /=*N f o-on na UA xj
155C FVF /=N !—/ \y Αν/νΑ CUC UL A V
156C F o-CCn-As CA UA X)
157C V ΓΛ /—/ Cl f\J VN A s^nt 1 υ \=C nAA aUA XXV XI
158C FyF r\ r—/ C1 fVn- A sAi 1 ° VA n tXU vn\A %XL^n-n JXJji
159C FyF r\ ''N r~/ F fXo-0-nnU^ sCI UA O
160C \F r-χ /-N r-λ A AAAu^, Ca AXA r) Cl^^A
161C FVF ΓΆ /—/ / f UU'As, OA. iXnAXx
162C F\ZF zr-A /=N Λ—A . F «Xx nnXa sCn^Z lXXa-n X.X 1
163C FyF ΓΆ Γ-/ Va f oXn na Ca UA U
113
ID Structure
164C F V ΓΆ Λ-Ζ 0Y. F Y) Y VN- Λ /Ιτ 1 F ° \=/ N /A •L^X^n-n yj
165C FyF zr-χ /=N ,—/ V- F O-V7 γΟΥ UX u
166C FVF ΓΆ I—/ , F «ΌvJ UY u
167C FyF r-χ /^N !—/ C1 F sJX f XXj
168C F EyF ΓΑ r—/ 0YF XJx^N-N XJ
169C V /~N Vp f ο-Ολυα oY? IXY Y) V Cl·^^
170C F FyF r-L /^N «Y oXF F o-LHv, sY îf XXiY U
171C FyF zr-χ /=N ,==/ F fmX\a <?n.± LLTn-n FX J
172C FVF /ΤΎ Λ=Υ i F oYnAa OA iXnAXi \
173C FVF #-χ /^N ^=/ , F θ'Υν Nn^YY XXnY u
114
ID Structure
174C FVF ζτ-χ /==N /=/ . F o-vJNnV\ CaX. ΧΧ^Ν-Ν XI
175C FyF zr-χ /=N —X . F 0-0Nn:::·' ,'· sOAx ιΧ,Χ x)
176C FVF zr-\ /=N /==/ \χ F °Ό'ΝΝΛγ> svnvX UUn-X Xj
177C FyF ,T\ /—\ F Y-N. \ S ) > 0T-T Ν%π X v_ \ΑχΝ U/
178C FyF x aX rN A s ) > °-W N-Sp, X \ YA^n-n AA
179C F\__/ Y-N J S > > FT\=/ iîX yn \- YaY>n-n γ=Ζ
180C FVF ΓΛ ^N /—\ FYY Y-N I s > °+-+ nX X χΙ^Ν-Ν \=/
181C γΑΥννΆ \ > ^=7 N Y 1 An ΐγΑ^Ν-Ν AA o-
182C FyF x λ~λ %-/ΧΝ Ν«ν^ s ) ^=7 N γη An XaAX-n A
ns
ID Structure
183C FyF /=N /—\ Q x YYn-n \=z \
184C FyF /'N /—\ F οΌλΑ/τ O ^=7 N Υη Xn AaA^n-n \=Z
185C FyF AA /^N /—s. ΥΝ· Λ s > N-γ. A
186C FyF AA /—\ JA^n-n V=A
187C FVF AA /^N /-Λ FXo<yN· O ^==7 II 1 Χγ Cl YAn-n )==/ cl^7
188C FVF AA \ F %__/ V-N. 3 s > \==/ N XN\ /Cl U/N-N )=/ F O
189C FyF /A /—k F rN- Λ s > ^=7 N~|XX l·- N F JA/N-n y=z F vJ
190C FyF rA /—\ F A-A VN- À S ) F °-A=y γΝ Xf k/A/N-N )=/ F clA z
191C F\7 V-N X s ) ^=7 N γ> An AA/N-n a=/
116
ID Structure
192C FyF A a-O- va o ' / Il | y~N z O-
193C FyF ΓΆ \ f da νΝ· λ s > A A A z
194C FyF /—\ z—, fVJ / n X s > XX °A n+a A LJ> YXn-N U=Z
195C f\J ΓΝ· Λ s > N >-n
196C FVF A ΛΛ VN- Λ s > °A-/ «A A )=/ cixJ
197C FVF A ΛΑ F \J/ VN 4 S > °A/ n-A A z ApAA-n va \
198C FyF A '“'N ΑΛ F XX rN· Λ s > N ifX / YpA^N-N >==(
199C FvF rA /—\ ' -c>-N.-p Q .,j, υ“~ Ô '
200C XF A \ F A / X— N. S S / f As A ox A\A~N >=< F
117
ID Structure
201C FVF ΓΆ /—\ F b-Z ZN A S > F YYn-N v=z h cixJ
202C /=N X rX X ΧνΧ\ΓΧχΝ o f m. och3
203C x Vnx X XVNn\XXn nXX f V'V' +/-7 VA Br
204C ,T SCÙ OCH3 /=N y-N / 3 AOXY y
205C X Vv X XXX \TXxN XX F oAA </ N-7
206C X Vx X XVnnXTX^n n 0 foAA h3co
207C X XXx X /Y^XX^ O F YA> VA CO2Et
208C X-iyvXs O ^=7 N y I )-N OEt vX^n-n y=/
209C f-J__/ y-N ï s > 1 ρν=/ NX|X Z-n L AX^n-n yy
118
ID Structure
210C F\T ΓΆ F θ-ΟΈ'Ύ Q L·
211C FyF ΓΛ /-N O / Vn. \ s' \ °-V/ W . DYn-n \=ζ
212C FyF \ /=N F w VN- Λ s' ) x 0 N γ> W U VYn-n
213C FyF r\ F%J VN Â S \— OA~^ N ΥΊ Z-
214C FyF n—\ ( f\J rN X s > °-\_Λ N%p, N F FAzN-n /-K F f
215C FyF r~^\ F\-Z rN· Λ s ) F P YY^N-N )=( h C1AJ
216C FyF /—\ fYY y-N. ï s F ^=/ N [TT )-N pYF Vx^N-N F
217C fXo-/ γν·ν*Μ^ \ V .F ^=7 N Υη >-n /^f Y^N-N )=7 F C1A_/
218C T7 /=N T FvF fVN ΥΎ / FXoAY N ΐ X/N-N >=< -V?
119
ID Structure
219C „ p _ /=N fXoa=t n>=k ΧΟ-
220C „ p , /==N \ / f oAx n T#
221C π F /=N X n-/F FVF fV-N y-y θ -< fXo-<J N >=< F
222C „ p „__, /=N S' \ \__ FvF γα-ν· y-y /V F oA=x n (i X /N-n >=\ \J
223C Γ>ο ; /=N\ VNvJ Fx ZVn’nTT^n n —O f Oxy X-X
224C /Vo ί c Γ I____ χΝ\ VNx=y Fx ΤΎν'ν \TX^n'n O F oü> W
225C xyo /=N\ VNs=A Ά AVn'n f ο-ΧΧ X-X
226C Xyo VNX f οΆΧ X/ VJ
227C YVo /=N\ /-. VNS=/ FX ΧΥΧ'ΥΥ^'αΛ/ F Ο-χΧ X/^ el VJ
228C /=N VNV-TF FX XYN'NÀTT^N'aAj F oA> XX^ X-X
120
ID Structure
229C τχ=° F /=N SV-N P“Jf fXXTn'nXAn'n 0
230C 1 s r \ / A / } F oAJ ++7 V-7
231C ΓΜ S < A AJ ’vû0 0-
232C TX=o | Q Γ te A α_λ A AYn'n \TXxn O F O-tete tete^ V-/
233C f Q / z-x / Fx AV n O F TAte tete^ v_/
234C s/^O g=N y-N^ P te jAteATteN-N J”) F '/ VJ
235C teN y-N J1 te
236C z^=o A Vv Ά /An'n \TX^n'nA/ f tetete tete^ V_/
237C sZ-y=O A V\-A Fx /An'n \TX^n n A) F O\> tete^ Vte
23 8C jte'y-O \ A JN\=/ A AYn'n \ΑΑν'νΑ/ F tete^ Vte
121
ID Structure
239C S-Y° μ /=n FxF /Ήν'ν F V-/
240C X.OH /=N V Hj XXYn'n ιΧνΛΌ
241C zN y® N Cl F^ F'l \ / F ^=7
242C /-A/Oh SI \_ /=N X HJ FxF /Y'N \fX^N N 4) foAZ v_j
243C Z^/OH s / \___/ H W/ fxf /Ύν'νΧΓΧ^ν o F O-^VY VJ
244C /'J'-OH /=N XN\_/C1 vF F ’<Z V-J
245C /^Voh S 1 '“’t z^, XJ CK- Q o—
246C Â* /\/OH SI \_ H kNvj FxF /Xn~n \TX^n'n (/ F O 'X J/ Z_J _
122
ID Structure
247C F P F-^/F S T \__/ JXn'nXX^n'n o f ό -y v_z
248C F F F V ο-X r N X \=X N ιΓΧ ?'V°H
249C °' Z n 0+γχ
250C Y /VX ?ΎΗ Yu N ιγνΥ)--- F V/
251C F F /=X o/x 0H vX Γ v^N- ? y_ ΡΥΎΓ NΊΧ^/νΖ X
252C F F __-x /y o^\ OH tX Γ v-N- i y—, NX3^N.ZNf\ XX
253C F F K Y rA oX VN- X^ \=X N^XX ?XyH 0 Jl μ
123
ID Structure
254C y u °Ά«/ n
255C F F OH Y ? V- fAo-v n Jb
256C Y ΓΜ ? y- fvj N tZYvYu O
257C fFX AnJu θΛχ Ν χΑΝ·ΥΝΑ \)
258C F F /=N OH rX fVN- ? y- uu nXwu θ F
259C F F __ /=N OH rX XVh ? y-, O F F
260C F F Jy /==n FÎVZ VN- Λ /uX N ΊιΑ ?Υ/θΗ FX L X n Λ y~ F F \Z\A 1n
124
Table 4: Analytical Data for Compounds in Table 3
ID Synthesis Method MS mp(°C) *H NMR, 13C, or 19F NMR (δ)1
IC D 540 (M+) - (DMSO-Jô) 8.61 (s, 1H), 8.48 (s, 1H), 8.22 (d, J= 8.24 Hz, 2H), 8.17 (s, 1H), 7.89 (d, J = 8.24 Hz, 2H), 7.80 (d, J = 8.28 Hz, 2H), 7.41 (d, J= 8.28 Hz, 2H), 7.19 (d, J = 8.24 Hz, 2H), 6.71 (d, J= 8.24 Hz, 2H), 2.99 (s, 6H), 2.42 (s, 3H)
125
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)'
2C D 580 (M+) 168-171 (DMSO-76) 9.42 (s, 1H), 8.18-8.03 (m, 5H), 7.78-7.69 (m, 2H), 7.61 (d, J= 8.26 Hz, 2H), 7.44 (d, J = 8.24 Hz, 2H), 7.18 (m, 1H), 3.09-2.99 (m, 2H), 1.39-1.32 (m, 3H)
3C D 594 180-182 (DMSO-îZô) 9.42 (s, 1H), 8.18-8.04 (m, 5H), 7.78-7.69 (m, 2H), 7.61 (d, J= 8.26 Hz, 2H), 7.48 (d, J= 8.24 Hz, 2H), 7.19 (m, 1H), 3.06-3.02 (m, 2H), 1.78-1.64 (m, 2H), 1.04-0.96 (m, 3H)
4C D 629 (M+) (DMSO-c/6) 8.57 (s, 1H), 8.48 (d, J= 5.5 Hz, 1H), 8.22 (d, 7 = 8.2 Hz, 2H), 7.91-7.75 (m, 5H), 7.38 (d, 7= 8.7 Hz, 2H), 7.22-7.07 (m, 3H), 6.50-6.19 (m, 2H), 3.85 (d, 7= 7.2 Hz, 1H), 3.75-3.64 (m, 1H), 2.33 (s, 6H)
5C E 636 (M+) (300 MHz, CDC13) 8.56 (s, 1H), 8.54 (s, 1H), 8.23 (d, 7= 8.3 Hz, 2H), 7.89 (d, 7 = 8.2 Hz, 3H), 7.79 (d, 7= 9.0 Hz, 2H), 7.38 (d, J= 8.7 Hz, 2H), 7.23-7.00 (m, 4H), 6.88- 6.74 (m, 2H), 4.44 (s, 2H), 2.33 (s, 6H)
6C D 645 (M+H) 196-198 (methanol-X) 9.16 (s, 1H), 8.46 (s, 1H), 8.21 (d, 7= 8.3 Hz, 2H), 8.03 (m, 6H), 7.52 (d, 7= 8.3 Hz, 4H), 7.28 - 6.91 (m, 3H), 4.39 (s, 2H), 2.08 (s, 6H)
7C E 636 (M+) (300 MHz, CDCI3) 8.56 (m, 2H), 8.23 (d, 7 = 8.3 Hz, 2H), 7.88 (d, 7= 8.3 Hz, 3H), 7.79 (d, 7= 9.0 Hz, 2H), 7.55-7.42 (m, 1H), 7.37 (d, 7= 9.0 Hz, 2H), 7.20-7.01 (m, 3H), 6.896.68 (m, 2H), 4.30 (s, 2H), 2.28 (s, 6H)
8C E 684 (M+) (CDCI3) 8.57 (s, 1H), 8.52 (s, 1H), 8.24 (d, 7 = 8.3 Hz, 2H), 7.91-7.84 (m, 3H), 7.80 (d, J = 9.1 Hz, 2H), 7.39 (d, J = 8.6 Hz, 4H), 7.18-7.03 (m, 5H), 4.32 (s, 2H), 2.29 (s, 6H)
9C E 620 (M+) (CDCI3) 8.57 (s, 1H), 8.47 (s, 1H), 8.23 (d,7 = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (m, 3H), 7.39 (d, 7= 8.4 Hz, 2H), 7.21-7.10 (m, 3H), 3.93 (s, 2H), 2.35 (s, 6H), 0.13 (s, 9H)
126
ID Synthesis Method MS mp(°C) 'H NMR, l3C, or l9FNMR (δ)1
10C D 600 (M+) (DMSO-î76) 8.57 (s, 1H), 8.54 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.89 (d, J= 8.3 Hz, 2H), 7.87 (s, 1H), 7.80 (d, J= 9.0 Hz, 2H), 7.447.32 (m, 4H), 7.31-7.19 (m, 3H), 7.19-7.00 (m, 3H), 4.34 (s, 2H), 2.31 (s, 6H)
11C D 618 (M+) (DMSO-J6) 8.57 (s, 1H), 8.55 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.89 (d, J= 8.3 Hz, 2H), 7.86 (s, 1H), 7.83-7.73 (m, 2H), 7.48 (td, J= 7.6, 1.7 Hz, 1H), 7.38 (d, J= 8.5 Hz, 2H), 7.23-6.91 (m, 6H), 4.39 (s, 2H), 2.30 (s, 6H)
12C D 658 (M+) (DMSO-Jô) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.94 (d, J= 8.3 Hz, 2H), 7.88 (d, J= 8.2 Hz, 2H), 7.86 (s, 1H), 7.79 (d, J= 9.0 Hz, 2H), 7.44 (d, J= 8.3 Hz, 2H), 7.38 (d, J= 8.6 Hz, 2H), 7.20-7.05 (m, 3H), 4.35 (s, 2H), 3.88 (s, 3H), 2.28 (s, 6H)
13C E 679 (M+) (DMSO-î/6) 8.59 (s, 1H), 8.51 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.93-7.76 (m, 7H), 7.53 (d, J= 8.2 Hz, 2H), 7.39 (d, J= 8.7 Hz, 2H), 7.20-7.06 (m, 3H), 4.88 (s, 2H), 4.36 (s, 2H), 2.28 (s, 6H)
14C E 658 (M+) (CDC13) 8.57 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.91-7.85 (m, 4H), 7.80 (d, J = 9.1 Hz, 2H), 7.73 (d, J= 6.8 Hz, 1H), 7.52 (dd, J= 8.8, 6.9 Hz, 1H), 7.39 (d, J= 9.0 Hz, 2H), 7.13-7.01 (m, 3H), 4.88 (s, 2H), 2.27 (s, 6H)
15C E 667 (M+) (CDCI3) 8.57 (s, 1H), 8.25-8.14 (m, 3H), 7.94-7.66 (m, 7H), 7.52-7.35 (m, 6H), 7.16- 7.03 (m, 3H), 4.54 (s, 2H), 2.32 (s, 6H)
16C E 658 (M+) (CDCI3) 8.57 (s, 1H), 8.49 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 7.88 (d, J= 8.3 Hz, 2H), 7.83-7.77 (m, 3H), 7.39 (d, J= 8.3 Hz, 2H), 7.19-7.07 (m, 3H), 6.69-6.65 (m, 1H), 6.396.35 (m, 1H), 4.36 (s, 2H), 2.29 (s, 6H)
127
ID Synthesis Method MS mp (°C) Ή NMR, 13C, or 19F NMR (δ)1
17C E 678 (M+) (CDC13) 8.58 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.94-7.74 (m, 7H), 7.59 (d, J = 8.4 Hz, 2H), 7.38 (d, J= 8.4 Hz, 2H), 7.20-7.04 (m, 3H), 4.37 (s, 2H), 3.01 (s, 3H), 2.29 (s, 6H)
18C E 773 (M+) (CDC13) 8.59 (s, 1H), 8.46 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.86 (d, J= 8.4 Hz, 2H), 7.83-7.75 (m, 3H), 7.63 (d, J= 8.4 Hz, 2H), 7.44 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 8.4 Hz, 2H), 7.17-7.05 (m, 3H), 7.03-6.98 (m, 3H), 6.89 (t, J = 8.6 Hz, 2H), 4.30 (s, 2H), 2.24 (s, 6H)
19C E 728 (M+) (CDCI3) 8.59 (s, 2H), 8.26 (d, J= 8.3 Hz, 2H), 7.93 (d, J= 8.3 Hz, 2H), 7.89 (s, 1H), 7.82 (d, J= 9.1 Hz, 2H), 7.40 (d, J= 8.3 Hz, 2H), 7.20-7.05 (m, 3H), 6.86 (s, 1H), 4.49 (s, 2H), 3.98 (s, 3H), 2.31 (s, 6H)
20C E 681 (M+) (CDCI3) 8.58 (s, 1H), 8.38 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.86 (d, J= 8.3 Hz, 3H), 7.81 (d, J= 9.1 Hz, 2H), 7.67-7.63 (m, 2H), 7.467.36 (m, 5H), 7.18-7.05 (m, 3H), 4.24 (s, 2H), 2.47 (s, 3H), 2.29 (s, 6H)
21C E 596 (M+) (DMSO-tZô) 8.58 (s, 1H), 8.15 (d, J= 8.4 Hz, 2H), 7.80 (d, J= 9.0 Hz, 2H), 7.47-7.35 (m, 4H), 7.21-6.93 (m, 5H), 3.68 (t, J = 5.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J= 6.2 Hz, 2H), 2.29 (s, 6H)
22C E 626 (M+) (DMSO-A) 8.59 (s, 1H), 8.52 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.95-7.75 (m, 5H), 7.39 (d, J= 8.4 Hz, 2H), 7.21-7.06 (m, 3H), 5.80 (s, 2H), 4.12 (s, 2H), 3.69-3.50 (m, 2H), 2.31 (s, 6H), 1.35-1.11 (m, 3H)
23C E 731 (M+) (DMSO-dô) 8.58 (s, 1H), 8.50 (s, 1H), 8.22 (d, J= 8.2 Hz, 2H), 7.93-7.70 (m, 5H), 7.457.28 (m, 8H), 7.23-7.03 (m, 3H), 5.79 (s, 2H), 5.38-5.27 (m, 1H), 5.11 (s, 2H), 4.073.98 (m, 2H), 2.30 (s, 6H)
128
ID Synthesis Method MS mp(°C) 'H NMR, 1JC, or19FNMR (δ)1
24C E 626 (M+) (DMSO-X) 8.58 (s, 1H), 8.51 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.93-7.73 (m, 5H), 7.39 (d, J= 8.9 Hz, 2H), 7.21-7.07 (m, 3H), 5.76 (s, 2H), 5.05-4.70 (m, 1H), 2.32 (s, 6H), 1.38-1.17 (m, 6H)
25C E 610 (M+) (DMSO-X) 8.59 (s, 1H), 8.52 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.91-7.79 (m, 5H), 7.40 (d, J= 8.5 Hz, 2H), 7.18-7.06 (m, 3H), 5.73 (s, 2H), 2.70-2.45 (m, 1H), 2.32 (s, 6H), 1.15 (s, 6H)
26C E 654 (M+) (DMSOM) 8.58 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 7.98 (d, J= 8.4 Hz, 2H), 7.81 (d, J = 6.9 Hz, 2H), 7.69 (s, 1H), 7.40 (d, J= 8.8 Hz, 2H), 6.63 (s, 2H), 5.73 (s, 2H), 3.80 (s, 3H), 2.64-2.53 (m, 1H), 2.58 (s, 3H), 2.28 (s, 6H), 1.17 (d, J = 7.0 Hz, 6H)
27C E 640 (M+) (DMSO-X) 8.58 (s, 1H), 8.50 (s, 1H), 8.23 (d, J= 8.2 Hz, 2H), 7.88 (d, J= 8.3 Hz, 2H), 7.81 (d, J= 9.0 Hz, 2H), 7.74 (s, 1H), 7.39 (d, J= 8.6 Hz, 2H), 6.63 (s, 2H), 5.71 (s, 2H), 3.79 (s, 3H), 2.74-2.43 (m, 1H), 2.27 (s, 6H), 1.16 (d, J =7.0 Hz, 6H)
28C E 761 (M+) (300 MHz, CDC13) 8.58 (s, 1H), 8.48 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.87 (d, J= 8.4 Hz, 2H), 7.80 (d, J= 9.0 Hz, 2H), 7.74 (s, 1H), 7.45-7.28 (m, 7H), 6.63 (s, 2H), 5.78 (s, 2H), 5.29 (m, 1H), 5.12 (s, 2H), 4.03 (d, J= 5.6 Hz, 2H), 3.79 (s, 3H), 2.27 (s, 6H)
29C E 656 (M+) (300 MHz, CDCI3) 8.58 (s, 1H), 8.49 (s, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.87 (d, J= 8.4 Hz, 2H), 7.81 (d, J= 9.0 Hz, 2H), 7.72 (s, 1H), 7.40 (d, J = 8.7 Hz, 2H), 6.63 (s, 2H), 5.78 (s, 2H), 4.11 (s, 2H), 3.80 (s, 3H), 3.59 (q, J= 7.0 Hz, 2H), 2.27 (s, 6H), 1.24 (t, J =7.1 Hz, 3H)
129
ID Synthesis Method MS mp(°C) lH NMR, 13C, or 19F NMR (δ)1
30C E 697 (M+) (300 MHz, CDC13) 8.60 (s, 1H), 8.50 (s, 1H), 8.22 (d, 7 = 8.3 Hz, 2H), 7.88 (d, 7 = 8.2 Hz, 2H), 7.82 (s, 1H), 7.80 (d, 7= 9.0 Hz, 2H), 7.38 (d, 7= 8.8 Hz, 3H), 7.23-7.02 (m, 3H), 5.78 (s, 2H), 3.96 (s, 2H), 2.31 (s, 6H), 1.44 (s, 9H)
31C E 582 (M+) (300 MHz, CDCI3) 8.58 (s, 1H), 8.52 (s, 1H), 8.23 (d, 7= 8.3 Hz, 2H), 7.88 (m, 3H), 7.80 (d, 7= 9.0 Hz, 2H), 7.38 (d, 7 = 8.6 Hz, 2H), 7.14 (m, 3H), 5.72 (s, 2H), 2.32 (s, 6H), 2.09 (s, 3H)
32C E 697 (M+) (CDCI3) (Mixture of atropisomers) [8.61 (s), 8.58 (s), 8.56 (s), 8.51 (s), 8.37 (d, J= 8.3 Hz), 8.23 (d, 7= 8.4 Hz), 8.21-8.14 (m), 8.00 (d, 7= 8.4 Hz), 7.89 (d, 7 = 8.2 Hz), 7.84-7.77 (m), 7.45-7.35 (m); 11H], 6.94 (s, 2H), [5.87 (s), 5.80 (s); 2H], [4.12 (s), 4.11 (s); 2H], 3.83 (s, 3H), 3.69-3.44 (m, 2H), 1.38-1.10 (m, 3H)
33C E 697 (M+) (CDCI3) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d,7 = 8.3 Hz, 2H), 7.88 (d, 7= 8.4 Hz, 2H), 7.83-7.77 (m, 3H), 7.39 (d, 7= 8.4 Hz, 2H), 6.94 (s, 2H), 5.76 (s, 2H), 4.96-4.77 (m, 1H), 3.82 (s, 3H), 1.30 (d,7= 6.3 Hz, 6H)
34C E 681 (M+) (CDCI3) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d,7 = 8.3 Hz, 2H), 7.92-7.76 (m, 5H), 7.39 (d, J = 8.4 Hz, 2H), 6.93 (s, 2H), 5.73 (s, 2H), 3.82 (s, 3H), 2.59 (m, 1H), 1.17 (d, 7= 7.0 Hz, 6H)
35C E 636 (M+) (CDCI3) 8.57 (s, 1H), 8.50 (s, 1H), 8.23 (d, 7 = 8.4 Hz, 2H), 7.92-7.73 (m, 5H), 7.38 (d, 7 = 8.3 Hz, 2H), 7.20-6.92 (m, 3H), 5.72 (s, 2H), 2.94-2.63 (m, 1H), 2.31 (s, 6H), 2.021.38 (m, 8H)
36C E 624 (M+) (CDCI3) 8.56 (s, 1H), 8.49 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, 7= 8.3 Hz, 2H), 7.84 (s, 1H), 7.79 (d, 7 = 9.0 Hz, 2H), 7.38 (d, 7 = 8.4 Hz, 2H), 7.19-7.05 (m, 3H), 5.71 (s, 2H), 2.31 (s, 6H), 1.20 (s, 9H)
130
ID Synthesis Method MS mp(°C) NMR, 13C, or 19F NMR (δ)1
37C E 691 (M+H) (CDC13) 8.59 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.93-7.77 (m, 4H), 7.72 (s, 1H), 7.40 (d, J= 9.0 Hz, 2H), 6.63 (s, 2H), 5.71 (s, 2H), 3.80 (s, 3H), 2.68-2.48 (m, 1H), 2.28 (s, 6H), 1.16 (d, J = 7.0 Hz, 6H)
38C E 724 (M+) (CDCI3) 8.58 (s, 1H), 8.47 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J= 8.3 Hz, 2H), 7.81 (d, J= 9.1 Hz, 2H), 7.71 (s, 1H), 7.39 (d, J = 9.0 Hz, 2H), 6.64 (s, 2H), 5.76 (dd, J= 37.3, 11.0 Hz, 2H), 4.19 (q, J = 6.9 Hz, 1H), 4.143.97 (m, 1H), 3.80 (s, 3H), 3.79-3.68 (m, 1H), 2.27 (s, 6H), 1.47 (d, J = 6.9 Hz, 3H)
39C E 694 (M+) (CDC13) 8.58 (s, 1H), 8.48 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.87 (d, J= 8.3 Hz, 2H), 7.83 (s, 1H), 7.81 (d, J= 9.1 Hz, 2H), 7.39 (d, J= 8.3 Hz, 2H), 7.23-6.99 (m, 3H), 5.77 (dd, J = 36.4, 11.0 Hz, 2H), 4.19 (q, J = 6.9 Hz, 1H), 4.14-3.97 (m, 1H), 3.84-3.65 (m, 1H), 2.31 (s, 6H), 1.47 (d, J = 6.9 Hz, 3H)
40C E 654 (M+) (CDC13) 8.57 (s, 1H), 8.48 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (d, 7 = 9.0 Hz, 2H), 7.72 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 6.62 (s, 2H), 5.70 (s, 2H), 3.79 (s, 3H), 2.27 (s, 6H), 1.20 (s, 9H)
41C E 670 (M+) (CDC13) 8.58 (s, 1H), 8.49 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.84 (s, 1H), 7.80 (d, J= 9.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.23-6.96 (m, 3H), 5.77 (dd, J = 27.4, 10.9 Hz, 2H), 4.07 (q, J = 6.9 Hz, 1H), 3.78-3.70 (m, 1H), 3.66-3.39 (m, 3H), 3.35 (s, 3H), 2.31 (s, 6H), 1.42 (d, J =6.9 Hz, 3H)
42C E 700 (M+) (CDC13) 8.58 (s, 1H), 8.48 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (d, J=9.1 Hz, 2H), 7.71 (s, 1H), 7.39 (d, J = 8.3 Hz, 2H), 6.63 (s, 2H), 5.76 (dd, J= 27.8, 10.9 Hz, 2H), 4.07 (q, J= 6.9 Hz, 1H), 3.79 (s, 3H), 3.79-3.70 (m, 1H), 3.63-3.45 (m, 3H), 3.35 (s, 3H), 2.27 (s, 6H), 1.42 (d, J = 6.9 Hz, 3H)
131
ID Synthesis Method MS mp(°C) NMR, 13C, or 19F NMR (δ)1
43C E 666 (M+) (CDC13) 8.57 (s, 1H), 8.49 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J= 8.3 Hz, 2H), 7.79 (d, J= 9.1 Hz, 2H), 7.74 (s, 1H), 7.38 (d, J= 8.3 Hz, 2H), 6.62 (s, 2H), 5.71 (s, 2H), 3.79 (s, 3H), 2.85-2.65 (m, 1H), 2.27 (s, 6H), 1.98-1.51 (m, 8H)
44C E 668 (M+) (CDC13) 8.59 (s, 1H), 8.55 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.84-7.74 (m, 3H), 7.38 (d, J= 8.4 Hz, 2H), 6.63 (s, 2H), 5.85-5.73 (m, 2H), 4.54-4.47 (m, 1H), 4.03 (dd, .7= 14.7, 6.9 Hz, 1H), 3.91 (dd, 13.8, 7.4 Hz, 1H), 3.79 (s, 3H), 2.27 (s, 6H), 2.09-1.83 (m, 4H)
45C E 746 (M+H) 132-137 (CDCI3) 8.68 (s, 1H), 8.49 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.93 (d, J= 8.4 Hz, 2H), 7.88 (d, 8.3 Hz, 2H), 7.81 (d, J= 8.5 Hz, 2H), 7.73 (s, 1H), 7.35 (s, 5H), 6.64 (s, 2H), 5.78 (s, 2H), 5.24 (s, 1H), 5.12 (s, 2H), 4.04 (d, J = 5.5 Hz, 2H), 3.80 (s, 3H), 2.28 (s, 6H)
46C E 624 108-113 (CDCI3) 8.68 (s, 1H), 8.50 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.98-7.69 (m, 7H), 6.63 (s, 2H), 5.71 (s, 2H), 3.80 (s, 3H), 2.59 (heptet, J= 7.0 Hz, 1H), 2.29 (d, J = 6.9 Hz, 6H), 1.16 (d, <7= 7.0 Hz, 6H)
47C E 149-151 (acetone-i/ô) 9.20 (s, 1H), 8.52 (s, 1H), 8.40 - 8.21 (m, 2H), 8.21 - 8.01 (m, 4H), 7.61 (d, J= 8.3 Hz, 2H), 7.32 - 6.94 (m, 3H), 3.83 (s, 2H), 2.34 (s, 6H)
48C E 599 (M+H) 128-137 (acetoneX) 9.18 (s, 1H), 8.83 (s, 1H), 8.67 - 7.82 (m, 8H), 7.60 (d, J= 8.4 Hz, 2H), 6.78 (s, 2H), 3.99 - 3.72 (m, 3H), 2.41 2.20 (m, 6H)
49C E 619 (M+H) 177-185 (methanol-cL) 9.23 (s, 1H), 8.62 (s, 1H), 8.29 (m, 2H), 8.17 - 7.98 (m, 4H), 7.60 7.45 (m, 2H), 7.41 - 7.19 (m, 3H), 4.22 (s, 2H), 2.34 (s, 6H)
132
ID Synthesis Method MS mp (°C) NMR, 13C, or 19F NMR (5)'
50C E 635 (M+H) 193-196 (methanol-i/4) 9.23 (s, 1H), 8.57 (s, 1H), 8.28 (m, 3H), 8.09 - 7.98 (m, 4H), 7.50 (m, 4H), 4.19-4.11 (m, 2H), 3.85 (s, 3H), 2.36 (s, 3H)
51C E 649 (M+H) 176-179 (methanol-i/4) 9.23 (s, 1H), 8.60 (s, 1H), 8.30 (m, 2H), 8.14 - 8.00 (m, 4H), 7.52 (m, 2H), 6.81 (s, 2H), 4.22 (s, 2H), 3.84-3.81 (m, 3H), 2.33 (s, 6H)
52C E 599 (M+H) 168-178 (methanol-JO 9.21 (s, 1H), 8.44 (s, 1H), 8.27 (d, J= 8.1 Hz, 2H), 8.09 - 7.98 (m, 4H), 7.52 (d, J= 8.3 Hz, 2H), 7.40 (d, J= 8.7 Hz, 2H), 6.97 (d, J= 8.8 Hz, 2H), 5.40 (s, 1H), 4.37 - 4.13 (m, 2H), 3.79 (s, 3H), 1.79 (m, 3H)
53C E 617 (M+H) 168-170 (methanol-i/4) 9.21 (s, 1H), 8.44 (m, 1H), 8.28 (d, J= 8.2 Hz, 2H), 8.11 - 7.99 (m, 4H), 7.52 (d, J= 8.4 Hz, 2H), 7.25 (m, 2H), 7.14 (t, J= 8.5 Hz, 1H), 5.42 (m, 1H), 4.25 (m, 2H), 3.88 (s, 3H), 1.75 (m, 3H)
54C E 569 (M+H) 167-170 (methanol-ah) 9.23 (s, 1H), 8.46 (s, 1H), 8.27 (m, 2H), 8.05 (m, 4H), 7.57 - 7.39 (m, 7H), 5.41 (m, 1H), 4.24 (m, 2H), 1.79 (m, 3H)
55C E 624 (M+H) 90-97 (methanol-cU) 9.12 (s, 1H), 8.46 (s, 1H), 8.14 (m, 2H), 7.99 (m, 3H), 7.78 (s, 1H), 7.49 (d, J= 8.5 Hz, 2H), 7.12 (m, 3H), 3.69 (s, 2H), 3.22 - 2.80 (m, 2H), 2.25 (s, 6H), 2.03 (s, 2H), 1.93 - 1.66 (m, 1H), 0.92 (m, J = 9.7 Hz, 6H)
56C E 765 (M+H) 148-151 (methanol-JO 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J= 8.1 Hz, 2H), 8.12 (m, 2H), 8.07 - 8.00 (m, 2H), 7.58 - 7.43 (m, 2H), 7.33 (dd, J= 8.6, 6.5 Hz, 1H), 7.25 (d, J= 7.6 Hz, 2H), 4.02 (m, 2H), 3.97 - 3.75 (m, 2H), 3.21 (d, J= 6.9 Hz, 2H), 2.90 (m, 1H), 2.59 (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 1.63 (m, 2H), 1.44 (s, 9H), 1.29 (m, 3H)
133
ID Synthesis Method MS mp(°C) *H NMR, 13C, or 19F NMR (S)1
57C E 737 (M+H) 151-153 (methanol-iV) 9.20 (s, IH), 8.65 (s, IH), 8.30 (m, 2H), 8.21 - 7.96 (m, 4H), 7.53 (d, J = 8.4 Hz, 2H), 7.35 (dd, J= 8.5, 6.5 Hz, IH), 7.28 (d, J= 7.5 Hz, 2H), 4.44 (s, 2H), 3.91 - 3.40 (m, 9H), 2.38 (s, 6H), 1.50 (s, 9H)
58C E 725 (M+H) 125-127 (methanol-i/4) 9.18 (s, IH), 8.61 (s, IH), 8.31 (m, 2H), 8.14 (m, 2H), 8.06 (d, J= 9.0 Hz, 2H), 7.53 (d, J= 8.5 Hz, 2H), 7.32 (dt, J = 26.0, 7.0 Hz, 3H), 4.02 (s, 2H), 3.38 3.34 (m, 2H), 3.22 - 3.03 (m, 2H), 2.37 (s, 6H), 1.74 (m, 2H), 1.45 (s, 9H)
59C E 755 (M+H) 147-149 (methanol-i/4) 9.18 (s, IH), 8.62 (s, IH), 8.38 - 7.97 (m, 6H), 7.51 (d, J= 8.4 Hz, 2H), 7.32 (dd, J = 8.5, 6.6 Hz, IH), 7.25 (d, J= 7.6 Hz, 2H), 4.40 (s, IH), 4.06 (m, 2H), 3.91 - 3.74 (m, 2H), 3.56 - 3.41 (m, IH), 2.36 (s, 6H), 1.44 (s, 9H)
60C E 755 (M+H) 136-139 (methanol-cQ 9.16 (s, IH), 8.58 (s, IH), 8.28 (d, J= 7.4 Hz, 2H), 8.16-7.76 (m, 4H), 7.52 (p, J= 8.8 Hz, 2H), 6.83 (m, 2H), 4.04 (d, J= 8.5 Hz, 2H), 3.90-3.73 (m, 3H), 3.55- 3.37 (m, 2H), 3.14-2.75 (m, 3H), 2.30 (s, 6H), 1.99-1.80 (m, 2H), 1.43-1.31 (m, 2H)
61C E 738 (M+H) 70-79 dec (methanol-i/4) 9.12 (s, IH), 8.12 - 8.07 (m, 2H), 8.02 - 7.96 (m, 2H), 7.55 - 7.50 (m, 2H), 7.50 - 7.45 (m, 2H), 7.43 (d, J= 7.7 Hz, IH), 7.31 (d, J= 7.6 Hz, 2H), 4.03 (s, 2H), 3.25 (dt, J= 15.5, 7.0 Hz, 4H), 2.84 (s, 3H), 2.04 (s, 6H), 1.81-1.66 (m, 2H), 1.44 (s, 9H) ____
62C K 665 (M+H) 110-120 (methanol-Z) δ 9.18 (s, IH), 8.56 (m, IH), 8.26 (m, 2H), 8.16 - 7.84 (m, 4H), 7.52 (m, 2H), 7.27 (m, IH), 7.22 (m, 2H), 4.00 (s, 2H), 3.28 (m, 3 H), 3.06 - 2.83 (m, IH), 2.75 (t, J= 12.2 Hz, IH), 2.34 (s, 6H), 2.21 1.83 (m, 4H), 1.72 (m, 1 H), 1.47 - 1.19 (m, 2H)
134
ID Synthesis Method MS mp (°C) *H NMR, 13C, or 19F NMR (δ)'
63C K 655 (M+H) 98-110 (methanol-A) 9.18 (s, 1H), 8.63 (s, 1H), 8.28 (m, 2H), 8.13 - 7.97 (m, 4H), 7.51 (d, J = 8.3 Hz, 2H), 7.31 (dd, J= 8.5, 6.5 Hz, 1H), 7.24 (d, J= 7.6 Hz, 2H), 4.32 - 4.07 (m, 3H), 3.98-3.81 (m, 1H), 3.72 (s, 1H), 2.35 (s, 6H)
64C K 655 (M+H) 83-112 (methanol-A) 9.19 (s, 1H), 8.58 (s, 1H), 8.28 (m, 2H), 8.14 - 7.97 (m, 4H), 7.51 (m, 2H), 6.78 (s, 2H), 4.00 (m, 2H), 3.81 (s, 3H), 3.10-2.93 (m, 4H), 2.30 (s, 6H), 1.91 (m, 2H)
65C K 667 (M+H) 128 dec (methanol-A) 9.20 (s, 1H), 8.65 (s, 1H), 8.27 (m 2H), 8.11 - 7.99 (m, 4H), 7.52 (d, J = 8.3 Hz, 2H), 6.78 (s, 2H), 4.40 (s, 2H), 3.87 (m, 4H), 3.53 (s, 3H), 2.32 (s, 6H), 1.33 (m, 4H)
66C K 625 (M+H) 100-105 (methanol-A) 9.20 (s, 1H), 8.56 (s, 1H), 8.27 (m, 2H), 8.12 - 7.99 (m, 3H), 7.53 (d, J = 8.4 Hz, 2H), 7.24 (m, 4H), 3.99 (s, 2H), 3.42 (m, 2H), 3.05 (m, 2H), 2.36 (s, 6H), 1.99- 1.88 (m, 2H)
67C K 636 (M+H) 237-240 dec (methanol-A) 9.20 (s, 1H), 8.74 (s, 1H), 8.33 - 8.25 (m, 2H), 8.12 - 7.98 (m, 4H), 7.53 (d, J= 8.3 Hz, 2H), 7.33 (dd, J = 8.5, 6.4 Hz, 1H), 7.26 (d, J = 7.5 Hz, 2H), 4.55 (s, 2H), 3.92 (m, 4H), 3.37 (m, 2H), 3.31 (m, 2H), 2.38 (s, 6H)
69C F 581 (M+H) 188-190 (CDCI3) 8.56 (s, 1H), 8.33 (s, 1H), 8.22 (d, J = 8.1 Hz, 2H), 7.90 - 7.70 (m, 4H), 7.39 (d, J = 8.7 Hz, 2H), 6.72 (s, 2H), 4.01 (s, 2H), 3.87 - 3.73 (s, 3H), 2.18 (s, 6H)
70C F 592 (M+) 134-138 (CDCI3) 8.65 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.83 (m, 4H), 7.50 (d, J= 8.1 Hz, 2H), 7.45 - 7.38 (m, 3H), 4.05 (s, 2H)
71C F 551 (M+H) 104-111 (CDCI3) 8.62 (s, 1H), 8.32 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 - 7.74 (m, 4H), 7.40 (d, J= 8.3 Hz, 2H), 7.34 - 7.26 (m, 1H), 7.20 (d, J= 7.5 Hz, 2H), 4.02 (s, 2H), 2.22 (s, 6H)
135
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
72C F 565 (M+H) 118-121 (CDC13) 8.58 (s, IH), 8.33 (s, IH), 8.23 (d, J = 8.3 Hz, 2H), 7.81 (m, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.01 (d, 7 = 0.4 Hz, 2H), 4.01 (s, 2H), 2.34 (s, 3H),2.17(s, 6H)
73C F 565 (M+H) 145-150 (CDC13) 8.58 (s, IH), 8.30 (s, IH), 8.23 (d, 7 = 8.3 Hz, IH), 7.81 (m, 2H), 7.49 (d, 7= 4.0 Hz, IH), 7.40 (d, 7= 8.4 Hz, IH), 7.34 (s, IH), 7.18 (d, 7= 7.8 Hz, IH), 4.01 (d,7 = 1.4 Hz, IH), 2.83 (heptet, 7= 6.8 Hz, IH), 1.23 (t, 7=6.6 Hz, 3H).
74C G 682 (M+H) 190-193 (methanol-TO 9.20 (s, IH), 8.38 (s, IH), 8.31 - 8.24 (m, 2H), 8.08 - 8.00 (m, 2H), 7.95 - 7.88 (m, 2H), 7.55 - 7.48 (m, 3H), 7.48 - 7.36 (m, 5H), 7.31 (d, 7 = 7.7 Hz, 2H), 3.60 (q, 7= 7.2 Hz, 4H), 2.20 (s, 6H), 1.07 (t, 7=7.2 Hz, 6H);
75C G 617 (M+) (CDCI3) 8.56 (s, IH), 8.23 (s, IH), 8.19 (d, 7 = 8.4 Hz, 2H), 7.84-7.73 (m, 5H), 7.41-7.33 (m, 3H), 7.21 (d, 7= 7.2 Hz, 2H), 7.16 (s, IH), 7.12 (d, 7= 3.2 Hz, IH), 2.20 (s, 6H).
76C G 711 (M+) (CDCI3) 8.56 (s, IH), 8.25 (s, IH), 8.20 (d, 7 = 8.4 Hz, 2H), 7.80 (dd, 7= 8.7, 5.6 Hz, 4H), 7.48-7.34 (m, 8H), 7.26 (d, 7= 7.7 Hz, 2H), 7.08 (s, IH), 2.20 (s, 6H)
77C G 655 (M+H) 261-263 (methanol-i/4) 9.14 (s, IH), 8.21 - 8.13 (m, 3H), 8.06 - 7.99 (m, 2H), 7.86 - 7.75 (m, 4H), 7.50 (d, 7 = 8.3 Hz, 2H), 7.28 - 7.18 (m, 3H), 7.14 (d, 7= 7.9 Hz, 2H), 6.72 (s, IH), 0.09 --0.09 (m, 6H)
78C G 694 (M+H) (CDCI3) 8.55 (s, IH), 8.22 (s, IH), 8.18 (d, J = 8.3 Hz, 2H), 7.79 (dd,7= 8.7, 5.1 Hz, 4H), 7.37 (d, 7= 9.0 Hz, 2H), 7.23-6.94 (m, 7H), 6.26 (s, IH), 2.17 (s, 6H)
79C G 678 (M+H) (CDCI3) 8.55 (s, IH), 8.23 (s, IH), 8.19 (d, 7 = 8.3 Hz, 2H), 7.79 (d, J = 8.7 Hz, 4H), 7.43 (d, 7 = 8.3 Hz, 2H), 7.37 (d, 7= 8.9 Hz, 2H), 7.23-7.16 (m, 3H), 7.08 (d,7= 7.4 Hz, 2H), 6.35 (s, IH), 2.18 (s, 6H)
136
ID Synthesis Method MS mp (°C) ‘H NMR, 13C, or 19F NMR (5)'
80C G 609 (M+H) 215-219 (methanol-taj) 9.23 (s, 1H), 8.40 (s, 1H), 8.26 (m, 2H), 8.22 (s, 1H), 8.07 - 8.00 (m, 3H), 7.91 (d, J =8.4 Hz, 2H), 7.51 (d, J= 8.3 Hz, 2H), 6.90 (s, 1H), 3.88 (s, 3H), 2.13 (s, 6H)
81C I 551 (M+H) 209-213 (CDC13) 9.42 (s, 1H), 8.59 (s, 1H), 8.28 (d, J = 8.4 Hz, 2H), 8.01 (d, J= 8.3 Hz, 2H), 7.80 - 7.77 (m, 2H), 7.43 - 7.34 (m, 2H), 7.07 (d, J= 7.5 Hz, 2H), 6.98 (dd, J= 8.2, 6.7 Hz, 1 H), 3.90 (s, 2H), 2.17 (s, 6H)
82C I 565 (M+H) 225-232 (CDCI3) 9.46 (s, 1H), 8.60 (s, 1H), 8.29 (d, J = 8.4 Hz, 2H), 8.02 (d, J= 8.4 Hz, 2H), 7.89 - 7.76 (m, 2H), 7.40 (d, J= 8.3 Hz, 2H), 6.88 (s, 2H), 3.90 (s, 2H), 2.28 (s, 3H), 2.13 (s, 6H).
83C I 581 (M+H) 211-215 (CDCI3) 9.44 (s, 1H), 8.60 (s, 1H), 8.30 (d, J = 8.4 Hz, 2H), 8.02 (d, J= 8.4 Hz, 2H), 7.82 (d, J= 9.1 Hz, 2H), 7.40 (d, J= 8.3 Hz, 2H), 6.63 (s, 2H), 3.90 (s, 2H), 3.78 (s, 3H), 2.15 (s, 6H)
84C I 591 250 dec (CDCI3) 9.42 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 8.24 Hz, 2H), 8.07 (d, J= 8.28 Hz, 2H), 7.89 (d, J= 8.24 Hz, 2H), 7.76 (d, J= 8.28 Hz, 2H), 7.64-7.58 (m, 3H), 4.42 (s, 2H)
85C I 551 (M+H) 146-149 (CDCI3) δ 9.36 (s, 1H), 8.60 (s, 1H), 8.30 (d, J= 8.4 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H), 7.86 - 7.77 (m, 2H), 7.40 (d, J = 8.3 Hz, 2H), 7.32 (dd, J= 6.9, 2.3 Hz, 1H), 7.24 7.12 (m, 2H), 6.91 (dd, J = 7.1, 2.0 Hz, 1H), 3.93 (s, 2H), 3.15-2.97 (m, 1H), 1.21 (d,J = 6.9 Hz, 6H)
86C J 566 (M+H) 163-169 (CDCI3) δ 8.81 (bs, 1H), 8.57 (s, 1H), 8.20 (d, J= 8.3 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.32 - 7.25 (m, 1H), 7.10 (2dt,J= 7.4,1.5 Hz, 2H), 6.83 (d, 6.5 Hz, 1H), 3.96 (t, J= 6.1 Hz, 2H), 3.13 (heptet, J= 6.9 Hz, 1H), 2.99 - 2.88 (m, 2H), 2.49 - 2.36 (m, 2H), 1.29 - 1.21 (m, 6H).
137
ID Synthesis Method MS mp (°C) 'H NMR, 13C, or l9F NMR (δ)1
87C J 550 (M+H) 187-189 (CDC13) δ 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J= 8.3 Hz, 2H), 7.92 (d, J= 8.4 Hz, 2H), 7.81 (t, J= 10.2 Hz, 4H), 7.30 - 7.26 (m, 2H), 7.17 - 7.04 (m, 1H), 6.83 (d, J= 6.4 Hz, 1H), 3.96 (t, J= 6.1 Hz, 2H), 3.13 (heptet, J= 6.9 Hz, 1H), 2.97 - 2.90 (m, 2H), 2.47 - 2.38 (m, 2H), 1.25 (d, J = 7.5 Hz, 6H).
88C F 579.2 (M+H) 178-182 (CDC13) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.82 (dd, J= 8.7, 7.2 Hz, 4H), 7.48 (dd, J= 4.1, 1.3 Hz, 2H), 7.40 (d, J= 8.3 Hz, 2H), 7.37 - 7.30 (m, 1H), 7.17 (m, 1H), 4.23 (dq, J= 14.5, 7.2 Hz, 1H), 2.83 (dd, J= 14.6, 6.9 Hz, 1H), 1.79 (d, J= 7.2Hz, 3H), 1.22 (ddd, J = 12.1, 6.9, 1.9 Hz, 6H).
89C F 559 (M+H) 205-206 (CDC13) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.90 - 7.75 (m, 4H), 7.52 _ 7.44 (m, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.10 (dd, J = 8.6, 7.4 Hz, 2H), 4.04 (s, 2H).
90C F 566 (M+H) 148-151 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.82 (t, J = 8.5 Hz, 4H), 7.46 - 7.31 (m, 3H), 7.25 - 7.18 (m, 2H), 4.02 (s, 2H), 2.53 (q, J = 7.6 Hz, 2H), 2.21 (s, 3H), 1.26-1.16 (m, 3H).
91C F 554 (M+H) 227-235 (CDC13) δ 8.58 (s, 1H), 8.36 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 - 7.76 (m, 4H), 7.49 - 7.35 (m, 3H), 7.01 (dd, J= 8.5, 2.5 Hz, 1H), 6.96 (dd, J =7.8, 1.0 Hz, 1H), 6.91 (t, J= 2.2 Hz, 1H), 3.98 (s, 2H), 3.85 (s, 3H).
92C F 554 (M+H) 104-108 (CDC13) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.86 - 7.77 (m, 4H), 7.50 - 7.43 (m, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.32 - 7.27 (m, 1H), 7.14 - 7.04 (m, 2H), 4.01 (d, J= 17.2 Hz, 1H), 3.94 (d, J= 17.3 Hz, 1H), 3.84 (s, 3H).
138
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
93C F 572 (M+H) 183-186 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.27 8.18 (m, 2H), 7.88 - 7.77 (m, 4H), 7.43 7.37 (m, 3H), 7.34 (t, J= 7.8 Hz, 1H), 7.30 - 7.26 (m, 1H), 4.07 (d, 7 = 17.4 Hz, 1H), 4.00 (d, 7= 17.4 Hz, 1H), 2.29 (s, 3H).
94C F 552 (M+H) 134-136 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, 7= 8.4 Hz, 2H), 7.86 - 7.78 (m, 4H), 7.49 - 7.32 (m, 5H), 7.24 - 7.18 (m, 1H), 4.06 - 3.94 (m, 2H), 2.56 (q, 7 = 7.6 Hz, 2H), 1.26-1.18 (m,3H).
95C F 576.1 (M+H) 195-201 (CDCI3) δ 8.59 (d, 7= 4.8 Hz, 1H), 8.26 (m, 3H), 7.89 - 7.74 (m, 4H), 7.52 - 7.31 (m, 4H), 7.24 - 7.13 (m, 1H), 4.05 (d, 7= 0.9 Hz, 2H).
96C F 600 (M+H) 182-185 (300 MHz, CDCI3) δ 8.58 (s, 1H), 8.33 (d, 7 = 7.9 Hz, 1H), 8.24 (s, 1H), 8.21 (s, 1H), 7.86 - 7.76 (m, 4H), 7.53 (t, 7 = 5.9 Hz, 3H), 7.44 - 7.29 (m, 8H), 3.80 - 3.73 (m, 1H), 3.59-3.51 (m, 1H).
97C F 567 (M+H) 234-236 (CDCI3) δ 8.57 (s, 1H), 8.37 (s, 1H), 8.23 (d, 7= 8.4 Hz, 2H), 7.89 - 7.73 (m, 4H), 7.45 - 7.29 (m, 3H), 6.79 (dd, 7= 8.2, 2.2 Hz, 1H), 6.70 (d, 1H), 6.57 (s, 1H), 3.96 (s, 2H), 2.98 (s, 6H)
98C F 612 (M+H) 225-226 (CDCI3) δ 8.55 (s, 1H), 8.29 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 7.86 - 7.71 (m, 4H), 7.42 - 7.23 (m, 3H), 6.63 (d, 7 = 8.5 Hz, 2H), 4.07 (q, 7= 7.0 Hz, 4H), 3.94 (s, 2H), 1.31 (t, 7= 7.0 Hz, 6H)
99C F 679 (ΜΗ) 230-231 (CDCI3) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, 7= 8.4 Hz, 2H), 7.89 - 7.77 (m, 4H), 7.70 (d, 7= 8.1 Hz, 2H), 7.40 (d, 7= 8.3 Hz, 2H), 7.29 - 7.20 (m, 1H), 4.04 (s, 2H)
100C F 602 (M+H) 118-120 (CDCI3) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.93 - 7.70 (m, 4H), 7.39 (d, 7= 9.0 Hz, 2H), 7.28 (t, 1H), 7.19 (d, 7= 7.7 Hz, 2H), 4.01 (s, 2H), 2.21 (s, 6H).
139
ID Synthesis Method MS mp (°C) ‘H NMR, 13C,or”FNMR (δ)1
101C F 583 (M+H) 106-107 (CDC13) δ 8.60 (s, 1H), 8.32 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.89 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.56 (s, 1H), 4.01 (s, 2H), 3.94 (s, 3H), 2.32 (s, 3H), 2.16 (s, 3H)
102C F 589 (ΜΗ) 123-126 (CDC13) δ 8.27 (s, 1H), 7.95 - 7.71 (m, 5H), 7.60 (d, J= 1.3 Hz, 1H), 7.53-7.43 (m, 4H), 7.45 - 7.32 (m, 3H), 4.04 (s, 2H)
103C F 551 (M+H) 194-196 (CDC13) δ 8.28 (s, 1H), 7.93 (dd, J= 5.4, 4.1 Hz, 3H), 7.78 (m, 4H), 7.36 - 7.23 (m, 3H), 7.19 (d, J= 7.6 Hz, 2H), 6.81 (d, J= 2.5 Hz, 1H), 4.00 (s, 2H), 2.21 (s, 6H)
104C F 551 (M+H) 100-102 (CDCI3) δ 8.27 (s, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 7.80 - 7.71 (m, 4H), 7.57 (d, J= 8.3 Hz, 2H), 7.30 (dd, J= 28.7, 5.8 Hz, 3H), 7.19 (d, J = 7.6 Hz, 2H), 4.01 (s, 2H), 2.21 (s, 6H)
105C F 586 (M+H) 209-211 (CDCI3) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J= 7.8 Hz, 2H), 7.82 (m, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.19 (s, 2H), 4.01 (s, 2H), 2.19 (s, 6H)
106C F 558 (M+H) 180-182 (CDCI3) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J= 8.2 Hz, 2H), 7.81 (m, 4H), 7.58 (dd, J= 6.0, 3.3 Hz, 1H), 7.43 (ddd, J= 23.4, 11.3, 5.5 Hz, 5H), 4.02 (dd, J= 29.9,17.4 Hz, 2H)
107C F 596 (M+H) 227-232 (CDCI3) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (dd, 10.0, 8.6 Hz, 4H), 7.82 (m, 4H), 7.49 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 4.42 (q, J = 7.1 Hz, 2H), 4.00 (s, 2H), 1.41 (t, J=7A Hz, 3H)
108C F 580 (M+H) 167-171 (CDCI3) δ 8.58 (s, 1H), 8.28 (d, J= 15.0 Hz, 1H), 8.23 (d, J= 8.3 Hz, 2H), 7.87 - 7.76 (m, 4H), 7.53 - 7.30 (m, 5H), 7.18 (ddd, J= 7.8, 4.2, 1.2 Hz, 1H), 4.03 - 3.98 (m, 2H), 2.53 (dd, J= 14.1, 7.0 Hz, 1H), 1.77 - 1.56 (m, 2H), 1.26- 1.16 (m, 3H), 0.78 (td, J = 7.4, 2.3 Hz, 3H).
140
ID Synthesis Method MS mp (°C) *H NMR, 13C, or 19F NMR (δ)*
109C F 652 (M+H) 105-111 (CDC13) δ 8.25 (s, 1H), 7.73 (d, J= 7.4 Hz, 4H), 7.55 - 7.43 (m, 2H), 7.43 - 7.36 (m, 1H), 7.10 (t, J = 11.6 Hz, 4H), 4.90 - 4.79 (m, 1H), 4.04 (s, 2H), 3.76 (s, 3H), 3.73 3.62 (m, 1H), 3.52 - 3.35 (m, 1H)
HOC F 611 (M+H) Oil (CDC13) δ 8.25 (s, 1H), 7.82 - 7.64 (m, 4H), 7.30 (t, 1H), 7.22 - 6.99 (m, 6H), 4.83 (dd, J = 12.8, 6.5 Hz, 1H), 4.00 (s, 2H), 3.89 3.59 (m, 4H), 3.44 (dd, J = 17.2, 6.5 Hz, 1H), 2.20 (s, 6H).
me F 580 (M+H) 209-210 (CDCI3) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.86 - 7.77 (m, 4H), 7.39 (t, J= 7.8 Hz, 3H), 7.34 - 7.27 (m, 1H), 7.20 (d, J= 7.4 Hz, 1H), 4.03 (s, 2H), 2.86-2.71 (m, 1H), 2.21 (s, 3H), 1.21 (2d, J =6.7 Hz, 6H).
112C F 564 (M+H) 154-158 (CDCI3) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.43 - 7.33 (m, 4H), 7.26 - 7.19 (m, 2H), 4.02 (s, 2H), 1.86- 1.77 (m, 1H), 0.900.83 (m, 2H), 0.77 - 0.68 (m, 1H), 0.67 0.59 (m, 1H).
113C F 538 (M+H) 111-116; 210-212 (Acetone-i/ô) δ 9.20 (s, 1H), 8.28 (d, J - 8.2 Hz, 3H), 8.13 (d, J = 9.0 Hz, 2H), 7.94 (d, J = 8.2 Hz, 2H), 7.60 (d, J= 8.8 Hz, 2H), 7.39 (t, J= 17.1 Hz, 4H), 4.15 (q, J = 17.3 Hz, 2H), 2.23 (s, 3H)
114C F 568 (M+H) 203-205 (CDCI3) δ 8.58 (s, 1H), 8.33 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.88 - 7.67 (m, 4H), 7.38 (d, J= 8.4 Hz, 2H), 7.14 (d, J= 8.3 Hz, 1H), 6.87 (d, J= 8.9 Hz, 2H), 3.98 (s, 2H), 3.83 (s, 3H), 2.20 (s, 3H)
115C F 554 (M+H) 261-264 (CDCI3) δ 8.58 (s, 1H), 8.35 (s, 1H), 8.23 (d, J= 8.2 Hz, 2H), 7.82 (m, 4H), 7.40 (d, J = 8.6 Hz, 2H), 7.30 (d, 2H), 7.03 (d, J= 8.8 Hz, 2H), 3.97 (s, 2H), 3.86 (s, 3H)
141
ID Synthesis Method MS mp(°C) *H NMR, 13C, or 19F NMR (δ)1
116C F 568 (M+H) 92-97 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.88 - 7.72 (m, 4H), 7.48 - 7.32 (m, 3H), 7.31 - 7.20 (m, 1H), 7.13 - 6.97 (m, 2H), 4.09 (q, J= 7.0 Hz, 2H), 3.95 (t, J= 11.7 Hz, 2H), 1.33 (t, J= 7.0 Hz, 3H).
117C F 539 (M+H) 127-132 (CDC13) δ 8.59 (s, 1H), 8.54 (dd, J= 4.8, 1.3 Hz, 1H), 8.28 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.84 - 7.77 (m, 4H), 7.77 - 7.72 (m, 1H), 7.38 (dd, J= 7.7, 5.0 Hz, 3H), 4.02 (d, J =1.2 Hz, 2H), 2.30(s, 3H)
118C F 539 (M+H) 215 (dec) (CDCI3) δ 8.67 (s, 1H), 8.59 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.4 Hz, 1H), 7.84 (dd, J = 8.3, 3.8 Hz, 4H), 7.80 (s, 1H), 7.42 - 7.39 (m, 3H), 4.03 (d, J = 1.3 Hz, 2H), 2.26 (s, 3H).
119C F 580 (M+H) 124-138 (CDCI3) δ 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.88 - 7.77 (m, 4H), 7.48 _ 7.34 (m, 5H), 7.23 - 7.18 (m, 1H), 4.06-3.93 (m, 2H), 2.40 (qd, J= 14.2,7.3 Hz, 2H), 1.94-1.81 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H).
120C F 549.7 (M+H) 153-159 (CDCI3) δ 8.67 (s, 1H), 8.30 (s, 1H), 8.24 (d, J= 8.3 Hz, 2H), 7.92 (d, J= 8.5 Hz, 2H), 7.82 (m, 3H), 4.01 (d, J= 1.5 Hz, 2H), 3.80 - 3.64 (m, 2H), 2.91 - 2.76 (m, 2H), 1.30 1.14 (m, 6H)
121C F 578 (M+H) 143-147; 148-151 (CDCI3) δ 8.57 (d, J = 7.4 Hz, 1H), 8.30 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 - 7.78 (m, 4H), 7.49 - 7.33 (m, 5H), 7.29 - 7.26 (m, 1H), 6.03 (s, 1H), 3.95 (s, 2H), 1.84 (d, .7=1.3 Hz, 3H), 1.71 (d, .7=1.2 Hz, 3H).
122C F 579.3 (M+1) 169-171 (CDCB) δ 8.58 (s, 1H), 8.24 - 8.18 (m, 2H), 7.99_ 7.94 (m, 2H), 7.84 - 7.78 (m, 2H), 7.47 (dd, J= 5.0, 1.1 Hz, 2H),7.40 (d, J= 8.3 Hz, 2H), 7.34 (ddd, J= 7.9, 5.1, 3.7 Hz, 1H), 7.18 (d, J= 7.6 Hz, 1H), 4.00 (d, J= 1.5 Hz, 2H), 3.72 (dd, J= 7.0, 5.1Hz, 2H), 2.94 - 2.80 (m, 1H), 2.22 (s, 3H), 1.23 (m, 9H).
142
ID Synthesis Method MS mp (°C) *H NMR, 13C, or 19F NMR (δ)1
123C F 553 (M+H) 130-135 (CDC13) δ 8.62 (s, 1H), 8.54 (d, J= 3.2 Hz, 1H), 8.28 - 8.19 (m, 3H), 7.82 (d, J= 8.8 Hz, 5H), 7.43 - 7.37 (m, 3H), 4.02 (s, 2H), 2.63 (d, J= 7.6 Hz, 2H), 1.22 (s, 3H)
124C F 608 (M+H) 140-145 (CDC13) δ 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.89 - 7.75 (m, 4H), 7.58 - 7.51 (m, 1H), 7.49 - 7.36 (m, 5H), 4.04 (d, J= 17.4 Hz, 1H), 3.97 (d, J= 17.4 Hz, 1H).
125C F 580 (M+H) 130-140 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.86 - 7.78 (m, 4H), 7.65 (dd, J = 8.1, 1.4 Hz, 1H), 7.49 - 7.42 (m, 1H), 7.40 (d, J= 8.3 Hz, 2H), 7.35 (dt, J = 7.6, 1.5 Hz, 1H), 7.05 (dd, J=7.8, 1.5 Hz, 1H), 3.95 (s, 2H), 1.38 (s, 9H).
126C F 590 (M+H) 175-177 (CDC13) δ 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.87 - 7.77 (m, 4H), 7.52 (ddd, J= 8.1, 6.0, 3.4 Hz, 1H), 7.44 7.34 (m, 5H), 6.46 (t, JHf = 73.5 Hz, 1H), 4.05-3.95 (m, 2H).
127C F 578 (M+H) 112-115 (CDC13) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (d, J= 8.3 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.43 - 7.32 (m, 4H), 7.26 - 7.24 (m, 2H), 4.23 (q, .7=7.3 Hz, 1H), 1.85- 1.78 (m, 4H), 0.90 - 0.78 (m, 2H), 0.78 - 0.69 (m, 1H), 0.65-0.55 (m, 1H).
128C F 580 (M+H) 164-171 (CDC13) δ 8.58 (s, 1H), 8.29 (d, J= 7.8 Hz, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.88 - 7.74 (m, 4H), 7.48 - 7.30 (m, 5H), 7.20 (t, J = 11.1 Hz, 1H), 4.26-4.14 (m, 1H), 2.502.46 (m, 2H), 1.79 (d, J= 7.3 Hz, 3H), 1.69 - 1.56 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H).
129C F 606 (M+H) 140-142 (CDC13) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.87 - 7.76 (m, 4H), 7.53 _ 7.47 (m, 2H), 7.44 - 7.35 (m, 3H), 4.27 (q, .7=7.3 Hz, 1H), 1.82 (d,J=7.3 Hz, 3H).
143
ID Synthesis Method MS mp(°C) *H NMR, 13C, or 19F NMR (δ)1
130C F 590 (M+H) 93-97; 191-194 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J= 8.4 Hz, 2H), 7.88 - 7.76 (m, 4H), 7.48 - 7.34 (m, 4H), 7.20 (tt, J= 12.4, 6.1 Hz, 1H), 4.35-4.18 (m, 1H), 1.81 (2d, J = 7.3 Hz, 3H).
131C F 572 (ΜΗ) 93-98; 185-186 (CDC13) δ 8.58 (s, 1H), 8.32 (s, 1H), 8.26 - 8.20 (m, 2H), 7.86 - 7.78 (m, 4H), 7.53 - 7.42 (m, 1H), 7.40 (d, 7= 8.3 Hz, 2H), 7.09 (t, 7= 8.1 Hz, 2H), 4.26 (q, 7= 7.3 Hz, 1H), 1.80 (d, 7=7.3 Hz, 3H).
132C J 552 (M+H) 193-196 (CDC13) δ 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, 7 = 8.4 Hz, 2H), 7.80 (ddd, 7 = 9.5, 6.9, 4.9 Hz, 4H), 7.43 - 7.33 (m, 4H), 7.31 7.21 (m, 2H), 4.05 (td, 7= 9.4, 7.1 Hz, 1H), 3.97 - 3.87 (m, 1H), 3.42 - 3.33 (m, 1H), 3.33-3.24 (m, 1 H), 3.12 (heptet, 7 = 6.8 Hz, 1H), 1.27 (d, 7=6.8 Hz, 3H), 1.22 (d,7 = 6.9 Hz, 3H).
133C J 538 (M+H) 167-169 (CDC13) δ 8.55 (d, 7= 7.1 Hz, 1H), 8.23 (s, 1H), 8.17 (d, 7= 8.4 Hz, 2H), 7.80 (dt, 7= 11.4, 6.2 Hz, 4H), 7.43 - 7.23 (m, 6H), 4.00 (s, 2H), 3.32 (s, 2H), 2.67 (q, 7= 7.6 Hz, 2H), 1.25 (dd, 7 = 9.6, 5.5 Hz, 3H).
134C J 536 (M+H) 217-220; 230-232 (CDC13) δ 8.65 (s, 1H), 8.22 (s, 1H), 8.18 (d, 7 = 8.4 Hz, 2H), 7.94 - 7.88 (m, 2H), 7.81-7.78 (m, 4H), 7.41 (dd,7=7.8,1.5 Hz, 1H), 7.39 - 7.33 (m, 1H), 7.30 - 7.24 (m, 1H), 7.23 (dd,7 = 7.8, 1.5 Hz, 1H), 4.09 - 4.02 (m, 1H), 3.98 - 3.88 (m, 1H), 3.43 3.24 (m, 2H), 3.12 (heptet, 7= 6.9 Hz, 1H), 1.27 (d, 7= 6.8 Hz, 3H), 1.22 (d, 7= 6.9 Hz, 3H).
135C J 566 (M+H) 167-169 (CDC13) δ 8.56 (s, 1H), 8.19 (dd, 7= 12.7, 9.0 Hz, 3H), 7.84 - 7.74 (m, 4H), 7.37 (dd, 7 = 14.9, 6.1 Hz, 4H), 7.26 (s, 1H), 7.21 (d, J = 7.6 Hz, 1H), 4.17 - 3.85 (m, 2H), 3.42 3.22 (m, 2H), 2.82 (d, 7= 23.6 Hz, 1H), 1.80 - 1.55 (m, 2H), 1.23 (2d, 7 = 6.9 Hz, 3H), 0.82 (2t, 7 = 7.4 Hz, 3H).
144
ID Synthesis Method MS mp(°C) lH NMR, 13C, or 19F NMR (δ)1
136C J 552 (M+H) 143-147 (CDC13) δ 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.24 (d, J= 7.5 Hz, 1H), 7.19 (d, J= 6.4 Hz, 1H), 7.15 (d, J= 7.3 Hz, 1H), 3.92 (qt, J= 10.1, 7.3 Hz, 2H), 3.43 - 3.28 (m, 2H), 2.72 - 2.51 (m, 2H), 2.27 (s, 3H), 1.25 (t, 7.6 Hz, 3H).
137C J 554 (M+H) 183-186 (CDC13) δ 8.56 (d, J= 5.3 Hz, 1H), 8.26 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.18 (d, J = 8.5 Hz, 1H), 6.81 (dt, J= 8.4, 2.9 Hz, 2H), 3.96 (t, J = 6.6 Hz, 2H), 3.81 (s, 3H), 3.30 (t, J= 6.9 Hz, 2H), 2.28 (s, 3H).
138C J 568 (M+H) 231-233 (CDC13) δ 8.56 (d, 5.4 Hz, 1H), 8.25 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.84 - 7.72 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.67 (s, 2H), 3.92 - 3.85 (m, 2H), 3.79 (s, 3H), 3.34 (t, J= 7.1 Hz, 2H), 2.25 (s, 6H).
139C J 552 (M+H) 195-197 (CDC13) δ 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J= 8.3 Hz, 2H), 7.83 - 7.73 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.95 (s, 2H), 3.90 (t, J=7.1 Hz, 2H), 3.35 (t, «7= 7.1 Hz, 2H), 2.30 (s, 3H), 2.23 (s, 6H).
140C J 540 (M+H) 181-184 (CDC13) δ 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J= 8.3 Hz, 2H), 7.84 - 7.75 (m, 4H), 7.43 - 7.36 (m, 3H), 7.30 (ddd, J= 12.6, 6.9, 3.1 Hz, 1H), 7.06 - 6.97 (m, 2H), 4.04 (t, J= 7.0 Hz, 2H), 3.86 (s, 3H), 3.29 (t, J = 7.0 Hz, 2H).
141C J 524 (M+H) 173-176 (CDCI3) δ 8.56 (s, 1H), 8.25 (s, 1H), 8.18 (d, J= 8.4 Hz, 2H), 7.83 - 7.75 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.34 - 7.23 (m, 4H), 4.01 (t, J= 6.9 Hz, 2H), 3.32 (t, J= 6.9 Hz, 2H), 2.31 (s, 3H).
142C J 538 (M+H) 210-213 (CDC13) δ 8.56 (s, 1H), 8.23 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.22 - 7.10 (m, 3H), 3.92 (t, J= 7.1 Hz, 2H), 3.36 (t, J= 7.1 Hz, 2H), 2.28 (s, 6H).
145
ID Synthesis Method MS mp (°C) *H NMR, 13C, or I9F NMR (δ)1
143C J 562 (M+H) 221-224 (CDC13) δ 8.56 (s, 1H), 8.23 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.83 - 7.74 (m, 4H), 7.38 (d, J= 8.3 Hz, 2H), 7.30 (dt, J= 7.4, 4.8 Hz, 2H), 7.15 - 7.09 (m, 1H), 4.05 (ddd, J= 9.4, 7.3, 5.2 Hz, 1H), 4.00 - 3.89 (m, 1H), 3.46-3.30 (m, 2H).
144C J 586 (M+H) 117-123; 134-138 (300 MHz, CDC13) δ 8.56 (d, J= 4.3 Hz, 1H), 8.34 (s, 1H), 8.21 (s, 1H), 8.18 (s, 1H), 7.81 (dd, J = 8.9, 2.3 Hz, 4H), 7.52 (d, J = 6.7 Hz, 1H), 7.50-7.31 (m, 1 OH), 3.53 - 3.49 (m, 2H), 2.95-2.90 (d, J = 6.8 Hz, 2H).
145C J 550 (M+H) 207-209 (CDCI3) δ 8.56 (s, 1H), 8.26 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.32 - 7.21 (m, 3H), 7.01 (dd, J= 8.9, 2.5 Hz, 1H), 4.12 4.04 (s, 2H), 3.34 (t, J= 6.9 Hz, 2H), 2.09 1.98 (m, 1H), 0.95 (dd, J= 8.5, 1.7 Hz, 2H), 0.72 (bs, 2H).
146C J 554 (M+H) 141-144 (CDCI3) δ 8.56 (d, J= 5.2 Hz, 1H), 8.24 (s, 1H), 8.17 (d, J = 8.3 Hz, 2H), 7.80 (dt, J= 8.2, 4.6 Hz, 4H), 7.45 - 7.36 (m, 3H), 7.30 7.24 (m, 1H), 7.05 - 6.95 (m, 2H), 4.13 4.02 (m, 4H), 3.28 (t, J= 7.0 Hz, 2H), 1.44 - 1.35 (m, 3H).
147C J 540 (M+H) 168-170 (CDCI3) δ 8.57 (s, 1H), 8.37 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 7.87 - 7.76 (m, 4H), 7.40 (d, J= 8.4 Hz, 2H), 7.29 (dd, J= 14.2, 6.0 Hz, 1H), 7.24 (d, J= 2.3 Hz, 1H), 7.09 7.02 (m, 1H), 6.72 (dd, 8.0, 2.1 Hz, 1H), 4.20 (t, J= 6.9 Hz, 2H), 3.83 (d, J= 8.7 Hz, 3H), 3.24 (t, J =6.9 Hz, 2H).
148C J 546 (M+H) 213-216 (CDCI3) δ 8.56 (s, 1H), 8.24 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.80 (dt, J = 4.0, 2.5 Hz, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.30 (ddd, J = 8.5, 7.4, 4.2 Hz, 1H), 7.05 - 6.97 (m, 2H), 4.02 (t, J= 6.9 Hz, 2H), 3.36 (t, J = 6.9 Hz, 2H).
146
ID Synthesis Method MS mp(°C) 'H NMR, 13C, or 19F NMR (δ)1
149C J 612 (M+H) 200-203 (CDC13) δ 8.56 (s, 1H), 8.18 (d, J= 2.6 Hz, 2H), 8.16 (s, 1H), 7.80 (dt, J= 8.3, 4.7 Hz, 4H), 7.71 (t, J= 8.6 Hz, 2H), 7.47 (t, J= 7.7 Hz, 1H), 7.39 (d, J= 8.3 Hz, 2H), 4.18 4.07 (m, 1H), 3.93 - 3.84 (m, 1H), 3.46 (td, J= 10.7, 7.3 Hz, 1H), 3.35 - 3.25 (m, 1H).
150C J 566 (M+H) 169-172 (CDC13) δ 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.80 (dt, J= 11.5, 6.2 Hz, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.31 7.27 (m, 3H), 7.26 - 7.24 (m, 1H), 4.10 3.89 (m, 2H), 3.38 - 3.32 (m, 2H), 2.48 (s, 2H), 2.01 - 1.84 (m, 1H), 0.91 (d, J= 6.2 Hz, 6H).
151C J 564 (M+H) 149-153 (CDC13) δ 8.57 (s, 1H), 8.25 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.99 (s, 1H), 7.81 (dt, J = 8.3, 4.5 Hz, 4H), 7.39 (dd, J= 6.1, 3.5 Hz, 3H), 7.33 - 7.27 (m, 2H), 6.21 (s, 1H), 3.92 (t, J= 6.9 Hz, 2H), 3.26 (t, J= 6.8 Hz, 2H), 1.89 (d, J = 1.1 Hz, 3H), 1.79 (d, J = 1.1 Hz, 3H).
152C J 576 (M+H) 161-163 (CDC13) δ 8.57 (s, 1H), 8.23 - 8.16 (m, 3H), 7.83 - 7.77 (m, 4H), 7.48 (dd, J= 7.5, 2.0 Hz, 1H), 7.39 (d, J= 8.3 Hz, 2H), 7.33 (dt, J = 7.2, 2.1 Hz, 2H), 7.28 (dd, J= 9.8, 1.9 Hz, 1H), 6.52 (t, Jhf = 74.1 Hz, 1H), 4.06 (t, J = 6.9 Hz, 2H), 3.33 (t, J= 6.9 Hz, 2H).
153C J 594 (M+H) 195-197 (CDC13) δ 8.57 (s, 1H), 8.25 (s, 1H), 8.19 (d, J= 8.4 Hz, 2H), 7.81 (dt, J= 4.1, 2.6 Hz, 4H), 7.58 - 7.52 (m, 1H), 7.42 - 7.33 (m, 5H), 4.05 (t, J = 6.9 Hz, 2H), 3.31 (t, J = 6.9 Hz, 2H).
154C J _ 538 (M+H) 164-167 CDC13) δ 8.56 (s, 1H), 8.23 (d, J= 9.8 Hz, 1H), 8.17 (d, J= 8.3 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.35 7.27 (m, 3H), 7.19 (s, 1H), 3.54-3.31 (m, 1H), 3.07-2.93 (m, 1H), 2.31 (d,J=9.0 Hz, 3H), 1.62 - 1.56 (m, 1H), 1.31-1.19 (m, 3H).
147
ID Synthesis Method MS mp (°C) ‘H NMR, 13C, or 19F NMR (δ)1
155C J 566 (M+H) 201-204 Two Isomers (CDC13) δ 8.56 (s, 2H), 8.18 (dd, J = 10.8, 7.4 Hz, 6H), 7.84 - 7.73 (m, 8H), 7.45 - 7.30 (m, 8H), 7.30 - 7.23 (m, 2H), 7.20 (d, J= 6.7 Hz, 1H), 7.12 (dd, J = 7.8, 1.2 Hz, 1H), 4.43 - 4.33 (m, 1H), 4.16 (dd, J= 12.6, 6.3 Hz, 1H), 3.48 (dt, J= 13.3, 6.7 Hz, 1H), 3.37 (dd, J= 10.8, 6.2 Hz, 1H), 3.24 (dt, J= 13.7, 6.9 Hz, 1H), 3.08 - 2.92 (m, 3H), 1.33-1.16 (m, 18H).
156C J 566 (M+H) 105-110 (CDCfi) δ 8.56 (s, 1H), 8.20 (d, J = 3.4 Hz, 1H), 8.16 (d, J= 8.4 Hz, 2H), 7.84 - 7.73 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.25 7.09 (m, 3H), 4.39 - 4.23 (m, 1H), 3.53 3.35 (m, 1H), 3.04 - 3.00 (m, 1H), 2.78 2.49 (m, 2H), 2.28 (2s, 3H), 1.34 - 1.08 (m, 6H).
157C J 592 (M+H) 175-176 (CDCI3) δ 8.56 (d, J= 0.6 Hz, 1H), 8.21 (s, 1H), 8.17 (d, J = 8.2 Hz, 2H), 7.82 - 7.77 (m, 4H), 7.49 - 7.35 (m, 4H), 7.30 - 7.28 (m, 1H), 4.64 - 4.57 (m, 1H), 3.44 (dd, J= 10.2, 6.3 Hz, 1H), 3.16-3.01 (m, 1H), 1.27 (d, J =6.3 Hz, 3H).
158C J 572 (M+H) 99-102 Two Isomers (CDC13) δ 8.56 (s, 2H), 8.20 (s, 2H), 8.19 - 8.12 (m, 4H), 7.84 - 7.73 (m, 8H), 7.39 (d, J= 8.3 Hz, 4H), 7.36 - 7.29 (m, 2H), 7.25 - 7.17 (m, 4H), 4.78 - 4.55 (m, 1H), 4.35 (dt, J = 9.4, 6.3 Hz, 1H), 3.48 (dd, J= 10.7, 6.5 Hz, 1H), 3.38 (dd, J= 10.7, 6.2 Hz, 1H), 3.11 (dd, J= 10.7, 9.4 Hz, 1H), 3.01 (dd, J = 10.7, 8.3 Hz, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 1.26 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 6.4 Hz, 3H)
159C J 607 (M+H) 85 (dec) (CDCI3) δ 8.56 (s, 1H), 8.18 (dd, J= 11.9, 5.3 Hz, 3H), 7.79 (dd, J= 8.7, 6.5 Hz, 4H), 7.47 (dd, J= 7.8, 2.3 Hz, 1H), 7.42 - 7.32 (m, 5H), 4.48 - 4.29 (m, 1H), 3.45 (dd, J = 10.7, 6.4 Hz, 1H), 2.98 (dd, J = 10.7, 7.1 Hz, 1H), 1.26 (d, J = 6.3 Hz, 3H)
148
ID Synthesis Method MS mp(°C) !H NMR, 13C, or 19F NMR (δ)1
160C J 626 (M+H) 93 (dec) Two Isomers (CDC13) δ 8.56 (s, 2H), 8.19 8.12 (m, 6H), 7.84 - 7.73 (m, 10H), 7.71 (d, J= 8.2 Hz, 2H), 7.47 (t, J= 8.0 Hz, 2H), 7.39 (d, J= 8.3 Hz, 4H), 4.76 - 4.64 (m, 1H), 4.48 (dd, J= 14.6, 6.3 Hz, 1H), 3.43 (dd, J= 10.6, 6.2 Hz, 1H), 3.29 (dd, J = 10.5, 5.5 Hz, 1H), 3.16-3.00 (m, 2H), 1.27 (d, J= 6.4 Hz, 3H), 1.17 (d, J= 6.4 Hz, 3H)
161C J 566 (M+H) 105 (dec) (CDC13) δ 8.56 (s, 1H), 8.22 (s, 1H), 8.16 (d, J= 8.4 Hz, 2H), 7.83 - 7.70 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.94 (d, J= 9.3 Hz, 2H), 4.43 - 4.22 (m, 1H), 3.42 (dd, J = 10.8, 6.5 Hz, 1H), 3.00 (dd, J= 10.8, 8.5 Hz, 1H), 2.30 (s, 3H), 2.25 (s, 3H), 2.21 (s, 3H), 1.20 (d, J =6.3 Hz, 3H)
162C J 568 (M+H) 100 (dec) (CDCI3) δ 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J= 8.4 Hz, 2H), 7.83 - 7.73 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.18 - 7.09 (m, 1H), 6.86 - 6.76 (m, 2H), 4.33 - 4.19 (m, 1H), 3.82 (s, 3H), 3.47 - 3.38 (m, 1H), 3.00 -2.99(m, 1H), 2.29-2.27 (m, 3H), 1.331.15 (m, 3H)
163C J 580 (M+H) 92-102 (CDCI3) δ 8.56 (s, 2H), 8.18 (dd, J= 10.7, 5.3 Hz, 6H), 7.84 - 7.74 (m, 8H), 7.42 7.30 (m, 8H), 7.23 - 7.10 (m, 2H), 4.37 (dd, J= 19.5, 13.6 Hz, 1H), 4.16 (dd, J= 13.1, 6.6 Hz, 1H), 3.56 - 3.42 (m, 1H), 3.34 (dd, J = 10.8, 6.0 Hz, 1H), 3.08 - 2.87 (m, 3H), 2.70 (dd, J= 16.0, 7.0 Hz, 1H), 1.71 - 1.56 (m, 4H), 1.34 - 1.25 (m, 6H), 1.24 - 1.14 (m, 6H), 0.93 - 0.73 (m, 6H)
164C J 589 (M+H) 80 (dec) (CDCI3) δ 8.56 (s, 1H), 8.22 - 8.14 (m, 3H), 7.84 - 7.76 (m, 4H), 7.42 - 7.27 (m, 6H), 6.51 (t, JHf= 74.3 Hz, 1H), 4.52 - 4.31 (m, 1H), 3.44 (dd, J= 10.8, 6.5 Hz, 1H), 2.99 (dd, J= 10.8, 7.6 Hz, 1H), 1.25 (d, J= 6.3 Hz, 3H)
149
ID Synthesis Method MS mp (°C) 'H NMR, 13C, or 19F NMR (δ)1
165C J 580 (M+H) 143 (dec) Two Isomers (CDCI3) δ 8.56 (s, 2H), 8.22 (s, IH), 8.20 (s, IH), 8.16 (d, J= 8.3 Hz, 4H), 7.84 - 7.74 (m, 8H), 7.58 (ddd, J= 9.7, 8.0, 1.7 Hz, 2H), 7.39 (d, J= 8.4 Hz, 4H), 7.36-7.27 (m, 4H), 7.15 (dd, 7=7.7, 1.6 Hz, IH), 7.09 (dd, J= 7.6, 1.7 Hz, IH), 4.38 -4.22 (m, 2H), 3.61 (dd, J= 10.8, 7.0 Hz, IH), 3.24 (dd, J= 10.7, 5.6 Hz, IH), 3.07 2.94 (m, IH), 2.91 (dd, J= 10.8, 1.5 Hz, IH), 1.47- 1.38 (m, 24H)
166C J 552 (M+H) 93 (dec) (CDCI3) δ 8.56 (s, IH), 8.21 (s, IH), 8.16 (d, J= 8.4 Hz, 2H), 7.84 - 7.73 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.32 - 7.28 (m, 3H), 7.20 (s, IH), 4.20 - 4.06 (m, IH), 3.41 (s, IH), 3.05 (dd, J= 10.8, 8.2 Hz, IH), 2.31 - 32.30 (m, 3H), 1.66 (s, 2H), 0.90 - 0.88 (m, 3H)
167C J 586 (M+H) 105 (dec) Two Isomers (CDCI3) δ 8.56 (s, 2H), 8.20 (s, 2H), 8.16 (d, J= 8.3 Hz, 4H), 7.83 - 7.74 (m, 8H), 7.43 - 7.28 (m, 6H), 7.21 (dd, J = 5.4, 3.3 Hz, 4H), 4.49 - 4.36 (m, IH), 4.17 4.05 (m, IH), 3.49 (dd, J= 10.7, 6.6 Hz, IH), 3.40 (dd, 7= 10.7, 6.3 Hz, IH), 3.10 (dd, J= 10.7, 9.4 Hz, 1 H), 3.04 (dd, J = 10.8, 8.2 Hz, IH), 2.34 (s, 3H), 2.30 (s, 3H), 1.73 - 1.48 (m, 4H), 0.91 (m, 6H)
168C J 560 (M+H) 199-200 (CDCI3) δ 8.56 (s, IH), 8.18 (m„ 2H), 7.79 (m, 4H), 7.47 (dd, J= 7.8, 2.3 Hz, IH), 7.42 - 7.32 (m, 5H), 4.48 - 4.29 (m, IH), 3.45 (dd, J = 10.7, 6.4 Hz, 1 H), 2.98 (dd, J = 10.7, 7.1 Hz, 1 H), 1.26 (d, J = 6.3 Hz, 3H)
169C G 623 (M+H) Oil (CDCI3) δ 10.45 (s, IH), 8.59 (s, IH), 8.25 (d, 7= 8.3 Hz, 2H), 7.88 (d, J = 8.3 Hz, 2H), 7.81 (d, J =8.9 Hz, 2H), 7.61 (t, 7=7.5 Hz, 2H), 7.40 (d, J= 8.7 Hz, 2H), 7.11 (t, J = 8.0 Hz, IH), 5.71 (d,7=l.l Hz, IH), 2.35 (s, 3H) 19F NMR (376 MHz, CDC13) δ -58.02, 62.31
150
ID Synthesis Method MS mp (°C) 'H NMR, 13C, or 19F NMR (δ)1
170C G 606 (M+H) 157-159 (CDC13) δ 8.56 (s, 1H), 8.19 - 8.14 (m, 3H), 7.79 (m, 4H), 7.56 - 7.46 (m, 2H), 7.46 7.43 (m, 2H), 7.39 (d, J= 8.3 Hz, 2H), 5.88 (d, J= 1.3 Hz, 1H), 1.86 (d, J= 1.2 Hz, 3H)
171C G 558 (M+H) 236-237 (CDC13) δ 8.56 (s, 1H), 8.19 (d, J = 5.9 Hz, 2H), 8.16 (s, 1H), 7.83 - 7.76 (m, 4H), 7.45 (tt, J= 8.4, 6.1 Hz, 1H), 7.39 (d, J= 8.3 Hz, 2H), 7.10 (dd, J= 8.5, 7.3 Hz, 2H), 5.90 (d, 1.3 Hz, 1H), 1.92 (s, 3H)
172C G 580 (M+H) 103-108 (CDCI3) δ 8.56 (d, J= 3.7 Hz, 1H), 8.21 (s, 1H), 8.16 (d, J= 8.4 Hz, 2H), 7.84 - 7.72 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.72 (s, 2H), 5.89 (d, J= 1.3 Hz, 1H), 3.82 (s, 3H), 2.14 (s, 6H), 1.75 (d, J= 1.2 Hz, 3H).
173C G 536 (M+H) 87 (dec) (CDCI3) δ 8.56 (s, 1H), 8.19-8.15 (m, 3H), 7.82 - 7.75 (m, 4H), 7.43 - 7.30 (m, 5H), 7.24 (d, J= 7.3 Hz, 1H), 5.88 (s, 1H), 2.21 (s, 3H), 1.80 (d,J= 1.2 Hz, 3H)
174C G 570 (M+H) 95 (dec) (CDCI3) δ 8.56 (s, 1H), 8.20 - 8.12 (m, 3H), 7.83 - 7.74 (m, 4H), 7.43 - 7.36 (m, 3H), 7.32 (t, J= 7.7 Hz, 1H), 7.29-7.27 (m, 1H), 5.92 (d, J= 1.3 Hz, 1H), 2.26 (s, 3H), 1.81 (d, J= 1.2 Hz, 3H)
175C G 550 (M+H) 132-136 (CDCI3) δ 8.56 (d, J= 5.0 Hz, 1H), 8.21 8.13 (m, 3H), 7.83 - 7.74 (m, 4H), 7.39 (d, J = 8.2 Hz, 2H), 7.29 - 7.23 (m, 1H), 7.19 (d, J= 7.7 Hz, 2H), 5.92 (d, J = 1.3 Hz, 1H), 2.18 (s, 6H), 1.75 (d, J= 1.2 Hz, 3H).
176C G 564 (M+H) 123-138 (CDCI3) δ 8.56 (s, 1H), 8.19 - 8.14 (m, 3H), 7.83 - 7.75 (m, 4H), 7.49 - 7.43 (m, 2H), 7.39 (d, J= 8.3 Hz, 2H), 7.33 (ddd, J= 7.8, 5.9, 3.0 Hz, 1H), 7.19 - 7.17 (m, 1H), 5.88 (d, J= 1.3 Hz, 1H), 2.96 - 2.76 (m, 1H), 1.81 (d, J = 1.2 Hz, 3H), 1.24 (t, J =6.4 Hz, 3H), 1.22-1.16 (m, 3H).
I5l
ID Synthesis Method MS mp (°C) *H NMR, 13C, or 19F NMR (δ)1
177C J 566 (M+H) 185-187 (CDC13) δ 8.55 (s, IH), 8.14 (d, J= 8.4 Hz, 2H), 8.05 (s, IH), 7.84 - 7.77 (m, 2H), 7.74 (d, 8.3 Hz, 2H), 7.42 - 7.35 (m, 3H), 7.32 (dd, J= 10.6, 4.3 Hz, IH), 7.28 - 7.24 (m, IH), 7.18 (dd, J =7.8, 1.4 Hz, IH), 3.80 -3.69(m, IH), 3.59-3.48 (m, 1H),3.11 (dd, J= 13.2, 6.8 Hz, 3H), 2.41 - 2.27 (m, 2H), 1.22 (t, J =5.6 Hz, 6H).
178C J 580 (M+H) 186-190 (CDC13) δ 8.55 (d, J= 3.6 Hz, IH), 8.14 (d, J= 8.4 Hz, 2H), 8.06 (s, IH), 7.84 - 7.77 (m, 2H), 7.74 (d, J= 8.4 Hz, 2H), 7.38 (d, J = 9.0 Hz, 3H), 7.32 (td, J= 7.5, 1.4 Hz, IH), 7.26 (s, IH), 7.17 (t, J = 7.1 Hz, IH), 3.69 - 3.26 (m, IH), 3.55-3.37 (m, 1H),3.182.98 (m, 2H), 2.93 - 2.80 (m, IH), 2.47 (d, J = 35.9 Hz, IH), 1.31 - 1.12 (m, 9H).
179C J 550 (M+H) 212-213 (CDCI3) δ 8.64 (s, IH), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, IH), 7.91 (d, J= 8.5 Hz, 2H), 7.79 (d, J= 8.6 Hz, 2H), 7.75 (d, J= 8.4 Hz, 2H), 7.38 (dd, J= 7.8, 1.6 Hz, IH), 7.33 (td, J= 7.5, 1.4 Hz, IH), 7.29 - 7.23 (m, IH), 7.18 (dd, J= 7.8, 1.4 Hz, IH), 3.78 - 3.72 (m, IH), 3.59-3.48 (m, IH), 3.18 - 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, 6H).
180C J 566 (M+H) 127-133 (300 MHz, CDCI3) δ 8.55 (s, IH), 8.13 (d, J = 8.3 Hz, 2H), 8.05 (s, IH), 7.76 (dd, J= 17.0, 8.7 Hz, 4H), 7.37 (t, J= 8.4 Hz, 2H), 7.18 (dd, J= 12.7, 9.6 Hz, 3H), 3.54 - 3.49 (m, 2H), 3.12 - 3.08 (m, 2H), 2.70 - 2.55 (m, 2H), 2.39 - 2.31 (m, 2H), 2.28 (s, 3H), 1.25 (t, J =7.6 Hz, 3H).
181C J 582 (M+H) 170-174 (CDCI3) δ 8.55 (s, IH), 8.14 (d, J= 8.3 Hz, 2H), 8.08 (s, IH), 7.84 - 7.76 (m, 2H), 7.74 (d, J= 8.3 Hz, 2H), 7.38 (d, J= 8.3 Hz, 2H), 6.65 (s, 2H), 3.79 (s, 3H), 3.52 - 3.45 (m, 2H), 3.10 - 3.07 (m, 2H), 2.38 - 2.31 (d, J = 5.7 Hz, 2H), 2.25 (s, 6H).
152
ID Synthesis Method MS mp(°C) *H NMR, 13C, or 19F NMR (δ)1
182C J 552 (M+H) 148-155; 166-168 (300 MHz, CDC13) δ 8.55 (d, J= 1.0 Hz, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.05 (s, 1H), 7.83 - 7.76 (m, 2H), 7.74 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 9.0 Hz, 2H), 7.14 - 7.09 (m, 3H), 3.51 (dd, J= 9.1, 3.5 Hz, 2H), 3.15 - 3.03 (m, 2H), 2.36 (s, 2H), 2.28 (s, 6H).
183C J 580 (M+H) 159-162 (CDCI3) δ 8.55 (d, J= 3.7 Hz, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.03 (d, J= 19.3 Hz, 1H), 7.84 - 7.77 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.38 (d, J= 8.3 Hz, 2H), 7.32 (d, J= 3.8 Hz, 2H), 7.25 (d, J= 6.6 Hz, 1H), 7.19 (t, J= 8.0 Hz, 1H), 3.76 (ddd, J= 24.2, 12.0, 5.9 Hz, 1H), 3.58 - 3.46 (m, 1H),3.11 (dd, J = 15.3, 6.1 Hz, 2H), 2.82 (dd, J= 14.6, 7.2 Hz, 1H), 2.41-2.29 (m, 2H), 1.71-1.55 (m, 2H), 1.20 (d, J= 6.8 Hz, 3H), 0.87 - 0.76 (m, 3H).
184C J 566 (M+H) 194-198 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.07 (s, 1H), 7.83 - 7.76 (m, 2H), 7.74 (d, J= 8.4 Hz, 2H), 7.40 (t, J= 10.1 Hz, 2H), 6.93 (s, 2H), 3.53 - 3.47 (m, 2H), 3.12 -3.05 (m, 2H), 2.34 (dt, J= 11.7, 5.8 Hz, 2H), 2.30 (s, 3H), 2.23 (s, 6H).
185C J 552 (M+H) 157-160 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.06 (s, 1H), 7.83 - 7.77 (m, 2H), 7.74 (d, J= 8.3 Hz, 2H), 7.38 (d, J= 8.3 Hz, 2H), 7.36 - 7.27 (m, 3H), 7.23 - 7.19 (m, 1H), 3.74 (m, 1H), 3.50 (m, 1H), 3.10 (d, J= 5.9 Hz, 2H), 2.64 (q, J= 7.6 Hz, 2H), 2.40 2.29 (m, 2H), 1.28 - 1.21 (m, 3H).
186C J 564 (M+H) 173-177 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.09 (s, 1H), 7.83 - 7.77 (m, 2H), 7.81 - 7.77 (m, 2H), 7.38 (d, J= 8.3 Hz, 2H), 7.24 - 7.22 (m, 3H), 7.05 - 6.95 (m, 1H), 3.77 - 3.63 (m, 2H), 3.14 - 3.07 (m, 2H), 2.45 - 2.29 (m, 2H), 2.09 - 1.92 (m, 1H), 0.97 - 0.82 (m, 3H), 0.53 (bs, 1H).
153
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
187C J 593 (M+H) 180-182 (300 MHz, CDC13) δ 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.05 (d, J= 4.9 Hz, 1H), 7.77 (dd, J= 11.4, 8.6 Hz, 4H), 7.39 (t, J= 8.1 Hz, 4H), 7.21 (dd, 7= 13.2, 5.6 Hz, 1H), 3.65 - 3.58 (m, 2H), 3.09 (t, J= 5.5 Hz, 2H), 2.45 - 2.35 (m, 2H).
188C J 576 (M+H) 209-212 (CDCI3) δ 8.56 (s, 1H), 8.15 (d, 7= 8.4 Hz, 2H), 8.07 (s, 1H), 7.79 (ddd, 7= 15.8, 7.8, 5.8 Hz, 4H), 7.38 (d,7= 8.3 Hz, 2H), 7.31 7.21 (m, 2H), 7.10 (ddd, 7= 9.7, 7.8, 2.0 Hz, 1H), 3.64 (t, 7 = 5.4 Hz, 2H), 3.11 (t, 7= 6.0 Hz, 2H), 2.46 - 2.33 (m, 2H).
189C J 560 (M+H) 217-219 (CDCI3) δ 8.56 (s, 1H), 8.15 (d, 7= 8.4 Hz, 2H), 8.08 (s, 1H), 7.83 - 7.74 (m, 4H), 7.38 (d, 7= 8.3 Hz, 2H), 7.31 - 7.21 (m, 1H), 7.03 - 6.94 (m, 2H), 3.72 - 3.62 (m, 2H), 3.15 - 3.07 (m, 2H), 2.40 - 2.34 (m, 2H).
190C J 626 (M+H) 190-193 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, 7= 8.3 Hz, 2H), 8.00 (s, 1H), 7.83 - 7.73 (m, 4H), 7.71 (d, 7=8.1 Hz, 1H), 7.67 (d,7=7.7 Hz, 1H), 7.40 (dd, 7 = 15.8, 8.2 Hz, 3H), 3.79 - 3.69 (m, 1H), 3.55 - 3.49 (m, 1H), 3.16 - 3.04 (m, 2H), 2.47 - 2.31 (m, 2H).
191C J 554 (M+H) 150-155 (CDCI3) δ 8.54 (d, 7= 4.3 Hz, 1H), 8.13 (d, 7= 8.3 Hz, 2H), 8.05 (d, 7= 6.3 Hz, 1H), 7.77 (dd, 7= 15.4, 8.7 Hz, 4H), 7.38 (d, 7 = 8.3 Hz, 2H), 7.29 (dd, 7= 8.0, 4.8 Hz, 2H), 7.04 - 6.93 (m, 2H), 3.85 (s, 3H), 3.65 3.61 (m, 2H), 3.10 - 3.06 (m, 2H), 2.36 2.28 (s, 2H).
192C J 568 (M+H) 164-167; 168-173 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.09 (s, 1H), 7.82 - 7.77 (m, 2H), 7.74 (d, 7= 6.7 Hz, 2H), 7.38 (d, 7= 8.3 Hz, 2H), 7.13 (d, 7= 8.3 Hz, 1H), 6.79 (dd,7= 11.9, 3.3 Hz, 2H), 3.81 (s, 3H), 3.74 - 3.66 (m, 1H), 3.57 - 3.48 (m, 1H), 3.12 - 3.04 (m, 2H), 2.36 - 2.30 (m, 2H), 2.25 (s, 3H).
154
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
193C J 580 (M+H) 155-158 (CDC13) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.04 (s, 1H), 7.83 - 7.77 (m, 2H), 7.74 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 8.3 Hz, 2H), 7.31 - 7.24 (m, 3H), 7.23 - 7.20 (m, 1H), 3.82 - 3.71 (m, 1H), 3.56 - 3.47 (m, 1H), 3.17 - 3.02 (m, 2H), 2.46 (t, J= 6.7 Hz, 2H), 2.39 - 2.27 (m, 2H), 1.99 (heptet, 6.8 Hz, 1H), 0.95 - 0.92 (m, 6H).
194C J 600 (M+H) 102-108 (CDC13) δ 8.56 (s, 1H), 8.17 (m 3H), 7.80 (m, 4H), 7.52 - 7.47 (m, 2H), 7.47 - 7.31 (m, 9H), 3.42 - 3.05 (m, 2H), 2.86 (bs, 2H), 2.04-1.71 (m, 2H).
195C J 538 (M+H) 159-162 (CDC13) δ 8.55 (s, 1H), 8.14 (d, J= 8.3 Hz, 2H), 8.08 (s, 1H), 7.84 - 7.77 (m, 2H), 7.75 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 8.5 Hz, 2H), 7.31 - 7.19 (m, 4H), 3.81 - 3.47 (m, 2H), 3.20 - 3.00 (m, 2H), 2.35 (dt, J= 11.7, 5.8 Hz, 2H), 2.28 (s, 3H).
196C J 572 (M+H) 140-143 (CDC13) δ 8.55 (s, 1H), 8.14 (d, J= 8.1 Hz, 2H), 8.05 (s, 1H), 7.80 (d, J= 8.9 Hz, 2H), 7.75 (d, J= 8.2 Hz, 2H), 7.38 (d, J= 8.8 Hz, 2H), 7.33 (dd, J- 6.1, 3.4 Hz, 1H), 7.21 - 7.15 (m, 2H), 3.72 - 3.66 (m, 1H), 3.55 - 3.41 (m, 1H), 3.16 - 3.05 (m, 2H), 2.48 2.34 (m, 2H), 2.32 (s, 3H).
197C J 578 (M+H) 151-155 (CDC13) δ 8.55 (s, 1H), 8.14 (d, J= 8.2 Hz, 2H), 8.06 (s, 1H), 7.80 (d, J = 8.9 Hz, 2H), 7.75 (d, J= 8.2 Hz, 2H), 7.38 (d, J= 8.8 Hz, 2H), 7.29 (dd, J= 10.7, 4.6 Hz, 4H), 6.20 (s, 1H), 3.59 - 3.48 (m, 2H), 3.10 - 3.01 (m, 2H), 2.34-2.20 (m, 2H), 1.90 (s, 3H), 1.78 (s, 3H).
198C J 539 (M+H) 186-189 (CDC13) δ 8.56 (s, 1H), 8.36 (dd, J=4.8, 1.3 Hz, 1H), 8.15 (d, J= 8.3 Hz, 2H), 8.09 (s, 1H), 7.78 (m, 4H), 7.54 (dd, J = 7.5, 0.9 Hz, 1H), 7.37 (d, J= 8.5 Hz, 2H), 7.13 (dd, J= 7 A, 4.8 Hz, 1H), 3.87 (t, J= 5.7 Hz, 2H), 3.12 - 3.03 (m, 2H), 2.40 - 2.32 (m, 2H), 2.24 (s, 3H).
155
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (§)*
199C J 608 (M+H) 207-208 (CDC13) δ 8.55 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.05 (s, 1H), 7.83 - 7.78 (m, 2H), 7.76 (d, J= 8.4 Hz, 2H), 7.43 - 7.36 (m, 3H), 7.34 (t, J= 4.7 Hz, 3H), 3.71 - 3.64 (m, 2H), 3.12 - 3.06 (m, 2H), 2.39 - 2.30 (m, 2H).
200C J 590 (M+H) 170-172 (CDC13) δ 8.56 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.03 (s, 1H), 7.83 - 7.77 (m, 2H), 7.76 (d, J = 8.3 Hz, 2H), 7.42 - 7.27 (m, 6H), 6.74 - 6.29 (m, 1H), 3.70 - 3.64 (m, 2H), 3.13 - 3.06 (m, 2H), 2.40 - 2.31 (m, 2H).
201C J 626 (M+H) 190-193 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.3 Hz, 2H), 8.00 (s, 1H), 7.83 - 7.73 (m, 4H), 7.71 (d, J= 8.1 Hz, 1H), 7.67 (d, J= 7.7 Hz, 1H), 7.40 (dd, J= 15.8, 8.2 Hz, 3H), 3.79 - 3.69 (m, 1H), 3.55 - 3.49 (m, 1H), 3.16 - 3.04 (m, 2H), 2.47-2.31 (m, 2H).
202C J 554 (M+H) 231-234 (CDCI3) δ 8.56 (s, 1H), 8.19 - 8.08 (m, 3H), 7.84 - 7.72 (m, 4H), 7.39 (d, J= 8.4 Hz, 2H), 7.25 - 7.20 (m, 2H), 6.96 - 6.88 (m, 2H), 3.83 (s, 3H), 3.76 - 3.68 (m, 2H), 3.13 - 3.03 (m, 2H), 2.39 - 2.27 (m, 2H).
203C J 631 (M+H) 200-201 (CDCI3) δ 8.56 (s, 1H), 8.15 (d, J = 8.2 Hz, 2H), 8.06 (s, 1H), 7.83 - 7.77 (m, 2H), 7.75 (d, J= 8.2 Hz, 2H), 7.39 (d, J= 8.5 Hz, 2H), 7.28 - 7.25 (m, 2H), 3.51-3.42 (m, 2H), 3.14 - 3.05 (m, 2H), 2.35 (s, 2H), 2.25 (s, 6H).
204C J 568 (M+H) 193-196 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.09 (s, 1H), 7.84 - 7.77 (m, 2H), 7.75 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 8.3 Hz, 2H), 7.08 (t, J= 4.0 Hz, 2H), 6.88 (d, J= 8.6 Hz, 1H), 3.82 (s, 3H), 3.66 - 3.58 (m, 2H), 3.11 - 3.03 (m, 2H), 2.36 - 2.27 (m, 5H).
156
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
205C J 539 (M+H) Oil (CDCl3)ô 8.55 (s, 1H), 8.45 (dd, 7=4.8, 1.6 Hz, 1H), 8.18 - 8.12 (m, 2H), 8.06 (s, 1H), 7.82-7.72 (m, 4H), 7.53 (dd, 7=7.9, 1.6 Hz, 1H), 7.40 - 7.33 (m, 2H), 7.24 - 7.18 (m, 1H), 3.63 (br s, 2H), 3.18 - 3.03 (m, 2H), 2.51 (s 3H), 2.35 (dt,7= 11.7, 5.7 Hz, 2H)
206C J 554 (M+H) 177-178 (CDC13) δ 8.56 (s, 1H), 8.16 (d, J= 8.9 Hz, 3H), 7.84 - 7.73 (m, 4H), 7.39 (d, 7= 8.8 Hz, 2H), 7.30 (t, J= 8.1 Hz, 1H), 6.95 6.85 (m, 2H), 6.78 (dt, 7= 11.1, 5.5 Hz, 1H), 3.81 (s, 3H), 3.79 - 3.73 (m, 2H), 3.12 - 3.04 (m, 2H), 2.38 - 2.28 (m, 2H).
207C J 596 (M+H) 171-173 (CDCI3) δ 8.57 (s, 1H), 8.23 - 8.13 (m, 3H), 8.06 (d, 7= 8.5 Hz, 2H), 7.80 (dd, 7= 8.5, 4.5 Hz, 4H), 7.39 (d, 7= 8.5 Hz, 4H), 4.38 (q, 7= 7.2 Hz, 2H), 3.82 (t, 7= 6.0 Hz, 2H), 3.14 - 3.03 (m, 2H), 2.37 (s, 2H), 1.40 (t, 7 = 7.1 Hz, 3H).
208C J 568 (M+H) 171-173 (CDCI3) δ 8.55 (s, 1H), 8.14 (d, J= 8.3 Hz, 2H), 8.07 (s, 1H), 7.84 - 7.77 (m, 2H), 7.75 (d, 7= 8.3 Hz, 2H), 7.38 (d, 7 = 8.3 Hz, 2H), 7.32 - 7.23 (m, 2H), 6.99 (ddd, 7= 8.3, 5.5, 1.4 Hz, 2H), 4.08 (q, 7= 7.0 Hz, 2H), 3.69 3.57 (m, 2H), 3.16 - 3.02 (m, 2H), 2.32 (dt, 7 = 11.7, 5.9 Hz, 2H), 1.39 (t, 7= 7.0 Hz, 3H).
209C J 550 (M+H) 212-213 (CDCI3) δ 8.64 (s, 1H), 8.15 (d, 7= 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, 7 = 8.5 Hz, 2H), 7.79 (d, 7= 8.6 Hz, 2H), 7.75 (d, 7 = 8.4 Hz, 2H), 7.38 (dd, 7= 7.8, 1.6 Hz, 1H), 7.33 (td, 7= 7.5, 1.4 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.18 (dd, 7= 7.8, 1.4 Hz, 1 H), 3.78 - 3.72 (m, 1H), 3.59 - 3.48 (m, 1H), 3.18 - 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, 6H).
157
ID Synthesis Method MS mp(°C) Ή NMR, 13C, or 19F NMR (δ)1
210C J 580 (M+H) 136-139 (CDC13) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.07 (s, 1H), 7.83 - 7.77 (m, 2H), 7.75 (d, J= 8.4 Hz, 2H), 7.55 - 7.49 (m, 1H), 7.38 (d, J= 8.3 Hz, 2H), 7.32 - 7.26 (m, 2H), 7.19 - 7.13 (m, 1H), 3.72 (ddd, 12.9, 9.3, 3.8 Hz, 1H), 3.60 - 3.51 (m, 1H), 3.15 (ddd, J= 13.3, 9.4, 4.0 Hz, 1H), 3.10 3.01 (m, 1H), 2.51 - 2.36 (m, 1H), 2.36 2.22 (m, 1H), 1.43 (s, 9H).
211C J 566 (M+H) 100-106 (CDC13) δ 8.55 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.10 (s, 1H), 7.79 (dt, J= 10.4, 5.8 Hz, 4H), 7.38 (d, 8.3 Hz, 2H), 7.11 (s, 3H), 3.85 - 3.78 (m, 2H), 3.20 - 3.12 (m, 2H), 2.30 (s, 6H), 2.13-2.07 (m, 2H), 1.871.82 (m, 2H).
212C J 580 (M+H) 186-188 (CDC13) δ 8.55 (s, 1H), 8.19 - 8.10 (m, 3H), 7.79 (dt, J= 10.7, 5.9 Hz, 4H), 7.38 (dd, J= 8.5, 2.6 Hz, 3H), 7.30 (td, J= 7.5, 1.4 Hz, 1H), 7.23 (td,J= 7.5, 1.7 Hz, 1H), 7.13 (dd, J= 7.8, 1.4 Hz, 1H), 3.94 (bs, 2H), 3.24 - 3.02 (m, 3H), 2.13-2.05 (m, 2H), 1.84- 1.73 (m, 2H), 1.24 (t, J = 10.5 Hz, 6H).
213C J 580 (M+H) 123-127 (CDC13) δ 8.55 (s, 1H), 8.13 (d, J= 8.4 Hz, 2H), 8.03 (d, J= 4.4 Hz, 1H), 7.83 - 7.76 (m, 2H), 7.74 (d, J= 8.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.24 - 7.15 (m, 2H), 7.12 (dd, J= 11.9, 4.6 Hz, 1H), 3.82 - 3.71 (m, 1 H), 3.30 - 3.18 (m, 1H), 3.07 - 2.94 (m, 1H), 2.72 - 2.40 (m, 3H), 2.30 - 2.16 (m, 4H), 1.30-1.12 (m, 6H).
214C J 622 (M+H) 160-162 (CDC13) δ 8.55 (s, 1H), 8.15 (d, J= 8.4 Hz, 2H), 8.06 (s, 1H), 7.83 - 7.72 (m, 4H), 7.38 (m, 3H), 7.34 (dd, J= 2.9, 1.5 Hz, 3H), 3.58 (ddd, J= 12.3, 3.9, 1.4 Hz, 1H), 3.39 (dd, J = 12.2, 9.2 Hz, 1H), 3.04 (ddd, 12.2, 3.9, 1.4 Hz, 1H), 2.84 (dd, J = 12.2, 9.5 Hz, 1H), 2.61-2.42 (m, 1H), 1.18 (d,J= 6.7 Hz, 3H)
158
ID Synthesis Method MS mp(°C) ‘H NMR, l3C, or l9F NMR (δ)1
215C J 640 (M+H) 116 (dec) (CDC13) δ 8.55 (s, IH), 8.14 (dd, 7= 8.3, 1.5 Hz, 2H), 8.00 (d, 7= 4.0 Hz, IH), 7.84 7.72 (m, 4H), 7.72 - 7.63 (m, 2H), 7.45 7.32 (m, 3H), 3.60 - 3.44 (m, IH), 3.37 3.27 (m, IH), 3.03 - 2.92 (m, IH), 2.92 2.82 (m, IH), 2.69-2.54 (m, IH), 1.191.12 (m, 3H)
216C J 622 (M+H) 132-135 (CDC13) δ 8.55 (s, IH), 8.14 (d, 7= 8.4 Hz, 2H), 8.02 (s, IH), 7.82 - 7.71 (m, 4H), 7.44 - 7.30 (m, 6H), 3.87 (d, 7= 6.3 Hz, IH), 3.23 (td, 7 = 11.9, 3.8 Hz, IH), 3.07-2.94 (m, IH), 2.54-2.43 (m, IH), 2.19 (ddd, 7 = 13.9,9.0,5.0 Hz, IH), 1.31 (d,7=6.6 Hz, 3H)
217C J 640 (M+H) 93 (dec) Two isomers (CDC13) δ 8.55 (s, 2H), 8.14 (dd, 7= 8.4, 2.7 Hz, 4H), 7.98 (d, 7= 4.2 Hz, 2H), 7.83 - 7.72 (m, 8H), 7.67 (dt, 7 = 12.9, 7.4 Hz, 4H), 7.40 (dd, 7= 15.3, 8.1 Hz, 6H), 4.17 (s, IH), 3.96 (td, 7= 6.6, 3.1 Hz, IH), 3.24 - 3.12 (m, 2H), 3.12 - 3.01 (m, 2H), 2.41 (dddd, 7= 10.8, 10.0, 8.9, 4.2 Hz, 2H), 2.30 - 2.15 (m, 2H), 1.24 (d, 7 = 6.7 Hz, 3H), 1.04 (d, 7= 6.7 Hz, 3H)
218C J 580 (M+H) 95 (dec) (CDC13) δ 8.55 (s, IH), 8.18-8.10 (m, 2H), 8.05 (s, IH), 7.83 - 7.76 (m, 2H), 7.73 (d, 7 = 8.4 Hz, 2H), 7.41 - 7.37 (m, 2H), 6.93 (d, J= 9.4 Hz, 2H), 3.76 (dd, 7= 10.8, 4.6 Hz, 1 H), 3.29 - 3.16 (m, IH), 2.99 (ddd, 7 = 12.2, 5.9, 3.9 Hz, IH), 2.54 - 2.37 (m, IH), 2.31 (s, 3H), 2.22 (d,7=6.4 Hz, 7H), 1.19 (d, 7=6.7 Hz, 3H)
219C J 592 (M+H) 100 (dec) (CDC13) δ 8.55 (s, IH), 8.14 - 8.06 (m, 3H), 7.91 - 7.65 (m, 4H), 7.44 - 7.37 (m, 2H), 7.16 - 7.09 (m, IH), 6.93 - 6.77 (m, 2H), 4.06 - 3.64 (m, 4H), 3.31 - 3.16 (m, IH), 3.02 - 2.92 (m, IH), 2.51 - 2.40 (m, IH), 2.25-2.17 (m, 4H), 1.41-1.14 (m, 3H)
159
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
220C J 593 (M+H) 95 (dec) Two isomers: (CDCfi) δ 8.55 (s, 1H), 8.16 8.09 (m, 2H), 8.01 (m, 1H), 7.86 - 7.76 (m, 2H), 7.76 - 7.70 (m, 2H), 7.64 - 7.28 (m, 4H), 7.24 - 7.14 (m, 2H), 4.08 - 3.65 (m, 1H), 3.37 - 3.15 (m, 1H), 3.09 - 2.92 (m, 1H), 2.80 (td, J= 14.2, 6.8 Hz, 1H), 2.45 m, 1H), 2.35 - 2.09 (m, 1H), 1.76 - 1.58 (m, 1H), 1.48 - 1.35 (m, 2H), 1.27 - 1.19 (m, 2H), 1.19-1.13 (m, 2H), 1.06-0.92 (m, 1H), 0.92-0.72 (m, 3H)
221C J 603 (M+H) 113 (dec) (400 MHz, CDCI3) δ 8.56 (s, 1H), 8.20 8.10 (m, 2H), 8.00 (s, 1H), 7.83 - 7.77 (m, 2H), 7.75 (d, 8.4 Hz, 2H), 7.42 - 7.28 (m, 6H), 6.72 - 6.25 (m, 1H), 3.90 (d, J= 6.4 Hz, 1H), 3.24 (td, J= 12.0, 3.6 Hz, 1H), 3.05-2.93 (m, 1H), 2.49 (tt, J= 11.7, 4.0 Hz, 1H), 2.21 (td, J= 8.7, 4.4 Hz, 1H), 1.29 (d, J =6.6 Hz, 3H)
222C J 594 (M+H) 124 (dec) (CDCI3) δ 8.55 (s, 1H), 8.14 (dd, J= 8.4, 2.1 Hz, 2H), 8.05 (d, J= 2.8 Hz, 1H), 7.87 7.72 (m, 4H), 7.61 - 7.49 (m, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.33 - 7.21 (m, 2H), 7.15 7.05 (m, 1H), 3.79 - 3.68 (m, 1H), 3.51 3.29 (m, 1H), 3.12 - 2.93 (m, 1H), 2.66 2.52 (m, 1H), 2.18-2.12 (m, 1H), 1.43 (m, 12H)
223C L 566 (M+H) 75-87 (CDCI3) δ 8.58 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 - 7.77 (m, 4H), 7.40 (d, J= 8.3 Hz, 2H), 7.23 (dd, J= 8.4, 6.6 Hz, 1H), 7.15 (d, J= 7.5 Hz, 2H), 3.24 3.14 (m, 4H), 2.18 (s, 6H).
224C L 580 (M+H) 118 (dec) (CDCI3) δ 8.57 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 - 7.75 (m, 4H), 7.46 - 7.36 (m, 4H), 7.33 - 7.26 (m, 1H), 7.10 (d, J= 7.6 Hz, 1H), 3.26 - 3.14 (m, 4H), 2.81 (sept, J =6.9 Hz, 1H), 1.21 (t, J =7.2 Hz, 6H).
160
ID Synthesis Method MS mp(°C) 'H NMR, 13C, or 19F NMR (δ)1
225C L 580 (M+H) 111 (dec) (CDC13) δ 8.57 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.15 (s, 1H), 7.86 - 7.76 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 7.29 (t, 7= 7.6 Hz, 1H), 7.21 - 7.15 (m, 2H), 3.27 - 3.10 (m, 4H), 2.50 (q, 7= 7.5 Hz, 2H), 2.18 (s, 3H), 1.20 (t, 7=7.6 Hz, 3H).
226C L 573 (M+H) 196-200 (CDC13) δ 8.57 (s, 1H), 8.24 - 8.16 (m, 3H), 7.85 - 7.76 (m, 4H), 7.43 - 7.34 (m, 3H), 7.03 (dd, 7= 8.5, 7.4 Hz, 2H), 3.21 (s, 4H)
227C L 586 (M+H) Oil (CDC13) δ 8.57 (s, 1H), 8.21 (d, J= 8.3 Hz, 2H), 8.15 (s, 1H), 7.81 (t, 7= 9.1 Hz, 4H), 7.43 - 7.31 (m, 3H), 7.28 - 7.21 (m, 2H), 3.36 - 3.07 (m, 4H), 2.24 (s, 3H); 19F NMR (376 MHz, CDC13) δ -58.02
228C L 640 (M+H) 99 (dec) (CDC13) δ 8.57 (s, 1H), 8.21 (d, 7 = 8.3 Hz, 2H), 8.11 (s, 1H), 7.81 (dd,7 = 11.5, 4.7 Hz, 4H), 7.72 (dd, 7= 17.3, 8.0 Hz, 2H), 7.51 (dd, J= 10.0, 5.4 Hz, 1H), 7.39 (d, 7= 8.3 Hz, 2H), 3.36-3.03 (m, 4H)
229C L 622 (M+H) 95 (dec) (CDC13) δ 8.57 (s, 1H), 8.21 (d, 7= 8.4 Hz, 2H), 8.13 (s, 1H), 7.80 (dt, 7= 5.5, 4.9 Hz, 4H), 7.44 - 7.34 (m, 6H), 3.29 - 3.10 (m, 4H)
230C L 594 (M+H) 94 (dec) (CDC13) δ 8.57 (s, 1H), 8.21 (d,7= 8.3 Hz, 2H), 8.14 (d, 7= 15.4 Hz, 1H), 7.83 - 7.76 (m, 4H), 7.43 - 7.37 (m, 4H), 7.32 - 7.26 (m, 1H), 7.16-7.09 (m, 1H), 3.24 - 3.12 (m, 4H), 2.61-2.44 (m, 1H), 1.75 - 1.50 (m, 2H), 1.17 (dd, 7= 6.9, 3.3 Hz, 3H), 0.87 - 0.73 (m, 3H)
231C L 582 (M+H) 105 (dec) (CDC13) δ 8.58 (s, 1H), 8.22 (s, 1H), 8.19 (d,7= 5.0 Hz, 2H), 7.81 (dd, 7= 8.7, 5.5 Hz, 4H), 7.40 (d, 7= 8.3 Hz, 2H), 7.05 (d, 7 = 8.3 Hz, 1H), 6.90 - 6.76 (m, 2H), 3.83 (s, 3H), 3.22 - 3.11 (m, 4H), 2.16 (s, 3H)
161
ID Synthesis Method MS mp(°C) ‘H NMR, 13C, or 19F NMR (δ)'
232C L 593 (M+H) 120 (dec) (CDC13) δ 8.57 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.16 (s, 1H), 7.81 (dd, J= 8.7, 5.3 Hz, 4H), 7.58 (dd, J= 8.1, 1.5 Hz, 1H), 7.38 (dd, J= 13.2, 5.1 Hz, 3H), 7.33-7.27 (m, 1H), 7.02 - 6.96 (m, 1H), 3.37 - 3.01 (m, 4H), 1.36 (s, 9H)
233C L 604 (M+H) 92 (dec) (CDC13) δ 8.58 (s, 1H), 8.21 (d, J= 8.4 Hz, 2H), 8.14 (s, 1H), 7.86 - 7.72 (m, 4H), 7.48 - 7.28 (m, 6H), 6.40 (t, JHf = 74.3 Hz, 1H), 3.25-3.11 (m, 4H)
240C M 576 (M+H) 105 (dec) (CDC13) δ 8.57 (s, 1H), 8.25 - 8.12 (m, 3H), 7.88 - 7.72 (m, 4H), 7.39 (d, J= 8.5 Hz, 3H), 7.06 (td, J= 8.9, 4.4 Hz, 2H), 3.58 (d, J = 11.5 Hz, 1H), 3.37 (d, J= 11.5 Hz, 1H), 3.24 (d, J= 2.7 Hz, 1H), 1.59 (s, 3H);
19F NMR (376 MHz, CDC13) δ -58.02, -113.71,-115.83,-115.84
241C M 642 (M+H) 97 (dec) (CDC13) δ 9.72 - 9.57 (m, 1H), 8.58 (s, 1H), 8.24 (d, J= 8.4 Hz, 2H), 7.88 - 7.72 (m, 4H), 7.56 (dt, J= 18.3, 5.8 Hz, 2H), 7.40 (d, J= 8.3 Hz, 2H), 7.09 (t, J= 8.0 Hz, 1H), 3.49 (d, J= 13.3 Hz, 1H), 3.35 (m, 2H), 1.86 (d, J= 14.0 Hz, 3H);
19F NMR (376 MHz, CDC13) δ -58.01, -62.05, -62.22
242C M 582 (M+H) 114-116 (CDC13) δ 8.57 (s, 1H), 8.19 (dd, J= 10.1, 6.2 Hz, 3H), 7.79 (dd, J= 11.5, 4.7 Hz, 4H), 7.50 - 7.44 (m, 1H), 7.44 - 7.36 (m, 4H), 7.29 - 7.25 (m, 1H), 3.55 (d, J= 11.5 Hz, 1H), 3.45 (s, 1H), 3.34 (d, J= 11.5 Hz, 1H), 2.98 (dt, J = 13.8, 6.9 Hz, 1H), 1.43 (s, 3H), 1.27-1.16 (m, 6H);
19F NMR (376 MHz, CDC13) δ -58.02
162
ID Synthesis Method MS mp(°C) 'H NMR, 13C, or ”F NMR («)‘
243C M 596 (M+H) 112 (dec) (CDClî) δ 8.57 (s, 1H), 8.23 - 8.13 (m, 3H), 7.84 - 7.74 (m, 4H), 7.55 - 7.44 (m, 1H), 7.43 - 7.32 (m, 4H), 7.28 - 7.24 (m, 1H), 3.55-3.51 (m, 2H), 3.32 (dd, J= 11.5, 1.0 Hz, 1H), 2.69 (td, J= 13.9, 7.0 Hz, 1H), 1.63 - 1.56 (m, 2H), 1.45 (d, J = 4.9 Hz, 3H), 1.26-1.16 (m, 3H), 0.83 (dt, J= 10.2, 7.4 Hz, 3H); 19F NMR (376 MHz, CDC13) δ -58.02
244C M 588 (M+H) 103 (dec) (CDC13) δ 8.57 (s, 1H), 8.22 (s, 1H), 8.18 (d, J= 8.4 Hz, 2H), 7.83 - 7.76 (m, 4H), 7.41 - 7.32 (m, 3H), 7.25 - 7.21 (m, 2H), 3.70 - 3.61 (m, 1H), 3.53 (s, 1H), 3.30 (d, J = 11.2 Hz, 1H), 2.49 (s, 3H), 1.51 (s, 3H); 19F NMR (376 MHz, CDC13) δ -58.02
245C M 584 (M+H) 129 (dec) (CDC13) δ 8.57 (s, 1H), 8.25 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.82 - 7.75 (m, 4H), 7.39 (t, J= 8.8 Hz, 3H), 6.86 - 6.76 (m, 2H), 3.83 (s, 3H), 3.52 (d, J= 11.5 Hz, 1H), 3.43 (s, 1H), 3.31 (d, J= 11.6 Hz, 1H),2.19 (s, 2H), 1.43 (s, 3H); 19F NMR (376 MHz, CDCI3) δ -58.02
246C M 636 (M+H) 185-187 (CDC13, both diastereomers) δ 8.56 (m, 2H), 8.22 - 8.14 (m, 6H), 7.83 - 7.75 (m, 8H), 7.49 - 7.34 (m, 10H), 7.32 - 7.23 (m, 2H), 4.22 (s, 1H), 3.82 (dd, J= 12.5, 4.8 Hz, 2H), 3.51 (d, J= 13.2 Hz, 1 H), 3.40 (d, J= 12.3 Hz, 1H), 3.31 (s, 1H), 3.09 (tt, J= 13.9, 7.0 Hz, 2H), 1.31-1.13 (m, 12H); 19F NMR (376 MHz, CDCI3) δ -58.02, -78.33, -78.77
163
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or 19F NMR (δ)1
247C M 650 (M+H) — (CDC13) δ 8.59 - 8.54 (m, 1H), 8.30 - 8.13 (m, 3H), 7.79 (dd, J = 8.6, 6.7 Hz, 4H), 7.45 - 7.34 (m, 5H), 7.32 - 7.21 (m, 1H), 3.99 (s, 1H), 3.83 (d, J= 12.2 Hz, 1H), 3.52 - 3.38 (m, 1H), 2.82-2.75 (m, 1H), 1.27 - 1.26 (m, 1 H), 1.21 - 1.12 (m, 3H), 0.97-0.75 (m, 4H); 19F NMR (376 MHz, CDCI3) δ -58.03, -78.23, -78.32, -78.76, -78.84
248C M 554 (M+H) 113-126 (CDC13) δ 8.57 (d, J= 2.3 Hz, 1H), 8.24 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.83 - 7.74 (m, 4H), 7.54 - 7.47 (m, 1H), 7.39 - 7.27 (m, 5H), 3.66 (s, 1H), 3.54 (d, J= 11.5 Hz, 1H), 3.33 (d, J= 11.5 Hz, 1H), 2.41 - 2.18 (m, 3H), 1.60-1.41 (m, 3H); 19F NMR (376 MHz, CDCI3) δ -58.02
249C M 607 (M+H) 134 (dec) (CDC13) δ 8.57 (s, 1H), 8.28 - 8.13 (m, 3H), 7.85 - 7.72 (m, 4H), 7.50 - 7.34 (m, 5H), 7.28-7.23 (m, 1H),3.54 (d, J= 11.5 Hz, 1H), 3.42 (s, 1H), 3.33 (d, J= 11.5 Hz, 1H), 3.04 (dd, J= 17.2, 9.3 Hz, 1H), 2.09 (s, 1H), 1.93 - 1.75 (m, 3H), 1.68 - 1.60 (m, 3H), 1.55 (s, 3H), 1.43 (s, 2H); 19F NMR (376 MHz, CDCI3) δ -58.02
250C M 600 (M+H) 112 (dec) (CDCfi) δ 8.57 (s, 1H), 8.19 - 8.17 (m, 3H), 7.83 - 7.75 (m, 4H), 7.42 - 7.33 (m, 3H), 7.23 (t, J= 7.0 Hz, 1H), 7.10 - 6.95 (m, 1H), 3.56 (dd, J=30.7, 11.4 Hz, 1H), 3.44- 2.90 (m, 3H), 1.54-1.48 (m, 3H), 1.271.15 (m, 6H); 19F NMR (376 MHz, CDC13) δ -58.02, -116.16, -117.35
164
ID Synthesis Method MS mp (°C) ’H NMR, 13C, or 19F NMR (δ)1
251C M 596 (M+H) 118 (CDC13) δ 8.57 (s, 1H), 8.23 (s, 1H), 8.20 - 8.14 (m, 2H), 7.83 - 7.72 (m, 4H), 7.39 - 7.33 (m, 3H), 7.20 (s, 1H), 7.10 - 7.05 (m, 1H), 3.53 (d, J= 11.5 Hz, 1H), 3.43 (s, 1H), 3.32 (d, J= 11.5 Hz, 1H), 2.98-2.88 (m, 1H), 2.39 (s, 3H), 1.43 (s, 3H), 1.28 - 1.14 (m, 6H); 19F NMR (376 MHz, CDC13) δ -58.03
252C M 596 (M+H) 118 (dec) (CDC13) δ 8.57 (s, 1H), 8.22 (s, 1H), 8.18 (d, J= 8.4 Hz, 2H), 7.81 - 7.77 (m, 4H), 7.38 (d, J= 8.4 Hz, 2H), 7.33 (t, J = 4.7 Hz, 1H), 7.17 (d, J = 5.0 Hz, 2H), 3.53 (d, J = 11.5 Hz, 1H), 3.42 (s, 1H), 3.37 - 3.18 (m, 2H), 2.52 (s, 3H), 1.42 (s, 3H), 1.32 (dd, J= 7.3, 3.7 Hz, 6H); 19F NMR (376 MHz, CDC13) δ -58.02
253C M 596 (M+H) 112 (dec) (CDC13) δ 8.57 (s, 1H), 8.23 (s, 1H), 8.21 8.15 (m, 2H), 7.79 (t, J= 8.1 Hz, 4H), 7.38 (d, J= 8.9 Hz, 2H), 7.31 - 7.27 (m, 2H), 7.21 (d, J= 8.1 Hz, 1H), 3.53 (d, J= 11.5 Hz, 1H), 3.44 (s, 1H), 3.33 (d, J= 11.5 Hz, 1H), 2.91 (dt, J= 13.8, 6.9 Hz, 1H), 2.34 (d, <7=3.1 Hz, 3H), 1.59- 1.43 (m, 3H), 1.19 (dd, J= 10.4,6.9 Hz, 6H); 19F NMR (376 MHz, CDC13) δ -58.02
254C M 568 (M+H) 111 (dec) (CDC13) δ 8.57 (s, 1H), 8.23 (s, 1H), 8.21 - 8.15 (m, 2H), 7.83 - 7.74 (m, 4H), 7.50 (d, J = 7.7 Hz, 1H), 7.39 7.37 (m, 4H), 7.31 - 7.27 (m, 1H), 3.54 (d, J= 11.5 Hz, 1H), 3.47 (s, 1H), 3.32 (d, J=11.5 Hz, 1H), 2.68 - 2.45 (m, 2H), 1.43 (s, 3H), 1.28 - 1.21 (m, 3H); 19F NMR (376 MHz, CDC13) δ -58.02
165
ID Synthesis Method MS mp(°C) ‘H NMR, 13C, or 19F NMR (δ)1
255C M 597 (M+H) 110 (dec) (CDC13) δ 8.57 (s, 1H), 8.25 (s, 1H), 8.18 (d, J= 8.3 Hz, 2H), 7.84 - 7.75 (m, 4H), 7.39 (d, J= 8.3 Hz, 2H), 6.76 - 6.64 (m, 2H), 3.80 (s, 3H), 3.51 (d, J= 11.3 Hz, 1H), 3.35 (s, 1H), 3.32 (d, J= 11.4 Hz, 1 H), 2.40 (s, 3H),2.14(s,3H), 1.43 (s, 3H);
19F NMR (376 MHz, CDC13) δ -58.02
256C M 580 (M+H) 100 (CDC13) δ 8.57 (s, 1H), 8.24 - 8.15 (m, 3H), 7.79 (dd, J= 8.8, 2.7 Hz, 4H), 7.51 (d, J= 7.6 Hz, 1H), 7.40 - 7.33 (m, 4H), 7.30 7.28 (m, 1H), 3.64 (s, 1H), 3.54 (d, J= 11.5 Hz, 1H), 3.32 (d, J= 11.5 Hz, 1H), 2.60 2.40 (m, 2H), 1.76 - 1.62 (m, 2H), 1.43 (s, 3H), 0.94 (t, J =7.3 Hz, 3H);
19F NMR (376 MHz, CDC13) δ -58.02
257C M 595 (M+H) 140 (dec) (CDC13) δ 8.57 (s, 1H), 8.22 - 8.16 (m, 3H), 7.82 - 7.74 (m, 4H), 7.55 - 7.47 (m, 1H), 7.42 - 7.35 (m, 4H), 7.29 - 7.24 (m, 1H), 3.92-2.96 (m, 3H), 1.57 (s, 1H), 1.57 1.50 (m, 3H), 1.35 - 1.17 (m, 9H);
19F NMR (376 MHz, CDC13) δ -58.02
258C M 597 (M-H) 117 (dec) (CDC13) δ 8.57 (s, 1H), 8.22 - 8.16 (m, 3H), 7.80 (dt, J= 8.4, 4.9 Hz, 4H), 7.46 (dd, J = 8.8, 5.6 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.09 (dd, J= 10.0, 2.9 Hz, 1H), 7.01 - 6.90 (m, 1H), 3.54 (d, J= 11.5 Hz, 1H), 3.39 (s, 1H), 3.33 (d, J= 11.6 Hz, 1H), 2.99-2.92 (m, 1H), 1.56 (d, J= 7.3 Hz, 3H), 1.42 (s, 3H), 1.20 (dd, J= 8.6, 6.9 Hz, 6H);
I 19F NMR (376 MHz, CDC13) δ -58.02, -112.57
166
ID Synthesis Method MS mp (°C) 'H NMR, 13C, or 19F NMR (δ)1
259C M 615 (M-H) 186-188 (CDC13) δ 8.57 (s, 1H), 8.21 (d, J = 3.5 Hz, 2H), 8.18 (s, 1H), 7.83 - 7.75 (m, 4H), 7.43 - 7.34 (m, 3H), 7.17 (dd, J= 11.8, 8.6 Hz, 1 H), 3.54 (d, .7 =11.6 Hz, 1 H), 3.44 (s, 1H), 3.32 (d,J= 11.6 Hz, 1H), 2.93 (dd, J= 13.0, 6.1 Hz, 1H), 1.45 (s, 3H), 1.18 (dd, J= 14.2, 6.9 Hz, 6H); 19F NMR (376 MHz, CDC13) δ -58.02, -136.51, -136.57, -138.80, -138.86
260C M 665 (M+H) 117 (dec) (CDC13) δ 8.66 (s, 1H), 8.24 - 8.15 (m, 3H), 7.93 (d, J= 8.8 Hz, 2H), 7.78 (dd, J= 8.2, 6.5 Hz, 4H), 7.52 - 7.45 (m, 1H), 7.45 7.36 (m, 2H), 7.29 - 7.25 (m, 1H), 3.55 (d, J = 1.5}iz, 1H), 3.50 (s, 1H), 3.34 (d,.7=11.5 Hz, 1H), 3.01-2.95 (m, 1H), 1.21 (dd, J = 8.3, 7.0 Hz, 6H); 19F NMR (376 MHz, CDC13)Ô -75.61, -182.14,-182.16,-182.18
261C M 565 (M+H) 113 (dec) (CDC13) δ 8.66 (s, 1H), 8.22 - 8.19 (m, 2H), 8.18 (s, 1H), 7.91 (d, .7=8.4 Hz, 2H), 7.79 (d, J= 8.4 Hz, 4H), 7.50 - 7.44 (m, 1H), 7.44 _ 7.36 (m, 2H), 7.29 - 7.25 (m, 1H), 3.55 (d,J=11.5 Hz, 1H), 3.50 (s, 1H),3.34 (d, J= 11.5 Hz, 1H), 3.04-2.91 (m, 1H), 1.21 (dd, J = 8.3, 6.9 Hz, 6H); 19F NMR (376 MHz, CDC13) δ -62.50
262C M 631 (M+H) 115 (dec) (CDC13) δ 8.58 (s, 1H), 8.19 (dd, J= 8.5, 6.8 Hz, 3H), 7.80 (dd, J= 12.5, 5.3 Hz, 4H), 7.50 _ 7.44 (m, 1H), 7.42 - 7.36 (m, 4H), 7.29 - 7.24 (m, 1H), 3.53 (dd, J = 14.9, 11.4 Hz, 2H), 3.34 (d, J= 11.5 Hz, 1H), 3.032.89 (m, 1H), 1.21 (dd, J= 8.4, 6.9 Hz, 6H); 19F NMR (376 MHz, CDC13) δ -85.90, -87.85
167
ID Synthesis Method MS mp(°C) ’H NMR, 13C, or ,9F NMR (δ)'
263C M 711 (M+H) 115.3- 117.6 (CDC13) δ 8.59 (s, 1H), 8.33 (s, 1H), 8.24 (d, J= 8.4 Hz, 2H), 8.13 (s, 1H), 7.86 - 7.77 (m, 5H), 7.73 (d, J= 7.2 Hz, 1H), 7.62 (dt, J = 21.6, 7.2 Hz, 2H), 7.40 (d,7= 8.2 Hz, 2H), 7.37 - 7.28 (m, 3H), 7.24 - 7.17 (m, 1H), 4.34 (s, 2H), 3.20 (dt, J= 13.7, 6.8 Hz, 2H), 1.25 (d, J =6.9 Hz, 6H);
19F NMR (376 MHz, CDC13) δ -58.02
264C M 647 (M+H) 116-120 (300 MHz, CDCI3) δ 8.57 (s, 1H), 8.23 (d, J = 4.9 Hz, 1H), 8.18 (dd, J= 8.3,1.7 Hz, 2H), 7.84 - 7.75 (m, 4H), 7.39 (dd, J= 8.8, 6.8 Hz, 3H), 6.89 (d, J= 3.0 Hz, 1H), 6.80 (dd, J= 8.6, 3.1 Hz, 1H), 3.84 (s, 3H), 3.51 (d, J= 11.6 Hz, 1H), 3.48-3.43 (m, 1H), 3.31 (d, 7= 11.5 Hz, 1H), 2.65-2.40 (m, 2H), 1.41 (s, 3H), 1.22 (t,7= 7.6 Hz, 3H)
NMR spectral data were acquired using a 400 MHz instrument except where noted.
Table 4A: Analytical Data for Optically Active Compounds in Table 3
ID Séparation Method MS Chiral Purity (%) lH NMR (δ)1
234C A 571 (M+H) 98.73 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, 7= 8.4 Hz, 2H), 7.87 - 7.78 (m, 4H), 7.41 (t, 7=6.3 Hz, 3H), 7.37-7.31 (m, 1H), 7.28 (d, 7= 7.0 Hz, 1H), 4.09 - 3.98 (m, 2H), 2.29 (s, 3H)
235C A 571 (M+H) 95.75 (CDCI3) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 - 7.78 (m, 4H), 7.41 (dd, J = 7.0, 5.6 Hz, 3H), 7.34 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 6.0 Hz, 1H), 4.09 - 3.98 (m, 2H), 2.29 (s, 3H)
168
ID Séparation Method MS Chiral Purity (%) Ή NMR (δ)1
236C A 565 (M+H) 96.32 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J= 8.4 Hz, 2H), 7.81 (dd, J= 11.7, 5.1 Hz, 4H), 7.40 (d, J= 8.4 Hz, 2H), 7.35 (t, J= 7.7 Hz, 1H), 7.24 - 7.18 (m, 2H), 4.02 (s, 2H), 2.53 (q, J= 7.5 Hz, 2H), 2.21 (s, 3H), 1.21 (t, J =7.6 Hz, 3H)
237C A 565 (M+H) 92.33 (CDC13) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J =8.4 Hz, 2H), 7.81 (dd, J= 11.7,5.1 Hz, 4H), 7.40 (d, J= 8.3 Hz, 2H), 7.35 (dd, J= 10.4, 4.9 Hz, 1H), 7.24 - 7.20 (m, 2H), 4.02 (s, 2H), 2.59 - 2.45 (m, 2H), 2.21 (s, 3H), 1.21 (t, J = 7.6 Hz, 3H)
238C B 579 (M+H) 95.41 (CDCI3) δ 8.58 (s, 1H), 8.29 (d, J= 3.9 Hz, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.82 (t, J= 8.8 Hz, 4H), 7.40 (d, J= 8.3 Hz, 3H), 7.31 (d, J = 6.9 Hz, 1 H), 7.19 (dd, J = 7.6, 5.2 Hz, 1H), 4.03 (s, 2H), 2.83 - 2.73 (m, 1H), 2.21 (s, 3H), 1.25 - 1.18 (m, 6H)
239C B 579 (M+H) 92.68 (CDCI3) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (t, J= 8.7 Hz, 2H), 7.82 (t, J = 8.7 Hz, 4H), 7.40 (d, J = 8.2 Hz, 3H), 7.31 (d, J = 8.0 Hz, 1H), 7.20 (d, J= 7.3 Hz, 1H), 4.03 (s, 2H), 2.83-2.73 (m, 1H), 2.21 (s, 3H), 1.25-1.18 (m, 6H)
NMR spectral data were acquired using a 400 MHz instrument except where noted.
Table 5: Biological Results
Compound Number % Mortality CEW 50 2 pg/cm % Mortality BAW50 pg/cni2 % Mortality GPA 200 ppm
IC A A D
2C A A D
3C A A D
4C ! A A B
|______________________________________________________________________|________________________________________________________________________________________________________________________________________________________I_________________________________________________________________I
169
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW50 2 pg/cm % Mortality GPA 200 ppm
5C A A B
6C A A D
7C A D D
8C A A B
9C A A D
10C A A D
ne A A D
12C A A B
13C A A B
14C A A B
15C A A A
16C A A D
17C A A B
18C A A B
19C A A B
20C A A D
21C C C D
22C A A B
23C A A D
24C A A B
25C A A D
26C C C D
27C A A B
170
Compound Number % Mortality CEW 50 2 pg/cm % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
28C A A B
29C A A B
30C A A B
31C A A B
32C C C B
33C A A B
34C C C B
35C A A B
36C A A D
37C A A D
38C A A D
39C C C D
40C A A B
41C A A D
42C A A D
43C A A B
44C A A D
45C A A C
46C A A D
47C A A B
48C A A C
49C A A B
50C A A C
171
Compound Number % Mortality CEW 50 μ g/cm2 % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
51C A A D
52C D B B
53C D B B
54C A A D
55C A A D
56C A A C
57C A A B
58C A A B
59C A A B
60C A A D
61C A A C
62C A A B
63C A A D
64C A A D
65C A A B
66C A A B
67C A A D
68C A A B
69C A A C
70C A A D
71C A A D
72C A A B
73C A A B
172
Compound Number % Mortality CEW 50 μ g/cm2 % Mortality BAW 50 pg/cm2 % Mortality GPA 200 ppm
74C A A D
75C A A B
76C A A B
77C A A B
78C A A B
79C A A B
80C A A D
81C A A D
82C A A C
83C A A C
84C A A D
85C A A B
86C A A D
87C C C B
88C A A B
89C A A D
90C A A B
91C D D C
92C A A B
93C A A D
94C A A D
95C A A B
96C A A B
173
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
97C A A C
98C C A C
99C A A C
100C A A c
101C A A c
102C A A c
103C A A c
104C A A c
105C A A c
106C A A c
107C D D c
108C A A D
109C A A C
HOC A A C
me A A B
112C A A B
113C A A C
114C A A C
115C D B C
116C A A C
117C A A D
118C A A D
119C A A D
174
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
120C A A C
121C A A B
122C A A C
123C A A C
124C A A C
125C A A C
126C A A C
127C A A C
128C A A C
129C A A c
130C A A c
131C A A D
132C A A B
133C A A B
134C A A C
135C A A D
136C A A D
137C A A D
138C A A B
139C A A B
140C A A B
141C A A D
142C A A D
175
Compound Number % Mortality CEW 50 pg/cni2 % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
143C A A C
144C A A C
145C A A B
146C A A B
147C A A B
148C A A C
149C A A D
150C A A D
151C A A B
152C A A C
153C A d C
154C A A B
155C A A D
156C A A B
157C A A B
158C A A B
159C A A C
160C A A C
161C A A C
162C A A C
163C A A C
164C A A C
165C A A C
176
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
166C A A C
167C A A C
168C A A D
169C A A C
170C A A C
171C A A C
172C A A D
173C A A D
174C A A B
175C A A D
176C A A C
177C A A D
178C A A D
179C A A D
180C A A B
181C A A B
182C A A B
183C A A D
184C A A D
185C A A D
186C A A B
187C A A D
188C A A B
177
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW 50 pg/cm2 % Mortality GPA 200 ppm
189C A A B
190C A A B
191C A A D
192C A A B
193C A A B
194C A A B
195C A A B
196C A A D
197C A A D
198C A A D
199C A A C
200C A A C
201C A A B
202C A A B
203C A A B
204C A A B
205C A A B
206C A A D
207C d D C
208C A A D
209C A A D
210C A A C
211C A A D
178
Compound Number % Mortality CEW 50 2 pg/cm % Mortality BAW50 pg/cm2 % Mortality GPA 200 ppm
212C A A D
213C A A B
214C A A C
215C A A C
216C A A C
217C A A C
218C A A C
219C A A C
220C A A C
221C A A C
222C A A C
223C A A C
224C A A B
225C A A C
226C A A C
227C A A C
228C A A C
229C A A C
230C A A C
231C A A C
232C A A C
233C A A C
234C A A c
179
Compound Number % Mortality CEW 50 μ g/ cm2 % Mortality BAW 50 pg/cni2 % Mortality GPA 200 ppm
235C A A C
236C A A C
237C A A C
23 8C A A C
239C A A C
240C A A D
241C A A C
242C A A B
243C A A B
244C A A D
245C A A B
246C A A C
247C A A C
248C A A B
249C A A C
250C A A B
251C A A B
252C A A C
253C A A D
254C A A B
255C A A D
256C A A B
257C A A D
180
Compound Number % Mortality CEW 50 pg/cm2 % Mortality BAW 50 pg/cm2 % Mortality GPA 200 ppm
258C A A C
259C A A D
260C A A D
261C A A D
262C A A B
263C A A B
264C C A C
181

Claims (4)

1.
A composition comprising a molécule according to Formulas Two or Three
Het
An
RI
X ,N
2 ,/S An NI X \
N3^r5
R^
Formula 2
Het^
Aff Yf2
RI zR5
JL ,N2 Js
Formula 3
N3 'R4 wherein:
(a) An is (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cg alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, Ci-Cô haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSOXQ-Cô alkyl), OSO2(C1-C6 haloalkyl), C(=O)NRxRy, (Ci-Cô alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cô alkoxy, Ci-Cô haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Cj-Cô alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl) phenyl, and phenoxy;
182 (b) Het is a 5 or 6 membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and where Ari and Ar2 are not ortho to each other (but may be meta or para, such as, for a five membered ring they are 1,3 and for a 6 membered ring they are either 1,3 or 1,4), and where said heterocyclic ring may also be substituted with one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, oxo, Ci-Cô alkyl, Ci-Cô haloalkyl, C3Cô cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Ce alkoxy, Ci-Cg haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(CrC6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(CiC6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cô alkyl, Ci-Cé haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, C|-Cf, haloalkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(CrC6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, and phenoxy;
(c) Ar2 is (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, hâve one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2, Ci-Cô alkyl, C|-Cg haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(Cr C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(CrC6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6
183 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-Cô alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy hâve one or more substituents independently seiected from H, F, Cl, Br, I, CN, NO2, Cj-Cô alkyl, C|-Cô haloalkyl, C3-Cô cycloalkyl, C3-Cô halocycloalkyl, C3-Cô cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, Cj-Cô haloalkoxy, C2-C6 alkenyl, C2-Cô alkynyl, S(=O)n(CiC6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-Cô haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(Ci-C6 haloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Cj-C6 alkyl)O(C!C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, and phenoxy;
(d) RI is seiected from H, CN, F, Cl, Br, I, Ci-Cô alkyl, C3-Cô cycloalkyl, C3-Cô cycloalkoxy, Ci-Cô alkoxy, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), OSO2(Ci-Cô alkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CrC6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(C!-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, or phenoxy, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, and phenoxy, are optionally substituted with one or more substituents independently seiected from F, Cl, Br, I, CN, NO2, oxo, Ci-C6 alkyl, Ci-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cf, alkoxy, Ci-Cô haloalkoxy, C2-C6 alkenyl, C2-Cf, alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-Cô alkyl), OSO2(Ci-C6 haloalkyl), C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CiCô alkyl)O(Ci-C6 alkyl), (CrC6 alkyl)S(Ci-C6 alkyl), C(=O)(CrC6 alkyl)C(=O)O(CrC6 alkyl), phenyl, and phenoxy;
(g) R4 is H, Ci-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6
184 cycloalkyl), C(=O)(C2-Cô alkenyl), C(=O)O(C2-Cô alkenyl), (Ci-Cô alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(CrC6 alkyl), phenyl, Ci-C6 alkylphenyl, Ci-Cô alkyl-O-phenyl, C(=O)Het-l, Het-1, Ci-Cô alkylHet-1, or Ci-Cg alkyl-OHet-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, NRxRy, Ci-C6 alkyl, Ci-Cé haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cf, alkoxy, C|-C6 haloalkoxy, C2-C6 alkenyl, C3C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(CrC6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3Cô cycloalkyl), C(=O)O(C3-Ce cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-Cô alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(CrC6 alkyl), phenyl, phenoxy, and Het-1 ;
(h) R5 is a 2 to 4 membered saturated or unsaturated hydrocarbyl linkage where said linkage may also be substituted with at least one OH and optionally one or more substituents selected from F, Cl, Br, I, CN, NO2, oxo, NRxRy, Ci-Cf, alkyl, Ci-Ce haloalkyl, C3-Cô cycloalkyl, C3-Cô halocycloalkyl, C3-C6 cycloalkoxy, C3-Cô halocycloalkoxy, Ci-Cô alkoxy, C|-Cf, haloalkoxy, C2-C6 alkenyl, C3-Cô cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-Cô alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(C]-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, phenoxy, and Het-1, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and Het-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, oxo, NRxRy, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-Cô cycloalkyl, C3-Cô halocycloalkyl, C3-Cô cycloalkoxy, C3-Cô halocycloalkoxy, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRxRy, (Ci-C6 alkyl)NRxRy, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl),
185
C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C,-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, halophenyl, phenoxy, and Het-1;
(i) n= 0,1, or 2;
(j) Rx and Ry are independently selected from H, Ci-Cg alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-Cô alkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)(Cj-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3Cô cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-Cé alkenyl), C(=O)O(C2-C6 alkenyl), (CrC6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Ci-C6 alkyl)C(=O)O(Ci-C6 alkyl), and phenyl, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and Het-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO2, oxo, Ci-Cô alkyl, Ci-Cô haloalkyl, C3-C6 cycloalkyl, C3Cô halocycloalkyl, C3-Cô cycloalkoxy, C3-C6 halocycloalkoxy, Ci-Cô alkoxy, Cj-Cf, haloalkoxy, C2-Cg alkenyl, C3-C6 cycloalkenyl, C2-Cg alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(Ci-C6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (Ci-C6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(Cr C6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, halophenyl, phenoxy, and Het-1, or Rx and Ry together can optionally form a 5- to 7-membered saturated or unsaturated cyclic group which may contain one or more heteroatoms selected from nitrogen, sulfur, and oxygen, and where said cyclic group can contain >C=O or >C=S, and where said cyclic group may be substituted with F, Cl, Br, I, CN, C|-Cô alkyl, Ci-Cg haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, Ci-C6 alkoxy, Ci-Cé haloalkoxy, C2-Cô alkenyl, C3-C6 cycloalkenyl, C2-Cô alkynyl, S(=O)n(Ci-C6 alkyl), S(=O)n(Ci-C6 haloalkyl), OSO2(Ci-C6 alkyl), OSO2(Ci-C6 haloalkyl), C(=O)(Ci-C6 alkyl), C(=O)O(Ci-C6 alkyl), C(=O)(CrC6 haloalkyl), C(=O)O(Ci-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CiC6 alkyl)O(Ci-C6 alkyl), (Ci-C6 alkyl)S(Ci-C6 alkyl), C(=O)(CrC6 alkyl)C(=O)O(Ci-C6 alkyl), phenyl, substituted phenyl, phenoxy, and Het-1; and
186 (k) Het-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen.
5 2. A composition according to claim 1 wherein said molécule
Ari is a substituted phenyl wherein said substituted phenyl, has one or more Ci-Ce haloalkoxy;
Het is a triazolyl;
Ar2 is a phenyl;
10 RlisH;
R4 is phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from F, Cl, NRxRy, Ci-Ce alkyl, or Ci-Ce alkoxy; and
R5 is a 2 to 4 membered saturated or unsaturated hydrocarbyl linkage where said linkage may also be substituted with at least one OH and optionally one or more substituents 15 selected from Ci-Cô alkyl, and Ci-Cô haloalkyl; and
Rx and Ry are independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F and Cl.
3. A composition according to claim 1 wherein said molécule is selected from
187
243C /J.OH S I \___/ FxF ΙΎΝ'Ν t) F oXU L/- V-/ 244C z\Loh /=N VV_/Cl Te f οΛ> L/7 VJ7 245C /Χ,ΟΗ S I _ hv? XoXVNnWn'n q o— 246C Fsz U Z». U uF XV Ou* FF /OH 247C F SI XN\ VN vF XV^'nvXT z n n fWX Wz /F /OH 248C F F F-X m rN λ \=/ N iW S-\ OH Il U NT J- z\ 249C f F /=N OH rX # X-N. ? y__/\ fxw n tXvxy 250C F F /==N OH rX r V'N- v/'u i y-K w n iV/f)-. F \ /
188
251C F. ,F Z=N OH fAoZz NXXN./Ny \S 252C F ,F Z=N OH pX Γν-Ν- zzz ? y- 0 vY J)— 253C F F F\zyZ \Z N |fZ ?\,OH T J. w Z^ z\ 254C F ,F ZN OH pX #Vn- Y^z*x ? yz FXZZ MU/Y 255C y nZY u fxzz nXXn./£, V/ 0 256C F FXF rx^rv. s-xH °A=Z O 257C z ryTU Y FZAZ nYj^n.nZ£\ O
189
258C E ,F /X OH KX /Vn- X/y ? X- °XP N Xv^n-n^n o F 259C F F A=N OH pX ΓνΝ· Χγγ, ? y- °VJ 'XQ^^X \ vJ F F 260C F F Χλι-μ 261C /yxx NXb x-?H 262C fX f \=X NXXX /Χγπ XX^n^n^n 263C F F fX P Y zr-^ /=N Χί _ F\ / V-N \ °-x=x nV sλα) XX^n.^aVoh
190
4. A process to apply a composition according to claims 1, 2, or 3 said process comprising applying a composition according to claim 1, to an area to control a pest, in an amount sufficient to control such pest.
OA1201400481 2012-04-27 2013-03-07 Pesticidal Compositions and Processes Related Thereto OA19159A (en)

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