DK145227B - Analogifremgangsmaade til fremstilling af 4',5-dinitro-3'-trifluormethyl-2-thiophencarboxylsyreanilid - Google Patents
Analogifremgangsmaade til fremstilling af 4',5-dinitro-3'-trifluormethyl-2-thiophencarboxylsyreanilid Download PDFInfo
- Publication number
- DK145227B DK145227B DK465772AA DK465772A DK145227B DK 145227 B DK145227 B DK 145227B DK 465772A A DK465772A A DK 465772AA DK 465772 A DK465772 A DK 465772A DK 145227 B DK145227 B DK 145227B
- Authority
- DK
- Denmark
- Prior art keywords
- dinitro
- preparation
- formula
- ananilide
- thiophencarboxylic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical group N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- SXEXMROTXMWPPJ-UHFFFAOYSA-N 3-methyl-n-phenylthiophene-2-carboxamide Chemical compound C1=CSC(C(=O)NC=2C=CC=CC=2)=C1C SXEXMROTXMWPPJ-UHFFFAOYSA-N 0.000 description 1
- UTKUVRNVYFTEHF-UHFFFAOYSA-N 4-nitro-3-(trifluoromethyl)aniline Chemical compound NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 UTKUVRNVYFTEHF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- -1 chloroform Chemical compound 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 231100000668 minimum lethal dose Toxicity 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/42—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms
- C07D333/44—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms attached in position 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/70—Nitro radicals
- C07D307/71—Nitro radicals attached in position 5
- C07D307/72—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2
- C07D307/73—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2 by amino or imino, or substituted amino or imino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Description
145227
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af den hidtil ukendte forbindelse 4',5-dinitro-3'-trifluormethyl-2-thiophencarboxylsyreanilid med formlen no2 r"ir II) (i) kH-c°^ JLN°2 s 5 Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at man i et opløsningsmiddel ved en temperatur på 20°C eller mere omsætter omtrent ækvimolekulære mængder af anilinen med formlen: N02 CFo (II) L2 10 og syrechloridet med formlen: Ϊ li (III) ci-co—y— no2
Anvendelige opløsningsmidler er de, der kan anvendes til udførelse af reaktionen mellem et syrechlorid og en amin.
Man kan især som egnede opløsningsmidler nævne tetrahydro= 15 furan, pyridin, dimethylformamid, aromatiske hydrocarboner såsom benzen, toluen, xylen,chlorerede hydrocarboner såsom chloroform, samt blandinger af disse opløsningsmidler. Foretrukne opløsningsmidler ved fremgangsmåden ifølge opfindelsen er benzen og pyridin, idet pyridin anvendes under de 20 specielle betingelser, der beskrives nedenfor.
145227 2
Fortrinsvis sætter man under omrøring en støkiometrisk mængde syrechlørid III til en opløsning af 100-200 g pr. liter af anilinen II i pyridin, holder reaktionsblandingen på en temperatur lig med eller over 20°C og udfælder den således dan-5 nede forbindelse med foralen I med IN saltsyre. Pyridin har den fordel, at den forener sig med HC1 dannet under reaktionen og giver pyridinhydrochlorid, som er opløseligt i vand.
Forbindelsen franstillet ifølge opfindelsen er anvendelig i terapien, især som antibakterielt middel. Forbindelsen er også virk-10 som overfor svampe og parasitter.
Opfindelsen illustreres nærmere af følgende eksempel.
Eksempel 45-dinitro-3 ' -trif luoraethyl-2-thiophencarboxylsyreanilid, kode nr. Rd 1087.
F3 _ 15 02N—— NH-CO—NQ2
Til en opløsning af 3,5 g 4-nitro-3-trifluormethylanilin i 20 ml tør pyridin sættes hurtigt under omrøring 3,2 g 2-(5-nitro= thiophen)-carboxylsyrechlorid. Der sker en spontan temperaturstigning til en værdi over 20°C. Man kan afvente nogle minut-20 ter, og derefter hældes opløsningen i et tilstrækkeligt rumfang IN saltsyre, og man afkøler. Derefter omkrystalliseres af ethanol ved -15°C. Der fremkom 3,5 g 4',5-dinitro-3*-trifluor= methyl-2-thiophencarboxylsyreanilid (udbytte 58%), smp. 164°C.
Ved oral administration til mus udviser forbindelsen fremstil-25 let ifølge opfindelsen en mindste lethal dosis, som er større end 3 mg/kg.
145227 3
Forbindelsen udviser bedre antibakterielle egenskaber end beslægtede kendte forbindelser, således som det fremgår af nedenstående sammenligningsforsøg. Sammenligningsforbindelsen A er forbindelse 1 i artiklen J. Med. Chera. 10 (1967), 5 side 93-95, med formlen |°2 |rCP3 !JH-C0-CH3
Sammenligningsforbindelsen B er forbindelse 25 i artiklen J. Med. Chem. 12 (1969), side 957-9, med formlen N02 /γ®3 rø-CO —N02 10 Den antibakterielle virkning blev bestemt på følgende måde: Forbindelser, der skal undersøges, opløses i acetone. Man fremstiller en række opløsninger med aftagende koncentration (fra 1000 ug/ml) ved hjælp af næringsbouillon. Opløs- 5 ningerne podes med ca. 10 bakterier (stafylokokker) pr.
15 ml ved anvendelse af en podekultur fremkommet ved dyrkning i 24 timer i næringsbouillon. Prøverne studeres hvert døgn under en uges inkubering ved 37°C. Den mindst hæmmende koncentration defineres som koncentrationen af den sidste opløsning, hvori der ikke sker nogen bakterieudvikling ved 20 afslutning af iagttagelsestiden.
Claims (2)
145227 Resultater Forbindelse Mindste hæmmende kone, ug/ml Fremstillet ifølge opfindelsen ® ^ A «1000
5 B >1000 Fatentkrav Analogifremgangsmåde til fremstilling af 4',5-dinitro-3'-trifluormethyl-2-thiophencarboxylsyreanilid, der har formlen P°2 jJ~CF3 (I) NH-CO —— NO 2 kendetegnet ved, at man i et opløsningsmiddel 10 ved en temperatur på 20°C eller mere omsætter omtrent ækvi-molekulære mængder af anilinen med formlen [°2 CF3 (II) X og syrechloridet med formlen C1-C0—- N02 (III)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4423971A GB1401975A (en) | 1971-09-22 | 1971-09-22 | 3-trifluoromethyl-anilides |
| GB4423971 | 1971-09-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK145227B true DK145227B (da) | 1982-10-11 |
| DK145227C DK145227C (da) | 1983-03-07 |
Family
ID=10432404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK465772A DK145227C (da) | 1971-09-22 | 1972-09-21 | Analogifremgangsmaade til fremstilling af 4',5-dinitro-3'-trifluormethyl-2-thiophencarboxylsyreanilid |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS4839450A (da) |
| AU (1) | AU474208B2 (da) |
| BE (1) | BE788983A (da) |
| CH (1) | CH560181A5 (da) |
| DK (1) | DK145227C (da) |
| ES (1) | ES406911A1 (da) |
| FR (1) | FR2154499B1 (da) |
| GB (1) | GB1401975A (da) |
| IL (1) | IL40398A (da) |
| LU (1) | LU66118A1 (da) |
| NL (1) | NL155829B (da) |
| NO (1) | NO137940C (da) |
| OA (1) | OA04181A (da) |
| RO (1) | RO67638A (da) |
| SE (1) | SE395695B (da) |
| ZA (1) | ZA726425B (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1252041A (en) * | 1983-09-28 | 1989-04-04 | Kamlesh Gaglani | Industrial fungicides |
| EP2195286A2 (en) * | 2007-09-10 | 2010-06-16 | Cipla Limited | Process for the preparation of a raf kinase inhibitor and intermediates for use in the process |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1593586A (da) * | 1967-10-17 | 1970-06-01 |
-
0
- BE BE788983D patent/BE788983A/xx not_active IP Right Cessation
-
1971
- 1971-09-22 GB GB4423971A patent/GB1401975A/en not_active Expired
-
1972
- 1972-09-12 FR FR7232293A patent/FR2154499B1/fr not_active Expired
- 1972-09-14 CH CH1348172A patent/CH560181A5/xx not_active IP Right Cessation
- 1972-09-20 ZA ZA726425A patent/ZA726425B/xx unknown
- 1972-09-20 LU LU66118A patent/LU66118A1/xx unknown
- 1972-09-20 IL IL40398A patent/IL40398A/xx unknown
- 1972-09-21 SE SE7212194A patent/SE395695B/xx unknown
- 1972-09-21 NL NL7212788.A patent/NL155829B/xx not_active IP Right Cessation
- 1972-09-21 AU AU46921/72A patent/AU474208B2/en not_active Expired
- 1972-09-21 NO NO3382/72A patent/NO137940C/no unknown
- 1972-09-21 RO RO7272296A patent/RO67638A/ro unknown
- 1972-09-21 DK DK465772A patent/DK145227C/da not_active IP Right Cessation
- 1972-09-21 ES ES406911A patent/ES406911A1/es not_active Expired
- 1972-09-22 JP JP47095656A patent/JPS4839450A/ja active Pending
- 1972-09-22 OA OA54695A patent/OA04181A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE788983A (fr) | 1973-01-15 |
| AU4692172A (en) | 1974-03-28 |
| DE2246308B2 (de) | 1977-02-17 |
| CH560181A5 (da) | 1975-03-27 |
| RO67638A (ro) | 1982-04-12 |
| LU66118A1 (da) | 1973-01-17 |
| FR2154499A1 (da) | 1973-05-11 |
| FR2154499B1 (da) | 1975-11-28 |
| IL40398A0 (en) | 1972-11-28 |
| SE395695B (sv) | 1977-08-22 |
| ES406911A1 (es) | 1975-09-16 |
| DK145227C (da) | 1983-03-07 |
| NO137940C (no) | 1978-05-24 |
| NO137940B (no) | 1978-02-13 |
| ZA726425B (en) | 1973-06-27 |
| OA04181A (fr) | 1979-12-31 |
| JPS4839450A (da) | 1973-06-09 |
| NL7212788A (da) | 1973-03-26 |
| DE2246308A1 (de) | 1973-03-29 |
| GB1401975A (en) | 1975-08-06 |
| AU474208B2 (en) | 1976-07-15 |
| IL40398A (en) | 1975-07-28 |
| NL155829B (nl) | 1978-02-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |