BG63542B1 - Методи и междинни съединения за получаване на заместени хроманолови производни - Google Patents

Методи и междинни съединения за получаване на заместени хроманолови производни Download PDF

Info

Publication number: BG63542B1
Authority: BG; Bulgaria
Prior art keywords: alkyl; compound; formula; phenyl; enantiomer
Prior art date: 1996-09-16

Application number

BG103231A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG103231A (en

Inventor

Joel HAWKINS

Anthony Piscopio

Stephane Caron

Sarah KELLY

Jefrey RAGGON

Michael CASTALDI

Robert DUGGER

Sally RUGGERI

Original Assignee

Pfizer Inc.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-09-16

Filing date

1999-03-09

Publication date

2002-04-30

1999-03-09 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

1999-12-30 Publication of BG103231A publication Critical patent/BG103231A/xx

2002-04-30 Publication of BG63542B1 publication Critical patent/BG63542B1/bg

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 239
238000000034 method Methods 0.000 title claims abstract description 52
SEBPXHSZHLFWRL-UHFFFAOYSA-N 3,4-dihydro-2,2,5,7,8-pentamethyl-2h-1-benzopyran-6-ol Chemical class O1C(C)(C)CCC2=C1C(C)=C(C)C(O)=C2C SEBPXHSZHLFWRL-UHFFFAOYSA-N 0.000 title description 13
238000002360 preparation method Methods 0.000 claims abstract description 42
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 claims abstract description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 5
125000000217 alkyl group Chemical group 0.000 claims description 99
-1 phenylsulfinyl Chemical group 0.000 claims description 70
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
229910052739 hydrogen Inorganic materials 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 40
125000001424 substituent group Chemical group 0.000 claims description 34
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 30
150000002431 hydrogen Chemical class 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 21
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 19
229910052731 fluorine Inorganic materials 0.000 claims description 18
239000011737 fluorine Substances 0.000 claims description 18
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical group [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 14
239000000460 chlorine Substances 0.000 claims description 14
229910052801 chlorine Inorganic materials 0.000 claims description 14
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 12
229910052796 boron Inorganic materials 0.000 claims description 12
206010056740 Genital discharge Diseases 0.000 claims description 11
239000010936 titanium Substances 0.000 claims description 11
229910052719 titanium Inorganic materials 0.000 claims description 11
125000001072 heteroaryl group Chemical group 0.000 claims description 10
239000003446 ligand Substances 0.000 claims description 10
125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
239000003054 catalyst Substances 0.000 claims description 9
150000004820 halides Chemical class 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
229910052744 lithium Inorganic materials 0.000 claims description 8
229910052763 palladium Inorganic materials 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
230000007062 hydrolysis Effects 0.000 claims description 7
238000006460 hydrolysis reaction Methods 0.000 claims description 7
150000007517 lewis acids Chemical class 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
239000002841 Lewis acid Substances 0.000 claims description 6
150000004673 fluoride salts Chemical class 0.000 claims description 6
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
239000003638 chemical reducing agent Substances 0.000 claims description 5
230000008878 coupling Effects 0.000 claims description 5
238000010168 coupling process Methods 0.000 claims description 5
238000005859 coupling reaction Methods 0.000 claims description 5
229910052751 metal Inorganic materials 0.000 claims description 5
239000002184 metal Substances 0.000 claims description 5
KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims description 4
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
150000002221 fluorine Chemical class 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 3
150000001879 copper Chemical class 0.000 claims description 3
150000004678 hydrides Chemical class 0.000 claims description 3
125000005619 boric acid group Chemical group 0.000 claims description 2
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
125000005741 alkyl alkenyl group Chemical group 0.000 claims 1
150000001559 benzoic acids Chemical group 0.000 claims 1
150000007942 carboxylates Chemical class 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
239000006166 lysate Chemical group 0.000 claims 1
125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
229910052814 silicon oxide Inorganic materials 0.000 claims 1
238000004519 manufacturing process Methods 0.000 abstract description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 98
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 86
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 62
239000000243 solution Substances 0.000 description 49
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
239000000203 mixture Substances 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
235000019439 ethyl acetate Nutrition 0.000 description 29
239000011541 reaction mixture Substances 0.000 description 29
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 23
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical group CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
239000012044 organic layer Substances 0.000 description 15
239000010410 layer Substances 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
239000002904 solvent Substances 0.000 description 13
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 12
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 12
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 11
239000004327 boric acid Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
229910000029 sodium carbonate Inorganic materials 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
239000012453 solvate Substances 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
150000001299 aldehydes Chemical class 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 7
239000000725 suspension Substances 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 6
239000012267 brine Substances 0.000 description 6
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
229910000024 caesium carbonate Inorganic materials 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000000284 extract Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
239000011698 potassium fluoride Substances 0.000 description 6
235000003270 potassium fluoride Nutrition 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
239000012448 Lithium borohydride Substances 0.000 description 5
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 5
229910001863 barium hydroxide Inorganic materials 0.000 description 5
238000009835 boiling Methods 0.000 description 5
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
239000012043 crude product Substances 0.000 description 5
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 5
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
NZQDWKCNBOELAI-KSFYIVLOSA-N 2-[(3s,4r)-3-benzyl-4-hydroxy-3,4-dihydro-2h-chromen-7-yl]-4-(trifluoromethyl)benzoic acid Chemical compound C([C@@H]1[C@H](C2=CC=C(C=C2OC1)C=1C(=CC=C(C=1)C(F)(F)F)C(O)=O)O)C1=CC=CC=C1 NZQDWKCNBOELAI-KSFYIVLOSA-N 0.000 description 4
UPCARQPLANFGQJ-UHFFFAOYSA-N 4-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC(Br)=CC=C1C=O UPCARQPLANFGQJ-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
239000000010 aprotic solvent Substances 0.000 description 4
239000011260 aqueous acid Substances 0.000 description 4
XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
150000002009 diols Chemical class 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
239000011630 iodine Substances 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 4
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical group Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 4
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 4
CDSPCWKYSYEPMH-QGZVFWFLSA-N (4r)-4-benzyl-3-(3-phenylpropanoyl)-1,3-oxazolidin-2-one Chemical compound C([C@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CCC1=CC=CC=C1 CDSPCWKYSYEPMH-QGZVFWFLSA-N 0.000 description 3
VIGOJLCCKCKIDA-UHFFFAOYSA-N 2,2-dimethylpropyl 2-(1,3,6,2-dioxazaborocan-2-yl)-4-(trifluoromethyl)benzoate Chemical compound CC(C)(C)COC(=O)C1=CC=C(C(F)(F)F)C=C1B1OCCNCCO1 VIGOJLCCKCKIDA-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
201000004624 Dermatitis Diseases 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
XRKIHUXCUIFHAS-UHFFFAOYSA-N [4-(3-methoxy-3-oxopropyl)phenyl]boronic acid Chemical compound COC(=O)CCC1=CC=C(B(O)O)C=C1 XRKIHUXCUIFHAS-UHFFFAOYSA-N 0.000 description 3
238000005575 aldol reaction Methods 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical class Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 description 3
150000001412 amines Chemical group 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
208000010668 atopic eczema Diseases 0.000 description 3
150000003935 benzaldehydes Chemical class 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000001506 calcium phosphate Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
239000006260 foam Substances 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 3
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
239000012071 phase Substances 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
150000003335 secondary amines Chemical class 0.000 description 3
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
150000003512 tertiary amines Chemical group 0.000 description 3
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
229940078499 tricalcium phosphate Drugs 0.000 description 3
229910000391 tricalcium phosphate Inorganic materials 0.000 description 3
235000019731 tricalcium phosphate Nutrition 0.000 description 3
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 3
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
RXNUIXXNFDJYCP-BLLLJJGKSA-N (3s,4r)-3-benzyl-7-bromo-3,4-dihydro-2h-chromen-4-ol Chemical compound C([C@@H]1[C@H](C2=CC=C(Br)C=C2OC1)O)C1=CC=CC=C1 RXNUIXXNFDJYCP-BLLLJJGKSA-N 0.000 description 2
OJOFMLDBXPDXLQ-SECBINFHSA-N (4r)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-SECBINFHSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
QFTKGHNHRXSVFI-UHFFFAOYSA-N 2-(1,3,6,2-dioxazaborocan-2-yl)-4-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=C1B1OCCNCCO1 QFTKGHNHRXSVFI-UHFFFAOYSA-N 0.000 description 2
OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
108010010369 HIV Protease Proteins 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
238000006069 Suzuki reaction reaction Methods 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
150000005347 biaryls Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000005620 boronic acid group Chemical group 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 2
FAVAVMFXAKZTMV-UHFFFAOYSA-N dibutylboranyl trifluoromethanesulfonate Chemical compound CCCCB(CCCC)OS(=O)(=O)C(F)(F)F FAVAVMFXAKZTMV-UHFFFAOYSA-N 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical group OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
YULOSWFIJROSMH-UHFFFAOYSA-N ethyl 2-iodo-4-(trifluoromethyl)benzoate Chemical compound CCOC(=O)C1=CC=C(C(F)(F)F)C=C1I YULOSWFIJROSMH-UHFFFAOYSA-N 0.000 description 2
239000002024 ethyl acetate extract Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 2
AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 2
KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 2
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000000047 product Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 1
PPIBJOQGAJBQDF-CBAPKCEASA-N (4s,5r)-4-methyl-5-phenyl-1,3-oxazolidin-2-one Chemical compound C[C@@H]1NC(=O)O[C@@H]1C1=CC=CC=C1 PPIBJOQGAJBQDF-CBAPKCEASA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
MWLUXIMHLPCFRZ-UHFFFAOYSA-N 2,2-dimethylpropyl 4-(trifluoromethyl)benzoate Chemical compound CC(C)(C)COC(=O)C1=CC=C(C(F)(F)F)C=C1 MWLUXIMHLPCFRZ-UHFFFAOYSA-N 0.000 description 1
HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 1
NTWDGOIHTNDHPA-UHFFFAOYSA-N 2-methylbutan-2-yl 4-(trifluoromethyl)benzoate Chemical compound CCC(C)(C)OC(=O)C1=CC=C(C(F)(F)F)C=C1 NTWDGOIHTNDHPA-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
GMMONXSVGFBOND-UHFFFAOYSA-N 3-[2-benzyl-3-(4-bromo-2-fluorophenyl)-3-hydroxypropanoyl]-1,3-oxazolidin-2-one Chemical compound C(C1=CC=CC=C1)C(C(=O)N1C(OCC1)=O)C(O)C1=C(C=C(C=C1)Br)F GMMONXSVGFBOND-UHFFFAOYSA-N 0.000 description 1
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
101100074998 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nmp-2 gene Proteins 0.000 description 1
KNAZNLQMFDUPTF-UHFFFAOYSA-N OCCC(O)C1=CC=C(Br)C=C1F Chemical compound OCCC(O)C1=CC=C(Br)C=C1F KNAZNLQMFDUPTF-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
238000005882 aldol condensation reaction Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
238000007080 aromatic substitution reaction Methods 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
150000001558 benzoic acid derivatives Chemical group 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
150000004985 diamines Chemical group 0.000 description 1
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
ACSQSQMTEKFKDX-UHFFFAOYSA-N fluorane Chemical compound F.F.F ACSQSQMTEKFKDX-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000012535 impurity Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000006138 lithiation reaction Methods 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
ASIHXBXGSXFMGM-UHFFFAOYSA-N magnesium;2,2,6,6-tetramethylpiperidin-1-ide Chemical compound CC1(C)CCCC(C)(C)N1[Mg]N1C(C)(C)CCCC1(C)C ASIHXBXGSXFMGM-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
229940111688 monobasic potassium phosphate Drugs 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
NZEVKZAEMSMLMC-UHFFFAOYSA-N nmp-7 Chemical compound C=1C=C2N(CCCCC)C3=CC=CC=C3C2=CC=1C(=O)N1CCCCC1 NZEVKZAEMSMLMC-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
229960000649 oxyphenbutazone Drugs 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
125000000075 primary alcohol group Chemical group 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
238000010583 slow cooling Methods 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003606 tin compounds Chemical class 0.000 description 1
CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
CMHHITPYCHHOGT-UHFFFAOYSA-N tributylborane Chemical compound CCCCB(CCCC)CCCC CMHHITPYCHHOGT-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
230000004572 zinc-binding Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/50—Halogenated unsaturated alcohols containing six-membered aromatic rings and other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

BG103231A 1996-09-16 1999-03-09 Методи и междинни съединения за получаване на заместени хроманолови производни BG63542B1 (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2637296P	1996-09-16	1996-09-16
PCT/IB1997/001024 WO1998011085A1 (en)	1996-09-16	1997-08-25	Processes and intermediates for preparing substituted chromanol derivatives

Publications (2)

Publication Number	Publication Date
BG103231A BG103231A (en)	1999-12-30
BG63542B1 true BG63542B1 (bg)	2002-04-30

Family

ID=21831429

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG103231A BG63542B1 (bg)	1996-09-16	1999-03-09	Методи и междинни съединения за получаване на заместени хроманолови производни

Country Status (39)

Country	Link
US (4)	US6096906A (da)
EP (1)	EP0925292B1 (da)
JP (1)	JP3117730B2 (da)
KR (1)	KR100339164B1 (da)
CN (1)	CN1108298C (da)
AP (1)	AP726A (da)
AT (1)	ATE249452T1 (da)
AU (1)	AU713701B2 (da)
BG (1)	BG63542B1 (da)
BR (1)	BR9711482A (da)
CA (1)	CA2265043C (da)
CO (1)	CO4600635A1 (da)
DE (1)	DE69724801T2 (da)
DK (1)	DK0925292T3 (da)
DZ (1)	DZ2308A1 (da)
EA (1)	EA002204B1 (da)
ES (1)	ES2206738T3 (da)
GT (3)	GT199700104A (da)
HN (1)	HN1997000127A (da)
HR (1)	HRP970497B1 (da)
ID (1)	ID19613A (da)
IL (1)	IL128732A0 (da)
IS (1)	IS4980A (da)
MA (1)	MA24319A1 (da)
NO (1)	NO991254L (da)
NZ (1)	NZ334214A (da)
OA (1)	OA10995A (da)
PA (1)	PA8437901A1 (da)
PE (1)	PE109798A1 (da)
PL (1)	PL332351A1 (da)
PT (1)	PT925292E (da)
SK (1)	SK31399A3 (da)
TN (1)	TNSN97155A1 (da)
TR (1)	TR199900592T2 (da)
TW (1)	TW449579B (da)
UA (1)	UA58520C2 (da)
WO (1)	WO1998011085A1 (da)
YU (1)	YU13299A (da)
ZA (1)	ZA978291B (da)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6436987B1 (en) *	2000-06-08	2002-08-20	Pfizer Inc.	Crystalline forms of (3S-trans)-2-[3,4-dihydro-4-hydroxy-3-(phenylmethyl)-2H-1-benzopyran-7-yl]-4-(trifluoromethyl)-benzoic acid
WO2002060888A1 (en) *	2001-01-30	2002-08-08	Pfizer Products Inc.	Processes for preparing chromanylbenzoic acids
AU4239302A (en) *	2001-06-28	2003-01-02	Pfizer Products Inc.	Benzoic acid substituted benzopyrans for the treatment of atherosclerosis
ES2551916T3 (es) *	2007-07-23	2015-11-24	The Board Of Trustees Of The University Of Illinois	Sistema para controlar la reactividad de los ácidos borónicos
US8338601B2 (en)	2008-09-26	2012-12-25	Board Of Trustees Of The University Of Illinois	Slow release of organoboronic acids in cross-coupling reactions
JP2013503943A (ja) *	2009-09-02	2013-02-04	イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー	フルオロビニルエーテル官能基化芳香族部分を含むポリアラミド
KR20120083366A (ko) *	2009-09-02	2012-07-25	이 아이 듀폰 디 네모아 앤드 캄파니	플루오로비닐에테르 작용화된 방향족 부분을 포함하는 폴리에스테르
CN102612509A (zh)	2009-09-02	2012-07-25	纳幕尔杜邦公司	氟醚官能化的芳族二酯及其衍生物
WO2011028766A2 (en) *	2009-09-02	2011-03-10	E. I. Du Pont De Nemours And Company	Fluorinated 4-oxo-chroman-carboxylates
US20110218319A1 (en) *	2009-09-02	2011-09-08	E. I. Du Pont De Nemours And Company	Polyaramid films comprising fluorovinylether functionalized aromatic moieties
WO2011028771A2 (en) *	2009-09-02	2011-03-10	E. I. Du Pont De Nemours And Company	Polyester films with improved oil repellency
US8557980B2 (en) *	2010-02-18	2013-10-15	The Board Of Trustees Of The University Of Illinois	Methods for forming protected organoboronic acids
US10500178B2 (en)	2015-03-13	2019-12-10	The Board Of Trustees Of The Leland Stanford Junior University	LTB4 inhibition to prevent and treat human lymphedema
KR102807066B1 (ko) *	2019-09-30	2025-05-15	주식회사 엘지화학	아민계 화합물 제조방법
CN117384617B (zh) *	2023-12-13	2024-03-29	中国石油大学(华东)	一种耐盐型胍胶压裂液交联剂水溶液及其制备方法和应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9119920D0 (en) *	1991-09-18	1991-10-30	Glaxo Group Ltd	Chemical compounds
HUT67929A (en) *	1992-01-23	1995-05-29	Pfizer	Benzopyran and related ltb4 antagonists
MX9300312A (es) *	1992-01-23	1993-07-31	Pfizer	Antagonistas benzopiranicos y relacionado de ltb.
PL308473A1 (en) *	1992-10-21	1995-08-07	Pfizer	Enabntiomeric cis-3-(4,6-dihydoxychroman-3-yl methyl)bezoic acids
EP0665842A1 (en) *	1992-10-21	1995-08-09	Pfizer Inc.	Sulfonamide derivatives of benzenefused hydroxy substituted cycloalkyl and heterocyclic ring compounds
AU703557B2 (en) *	1994-10-13	1999-03-25	Pfizer Inc.	Benzopyran and benzo-fused compounds, their preparation and their use as leukotriene B4' (LTB4) antagonists
CZ111797A3 (cs) *	1994-10-13	1998-07-15	Pfizer Inc.	Benzopyranové a jiné sloučeniny s přikondenzovaným benzenovým kruhem a farmaceutické prostředky na jejich bázi
US5539128A (en) *	1994-11-30	1996-07-23	Pfizer Inc.	Processes and intermediates for preparing cis(+)3-[4,6-dihydroxy chroman-3-ylmethyl]-4-methoxyaniline

1997
- 1997-08-25 PL PL97332351A patent/PL332351A1/xx unknown
- 1997-08-25 KR KR1019997002175A patent/KR100339164B1/ko not_active Expired - Fee Related
- 1997-08-25 WO PCT/IB1997/001024 patent/WO1998011085A1/en not_active Ceased
- 1997-08-25 AT AT97934679T patent/ATE249452T1/de not_active IP Right Cessation
- 1997-08-25 BR BR9711482A patent/BR9711482A/pt not_active Application Discontinuation
- 1997-08-25 SK SK313-99A patent/SK31399A3/sk unknown
- 1997-08-25 CN CN97197985A patent/CN1108298C/zh not_active Expired - Fee Related
- 1997-08-25 UA UA99031394A patent/UA58520C2/uk unknown
- 1997-08-25 YU YU13299A patent/YU13299A/sh unknown
- 1997-08-25 TR TR1999/00592T patent/TR199900592T2/xx unknown
- 1997-08-25 PT PT97934679T patent/PT925292E/pt unknown
- 1997-08-25 AU AU37814/97A patent/AU713701B2/en not_active Ceased
- 1997-08-25 DK DK97934679T patent/DK0925292T3/da active
- 1997-08-25 EP EP97934679A patent/EP0925292B1/en not_active Expired - Lifetime
- 1997-08-25 EA EA199900204A patent/EA002204B1/ru not_active IP Right Cessation
- 1997-08-25 IL IL12873297A patent/IL128732A0/xx unknown
- 1997-08-25 ES ES97934679T patent/ES2206738T3/es not_active Expired - Lifetime
- 1997-08-25 DE DE69724801T patent/DE69724801T2/de not_active Expired - Fee Related
- 1997-08-25 NZ NZ334214A patent/NZ334214A/xx unknown
- 1997-08-25 CA CA002265043A patent/CA2265043C/en not_active Expired - Fee Related
- 1997-08-25 JP JP10513430A patent/JP3117730B2/ja not_active Expired - Fee Related
- 1997-08-25 US US09/367,235 patent/US6096906A/en not_active Expired - Fee Related
- 1997-08-29 HN HN1997000127A patent/HN1997000127A/es unknown
- 1997-09-04 CO CO97051475A patent/CO4600635A1/es unknown
- 1997-09-05 PA PA19978437901A patent/PA8437901A1/es unknown
- 1997-09-08 GT GT199700104A patent/GT199700104A/es unknown
- 1997-09-11 AP APAP/P/1997/001083A patent/AP726A/en active
- 1997-09-12 TW TW086113297A patent/TW449579B/zh active
- 1997-09-12 PE PE1997000813A patent/PE109798A1/es not_active Application Discontinuation
- 1997-09-15 ZA ZA978291A patent/ZA978291B/xx unknown
- 1997-09-15 MA MA24797A patent/MA24319A1/fr unknown
- 1997-09-15 ID IDP973183A patent/ID19613A/id unknown
- 1997-09-15 DZ DZ970158A patent/DZ2308A1/xx active
- 1997-09-15 TN TNTNSN97155A patent/TNSN97155A1/fr unknown
- 1997-09-16 HR HR970497A patent/HRP970497B1/xx not_active IP Right Cessation
- 1997-10-04 GT GT199700104BL patent/GT199700104BA/es unknown
- 1997-10-04 GT GT199700104AK patent/GT199700104AA/es unknown
1999
- 1999-02-16 IS IS4980A patent/IS4980A/is unknown
- 1999-03-09 BG BG103231A patent/BG63542B1/bg unknown
- 1999-03-12 OA OA9900056A patent/OA10995A/en unknown
- 1999-03-15 NO NO991254A patent/NO991254L/no not_active Application Discontinuation
2000
- 2000-02-23 US US09/511,475 patent/US6288242B1/en not_active Expired - Fee Related
2001
- 2001-03-21 US US09/813,546 patent/US6355825B1/en not_active Expired - Fee Related
- 2001-10-31 US US09/999,240 patent/US6444826B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
YU13299A (sh)	2001-03-07
US6444826B1 (en)	2002-09-03
PE109798A1 (es)	1999-01-13
CN1230954A (zh)	1999-10-06
EP0925292A1 (en)	1999-06-30
KR20000036136A (ko)	2000-06-26
KR100339164B1 (ko)	2002-06-01
CA2265043C (en)	2003-01-14
NZ334214A (en)	2000-09-29
CN1108298C (zh)	2003-05-14
BR9711482A (pt)	1999-08-24
JP2000502726A (ja)	2000-03-07
ES2206738T3 (es)	2004-05-16
HRP970497A2 (en)	1998-08-31
CA2265043A1 (en)	1998-03-19
NO991254D0 (no)	1999-03-15
UA58520C2 (uk)	2003-08-15
ID19613A (id)	1998-07-23
AP9701083A0 (en)	1997-10-31
NO991254L (no)	1999-05-14
GT199700104AA (es)	1999-03-28
GT199700104A (es)	1999-03-02
DE69724801D1 (de)	2003-10-16
EA002204B1 (ru)	2002-02-28
PA8437901A1 (es)	2000-05-24
MA24319A1 (fr)	1998-04-01
IS4980A (is)	1999-02-16
DK0925292T3 (da)	2004-01-12
US6096906A (en)	2000-08-01
AP726A (en)	1999-01-29
US6355825B1 (en)	2002-03-12
PL332351A1 (en)	1999-09-13
CO4600635A1 (es)	1998-05-08
AU713701B2 (en)	1999-12-09
HRP970497B1 (en)	2002-06-30
TR199900592T2 (xx)	1999-06-21
GT199700104BA (es)	1999-03-28
BG103231A (en)	1999-12-30
SK31399A3 (en)	2000-05-16
AU3781497A (en)	1998-04-02
DE69724801T2 (de)	2004-06-17
OA10995A (en)	2001-11-06
JP3117730B2 (ja)	2000-12-18
ZA978291B (en)	1999-03-15
TNSN97155A1 (fr)	2005-03-15
EP0925292B1 (en)	2003-09-10
IL128732A0 (en)	2000-01-31
HN1997000127A (es)	1997-12-20
TW449579B (en)	2001-08-11
DZ2308A1 (fr)	2002-12-28
EA199900204A1 (ru)	1999-08-26
US6288242B1 (en)	2001-09-11
ATE249452T1 (de)	2003-09-15
PT925292E (pt)	2004-01-30
US20020099227A1 (en)	2002-07-25
US20020042526A1 (en)	2002-04-11
WO1998011085A1 (en)	1998-03-19

Publication	Publication Date	Title
BG63542B1 (bg)	2002-04-30	Методи и междинни съединения за получаване на заместени хроманолови производни
CA2751741C (en)	2018-07-10	Process for the preparation of (-) -delta 9-tetrahydrocannabinol
JP2567430B2 (ja)	1996-12-25	カルビノール誘導体及びその製造方法
TWI897607B (zh)	2025-09-11	製備苯并前列環素類似物之方法及中間物，及由其製得之苯并前列環素類似物
CN1204647A (zh)	1999-01-13	吡唑啉酮化合物的制备方法
JP4540197B2 (ja)	2010-09-08	（ｅ）−３−メチル−２−シクロペンタデセノンの製造法
CN111556861A (zh)	2020-08-18	茉莉酸酯化合物的制备方法
MXPA01010768A (en)	2002-06-05	Processes and intermediates for preparing substituted chromanol derivatives
CN101087751B (zh)	2011-11-02	制备3-(2-羟基-5-甲基苯基)-n,n-二异丙基-3-苯基丙胺的方法
JP2571081B2 (ja)	1997-01-16	光学活性１，２−アルカンジオールの製造方法
CA2578342A1 (en)	2006-03-02	Method for the production of diarylcycloalkyl derivatives
CZ86799A3 (cs)	2000-02-16	Způsob výroby substituovaných derivátů chromanolu a meziprodukty pro tyto způsoby
HUP9903247A2 (hu)	2000-02-28	Eljárások helyettesített kromanolszármazékok előállítására és közbenső termékeik
WO2002060888A1 (en)	2002-08-08	Processes for preparing chromanylbenzoic acids
US20030158428A1 (en)	2003-08-21	Intermediates and processes for preparing substituted chromanol derivatives
JP5194257B2 (ja)	2013-05-08	フラバン誘導体の製造方法
JPH07242572A (ja)	1995-09-19	ジメチルヘプタトリアコンタンおよびその類似体の製造方法
HK1022309A (en)	2000-08-04	Processes and intermediates for preparing substituted chromanol derivatives
JP2019513808A (ja)	2019-05-30	ビマトプロストの調製方法
JPH04283526A (ja)	1992-10-08	光学活性アリルアルコールの製造方法