TW200904810A - 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester, its regio-specific synthesis and intermediate thereto - Google Patents

4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester, its regio-specific synthesis and intermediate thereto Download PDF

Info

Publication number: TW200904810A
Authority: TW; Taiwan
Prior art keywords: methyl; propoxythiophene; carboxylic acid; coupling; reaction
Prior art date: 2007-03-29

Application number

TW097111151A

Other languages

English (en)

Chinese (zh)

Inventor

Ann Marie Gelormini

John J Shay

Adam W Sledeski

Original Assignee

Sanofi Aventis

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.)

2007-03-29

Filing date

2008-03-28

Publication date

2009-02-01

2008-03-28 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

2009-02-01 Publication of TW200904810A publication Critical patent/TW200904810A/zh

Links

238000003786 synthesis reaction Methods 0.000 title claims abstract description 6
230000015572 biosynthetic process Effects 0.000 title abstract description 7
IOKNJMJJWUNVRG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-bromo-3-methyl-5-propoxythiophene-2-carboxylate Chemical compound BrC1=C(OCCC)SC(C(=O)ON2C(CCC2=O)=O)=C1C IOKNJMJJWUNVRG-UHFFFAOYSA-N 0.000 title abstract 3
239000002904 solvent Substances 0.000 claims abstract description 23
-1 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2, 5-dioxo-pyrrolidin-1-yl ester compound Chemical class 0.000 claims abstract description 21
238000005859 coupling reaction Methods 0.000 claims abstract description 16
239000004215 Carbon black (E152) Substances 0.000 claims abstract description 10
229930195733 hydrocarbon Natural products 0.000 claims abstract description 10
150000002430 hydrocarbons Chemical class 0.000 claims abstract description 10
230000008878 coupling Effects 0.000 claims abstract description 8
238000010168 coupling process Methods 0.000 claims abstract description 8
239000010949 copper Substances 0.000 claims abstract description 7
XAOJMTRGEZJSQN-UHFFFAOYSA-N 3-methyl-5-propoxythiophene-2-carboxylic acid Chemical compound CCCOC1=CC(C)=C(C(O)=O)S1 XAOJMTRGEZJSQN-UHFFFAOYSA-N 0.000 claims abstract description 6
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 6
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 6
239000003054 catalyst Substances 0.000 claims abstract description 6
229910052802 copper Inorganic materials 0.000 claims abstract description 6
239000003795 chemical substances by application Substances 0.000 claims abstract description 5
239000007822 coupling agent Substances 0.000 claims abstract description 5
239000012442 inert solvent Substances 0.000 claims abstract description 5
238000006887 Ullmann reaction Methods 0.000 claims abstract description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims abstract description 3
238000000034 method Methods 0.000 claims description 35
238000006243 chemical reaction Methods 0.000 claims description 21
150000001875 compounds Chemical class 0.000 claims description 8
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 6
238000005886 esterification reaction Methods 0.000 claims description 6
230000032050 esterification Effects 0.000 claims description 5
150000001340 alkali metals Chemical class 0.000 claims description 4
238000005893 bromination reaction Methods 0.000 claims description 4
229910052751 metal Inorganic materials 0.000 claims description 4
239000002184 metal Substances 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000002798 polar solvent Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 3
239000000052 vinegar Substances 0.000 claims description 3
235000021419 vinegar Nutrition 0.000 claims description 3
IXADHCVQNVXURI-UHFFFAOYSA-N 1,1-dichlorodecane Chemical group CCCCCCCCCC(Cl)Cl IXADHCVQNVXURI-UHFFFAOYSA-N 0.000 claims description 2
125000005907 alkyl ester group Chemical group 0.000 claims description 2
230000031709 bromination Effects 0.000 claims description 2
150000008282 halocarbons Chemical class 0.000 claims description 2
238000010438 heat treatment Methods 0.000 claims description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
229960002317 succinimide Drugs 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
NOCGTFKCRFTUQN-UHFFFAOYSA-N 3-propoxythiophene-2-carboxylic acid Chemical compound CCCOC=1C=CSC=1C(O)=O NOCGTFKCRFTUQN-UHFFFAOYSA-N 0.000 claims 1
241000239226 Scorpiones Species 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
239000008267 milk Substances 0.000 claims 1
210000004080 milk Anatomy 0.000 claims 1
235000013336 milk Nutrition 0.000 claims 1
238000006386 neutralization reaction Methods 0.000 claims 1
229910052760 oxygen Inorganic materials 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
239000002585 base Substances 0.000 abstract description 11
QENGPZGAWFQWCZ-UHFFFAOYSA-N 3-Methylthiophene Chemical compound CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 abstract description 4
VWAPODDPPKUMAW-UHFFFAOYSA-N 4-methyl-2-propoxythiophene Chemical compound CCCOC1=CC(C)=CS1 VWAPODDPPKUMAW-UHFFFAOYSA-N 0.000 abstract description 4
239000012336 iodinating agent Substances 0.000 abstract description 3
150000005826 halohydrocarbons Chemical class 0.000 abstract description 2
ZQSMSBJSFOBHHC-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-methyl-5-propoxythiophene-2-carboxylate Chemical compound S1C(OCCC)=CC(C)=C1C(=O)ON1C(=O)CCC1=O ZQSMSBJSFOBHHC-UHFFFAOYSA-N 0.000 abstract 3
MWHJEWBLTYDUKD-UHFFFAOYSA-N 2-iodo-4-methylthiophene Chemical compound CC1=CSC(I)=C1 MWHJEWBLTYDUKD-UHFFFAOYSA-N 0.000 abstract 2
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 abstract 1
230000002083 iodinating effect Effects 0.000 abstract 1
239000000203 mixture Substances 0.000 description 24
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
239000000243 solution Substances 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
235000019439 ethyl acetate Nutrition 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000002002 slurry Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
239000012267 brine Substances 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
238000005576 amination reaction Methods 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
229940126142 compound 16 Drugs 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
239000004744 fabric Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
230000026045 iodination Effects 0.000 description 3
238000006192 iodination reaction Methods 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
XSJVWZAETSBXKU-UHFFFAOYSA-N 2-ethoxypropane Chemical compound CCOC(C)C XSJVWZAETSBXKU-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
LMUFKHXTMZDSLV-UHFFFAOYSA-N CCCOC1=C(C(=C(S1)C(=O)O)C2=CC3=CC=CC=C3N2)Br Chemical compound CCCOC1=C(C(=C(S1)C(=O)O)C2=CC3=CC=CC=C3N2)Br LMUFKHXTMZDSLV-UHFFFAOYSA-N 0.000 description 2
108010068370 Glutens Proteins 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000001400 Tryptase Human genes 0.000 description 2
108060005989 Tryptase Proteins 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229920001971 elastomer Polymers 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
235000021312 gluten Nutrition 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-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
239000001294 propane Substances 0.000 description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
239000002994 raw material Substances 0.000 description 2
239000000779 smoke Substances 0.000 description 2
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 2
238000005406 washing Methods 0.000 description 2
XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 1
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
JCMVPOVHKWWBAU-UHFFFAOYSA-N 1,2-dichlorohydrazine Chemical compound ClNNCl JCMVPOVHKWWBAU-UHFFFAOYSA-N 0.000 description 1
OFHQVNFSKOBBGG-UHFFFAOYSA-N 1,2-difluoropropane Chemical compound CC(F)CF OFHQVNFSKOBBGG-UHFFFAOYSA-N 0.000 description 1
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000005160 1H NMR spectroscopy Methods 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
VWFVJVPPXXCWAW-UHFFFAOYSA-N 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid Chemical compound CCCOC=1SC(C(O)=O)=C(C)C=1Br VWFVJVPPXXCWAW-UHFFFAOYSA-N 0.000 description 1
GZVHEAJQGPRDLQ-UHFFFAOYSA-N 6-phenyl-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(C=2C=CC=CC=2)=N1 GZVHEAJQGPRDLQ-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
241000239290 Araneae Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
PQVSXGVVNMUVKK-UHFFFAOYSA-N C1=C(SC=C1S)I Chemical compound C1=C(SC=C1S)I PQVSXGVVNMUVKK-UHFFFAOYSA-N 0.000 description 1
GQDAWJCBZUVAPH-UHFFFAOYSA-N CCCOC1=C(C(=C(S1)C(=O)ON2OCCO2)C3=CC4=CC=CC=C4N3)Br Chemical compound CCCOC1=C(C(=C(S1)C(=O)ON2OCCO2)C3=CC4=CC=CC=C4N3)Br GQDAWJCBZUVAPH-UHFFFAOYSA-N 0.000 description 1
HXMXKTLCQSMDSQ-UHFFFAOYSA-N CCCOC1=CC(=C(S1)C(=O)O)S Chemical compound CCCOC1=CC(=C(S1)C(=O)O)S HXMXKTLCQSMDSQ-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
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GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
241001529870 Meoma Species 0.000 description 1
YBHQCJILTOVLHD-YVMONPNESA-N Mirin Chemical compound S1C(N)=NC(=O)\C1=C\C1=CC=C(O)C=C1 YBHQCJILTOVLHD-YVMONPNESA-N 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
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206010036790 Productive cough Diseases 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
229940122598 Tryptase inhibitor Drugs 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
150000001408 amides Chemical group 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
FSAJRXGMUISOIW-UHFFFAOYSA-N bismuth sodium Chemical compound [Na].[Bi] FSAJRXGMUISOIW-UHFFFAOYSA-N 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
PDZKZMQQDCHTNF-UHFFFAOYSA-M copper(1+);thiocyanate Chemical compound [Cu+].[S-]C#N PDZKZMQQDCHTNF-UHFFFAOYSA-M 0.000 description 1
BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
CHVYWISGAZDJOG-UHFFFAOYSA-N disodium;diazide Chemical compound [Na+].[Na+].[N-]=[N+]=[N-].[N-]=[N+]=[N-] CHVYWISGAZDJOG-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000011521 glass Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
239000005457 ice water Substances 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000006146 oximation reaction Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
229940067157 phenylhydrazine Drugs 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000004848 polyfunctional curative Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
238000005070 sampling Methods 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
BBCAQPYJVYMQFB-UHFFFAOYSA-N sodium;2-methylpropane Chemical compound [Na+].C[C-](C)C BBCAQPYJVYMQFB-UHFFFAOYSA-N 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
210000003802 sputum Anatomy 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
239000007858 starting material Substances 0.000 description 1
POOSGDOYLQNASK-UHFFFAOYSA-N tetracosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC POOSGDOYLQNASK-UHFFFAOYSA-N 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
239000002750 tryptase inhibitor Substances 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Pyrrole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

TW097111151A 2007-03-29 2008-03-28 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester, its regio-specific synthesis and intermediate thereto TW200904810A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US90883907P	2007-03-29	2007-03-29

Publications (1)

Publication Number	Publication Date
TW200904810A true TW200904810A (en)	2009-02-01

Family

ID=39530622

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW097111151A TW200904810A (en)	2007-03-29	2008-03-28	4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester, its regio-specific synthesis and intermediate thereto

Country Status (3)

Country	Link
AR (1)	AR065859A1 (fr)
TW (1)	TW200904810A (fr)
WO (1)	WO2008121669A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2556764T3 (es) *	2008-08-22	2016-01-20	Sanofi	[4-(5-Aminometil-2-fluoro-fenil)-piperidin-1-il]-[7-fluoro-1-(2-metoxietil)-4-trifluorometoxi-1H-indol-3-il]metanona como inhibidor de triptasa de mastocitos

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DOP2005000039A (es) *	2004-03-26	2005-10-31	Aventis Pharma Inc	Hidrocloruro de [4-(5-aminometil-2-fluoro-fenil)- piperidin-1-il]-(4-bomo-3-metil-5-propoxi-tiofen-2-il)-metanona como un inhibidor de la triptasa de mastocitos

2008
- 2008-03-27 AR ARP080101261A patent/AR065859A1/es not_active Application Discontinuation
- 2008-03-27 WO PCT/US2008/058346 patent/WO2008121669A1/fr not_active Ceased
- 2008-03-28 TW TW097111151A patent/TW200904810A/zh unknown

Also Published As

Publication number	Publication date
AR065859A1 (es)	2009-07-08
WO2008121669A1 (fr)	2008-10-09

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