TW200904811A - Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone - Google Patents

Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone Download PDF

Info

Publication number: TW200904811A
Authority: TW; Taiwan
Prior art keywords: methyl; thiophene; bromo; propoxy; carboxylic acid
Prior art date: 2007-03-29

Application number

TW097111154A

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 TW200904811A publication Critical patent/TW200904811A/zh

Links

229940122598 Tryptase inhibitor Drugs 0.000 title description 2
239000002750 tryptase inhibitor Substances 0.000 title description 2
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 1
IFWLUOOAWLUBQN-UHFFFAOYSA-N [4-[5-(aminomethyl)-2-fluorophenyl]piperidin-1-yl]-(4-bromo-3-methyl-5-propoxythiophen-2-yl)methanone Chemical compound BrC1=C(OCCC)SC(C(=O)N2CCC(CC2)C=2C(=CC=C(CN)C=2)F)=C1C IFWLUOOAWLUBQN-UHFFFAOYSA-N 0.000 title 1
239000002904 solvent Substances 0.000 claims abstract description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 11
238000000034 method Methods 0.000 claims description 32
238000005859 coupling reaction Methods 0.000 claims description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 6
238000010511 deprotection reaction Methods 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 4
150000003512 tertiary amines Chemical class 0.000 claims description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
239000004472 Lysine Substances 0.000 claims 1
238000005576 amination reaction Methods 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
-1 4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid compound Chemical class 0.000 abstract description 17
239000002585 base Substances 0.000 abstract description 15
230000015572 biosynthetic process Effects 0.000 abstract description 5
239000010949 copper Substances 0.000 abstract description 5
239000004215 Carbon black (E152) Substances 0.000 abstract description 4
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 abstract description 4
229910052783 alkali metal Inorganic materials 0.000 abstract description 4
239000003054 catalyst Substances 0.000 abstract description 4
229910052802 copper Inorganic materials 0.000 abstract description 4
229930195733 hydrocarbon Natural products 0.000 abstract description 4
150000002430 hydrocarbons Chemical class 0.000 abstract description 4
238000006887 Ullmann reaction Methods 0.000 abstract description 3
150000002576 ketones Chemical class 0.000 abstract description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 abstract description 3
238000003786 synthesis reaction Methods 0.000 abstract description 2
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 abstract 3
BSQKBHXYEKVKMN-UHFFFAOYSA-N 3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=CSC=1C=O BSQKBHXYEKVKMN-UHFFFAOYSA-N 0.000 abstract 3
UTFHYWYDDMHEIL-UHFFFAOYSA-N 5-iodo-3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=C(I)SC=1C=O UTFHYWYDDMHEIL-UHFFFAOYSA-N 0.000 abstract 2
NBLCMBNKWZHYLB-UHFFFAOYSA-N 5-iodo-3-methylthiophene-2-carboxylic acid Chemical compound CC=1C=C(I)SC=1C(O)=O NBLCMBNKWZHYLB-UHFFFAOYSA-N 0.000 abstract 2
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 abstract 1
230000003301 hydrolyzing effect Effects 0.000 abstract 1
230000002083 iodinating effect Effects 0.000 abstract 1
230000001590 oxidative effect Effects 0.000 abstract 1
239000000203 mixture Substances 0.000 description 23
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000000243 solution Substances 0.000 description 16
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 7
230000008569 process Effects 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
239000007789 gas Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
239000004744 fabric Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 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
239000011734 sodium Substances 0.000 description 4
238000003756 stirring Methods 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
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-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
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
102000001400 Tryptase Human genes 0.000 description 3
108060005989 Tryptase Proteins 0.000 description 3
239000002253 acid Substances 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
229940126142 compound 16 Drugs 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
239000002002 slurry Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
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
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
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 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical class N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
239000007822 coupling agent 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
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000012336 iodinating agent Substances 0.000 description 2
230000026045 iodination Effects 0.000 description 2
238000006192 iodination reaction Methods 0.000 description 2
229910052744 lithium Inorganic materials 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
239000002798 polar solvent Substances 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
239000002994 raw material Substances 0.000 description 2
150000003839 salts Chemical class 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
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
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
CVOGMKGEVNGRSK-UHFFFAOYSA-N 1,2-diiodoethene Chemical group IC=CI CVOGMKGEVNGRSK-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
KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
JQJBQVRTSMGDJX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxy]decane Chemical compound CCCCCCCCCCOC(C)(C)C JQJBQVRTSMGDJX-UHFFFAOYSA-N 0.000 description 1
IANXAXNUNBAWBA-UHFFFAOYSA-N 2,2,3-trimethylundecane Chemical compound CCCCCCCCC(C)C(C)(C)C IANXAXNUNBAWBA-UHFFFAOYSA-N 0.000 description 1
ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 description 1
XSJVWZAETSBXKU-UHFFFAOYSA-N 2-ethoxypropane Chemical compound CCOC(C)C XSJVWZAETSBXKU-UHFFFAOYSA-N 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 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
OECCERLPNOREAF-UHFFFAOYSA-N Cl.FC(C(=O)NNNC1=CC(=C(C=C1)F)C1CCNCC1)(F)F Chemical compound Cl.FC(C(=O)NNNC1=CC(=C(C=C1)F)C1CCNCC1)(F)F OECCERLPNOREAF-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
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
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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
238000007605 air drying Methods 0.000 description 1
125000002723 alicyclic group Chemical group 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
238000004458 analytical method Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000008346 aqueous phase Substances 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
210000000621 bronchi Anatomy 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 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
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003245 coal Substances 0.000 description 1
229940125758 compound 15 Drugs 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
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-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
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
PPCXFTKZPBHXIW-UHFFFAOYSA-N ethyl ethanesulfonate Chemical compound CCOS(=O)(=O)CC PPCXFTKZPBHXIW-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000001272 nitrous oxide Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 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
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Inorganic materials [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 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
239000002689 soil Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000007704 transition 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

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)
Plural Heterocyclic Compounds (AREA)

TW097111154A 2007-03-29 2008-03-28 Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone TW200904811A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US90884407P	2007-03-29	2007-03-29

Publications (1)

Publication Number	Publication Date
TW200904811A true TW200904811A (en)	2009-02-01

Family

ID=39535396

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW097111154A TW200904811A (en)	2007-03-29	2008-03-28	Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone

Country Status (3)

Country	Link
AR (1)	AR065858A1 (es)
TW (1)	TW200904811A (es)
WO (1)	WO2008121666A1 (es)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PE20100235A1 (es) *	2008-08-22	2010-03-29	Sanofi Aventis	[4-(5-aminometil-2-fluoro-fenil)-piperidin-1-il]-[7-fluoro-1-(2-metoxi-etil)-4-trifluorometoxi-1h-indol-3-il]-metanona como un inhibidor de la triptasa de mastocitos
GB0905955D0 (en)	2009-04-06	2009-05-20	Respivert Ltd	Novel compounds
US9024041B2 (en)	2010-04-08	2015-05-05	Respivert Ltd.	P38 MAP kinase inhibitors
WO2011158044A2 (en)	2010-06-17	2011-12-22	Respivert Limited	Respiratory formulations and compounds for use therein

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 ARP080101260A patent/AR065858A1/es not_active Application Discontinuation
- 2008-03-27 WO PCT/US2008/058341 patent/WO2008121666A1/en active Application Filing
- 2008-03-28 TW TW097111154A patent/TW200904811A/zh unknown

Also Published As

Publication number	Publication date
AR065858A1 (es)	2009-07-08
WO2008121666A1 (en)	2008-10-09

Publication	Publication Date	Title
JP6284928B2 (ja)	2018-02-28	ヒドロキシル化シクロペンチルピリミジン化合物を作製するためのプロセス
TW201029975A (en)	2010-08-16	Process for manufacturing substituted 3-pyridylmethyl ammonium bromides
KR20170029501A (ko)	2017-03-15	4-알콕시-3-히드록시피콜린산의 제조 방법
TW200904811A (en)	2009-02-01	Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone
CN109956906A (zh)	2019-07-02	一种噁拉戈利关键中间体的制备方法
JP2015531408A (ja)	2015-11-02	２−アミノ−４，６−ジメトキシベンズアミド及び他のベンズアミド化合物の合成方法
TWI343909B (en)	2011-06-21	Process for making galantamine
WO2022002116A1 (zh)	2022-01-06	一种苯基异恶唑啉类化合物的制备方法
JP2010535185A (ja)	2010-11-18	アルフゾシン塩酸塩の製造方法
CN109485567B (zh)	2021-07-09	一种4-羟甲基噻唑的清洁制备方法及其中间体
CN1231482C (zh)	2005-12-14	噻唑烷二酮衍生物和中间体的制备方法
CN102675385A (zh)	2012-09-19	制备阿霉素13-位腙衍生物的方法
TW200904810A (en)	2009-02-01	4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester, its regio-specific synthesis and intermediate thereto
US7304158B2 (en)	2007-12-04	Method for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone)
WO2001064683A1 (fr)	2001-09-07	Procedes de production de derives de thienopyramidine
TW200902510A (en)	2009-01-16	Regio-specific synthesis of 4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid
CN103570724B (zh)	2015-12-16	ponatinib 的合成方法
JP2019014716A (ja)	2019-01-31	４，４，７−トリフルオロ−１，２，３，４−テトラヒドロ−５ｈ−１−ベンゾアゼピン化合物の製造方法及びその合成中間体
KR100893756B1 (ko)	2009-04-22	몬테루카스트의 효율적 제조방법
KR100836528B1 (ko)	2008-06-10	이토프리드 염산염의 제조방법
JP4675234B2 (ja)	2011-04-20	光学活性なキノロンカルボン酸誘導体の製造中間体およびその製造法
JP2001316391A (ja)	2001-11-13	チエノピリミジン誘導体の製造法
JP4788049B2 (ja)	2011-10-05	ジカルボン酸ジエステル誘導体およびその製造方法
CN110903245A (zh)	2020-03-24	一种合成1-烷基-2-三氟甲基-5-氨基-1h-咪唑的关键中间体及其制备方法
JP4752121B2 (ja)	2011-08-17	ニトリル誘導体の製造方法、その中間体および中間体の製造方法