CA2352520C - Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine - Google Patents

Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine Download PDF

Info

Publication number: CA2352520C
Authority: CA; Canada
Prior art keywords: formula; compound; thienyl; methyl; chlorophenylglycinate
Prior art date: 2001-07-06
Legal status (The legal status 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 status listed.): Expired - Fee Related

Application number

CA 2352520

Other languages

English (en)

Other versions

CA2352520A1 (fr

Inventor

Stephen E. Horne

Jaipal Reddy Nagireddy

Laura Kaye Mcconachie

Gamini Weeratunga

Bogdan M. Comanita

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Apotex Pharmachem Inc

Original Assignee

Apotex Pharmachem 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.)

2001-07-06

Filing date

2001-07-06

Publication date

2007-10-02

2001-07-06 Application filed by Apotex Pharmachem Inc filed Critical Apotex Pharmachem Inc

2001-07-06 Priority to CA 2352520 priority Critical patent/CA2352520C/fr

2001-07-11 Priority to US09/902,165 priority patent/US6495691B1/en

2002-07-05 Priority to EP02745008A priority patent/EP1404681A1/fr

2002-07-05 Priority to PCT/CA2002/001017 priority patent/WO2003004502A1/fr

2003-01-06 Publication of CA2352520A1 publication Critical patent/CA2352520A1/fr

2007-10-02 Application granted granted Critical

2007-10-02 Publication of CA2352520C publication Critical patent/CA2352520C/fr

2021-07-06 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 36
230000008569 process Effects 0.000 title claims abstract description 35
238000002360 preparation method Methods 0.000 title claims abstract description 14
OJYDKYKQCVPTFG-UHFFFAOYSA-N 2,3,3a,4-tetrahydrothieno[3,2-c]pyridine Chemical class C1N=CC=C2SCCC21 OJYDKYKQCVPTFG-UHFFFAOYSA-N 0.000 title claims abstract description 7
150000001875 compounds Chemical class 0.000 claims abstract description 40
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 19
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims abstract description 9
125000000217 alkyl group Chemical group 0.000 claims abstract description 8
239000001257 hydrogen Substances 0.000 claims abstract description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
125000003118 aryl group Chemical group 0.000 claims abstract description 7
239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
229910052736 halogen Inorganic materials 0.000 claims abstract description 5
150000002367 halogens Chemical class 0.000 claims abstract description 5
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
150000002431 hydrogen Chemical group 0.000 claims abstract description 5
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
125000005333 aroyloxy group Chemical group 0.000 claims abstract description 4
125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
150000004649 carbonic acid derivatives Chemical group 0.000 claims abstract description 3
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims abstract 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 43
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 16
GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 16
229960003009 clopidogrel Drugs 0.000 claims description 16
239000000203 mixture Substances 0.000 claims description 15
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 12
NHZLLKNRTDIFAD-UHFFFAOYSA-N 2,5-dihydro-1,3-oxazole Chemical compound C1OCN=C1 NHZLLKNRTDIFAD-UHFFFAOYSA-N 0.000 claims description 10
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 8
230000002378 acidificating effect Effects 0.000 claims description 6
239000012279 sodium borohydride Substances 0.000 claims description 6
229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
UHWNENCHFSDZQP-UHFFFAOYSA-N 2-bromo-1-thiophen-2-ylethanone Chemical compound BrCC(=O)C1=CC=CS1 UHWNENCHFSDZQP-UHFFFAOYSA-N 0.000 claims description 5
239000003849 aromatic solvent Substances 0.000 claims description 5
239000003880 polar aprotic solvent Substances 0.000 claims description 5
239000003586 protic polar solvent Substances 0.000 claims description 5
-1 5-(2-thienyl)-3-(methoxycarbonyl-o-chlorobenzyl)-1,3-oxazoline compound Chemical class 0.000 claims description 4
KWYAPVDFVZNAHF-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-[(2-oxo-2-thiophen-2-ylethyl)amino]acetate Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)OC)NCC(=O)C1=CC=CS1 KWYAPVDFVZNAHF-UHFFFAOYSA-N 0.000 claims description 4
HZZFRGVOIXDTSE-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(methylamino)acetic acid Chemical compound CNC(C(O)=O)C1=CC=CC=C1Cl HZZFRGVOIXDTSE-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
239000002253 acid Substances 0.000 claims description 3
238000001212 derivatisation Methods 0.000 claims description 3
238000005906 dihydroxylation reaction Methods 0.000 claims description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims description 2
WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical class CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 claims description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 2
230000008030 elimination Effects 0.000 claims description 2
238000003379 elimination reaction Methods 0.000 claims description 2
238000010438 heat treatment Methods 0.000 claims description 2
150000003141 primary amines Chemical class 0.000 claims description 2
239000002516 radical scavenger Substances 0.000 claims description 2
239000001119 stannous chloride Substances 0.000 claims description 2
235000011150 stannous chloride Nutrition 0.000 claims description 2
238000006722 reduction reaction Methods 0.000 claims 4
QBWAQNXFYYZFJK-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-[(2-hydroxy-2-thiophen-2-ylethyl)amino]acetate Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)OC)NCC(O)C1=CC=CS1 QBWAQNXFYYZFJK-UHFFFAOYSA-N 0.000 claims 2
125000003944 tolyl group Chemical group 0.000 claims 2
OCYJXSUPZMNXEN-UHFFFAOYSA-N 2-amino-1-(4-nitrophenyl)propane-1,3-diol Chemical class OCC(N)C(O)C1=CC=C([N+]([O-])=O)C=C1 OCYJXSUPZMNXEN-UHFFFAOYSA-N 0.000 claims 1
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims 1
ITLKVIUDQDLIDL-UHFFFAOYSA-N methyl 6-chloro-1-[(5-thiophen-2-yl-2h-1,3-oxazol-3-yl)methyl]cyclohexa-2,4-diene-1-carboxylate Chemical compound C1OC(C=2SC=CC=2)=CN1CC1(C(=O)OC)C=CC=CC1Cl ITLKVIUDQDLIDL-UHFFFAOYSA-N 0.000 claims 1
150000002825 nitriles Chemical group 0.000 abstract description 4
239000000126 substance Substances 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
101150041968 CDC13 gene Proteins 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
239000000543 intermediate Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
KAJBPNFVEZFTIU-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(5-thiophen-2-yl-2h-1,3-oxazol-3-yl)acetate Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)OC)N(C=1)COC=1C1=CC=CS1 KAJBPNFVEZFTIU-UHFFFAOYSA-N 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
239000005528 B01AC05 - Ticlopidine Substances 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
238000003756 stirring Methods 0.000 description 4
229960005001 ticlopidine Drugs 0.000 description 4
PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 4
KTRZJULHTZAXIS-UHFFFAOYSA-N 2-thiophen-2-yloxirane Chemical compound C1OC1C1=CC=CS1 KTRZJULHTZAXIS-UHFFFAOYSA-N 0.000 description 3
OGUWOLDNYOTRBO-UHFFFAOYSA-N 4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1NCCC2=C1C=CS2 OGUWOLDNYOTRBO-UHFFFAOYSA-N 0.000 description 3
229910008066 SnC12 Inorganic materials 0.000 description 3
239000012458 free base Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
230000008707 rearrangement Effects 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 2
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 2
GKTWGGQPFAXNFI-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetic acid methyl ester Chemical compound C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl GKTWGGQPFAXNFI-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
229930040373 Paraformaldehyde Natural products 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
239000003146 anticoagulant agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
150000004683 dihydrates Chemical class 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000002050 international nonproprietary name Substances 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
150000002924 oxiranes Chemical group 0.000 description 2
229920002866 paraformaldehyde Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000007142 ring opening reaction Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000002904 solvent Substances 0.000 description 2
208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
239000007858 starting material Substances 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 description 1
ZEKCIGUKWWCEBM-UHFFFAOYSA-N 5-thiophen-2-yl-1,3-oxazolidine Chemical compound O1CNCC1C1=CC=CS1 ZEKCIGUKWWCEBM-UHFFFAOYSA-N 0.000 description 1
FCHZFFITTSJBBE-UHFFFAOYSA-N C1OC1C(=O)OC1=CC=CS1 Chemical compound C1OC1C(=O)OC1=CC=CS1 FCHZFFITTSJBBE-UHFFFAOYSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
238000007059 Strecker synthesis reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000002785 anti-thrombosis Effects 0.000 description 1
229940127217 antithrombotic drug Drugs 0.000 description 1
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
239000002585 base Substances 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000012267 brine Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
229940079593 drug Drugs 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
150000002148 esters Chemical class 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
UTWOZNRDJNWTPS-QMMMGPOBSA-N methyl (2s)-2-amino-2-(2-chlorophenyl)acetate Chemical compound COC(=O)[C@@H](N)C1=CC=CC=C1Cl UTWOZNRDJNWTPS-QMMMGPOBSA-N 0.000 description 1
MPRLVCAMGALKKA-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(5-thiophen-2-yl-1,3-oxazolidin-3-yl)acetate Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)OC)N(C1)COC1C1=CC=CS1 MPRLVCAMGALKKA-UHFFFAOYSA-N 0.000 description 1
UTWOZNRDJNWTPS-UHFFFAOYSA-N methyl 2-amino-2-(2-chlorophenyl)acetate Chemical compound COC(=O)C(N)C1=CC=CC=C1Cl UTWOZNRDJNWTPS-UHFFFAOYSA-N 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
230000006340 racemization Effects 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

CA 2352520 2001-07-06 2001-07-06 Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine Expired - Fee Related CA2352520C (fr)

Priority Applications (4)

Application Number	Priority Date	Filing Date	Title
CA 2352520 CA2352520C (fr)	2001-07-06	2001-07-06	Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine
US09/902,165 US6495691B1 (en)	2001-07-06	2001-07-11	Process for the preparation of tetrahydrothieno[3,2-c]pyridine derivatives
EP02745008A EP1404681A1 (fr)	2001-07-06	2002-07-05	Procede de preparation de derives de tetrahydrothieno 3,2-c]pyridine
PCT/CA2002/001017 WO2003004502A1 (fr)	2001-07-06	2002-07-05	Procede de preparation de derives de tetrahydrothieno[3,2-c]pyridine

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA 2352520 CA2352520C (fr)	2001-07-06	2001-07-06	Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine

Publications (2)

Publication Number	Publication Date
CA2352520A1 CA2352520A1 (fr)	2003-01-06
CA2352520C true CA2352520C (fr)	2007-10-02

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CA 2352520 Expired - Fee Related CA2352520C (fr)	2001-07-06	2001-07-06	Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine

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EP (1)	EP1404681A1 (fr)
CA (1)	CA2352520C (fr)
WO (1)	WO2003004502A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR100678287B1 (ko) *	2005-06-23	2007-02-02	한미약품 주식회사	클로피도그렐의 제조방법 및 이에 사용되는 중간체
US20070191609A1 (en) *	2006-02-13	2007-08-16	Lee Pharma Limited	Process for preparation of clopidogrel bisulphate form-1
PL380849A1 (pl) *	2006-10-17	2008-04-28	Adamed Spółka Z Ograniczoną Odpowiedzialnością	Krystaliczna postać racemicznego -(2-chlorofenylo)-6,7-dihydrotieno[3,2-c]pirydylo-5(4H)-octanu metylu, sposób jej wytwarzania i zastosowanie

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2424278A1 (fr) *	1978-04-24	1979-11-23	Parcor	Procede de preparation de thieno(2,3-c) et thieno(3,2-c)pyridines
FR2530247B1 (fr) *	1982-07-13	1986-05-16	Sanofi Sa	Nouveaux derives de la thieno (3, 2-c) pyridine, leur procede de preparation et leur application therapeutique

2001
- 2001-07-06 CA CA 2352520 patent/CA2352520C/fr not_active Expired - Fee Related
2002
- 2002-07-05 WO PCT/CA2002/001017 patent/WO2003004502A1/fr not_active Ceased
- 2002-07-05 EP EP02745008A patent/EP1404681A1/fr not_active Withdrawn

Also Published As

Publication number	Publication date
CA2352520A1 (fr)	2003-01-06
WO2003004502A1 (fr)	2003-01-16
EP1404681A1 (fr)	2004-04-07

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2001-07-06	EEER	Examination request
2012-07-06	MKLA	Lapsed

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