OA11061A - Preparation of Ä1s-Ä1a 2b 3b 4a(s*)ÜÜ1-(3-chloro-2-thienyl)methylÜpropylÜaminoÜ-3h-imidazoÄ4 5-bÜpyridin-3-ylÜ-n-ethyl-2 3-dihydroxycyclopentanecarboxamide - Google Patents

Preparation of Ä1s-Ä1a 2b 3b 4a(s*)ÜÜ1-(3-chloro-2-thienyl)methylÜpropylÜaminoÜ-3h-imidazoÄ4 5-bÜpyridin-3-ylÜ-n-ethyl-2 3-dihydroxycyclopentanecarboxamide Download PDF

Info

Publication number: OA11061A
Authority: OA; OAPI
Prior art keywords: amino; chloro; thienyl; propyl; methyl
Prior art date: 1996-12-11

Application number

OA9900123A

Other languages

English (en)

Inventor

Herve Garcia

Patrick Leon

Michael K O'brien

Tory H Powner

Laurence W Reilly

Harshavadan C Shah

Michael D Thompson

Ching T Tsuei

Benoit J Vanasse

Francis L Walther

Original Assignee

Rhone Poulenc Rorer Pharma

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.)

1996-12-11

Filing date

1999-06-11

Publication date

2002-02-27

1999-06-11 Application filed by Rhone Poulenc Rorer Pharma filed Critical Rhone Poulenc Rorer Pharma

2002-02-27 Publication of OA11061A publication Critical patent/OA11061A/en

Links

238000000034 method Methods 0.000 claims abstract description 60
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 73
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 71
150000001875 compounds Chemical class 0.000 claims description 69
-1 3-chloro-2-thienyl Chemical group 0.000 claims description 47
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 22
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 20
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 14
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 claims description 11
230000003301 hydrolyzing effect Effects 0.000 claims description 9
239000003513 alkali Substances 0.000 claims description 8
UKIZCTHOMJXNIX-UHFFFAOYSA-N 4-chloro-3-nitro-1h-pyridin-2-one Chemical compound [O-][N+](=O)C1=C(Cl)C=CNC1=O UKIZCTHOMJXNIX-UHFFFAOYSA-N 0.000 claims description 7
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
239000012458 free base Substances 0.000 claims description 7
238000002955 isolation Methods 0.000 claims description 7
ZEZJPIDPVXJEME-UHFFFAOYSA-N 2,4-Dihydroxypyridine Chemical compound OC=1C=CNC(=O)C=1 ZEZJPIDPVXJEME-UHFFFAOYSA-N 0.000 claims description 6
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 6
239000005695 Ammonium acetate Substances 0.000 claims description 6
229940043376 ammonium acetate Drugs 0.000 claims description 6
235000019257 ammonium acetate Nutrition 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
238000000746 purification Methods 0.000 claims description 6
GVWIBAQTEVKJFP-ZCFIWIBFSA-N (2r)-1-(3-chlorothiophen-2-yl)butan-2-amine Chemical compound CC[C@@H](N)CC=1SC=CC=1Cl GVWIBAQTEVKJFP-ZCFIWIBFSA-N 0.000 claims description 5
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
BKYGVGWYPFVKTK-UHFFFAOYSA-N 4-hydroxy-3-nitro-1h-pyridin-2-one Chemical compound OC=1NC=CC(=O)C=1[N+]([O-])=O BKYGVGWYPFVKTK-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
230000000911 decarboxylating effect Effects 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
238000006396 nitration reaction Methods 0.000 claims description 4
229910052725 zinc Inorganic materials 0.000 claims description 4
MWGIDWPSRDMIQN-UHFFFAOYSA-N 4-methoxy-2-oxo-1h-pyridine-3-carbonitrile Chemical compound COC=1C=CNC(=O)C=1C#N MWGIDWPSRDMIQN-UHFFFAOYSA-N 0.000 claims description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
229910052697 platinum Inorganic materials 0.000 claims description 3
RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims 2
239000004246 zinc acetate Substances 0.000 claims 2
VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 claims 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 1
KWUVPYOGESDCNX-UHFFFAOYSA-N n-ethylcyclopentanecarboxamide Chemical compound CCNC(=O)C1CCCC1 KWUVPYOGESDCNX-UHFFFAOYSA-N 0.000 claims 1
229960000314 zinc acetate Drugs 0.000 claims 1
235000013904 zinc acetate Nutrition 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 27
239000000243 solution Substances 0.000 description 24
239000003960 organic solvent Substances 0.000 description 23
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 22
239000012044 organic layer Substances 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
229940093499 ethyl acetate Drugs 0.000 description 13
235000019439 ethyl acetate Nutrition 0.000 description 13
239000010410 layer Substances 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000002585 base Substances 0.000 description 8
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
239000007787 solid Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000725 suspension Substances 0.000 description 8
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 7
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 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
238000013019 agitation Methods 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000008367 deionised water Substances 0.000 description 5
229910021641 deionized water Inorganic materials 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
235000017550 sodium carbonate Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000012455 biphasic mixture Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
229960001407 sodium bicarbonate Drugs 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
239000011701 zinc Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
150000003857 carboxamides Chemical class 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
239000002002 slurry Substances 0.000 description 3
229940001593 sodium carbonate Drugs 0.000 description 3
239000002904 solvent Substances 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
230000003276 anti-hypertensive effect Effects 0.000 description 2
230000003243 anti-lipolytic effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012267 brine Substances 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000008241 heterogeneous mixture Substances 0.000 description 2
150000004806 hydroxypyridines Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
150000004682 monohydrates Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
150000005299 pyridinones Chemical class 0.000 description 2
238000010992 reflux Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
125000003944 tolyl group Chemical group 0.000 description 2
229910052721 tungsten Inorganic materials 0.000 description 2
229940124024 weight reducing agent Drugs 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 1
ZENOMUAZAQGGNS-UHFFFAOYSA-N 1,2-dihydroxycyclopentane-1-carboxamide Chemical compound NC(=O)C1(O)CCCC1O ZENOMUAZAQGGNS-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-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
MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
MTYYAJNTQMAFKH-MRVPVSSYSA-N 4-[[(2r)-1-(3-chlorothiophen-2-yl)butan-2-yl]amino]-3-nitro-1h-pyridin-2-one Chemical compound C([C@@H](CC)NC=1C(=C(O)N=CC=1)[N+]([O-])=O)C=1SC=CC=1Cl MTYYAJNTQMAFKH-MRVPVSSYSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Inorganic materials [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 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
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000002253 anti-ischaemic effect Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
229940045200 cardioprotective agent Drugs 0.000 description 1
239000012659 cardioprotective agent Substances 0.000 description 1
230000003293 cardioprotective effect Effects 0.000 description 1
229940125692 cardiovascular agent Drugs 0.000 description 1
239000002327 cardiovascular agent Substances 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
238000004821 distillation Methods 0.000 description 1
OZECFIJVSAYAPH-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;chloride Chemical compound Cl.CCN(C(C)C)C(C)C OZECFIJVSAYAPH-UHFFFAOYSA-N 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
229960000443 hydrochloric acid Drugs 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 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
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/69—Two or more oxygen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (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)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)

OA9900123A 1996-12-11 1999-06-11 Preparation of Ä1s-Ä1a 2b 3b 4a(s*)ÜÜ1-(3-chloro-2-thienyl)methylÜpropylÜaminoÜ-3h-imidazoÄ4 5-bÜpyridin-3-ylÜ-n-ethyl-2 3-dihydroxycyclopentanecarboxamide OA11061A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US3276496P	1996-12-11	1996-12-11

Publications (1)

Publication Number	Publication Date
OA11061A true OA11061A (en)	2002-02-27

Family

ID=21866680

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900123A OA11061A (en)	1996-12-11	1999-06-11	Preparation of Ä1s-Ä1a 2b 3b 4a(s*)ÜÜ1-(3-chloro-2-thienyl)methylÜpropylÜaminoÜ-3h-imidazoÄ4 5-bÜpyridin-3-ylÜ-n-ethyl-2 3-dihydroxycyclopentanecarboxamide

Country Status (26)

Country	Link
US (2)	US6143894A (de)
EP (2)	EP0946550B1 (de)
JP (1)	JP2001506626A (de)
KR (4)	KR100510389B1 (de)
CN (3)	CN1191251C (de)
AP (1)	AP1063A (de)
AT (1)	ATE301120T1 (de)
AU (1)	AU738581B2 (de)
BG (1)	BG63805B1 (de)
BR (1)	BR9713705A (de)
CA (1)	CA2274630C (de)
DE (1)	DE69733897T2 (de)
DK (1)	DK0946550T3 (de)
EA (1)	EA001989B1 (de)
ES (1)	ES2242984T3 (de)
HU (1)	HUP0000342A3 (de)
IL (1)	IL130397A (de)
MX (1)	MXPA03006730A (de)
NO (2)	NO319722B1 (de)
OA (1)	OA11061A (de)
PT (1)	PT946550E (de)
SI (1)	SI0946550T1 (de)
SK (1)	SK71199A3 (de)
UA (1)	UA54479C2 (de)
WO (1)	WO1998025921A1 (de)
ZA (1)	ZA9711035B (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PT1140933E (pt)	1998-12-31	2004-12-31	Aventis Pharma Inc	Processo para preparar derivados n6-substituidos de desaza-adenosina
US7291603B2 (en) *	2002-07-24	2007-11-06	Ptc Therapeutics, Inc.	Nucleoside compounds and their use for treating cancer and diseases associated with somatic mutations
FR2846656B1 (fr) *	2002-11-05	2004-12-24	Servier Lab	Nouveaux derives d'imidazopyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU654507B2 (en) *	1990-09-25	1994-11-10	Rhone-Poulenc Rorer International (Holdings) Inc.	Compounds having antihypertensive and anti-ischemic properties
PL337888A1 (en) *	1997-07-03	2000-09-11	Du Pont Pharm Co	Imidazoprimidines and imidazopyridines for use in treating neurological disorders
KR20010087425A (ko) *	1998-12-21	2001-09-15	오흘러 로스 제이.	Ｎ6-치환된 데아자-아데노신 유도체의 제조방법

1997
- 1997-11-24 ES ES97950663T patent/ES2242984T3/es not_active Expired - Lifetime
- 1997-11-24 DE DE69733897T patent/DE69733897T2/de not_active Expired - Fee Related
- 1997-11-24 EA EA199900527A patent/EA001989B1/ru not_active IP Right Cessation
- 1997-11-24 EP EP97950663A patent/EP0946550B1/de not_active Expired - Lifetime
- 1997-11-24 EP EP05075298A patent/EP1609791A1/de not_active Withdrawn
- 1997-11-24 UA UA99073906A patent/UA54479C2/uk unknown
- 1997-11-24 HU HU0000342A patent/HUP0000342A3/hu unknown
- 1997-11-24 JP JP52670598A patent/JP2001506626A/ja not_active Ceased
- 1997-11-24 IL IL13039797A patent/IL130397A/xx not_active IP Right Cessation
- 1997-11-24 CN CNB011370718A patent/CN1191251C/zh not_active Expired - Fee Related
- 1997-11-24 KR KR10-1999-7005191A patent/KR100510389B1/ko not_active Expired - Fee Related
- 1997-11-24 KR KR1020057023521A patent/KR20060002029A/ko not_active Ceased
- 1997-11-24 BR BR9713705-7A patent/BR9713705A/pt not_active Application Discontinuation
- 1997-11-24 SI SI9730709T patent/SI0946550T1/xx unknown
- 1997-11-24 AU AU53607/98A patent/AU738581B2/en not_active Ceased
- 1997-11-24 SK SK711-99A patent/SK71199A3/sk unknown
- 1997-11-24 PT PT97950663T patent/PT946550E/pt unknown
- 1997-11-24 CN CN2005100037721A patent/CN1660842A/zh active Pending
- 1997-11-24 KR KR1020057004675A patent/KR100571690B1/ko not_active Expired - Fee Related
- 1997-11-24 MX MXPA03006730A patent/MXPA03006730A/es not_active Application Discontinuation
- 1997-11-24 KR KR1020057023522A patent/KR20060002030A/ko not_active Withdrawn
- 1997-11-24 CN CN97180580A patent/CN1090630C/zh not_active Expired - Fee Related
- 1997-11-24 CA CA002274630A patent/CA2274630C/en not_active Expired - Fee Related
- 1997-11-24 AT AT97950663T patent/ATE301120T1/de not_active IP Right Cessation
- 1997-11-24 DK DK97950663T patent/DK0946550T3/da active
- 1997-11-24 WO PCT/US1997/021439 patent/WO1998025921A1/en not_active Ceased
- 1997-11-24 AP APAP/P/1999/001550A patent/AP1063A/en active
- 1997-12-09 ZA ZA9711035A patent/ZA9711035B/xx unknown
1999
- 1999-01-19 US US09/233,591 patent/US6143894A/en not_active Expired - Fee Related
- 1999-06-09 NO NO19992795A patent/NO319722B1/no unknown
- 1999-06-11 BG BG103484A patent/BG63805B1/bg unknown
- 1999-06-11 OA OA9900123A patent/OA11061A/en unknown
2000
- 2000-07-28 US US09/627,657 patent/US6235909B1/en not_active Expired - Fee Related
2005
- 2005-05-12 NO NO20052327A patent/NO20052327D0/no unknown

Also Published As

Publication number	Publication date
AU738581B2 (en)	2001-09-20
US6235909B1 (en)	2001-05-22
EP0946550A1 (de)	1999-10-06
NO992795D0 (no)	1999-06-09
NO319722B1 (no)	2005-09-05
BG103484A (en)	2000-06-30
NO992795L (no)	1999-08-10
DK0946550T3 (da)	2005-08-29
AP1063A (en)	2002-04-26
HUP0000342A3 (en)	2001-01-29
HK1023998A1 (en)	2000-09-29
CN1240445A (zh)	2000-01-05
CN1191251C (zh)	2005-03-02
KR20000057505A (ko)	2000-09-15
PT946550E (pt)	2005-09-30
DE69733897D1 (de)	2005-09-08
CN1090630C (zh)	2002-09-11
KR100510389B1 (ko)	2005-08-31
MXPA03006730A (es)	2003-10-24
EA199900527A1 (ru)	2000-02-28
KR100571690B1 (ko)	2006-04-18
EP1609791A1 (de)	2005-12-28
WO1998025921A1 (en)	1998-06-18
IL130397A (en)	2005-11-20
HK1051862A1 (en)	2003-08-22
ZA9711035B (en)	1998-06-15
ES2242984T3 (es)	2005-11-16
HUP0000342A2 (hu)	2000-10-28
KR20060002030A (ko)	2006-01-06
CN1394859A (zh)	2003-02-05
BR9713705A (pt)	2000-05-09
BG63805B1 (bg)	2003-01-31
SI0946550T1 (en)	2005-10-31
EP0946550A4 (de)	2003-05-14
IL130397A0 (en)	2000-06-01
UA54479C2 (uk)	2003-03-17
US6143894A (en)	2000-11-07
NO20052327D0 (no)	2005-05-12
KR20050046793A (ko)	2005-05-18
NO20052327L (no)	1999-08-10
JP2001506626A (ja)	2001-05-22
SK71199A3 (en)	2000-07-11
CN1660842A (zh)	2005-08-31
CA2274630C (en)	2000-10-03
KR20060002029A (ko)	2006-01-06
EA001989B1 (ru)	2001-10-22
AP9901550A0 (en)	1999-06-30
AU5360798A (en)	1998-07-03
EP0946550B1 (de)	2005-08-03
ATE301120T1 (de)	2005-08-15
DE69733897T2 (de)	2006-06-01

Publication	Publication Date	Title
KR940006594B1 (ko)	1994-07-23	이미다조피리딘 화합물의 제조방법
KR910000897B1 (ko)	1991-02-12	레베카마이신 동족체
US6924291B2 (en)	2005-08-02	Process for making spiro isobenzofuranone compounds
US6429315B1 (en)	2002-08-06	Process for preparing N6-substituted adenosine derivatives
HUP0200839A2 (en)	2002-08-28	Novel synthesis and crystallization of piperazine ring-containing compounds and pharmaceutical compositions containing them
OA11061A (en)	2002-02-27	Preparation of Ä1s-Ä1a 2b 3b 4a(s*)ÜÜ1-(3-chloro-2-thienyl)methylÜpropylÜaminoÜ-3h-imidazoÄ4 5-bÜpyridin-3-ylÜ-n-ethyl-2 3-dihydroxycyclopentanecarboxamide
EP0453731A2 (de)	1991-10-30	Verfahren zur Herstellung von N-3-(1H-Imidazol-1-yl)- phenyl-4-(substituierten)-2-pyrimidinaminen
KR20180116371A (ko)	2018-10-24	4-알콕시-3-히드록시피콜린산의 제조 방법
IL152921A (en)	2004-05-12	Preparation of 4-hydroxy-3-nitro-2(1h)-pyridone from 2-hydroxy-3-cyano-4-methoxypyridine
EP1175420B1 (de)	2003-03-26	Verfahren zur herstellung von n6-substituierten deaza-adenosinderivaten
MXPA99005488A (en)	2000-01-21	PREPARATION OF [1S-[1a,2b,3b,4a(S*)]]-4-[7-[[1-(3-CHLORO-2-THIENYL) METHYL]PROPYL]AMINO]-3H-IMIDAZO[4,5-b]PYRIDIN-3-yl]-N-ETHYL-2,3-DIHYDROXYCYCLOPENTANECARBOXAMIDE
KR0151818B1 (ko)	1998-10-15	피리딜 이미다졸 유도체의 제조방법
HK1023998B (en)	2003-05-02	Preparation of[is-[1a,2b,3b,4a(s*)]]-4-[7-[[1-(3-chloro-2-thienyl) methyl] propyl]amino] -3h-imidazo [4,5-b]pyridin-3-yl] -n - ethyl-2,3-dihydroxycyclopentanecarboxamide
HK1051862B (en)	2005-09-23	Preparation of [1s-[1a,2b,3b,4a(s*)]]-4-[7-[[1-(3-chloro-2-thienyl)methyl]propyl]amino]-3h-imidazo[4,5-b]pyridin-3-yl]-n-ethyl-2,3-dihydroxycyclopentanecarboxamide
HK1081190A (en)	2006-05-12	Preparation of [1s-[1a,2b,3b,4a(s*)]]-4-[7-[[1-(3-chloro-2-thienyl) methyl]propyl]amino]-3h-imidazo[4,5-b]pyridii
JPH01268700A (ja)	1989-10-26	２’‐デオキシ‐５，６‐ジヒドロ‐５‐フルオロ‐６‐ヒドロキシウリジンおよびその製造法
JPWO2001017980A1 (ja)	2003-03-25	新規オキサゼピン誘導体の製造方法