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    • 1. 发明授权
    • Process for the preparation of CGRP antagonist
    • 制备CGRP拮抗剂的方法
    • US07829699B2
    • 2010-11-09
    • US12226244
    • 2007-04-06
    • Kevin BelykNelo Rivera
    • Kevin BelykNelo Rivera
    • C07D471/04
    • C07D471/04
    • An efficient synthesis for the preparation of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1 -carboxamide, by coupling (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one and 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride with 1,1′-carbonyldiimidazole (“CDI”) as carbonyl source; and an efficient preparation of the potassium salt of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide.
    • 制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] -4- (3R,6S)-3-氨基-6-(2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺, (2,2-二氟苯基)-1-(2,2,2-三氟乙基)氮杂环庚烷-2-酮和2-氧代-1-(4-哌啶基)-2,3-二氢-1H-咪唑并[4,5-b] 吡啶二盐酸盐与1,1'-羰基二咪唑(“CDI”)作为羰基源; 并且有效制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] - 4-(2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺。
    • 2. 发明申请
    • Process for the Preparation of Cgrp Antagonist
    • Cgrp拮抗剂的制备方法
    • US20090281306A1
    • 2009-11-12
    • US12226244
    • 2007-04-06
    • Kevin BelykNelo Rivera
    • Kevin BelykNelo Rivera
    • C07D401/14
    • C07D471/04
    • An efficient synthesis for the preparation of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide, by coupling (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one and 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride with 1,1′-carbonyldiimidazole (“CDI”) as carbonyl source; and an efficient preparation of the potassium salt of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide.
    • 制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] -4- (3R,6S)-3-氨基-6-(2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺, (2,2-二氟苯基)-1-(2,2,2-三氟乙基)氮杂环庚烷-2-酮和2-氧代-1-(4-哌啶基)-2,3-二氢-1H-咪唑并[4,5-b] 吡啶二盐酸盐与1,1'-羰基二咪唑(“CDI”)作为羰基源; 并且有效制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] - 4-(2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺。
    • 5. 发明申请
    • CGRP Antagonist Salt
    • CGRP拮抗剂盐
    • US20100286122A1
    • 2010-11-11
    • US12086670
    • 2007-04-06
    • Kevin Belyk
    • Kevin Belyk
    • A61K31/55C07D401/14A61P25/06
    • C07D471/04
    • An efficient synthesis for the preparation of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide, by coupling (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one and 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride with 1,1′-carbonyldiimidazole (“CDI”) as carbonyl source; an efficient preparation of the potassium salt of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide; efficient syntheses for the preparation of intermediates (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one and 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride, and the potassium salt of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide including the potassium salt ethanolate and potassium salt hydrate.
    • 制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] -4- (3R,6S)-3-氨基-6-(2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺, (2,2-二氟苯基)-1-(2,2,2-三氟乙基)氮杂环庚烷-2-酮和2-氧代-1-(4-哌啶基)-2,3-二氢-1H-咪唑并[4,5-b] 吡啶二盐酸盐与1,1'-羰基二咪唑(“CDI”)作为羰基源; 有效制备N - [(3R,6S)-6-(2,3-二氟苯基)-2-氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] -4 - (2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)哌啶-1-甲酰胺; 制备中间体(3R,6S)-3-氨基-6-(2,3-二氟苯基)-1-(2,2,2-三氟乙基)氮杂环庚烷-2-酮和2-氧代-1- (4-哌啶基)-2,3-二氢-1H-咪唑并[4,5-b]吡啶二盐酸盐和N - [(3R,6S)-6-(2,3-二氟苯基)-2 - 氧代-1-(2,2,2-三氟乙基)氮杂环庚烷-3-基] -4-(2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基) 哌啶-1-甲酰胺,包括钾盐乙醇化物和钾盐水合物。