(R)-N-(4-((2-(2-(benzyloxy)propanamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide → (R)-N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476386노트

반응식

HRID 476386 반응식
C([O:8][C@H:9]([CH3:44])[C:10]([NH:12][C:13]1[CH:18]=[C:17]([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([NH:27][C:28]([C:30]3([C:33]([NH:35][C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)=[O:34])[CH2:32][CH2:31]3)=[O:29])=[C:22]([F:43])[CH:21]=2)[CH:16]=[CH:15][N:14]=1)=[O:11])C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[F:43][C:22]1[CH:21]=[C:20]([O:19][C:17]2[CH:16]=[CH:15][N:14]=[C:13]([NH:12][C:10](=[O:11])[C@H:9]([OH:8])[CH3:44])[CH:18]=2)[C:25]([F:26])=[CH:24][C:23]=1[NH:27][C:28]([C:30]1([C:33]([NH:35][C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)=[O:34])[CH2:32][CH2:31]1)=[O:29]

참가 물질

4

반응물 1

HCID 66604800(R)-N-(4-((2-(2-(benzyloxy)propanamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

생성물 1

HCID 54576733(R)-N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide수율 11.7%

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매HCID 887Methanol용매

실험 절차

To a solution of (R)—N-(4-((2-(2-(benzyloxy)propanamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (200 mg, 0.331 mmol) in methanol (20 mL) was added Pd(OH)2 (50 mg). The mixture was then hydrogenated (1 atm) for 12 h. The reaction mixture was filtered, concentrated and purified by HPLC chromatography to give (R)—N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (20 mg, 11.7% yield). 1H NMR (400 MHz, CD3OD): δ 8.23-8.18 (m, 2H), 7.69 (s, 1H), 7.54-7.50 (m, 2H), 7.31-7.28 (m, 1H), 7.09-7.05 (m, 2H), 6.86-6.84 (m, 1H), 4.28-4.23 (q, J=6.8 Hz, 1H), 1.76-1.67 (m, 4H), 1.39 (d, J=6.8 Hz, 3H); MS (ESI); m/z 515.1 [M+H]+

후처리

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. custompurified by HPLC chromatography

출처 및 근거

ORD 기록
ord-d64c47b049b24b68a252295e8df41732
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637672B2

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