(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 476386ノート

反応式

HRID 476386 の反応式
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]

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9942167Palladium hydroxide触媒HCID 887Methanol溶媒

実験手順

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]+

後処理

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

出典と根拠

ORDレコード
ord-d64c47b049b24b68a252295e8df41732
出典データセット
uspto-grants-2014_01
特許番号
US08637672B2

反応ノート

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