(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 476386Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 476386
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]

Komponenten

4

Edukt 1

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

Produkt 1

HCID 54576733(R)-N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideAusbeute 11,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

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]+

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-d64c47b049b24b68a252295e8df41732
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637672B2

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