Potassium Carbonate → (S)-N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476389Notes

Reaction equation

C([O:4][C@@H:5]([CH3:40])[C:6]([NH:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[C:20]([F:22])[C:19]([NH:23][C:24]([C:26]3([C:29](=[O:38])[NH:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH2:28][CH2:27]3)=[O:25])=[CH:18][C:17]=2[F:39])[CH:12]=[CH:11][N:10]=1)=[O:7])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.O>[F:22][C:20]1[CH:21]=[C:16]([O:15][C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6](=[O:7])[C@@H:5]([OH:4])[CH3:40])[CH:14]=2)[C:17]([F:39])=[CH:18][C:19]=1[NH:23][C:24]([C:26]1([C:29]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=2)=[O:38])[CH2:28][CH2:27]1)=[O:25]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of (S)-1-((4-(2,5-difluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-yl)amino)-1-oxopropan-2-yl acetate (180 mg, 0.323 mmol) in a solution of MeOH—H2O (3:1, 20 mL) was added potassium carbonate (111.6 mg, 0.809 mmol), the mixture was stirred at 25° C. for 12 h. The reaction mixture was concentrated and purified by prep-TLC to give (S)—N-(2,5-difluoro-4-((2-(2-hydroxypropanamido)pyridin-4-yl)oxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (100 mg, 60% yield). 1H NMR (400 MHz, Methanol-d4): δ 8.21-8.16 (m. 2H), 7.78 (d, J=2.4 Hz, 1H), 7.54-7.51 (m, 2H), 7.28-7.24 (m, 1H), 7.10-7.05 (m, 2H), 6.76-6.74 (dd, J=6.0, 2.4 Hz, 1H), 4.23 (q, J=6.8 Hz, 1H), 1.75-1.67 (m, 4H), 1.39 (d, J=6.8 Hz, 3H); MS (ESI): m/z 515.2 [M+H]+.

Workup

concentrationThe reaction mixture was concentrated
custompurified by prep-TLC

Sources & evidence

ORD record: ord-a4880afed705481892a3bde4702fbe29
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637672B2

Reaction notes

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