Cesium carbonate → N-(3-fluoro-4-((7-(2-hydroxy-2-methylpropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2277377Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH:22][C:23]([C:25]2[C:26](=[O:38])[N:27]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:28]([CH3:31])[C:29]=2[CH3:30])=[O:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:45][C:46]1([O:49][CH2:48]1)[CH3:47]>CN(C=O)C.CC(O)(C)C>[F:1][C:2]1[CH:3]=[C:4]([NH:22][C:23]([C:25]2[C:26](=[O:38])[N:27]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:28]([CH3:31])[C:29]=2[CH3:30])=[O:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:45][C:46]([OH:49])([CH3:48])[CH3:47])=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of N-(3-fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carb oxamide (5.00 g, 9.73 mmol) and Cs2CO3 (1.35 g, 4.14 mmol) in DMF/t-BuOH (15.60 mL/3.90 mL) was added isobutylene oxide (8.60 mL, 97.30 mmol). The reaction was warmed to 50° C. and stirred for three days. The reaction mixture was concentrated in vacuo and purified by a silica gel column chromatography (1:25 (v/v)=methanol/dichloromethane) to give the title compound as a white solid (2.28 g, 40%).

Workup

concentrationThe reaction mixture was concentrated in vacuo
custompurified by a silica gel column chromatography (1:25 (v/v)=methanol/dichloromethane)

Sources & evidence

ORD record: ord-0b871b75c3444f8d9a5a1b395fe98704
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133162B2

Reaction notes

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