Cesium carbonate → 1-((4-(4-(1-(Carbamoyl)cyclopropanecarboxamido)-2-fluorophenoxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropyl benzoate

HRID 1517908Notes

Reaction equation

[C:1]([O:9][C:10]1([CH2:13][O:14]S(C)(=O)=O)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]1[CH:21]=[C:22]([N:40](C2C=CC(F)=CC=2)[C:41]([C:43]2([C:46]([NH2:48])=[O:47])[CH2:45][CH2:44]2)=[O:42])[CH:23]=[CH:24][C:25]=1[O:26][C:27]1[C:36]2[C:31](=[CH:32][C:33](O)=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[C:1]([O:9][C:10]1([CH2:13][O:14][C:33]2[CH:32]=[C:31]3[C:36]([C:27]([O:26][C:25]4[CH:24]=[CH:23][C:22]([NH:40][C:41]([C:43]5([C:46](=[O:47])[NH2:48])[CH2:45][CH2:44]5)=[O:42])=[CH:21][C:20]=4[F:19])=[CH:28][CH:29]=[N:30]3)=[CH:35][C:34]=2[O:37][CH3:38])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 45 °C

Procedure

To a mixture of 1-((methylsulfonyloxy)methyl)cyclopropyl benzoate (801 mg, 2.97 mmol) and N-(3-fluoro-4-(7-hydroxy-6-methoxy quinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1 g, 1.98 mmol) in DMA (5 mL) were added Cs2CO3 (1.93 g, 5.94 mmol, Aladdin). The reaction was heated at 45° C. overnight. The solvent was then removed in vacuo, and the residual was diluted with CHCl3 (30 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residual was purified by a silica gel column chromatography (EtOAc) to afford the title compound as a light yellow solid (800 mg, 60%).

Workup

customThe solvent was then removed in vacuo
additionthe residual was diluted with CHCl3 (30 mL)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customThe residual was purified by a silica gel column chromatography (EtOAc)

Sources & evidence

ORD record: ord-8926a9727da64f71a844e7f5d7b3542d
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232294B2

Reaction notes

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