Cesium carbonate → N-(4-(7-(((5R)-4-oxaspiro[2.4]heptane-5-yl)methoxyl)quinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxamide

HRID 1969383Notes

Reaction equation

[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]4[C:23](=[O:35])[N:24]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[N:25]([CH3:28])[C:26]=4[CH3:27])=[O:21])=[CH:15][C:14]=3[F:36])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:48][C@H:49]1[CH2:55][CH2:54][C:51]2([CH2:53][CH2:52]2)[O:50]1)(=O)=O>CN(C)C(=O)C>[CH2:52]1[C:51]2([CH2:54][CH2:55][C@H:49]([CH2:48][O:1][C:2]3[CH:11]=[C:10]4[C:5]([C:6]([O:12][C:13]5[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]6[C:23](=[O:35])[N:24]([C:29]7[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=7)[N:25]([CH3:28])[C:26]=6[CH3:27])=[O:21])=[CH:15][C:14]=5[F:36])=[CH:7][CH:8]=[N:9]4)=[CH:4][CH:3]=3)[O:50]2)[CH2:53]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a mixture of N-(4-(7-hydroxyquinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxamide (300 mg, 0.62 mmol) and cesium carbonate (1.0 g, 3.1 mmol, Aladdin) in N,N-dimethylacetamide (1 mL) was added ((5R)-4-oxaspiro[2.4]heptane-5-yl)methyl methanesulfonate (187.5 mg, 0.91 mmol) in 3 mL of N,N-dimethylacetamide. After stirring at 40° C. for 3 days, the reaction mixture was concentrated in vacuo and was chromatographed with a silica gel column (1:6 (v/v) n-hexane/EtOAc) to afford the title compound as a colorless solid (220 mg, 60%).

Workup

concentrationthe reaction mixture was concentrated in vacuo
customwas chromatographed with a silica gel column (1:6 (v/v) n-hexane/EtOAc)

Sources & evidence

ORD record: ord-8bc54604dc3742588a9952e90dc2f58f
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426585B2

Reaction notes

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