Cesium carbonate → Tert-butyl 4-hydroxy-4-((2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)piperidine-1-carboxylate

HRID 876511Notes

Reaction equation

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

Participants

Conditions

Temperature: 98 °C

Procedure

A mixture of 2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-ol (prepared according to Example 1; 20 mg, 0.72 mmol), tert-butyl-1-oxa-6-azaspiro[2.5]octane-6-carboxylate (178 mg, 0.83 mmol) and cesium carbonate (472 mg, 1.5 mmol) in dimethylacetamide (2.5 mL) was heated to 98° C. overnight. The mixture cooled to ambient temperature, filtered through celite and concentrated under reduced pressure. The residue was purified by silica gel chromatography with a gradient of dichloromethane to 1:9 methanol/dichloromethane to provide 170 mg (48%) of desired product.

Workup

temperatureThe mixture cooled to ambient temperature
filtrationfiltered through celite and
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography with a gradient of dichloromethane to 1:9 methanol/dichloromethane

Sources & evidence

ORD record: ord-1c7cdb203ebc4542adf8c04694e810b5
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987251B2

Reaction notes

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