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

HRID 876509Notes

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.CS(O[CH2:27][C:28]([CH3:39])([CH3:38])[CH2:29][NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[CH3:27][C:28]([CH3:39])([CH2:38][O:21][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[N:12]=[C:11]([C:8]1[N:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][C:4]3=[N:10][N:9]=1)[CH:20]=[CH:19]2)[CH2:29][NH:30][C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35]

Participants

Conditions

Temperature: 50 °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; 50 mg, 0.18 mmol), 3-(tert-butoxycarbonylamino)-2,2-dimethylpropyl methanesulfonate (102 mg, 0.36 mmol) and cesium carbonate (118 mg, 0.36 mmol) in dimethylacetamide (2 mL) was heated to 50° C. overnight. The mixture was concentrated under reduced pressure and purified by successive silica gel chromatography, eluting with 1:9 methanol/dichloromethane and a gradient of dichloromethane to 1:9 methanol/dichloromethane. The residue was then purified by preparative thin layer chromatography eluting with 3:7 acetone/dichloromethane to provide 35 mg (42%) of desired product as a light yellow solid.

Workup

concentrationThe mixture was concentrated under reduced pressure
custompurified by successive silica gel chromatography
washeluting with 1:9 methanol/dichloromethane
customThe residue was then purified by preparative thin layer chromatography
washeluting with 3:7 acetone/dichloromethane

Sources & evidence

ORD record: ord-e55f3a6e9b7f433098a6f988c483dff8
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987251B2

Reaction notes

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