Cesium carbonate → 2-[{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]pyrimidin-4-yl}(pyridin-4-yl)amino]ethanol

HRID 1776420Notes

Reaction equation

[CH2:1]([O:3][C:4]1[CH:32]=[C:31]([F:33])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[CH:21]=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:34])[CH:5]=1)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[O:41]1[CH2:45][CH2:44]OS1=O>CN(C=O)C>[CH2:1]([O:3][C:4]1[CH:32]=[C:31]([F:33])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([N:24]([C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[CH2:44][CH2:45][OH:41])[CH:21]=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:34])[CH:5]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

120 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)-pyrimidin-4-amine (5-1-1, 0.262 mmol, 1. eq.) were suspended in 12 ml of dry DMF. 426 mg of cesium carbonate (1.31 mmol, 5 eq.) and 142 mg of 1,3,2-dioxathiolane 2-oxide (1.31 mmol, 5 eq.) were added under nitrogen atmosphere. The reaction mixture was stirred at 60° C. bath temperature for 18 hours. 142 mg of 1,3,2-dioxathiolane 2-oxide (1.31 mmol, 5 eq.) were added and the mixture was stirred at 60° C. bath temperature for further 22 hours. Then the mixture was partitioned between water and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography and preparative TLC to yield 14.2 mg (0.03 mmol, 10.5%) of the analytically pure target compound.

Workup

stirringthe mixture was stirred at 60° C. bath temperature for further 22 hours
customThen the mixture was partitioned between water and dichloromethane/isopropanol 4:1
customThe phases were separated
extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
dry with materialThe combined organic layers were dried over magnesium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography and preparative TLC
customto yield 14.2 mg (0.03 mmol, 10.5%) of the analytically pure target compound

Sources & evidence

ORD record: ord-181902f6126c4929b00925a825a9f94b
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265763B2

Reaction notes

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