Water → N-(4-((4-Aminopyrimidin-2-yloxy)methyl)benzyl)-2,2,2-trifluoroacetamide

HRID 1516779Notes

Reaction equation

[F:1][C:2]([F:16])([F:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].Cl[C:20]1[N:25]=[C:24]([NH2:26])[CH:23]=[CH:22][N:21]=1.O>CC(N(C)C)=O>[NH2:26][C:24]1[CH:23]=[CH:22][N:21]=[C:20]([O:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([CH2:6][NH:5][C:3](=[O:4])[C:2]([F:15])([F:16])[F:1])=[CH:8][CH:9]=2)[N:25]=1

Participants

Conditions

Temperature: 90 °C

Procedure

760 mg (3.25 mmol) 2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide is dissolved in 3 mL dry dimethylacetamide under argon atmosphere, and 273 mg (8.15 mmol) NaH is added over 5 min. 211 mg (1.63 mmol) 2-Chloropyrimidin-4-amine is then added and the solution stirred at 90° C. over night. 1 mL Water is added carefully to quench all excess NaH, and the mixture poured into 50 ml of 0.5 N HCl. The crude product is extracted with ethyl acetate, the combined organic phases washed with brine and dried over MgSO4. After evaporation of the solvent, the product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1). Yield: 350 mg (52%). ESI-MS m/z 327 [M+H]+.

Workup

customto quench all excess NaH
additionthe mixture poured into 50 ml of 0.5 N HCl
extractionThe crude product is extracted with ethyl acetate
washthe combined organic phases washed with brine
dry with materialdried over MgSO4
customAfter evaporation of the solvent
customthe product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1)

Sources & evidence

ORD record: ord-b5beb94f72b34ae3b4a7a8f1a8096989
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08227602B2

Reaction notes

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