Hydrochloric Acid → 2,6-Diamino-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidine

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Reaction Steps

N-(4-Hydroxymethyl-benzyl)-2,2,2-trifluoro-acetamide (12.0 g, 52 mmol) is dissolved in 80 ml dry DMSO, and NaH (4.08 g, 102 mmol, suspension 60% in mineral oil) is added in portions over 30 min under an argon atmosphere. After stirring at room temperature for 1 h, 2,6-diamino-4-chloropyrimidine (7.52 g, 52 mmol) is added and the reaction mixture heated to 60° C. over night. After cooling to room temperature, the mixture is poured into 1 L of 1 N HCl, and the product extracted with ethyl acetate (500 mL). The combined organic phases are washed with water and brine, dried over MgSO4, and the solvent evaporated. The residue is purified by flash column chromatography (ethyl acetate/methanol 100:0 to 80:20) to yield the title compound as a colorless solid (4.7 g, 13.78 mmol, 27%). 1H-NMR (400 MHz, DMSO-d6): δ=9.99 (t, J=6.1, 1H, CONH), 7.34 (d, J=8.1, 2H, ArH), 7.26 (d, J=8.1, 2H, ArH), 6.02 (s br, 2H, NH2), 5.89 (s br, 2H, NH2), 5.16 (s, 2H, OCH2), 5.01 (s, 1H, 4-H), 4.36 (d, J=6.1, 2H, CH2NCO) ppm.

Provenance & Evidence