[C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[C:6]([NH:11][C:12]1[N:17]=[CH:16][C:15]([C:18](=[O:21])[CH2:19]Br)=[CH:14][N:13]=1)(=[O:10])[CH:7]([CH3:9])[CH3:8].C(O)(=O)C.N>C(#N)C>[C:6]([NH:11][C:12]1[N:17]=[CH:16][C:15]([CH:18]([CH2:19][NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])[OH:21])=[CH:14][N:13]=1)(=[O:10])[CH:7]([CH3:9])[CH3:8]To a solution of 1.146 g of tert. -butylamine in 200 ml of dry acetonitrile, 2.05 g of solid 2-isobutyramido-5-(bromoacetyl)pyrimidine was added. The reaction mixture was stirred for 30 minutes and then gaseous hydrochloric acid was bubbled into the reaction mixture. The reaction mixture was then diluted with 300 ml of ether and the resulting precipitate collected by filtration. The precipitate was dissolved in 43 ml of anhydrous methanol and the resulting solution cooled to 5° C. Sodium borohydride (1.46 g) was slowly added (vigorous reaction) to this solution and the resulting mixture stirred for 1 hour in the cold. Acetic acid (5 ml) was added and then the pH of the reaction mixture was adjusted with concentrated aqueous ammonia to approximately pH 6. This solution was extracted with methylene chloride (3×50 ml). The combined extracts were washed with saturated sodium chloride solution and dried with anhydrous magnesium sulfate. The extracts were concentrated and the residue chromatographed on silica gel (90/10/1 methylene chloride/methanol/ ammonia) to afford 980 mg of product.
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