Water → 6-Chloro-2-[1-(1-isoquinolyl)ethylsulfanyl]pyrimidin-4-amine

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Reaction Steps

4-Amino-6-chloro-2-mercapto-pyrimidine mesylate salt (1.29 g, 5 mmole) is dissolved in 8 ml dry dimethylformamide in a 50 ml one neck round bottom flask under nitrogen. The solution is treated with 60% sodium hydride (400 mg, 10 mmole) (exotherm) and the mixture is stirred 45 min. 1-(1-chloroethyl)-isoquinoline (958 mg, 5 mmole) in 2×2 ml dry dimethylformamide, is added to the reaction and the mixture is stirred overnight at room temperature. The reaction mixture is poured into 200 ml water and is extracted with 4×50 ml ethyl acetate. The combined organics are backwashed with 4×50 ml 50% saturated sodium chloride. The organics are dried over potassium carbonate and are concentrated in vacuo to a yellow oil. The crude material is chromatographed over 100 g silica gel (230-400 mesh), eluting with 25% acetone/hexane while collecting 22 ml fractions. Fractions 27-39 are combined and concentrated to given a pale yellow foam. Crystallization from diethyl ether afforded 847 mg (54%) of 4-Amino-6-chloro-2-(1-(1-isoquinolyl)ethyl)thio-pyrimidine (Cpd #232) as an off-white solid.

Provenance & Evidence