2,4-Dichloropyrimidine → HCID 178463181, compound

Participants

Reaction Conditions

Reaction Steps

(2R,3R,4R,5R)-2-(2-Chloro-6-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclohexyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-3,4-diyl diacetate (Intermediate 1) (5.4 mmol) was treated with 1:1 trifluoroacetic acid/dichloromethane (20 ml) at room temperature for ca. 1 h. This was concentrated in vacuo and the residue was partitioned between dichloromethane (50 ml) and aqueous sodium bicarbonate (50 ml). The organics were washed with aqueous sodium bicarbonate (50 ml), dried over sodium sulfate and concentrated in vacuo to give a white solid. This was dissolved in propan-2-ol (100 ml). To this was added N,N-diisopropylethylamine (4 m. eq.) and 2,4-dichloropyrimidine (1 m. eq.). The reaction mixture was heated at 60° C. overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (50 ml) and water (50 ml). The organics were washed with water (50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by SPE (50 g, silica) eluting with x% ethyl acetate in dichloromethane where x=25, 50, 75. Fractions containing desired product were combined and concentrated in vacuo to yield the title compound as a colourless gum, 1.49 g.

Provenance & Evidence