Hydrochloric Acid → (1S,4R)-4-(2-Amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1-methanol hydrochloride

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Reaction Steps

A mixture of (1 S,4R)-4-[(2-amino-6-chloro-5-formamido-4-pyrimidinyl)amino]-2-cyclopentene-1-methanol (Example 7, 1.00 g, 3.50 mmol) and triethylorthoformate (Aldrich, Sure Seat 18 mL) was stirred while concentrated hydrochloric acid (37%, 1.25 mL) was added in one portion. The resulting clear, colorless solution was stirred under nitrogen. A white precipitate began to form after 15 minutes. After 4 hours, TLC of a drop of the reaction mixture dissolved in methanol and neutralized with sodium hydroxide (silica gel plates developed in 10% methanol-chloroform, visualized in UV light) showed almost complete conversion of VIa to a higher-Rf material. The precipitate was filtered, washed with t-butyl methyl ether (15 mL) and dried at 0.2 mm Hg/25° C. for 18 hours to give the title compound as a white powder (975 mg, 92%), m.p. >300° C. dec.; mass spectrum (CI/CH4): 266(M+1); 1H-NMR (DMSO-d6) δ: 8.18 (s, 1, purine CH), 7.2-6.7 (br s, NH2, OH overlapped by water), 6.20 and 5.90 (both m, 1 each, CH═CH), 5.48 (m, 1, NCH), 3.47 (d, J=5.7 Hz, 2, CH20), 2.90 (m, 1, CH), 2.75-2.55 and 1.75-1.60 (both m, 1 each, CH2).

Provenance & Evidence