Stavudine → Stavudine DMA

Participants

Reaction Conditions

Reaction Steps

Crude slightly beige Stavudine (15.9 g, 92.03% pure, 0.0653 mole) was combined with N,N-dimethylacetamide (23.86 g, 1.5 parts) and heated to 75-80° C. when all solids had dissolved. Heating was stopped and the solution was allowed to cool on its own and within minutes crystals began to form. The mixture was further cooled to 0-50° C. and maintained for 2.5 hours. The crystals were filtered, washed with acetone (2×8 mL) and dried to give white Stavudine-DMA solvate (16.04 g, 0.0515 mole, 78.9%) with a chromatographic purity of 99.59%. Since a filtration step was not employed above, when isolating pure stavudine a filtration step would have to be introduced. A further purified Stavudine.DMA solvate had an HPLC purity of 99.98% and the following characterization. The melting point was 132.4-134.8° C. The optical rotation [α]D25=−31.2°. Analyzed for C14H21N3O5 (MW=311.33): C;54.01; H,6.80; N;13:50 Found: C, 53.96; H,6.76; N,13.35. The 300 MHz 1HNMR in DMSO-d6 showed. δ1.74 (s, 3H, Stavudine-CH3); 1.97 (s,3H, CH3); 2.80 and 2.95 (2×s, 2×3H, N(CH3)2); 3.61 (m,2H, 2×H-5′); 4.78 (s, 1H,H-4′); 6.80 (t, 1H, 2×J=1.4, H-2′); 7.66 (s, 1H, H-6); 11.30 (s, 1H, NH). The Stavudine portion of the above spectrum agrees with the literature values (J. Med, Chem, 32, 461 (1989))

Provenance & Evidence