5-amino-1,2,4-thiadiazol-3(2H)-one → HCID 54180947, compound

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Reaction Steps

5-Amino-1,2,4-thiadiazol-3-one (1, 2.0 g, 0.017 mole) was silylated as described in example II, and dissolved in dry dichloroethane (100 ml). 1,3,5-Tri-O-acetyl-2-deoxy-D-ribofuranose [M. J. Robins and R. K. Robins, J. Amer. Chem. Soc., 87, 4934 (1965); 4.4 g, 0.017 mole] in dichloroethane (25 ml) was added followed by stannic chloride (2.1 ml). The reaction mixture was protected from moisture and stirred at ambient temperature overnight, before it was poured into 250 ml of cold, saturated aqueous sodium bicarbonate solution containing 200 ml of chloroform keeping the mixture basic at all times. The organic layer was separated and washed with water (2 × 100 ml) before it was dried over anhydrous sodium sulfate. The solvent was evaporated to dryness and the residual gum was chromatographed on silica gel column (4 × 70 ml) using chloroform:methanol (95:5, v/v) as the solvent. The band carrying the products was collected and evaporated to dryness, leaving 0.4 g of gummy blocked anomeric nucleosides (5) which was dissolved in anhydrous methanol (25 ml). The methanolic solution was treated with 1N sodium methoxide in methanol till the pH of the solution was 8.5 and stirred at ambient temperature for 2 hr. The sodium ions were removed by stirring the reaction mixture with Amberlite IRC-50 (H+) resin (5 g, dry weight) for 15 min before the neutral solution, free from resin, was evaporated to dryness. The residual gum was subjected to preparative tlc (silica gel) using ethyl acetate:water:n-propanol(4:2:1, v/v, upper phase) as the developer. The bands carrying the homogeneous products were eluted with the same solvent system and evaporated to dryness. The residue was crystallized from water to yield 80 mg of 5-amino-2-(2-deoxy-α-D-ribofuranosyl)-1,2,4-thiadiazol-3-one (11), m.p. > 150° (dec.) 1H nmr (Me2SO-d6) multiplet of four centered at δ6.1 and other protons.

Provenance & Evidence