Oxalyl chloride → HCID 59268022, compound

Participants

Reaction Conditions

Reaction Steps

Activation of 300 mg (1.27 mmol) of 2-methyl-2-{[(2R)-oxan-2-ylmethyl]sulfanyl}propanoic acid as the corresponding acid chloride is achieved by treatment with oxalyl chloride (305 mg, 2.54 mmol) and DMF (1 drop) in DCM (10 mL) at room temperature for 18 h. The solvent is removed by distillation, and then azeotroped with toluene (3×5 mL). This acid chloride is dissolved in toluene (5 mL) and added dropwise to a stirred suspension of 565 mg (1.37 mmol) of 5-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-[1,3,4]thiadiazol-2-ylamine and 0.48 mL (2.75 mmol) of N,N-diisopropylethylamine in toluene (10 mL) at room temperature. After complete addition the reaction is heated to 60° C. for 18 h. The reaction is cooled to room temperature and the solvent is removed under reduced pressure. The residue is purified by column chromatography (silica, eluent: heptanes, 0-20% ethyl acetate) to yield 658 mg of N-(5-{1-[(tert-butyldiphenylsilyl)oxy]-2-methylpropan-2-yl}-1,3,4-thiadiazol-2-yl)-2-methyl-2-{[(2R)-oxan-2-ylmethyl]sulfanyl}propanamide. Yield: 73%; m/z 612 [M+H], 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.01-1.09 (9H, m), 1.21-1.70 (17H, m), 1.75-1.84 (1H, m), 2.57-2.72 (2H, m), 3.33 (1H, td, J=11.71, 2.06 Hz), 3.38-3.47 (1H, m), 3.70-3.75 (2H, m), 4.10-4.17 (1H, m), 7.34-7.47 (6H, m), 7.56-7.64 (4H, m), 10.94 (1H, br. s.)

Provenance & Evidence