Dimethyl Sulfoxide → HCID 54336098, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (-78° C.) solution of DMSO (0.29 mL, 4.17 mmol) in CH2Cl2 (10 mL) was added a solution of trifluoroacetic anhydride (0.30 mL, 2.09 mmol) in CH2Cl2 (1 mL) dropwise. After ten minutes, a solution of (1R,2R)-2-(4-cyanophenyl)-N-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-N-(2-hydroxyethyl)-4-methylthiazole-5-carboxamide (0.9 g, 1.67 mmol, obtained in example 82) in CH2Cl2 (3 mL) was added. The mixture was stirred for 1 h, and then triethylamine (1.1 mL, 8.3 mmol) was added. The reaction mixture was allowed to warm up to -40° C. and was stirred at this temperature for 1.5 h and then at -10° C. for 30 min. 10% aqueous NaHCO3 solution was added, the organic phase was separated and the aqueous phase was extracted with chloroform. The combined organic extracts were washed with water, dried over anhydrous Na2SO4, filtered and concentrated to a crude product. Purification by flash chromatography afforded the title compound as a white solid: mp 225°-228° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 8.06 and 8.05 (d, J=8.4, 2H, arom), 7.77 (s, 1H, triazole), 7.76 (d, J=8.4, 2H, arom), 7.35 (dt, Jd =6.5, Jt =8.8, 1H, arom), 7.30 (s, 1H, triazole), 7.0-6.7 (m, 2H, arom), 5.83 (m, 1H, OCHOH), 5.8-3.2 (several broad signals), 2.57 and 2.55 (s, 3H, Me-thiazole), 1.14 (d, J=6.8, 3H, MeCH); [α]D =-79.8° (c 1, CHCl3). Analysis calculated for C26H22F2N6O3S.1/2H2O: C 57.24; H 4.21; N 15.40; S 5.86. Found: C 57.49; H 4.03; N 15.08; S 5.69.

Provenance & Evidence