Reaction Steps
To a solution of NH4OH in a H2O--THF mixture was added (1R,2R)-2-(4-cyanophenyl)-N-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-methyl thiazole-5-carboxamide methanesulfonate (0.5 g, 0.84 mmol, obtained in example 31). The mixture was refluxed for 2 days, then was concentrated and the aqueous residue was extracted with CHCl3. The organic layer was separated, dried over Na2SO4, filtered and the filtrate was concentrated to a solid (0.53 g). This was purified by flash chromatography to give the title compound as a white solid: 133°-135° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 7.98 (d, J=8.3, 2H, arom), 7.87 (d, J=8.3, 2H, arom), 7.81 (s, 1H, triazole), 7.71 (s, 1H, triazole), 7.40 (dt, Jd =6.5, Jt =8.8, 1H, arom), 6.8-6.6 (m, 2H, ) arom), 6.57 (br d, J=9.5, 1H, NH), 6.27 (br s, 2H, NH2), 5.63 (s, 1H, OH), 5.05 (d, J=14.5, 1H, TrCH(H)), 4.98 (br quint, J=7, 1H, CHMe), 4.57 (d, J=14.5, 1H, TrCH(H)), 2.81 (s, 3H, Me-thiazole), 1.05 (d, J=6.8, 3H, MeCH); MS 288 and 289 (ethylaminoacyl group, C14H15N3O2S), 245 (acyl group, C12H9N2O2S), 224 (Tr--CH2COHAr, C10H8F2N3O); [α]D =-74.5° (c 1, MeOH). Analysis calculated for C24H22F2N6O3S: C 56.24; H 4.33; N 16.40; S 6.26. Found: C 55.90; H 4.64; N 15.29; S 5.62.
