Reaction Steps
To a solution of Na2CO3 (0.72 g, 6.77 mmol) in a mixture of H2O (5 mL) and THF (5 mL) 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) and hydroxylamine hydrochloride (0.29 g, 4.23 mmol). The reaction mixture was stirred at room temperature overnight, and was then concentrated and the aqueous residue extracted with CHCl3. The organic phase was separated, dried over Na2SO4, filtered and the filtrate was concentrated to a solid. Purification by flash chromatography afforded the title compound as a pale yellow solid: mp 135°-148° C.; 1H NMR (300 MHz, MeOH--d4) δ (MeOH--d4) 8.24 (s, 1H, triazole), 8.03 (dt, Jt =1.6, Jd =8.5, 2H, arom), 7.78 (dt, Jt =1.6, Jd =8.5, 2H, arom), 7.71 (s, 1H, triazole), 7.38 (dt, Jd =6.5, Jt =8.8, 1H, arom), 6.97 (ddd, J=2.4, J=8.7, J=11.5, 1H, arom), 6.84 (dt, Jd =2.1, Jt =8.0, 1H, arom), 5.00 (q, J=7, 1H, CHMe), 4.99 (d, J=14.3, 1H, TrCH(H)), 4.58 (d, J=14.3, 1H, TrCH(H)), 2.74 (s, 3H, thiazole-Me), 1.05 (d, J=7, 3H, MeCH); MS 496 (M+ -NH2); [α]D =-77.2° (c 1, MeOH). Analysis calculated for C24H23F2N7O3S.H2O: C 52.84; H 4.62; N 17.97; S 5.88 Found: C 53.48; H 4.61; N 17.19; S 5.34.
