Reaction Steps
A solution of (1R,2R)-7-cyano-3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]quinazolin-4(3H)-one (obtained in example 2, 500 mg, 1.2 mmol) in MeOH (5 mL) and CHCl3 (5 mL) was cooled to 0° C. and HCl gas was bubbled until saturation (1.5 h). The mixture was allowed to stand at 0° C. overnight and was then concentrated and the residue was slowly added to aqueous K2CO3 solution (2.5 g). The yellowish precipitate formed was filtered, dried, taken up in methanol and allowed to react with sulfamide (350 mg, 3.6 mmol) at reflux for 3 h. The reaction mixture was then concentrated and partitioned between water and CHCl3. The organic layer was separated, dried over Na2SO4, filtered, concentrated and the resulting residue, whose thin layer chromatography showed the presence of three different compounds, was flash chromatographed. The first compound to elute was identified as the methyl imidate. The second compound to elute was the amide (title compound), the physical parameters of which are as follows: mp 235°-236° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 8.63 (s, 1H, N=CH--N), 8.42 (d, J=8.2, 1H, arom), 8.13 (d, J=1.5, 1H, arom), 7.98 (dd, J=8.2, J=1.5, 1H, arom), 7.77 (s, 1H, triazole), 7.74 (s, 1H, triazole), 7.48 (dt, Jd =6.4, Jt =8.8, 1H, arom), 6.9-6.8 (m, 2H, arom), 6.3 (broad s, 2H, NH2), 5.92 (dq, Jd =1.2, Jq =7.3, 1H, MeCH), 5.56 (d, J=1.3, 1H, OH), 5.16 (d, J=14.1, 1H, CH(H)), 4.03 (d, J=14.1, 1H, CH(H)), 1.32 (d, J=7.3, 3H, CHMe); GC/MS 224 (Tr--CH2COHAr, C10H8F2N3O), 216 (N-ethylheterocycle-1, C11H11N3O2).
