[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[F:24][C:25]([F:34])([F:33])[C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1.CN1CCOCC1>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([NH:32][C:29]3[CH:28]=[CH:27][C:26]([C:25]([F:33])([F:24])[F:34])=[CH:31][N:30]=3)=[O:16])[C:9]2=[O:17])=[CH:6][CH:7]=1To a suspension of 2-(3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.088 g, 0.370 mmol; Example 216A) in dichloromethane (1 mL) was added oxalyl dichloride (0.308 mL, 0.617 mmol). After 30 minutes, the reaction was concentrated and dried. This residue was dissolved in dichloromethane (1 mL) and 5-(trifluoromethyl)pyridin-2-amine (0.050 g, 0.308 mmol) was added followed by 4-methylmorpholine (0.068 mL, 0.617 mmol). After stirring for 30 minutes, the reaction was loaded onto a GraceResolv™ 12 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.67 (s, 1H), 8.57-8.52 (m, 1H), 8.28 (d, J=8.7, 1H), 7.92 (dd, J=2.3, 8.8, 1H), 7.35-7.21 (m, 2H), 7.09-6.99 (m, 2H), 4.25 (d, J=16.0, 1H), 4.18 (d, J=16.0, 1H), 3.78 (t, J=9.0, 1H), 3.69-3.59 (m, 2H), 2.63 (m, 1H), 2.23 (m, 1H); MS (ESI+) m/z 382.0 (M+H)+.
Wird geladen…