Dimethyl Sulfoxide → 2-(4-Fluoro-6-(4-isopropoxyphenyl)pyridin-2-yl)pyrimidine

반응식

Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:18]2[N:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:3]=1.[F-:24].[Cs+].CS(C)=O>CCOC(C)=O>[F:24][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:18]2[N:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:3]=1

참가 물질

실험 절차

To a 2 dram vial equipped with a stir bar and charged with 2-(4-chloro-6-(4-isopropoxyphenyl)pyridin-2-yl)pyrimidine (all material from step 1) was added CsF (200 mg, 1.32 mmol) and DMSO (0.7 mL). The vial was sealed with a septum cap and then placed in a 140° C. heating block with stirring for 18 hours. The reaction mixture was allowed to cool to room temperature and then was transfered to a 125 mL separatory funnel. The mixture was diluted with EtOAc (50 mL) and twice washed with water:brine (25 mL:25 mL). The organic solution was dried over MgSO4; filtered; then concentrated in vacuo to afford a solid amber residue. This material was subjected to silica gel purification (hexanes:EtOAc) to afford 2-(4-fluoro-6-(4-isopropoxyphenyl)pyridin-2-yl)pyrimidine as a white solid (15 mg, 27% over two steps). 1H-NMR (400 MHz, CDCl3) δ 8.96 (d, J=5.0 Hz, 2H), 8.12 (dd, J=9.5, 2.3 Hz, 1H), 8.09-8.04 (m, 2H), 7.50 (dd, J=9.8, 2.3 Hz, 1H), 7.36 (t, J=4.9 Hz, 1H), 7.02-6.97 (m, 2H), 4.65 (spt, J=6.0 Hz, 1H), 1.38 (d, J=6.0 Hz, 6H); MS: MS m/z 310.2 (M++1).