[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:16][C@@:13]3([O:15][CH2:14]3)[CH2:12][CH2:11][CH2:10]2)[C:5]([F:17])=[CH:4][N:3]=1.[C-:18]#[N:19].[Na+].Cl([O-])(=O)(=O)=O.[Li+].CCOC(C)=O>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:10][CH2:11][CH2:12][C@:13]([CH2:14][C:18]#[N:19])([OH:15])[CH2:16]2)[C:5]([F:17])=[CH:4][N:3]=1A suspension of 2-chloro-5-fluoro-N-[(3S)-1-oxaspiro[2.5]octan-7-yl]pyrimidin-4-amine, 49c, (0.50 g, 1.94 mmol), NaCN (0.11 g, 2.33 mmol) and lithium perchlorate (0.25 g, 2.33 mmol) in CH3CN was heated at 100° C. in a pressure tube for 3 h. The mixture was diluted into EtOAc and the organic phase was washed with aqueous saturated NaHCO3 solution, dried with MgSO4, filtered and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel chromatography (EtOAc/hexanes) afforded the desired product: 1H NMR (300.0 MHz, CDCl3) δ 7.78 (d, J=2.7 Hz, 1H), 4.85 (d, J=6.6 Hz, 1H), 4.28 (qn, J=4.0 Hz, 1H), 2.45 (s, 2H), 2.16 (d, J=13.0 Hz, 1H), 2.05 (d, J=11.7 Hz, 1H), 1.80-1.71 (m, 3H), 1.46-1.28 (m, 2H) and 1.17-1.06 (m, 1H) ppm; LCMS RT=2.15 (M+H) 285.34.
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