C[O:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[CH2:10][C:11]1[C:12]([NH2:18])=[N:13][CH:14]=[C:15]([Br:17])[CH:16]=1)=O.[H-].[Na+]>CS(C)=O.O>[Br:17][C:15]1[CH:14]=[N:13][C:12]2[NH:18][C:3](=[O:2])[C@@H:5]3[N:6]([CH2:7][CH2:8][CH2:9]3)[CH2:10][C:11]=2[CH:16]=1A solution of (R)-1-(2-amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl ester (6.52 g, 20.8 mmol) in DMSO (200 mL) was treated with NaH (60% dispersion in mineral oil, 0.83 g, 20.7 mmol). After stirring at room temperature for 3 h, the mixture was stored in the freezer for 3 d. The mixture was allowed to warm to room temperature, diluted with H2O (400 mL), and extracted with EtOAc (4×200 mL). The combined organic layers were washed with H2O (3×100 mL) and brine (100 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2,/MeOH, 99:1) gave the title compound (3.94 g, 67%) as an off-white solid: MS (ESI) m/e 282 (M+H)+.
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