[NH2:1][CH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1.C(N(C(C)C)CC)(C)C.[Br:24][C:25]1[CH:26]=[N:27][C:28]([O:31][CH2:32][C:33](O)=[O:34])=[N:29][CH:30]=1.O.ON1C2C=CC=CC=2N=N1>ClC(Cl)C.O1CCCC1.C(OCC)(=O)C>[C:11]([O:10][C:8]([N:5]1[CH2:6][CH2:7][CH:3]([CH2:2][NH:1][C:33](=[O:34])[CH2:32][O:31][C:28]2[N:27]=[CH:26][C:25]([Br:24])=[CH:30][N:29]=2)[CH2:4]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]To a solution of 3-(RS)-aminomethyl-1-tert-butoxycarbonylpyrrolidine in dichloroethane (17 mL) were sequentially added diisopropylethylamine (5.1 mL), a solution of 2-(5-bromopyrimidin-2-yloxy)acetic acid (2.9 g, 12.2 mmol, 1.1 equiv.) in tetrahydrofuran (43 mL), 1-hydroxybenzotriazole hydrate (2.4 g, 17.5 mmol, 1.5 equiv.) and 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (3.4 g, 17.6 mmol, 1.5 equiv.). The solution was stirred under N2 overnight. The reaction mixture was diluted with ethyl acetate, washed with 1 M aqueous sodium hydroxide, 1 M hydrochloric acid, water and brine, then dried over sodium sulfate and concentrated. The residue was subjected to flash chromatography to afford clean N-(1-tert-butoxycarbonylpyrrolidin-3-(RS)-ylmethyl)-2-(5-bromopyrimidin-2-yloxy)acetamide (4.2 g).
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