[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH:7]([C:10]#[N:11])[CH2:6]1.BrCCCN1[C:20](=[O:21])[C:19]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]2[C:17]1=[O:26].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[O:21]=[C:20]1[C:19]2[C:18](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17](=[O:26])[N:1]1[CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH:7]([C:10]#[N:11])[CH2:6]1A suspension of 3-pyrrolidinecarbonitrile (302) (Swidinsky, J., et al., J. Pharm. Sci. 1967, 56, 192-196) (4.5 g, 15.6 mmol), N-(3-bromopropyl)phthalimide (3.48 g, 13.0 mmol), and K2CO3 (2.16 g, 15.6 mmol) in DMF (20 mL) was stirred at 100° C. for 1.5 h. The solution was cooled, the solvent evaporated and the residue partitioned between water (50 mL) and EtOAc (50 mL). The organic fraction was extracted with 1 M HCl (2×50 mL) and the acidic fraction washed with Et2O (2×20 mL). The acidic fraction was made basic with dilute aqueous NH3 solution and the alkaline solution was extracted with DCM (3×25 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with EtOAc, to give phthalimide 303 (1.70 g, 46%) as a colourless oil: 1H NMR δ 7.82-7.87 (m, 2H, Harom), 7.69-7.74 (m, 2H, Harom), 3.75-3.79 (m, 2H, CH2), 2.87-2.93 (m, 2H, CH2N), 2.52-2.60 (m, 5H, CH2, CH2N, CH), 2.06-2.15 (m, 1H, CH2), 1.96-2.04 (m, 1H, CH2), 1.87 (p, J=7.0 Hz, 2H, CH2); 13C NMR δ 168.4 (2), 133.9 (2), 132.2 (2), 123.1 (2), 122.1, 57.2, 52.6 (2), 36.3, 29.1, 27.2, 26.1; HRMS (FAB+) calcd for C16H17N3O2 (M+) m/z 283.1321, found 283.1318.
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