[Cl:1][C:2]1[C:3]([CH2:8]O)=[N:4][CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CS(Cl)(=O)=O.C(OC(=O)[NH:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][CH2:34][C:35]1[C:40]([Cl:41])=[CH:39][CH:38]=[CH:37][N:36]=1)(C)(C)C>C(Cl)Cl.CC#N>[Cl:1][C:2]1[C:3]([CH2:8][N:33]([CH2:34][C:35]2[C:40]([Cl:41])=[CH:39][CH:38]=[CH:37][N:36]=2)[CH2:32][CH2:31][CH2:30][CH2:29][NH2:28])=[N:4][CH:5]=[CH:6][CH:7]=1Using General Procedure C: (3-Chloro-pyridin-2-yl)-methanol (167 mg, 1.17 mmol) (Iqbal, N. et al. J. Med. Chem. 1998, 41, 1827-1837) was dissolved in CH2Cl2 (10 mL) at 0° C. Et3N (212 μL, 1.52 mmol) was added to the colorless solution followed by subsequent addition of MsCl (90 μL, 1.17 mmol). The reaction mixture was stirred at 0° C. for one hour and then the solvent was removed under reduced pressure. The resulting crude mesylate mixture was dissolved in CH3CN (5 mL) and added to a mixture of {4-[(3-chloro-pyridin-2-ylmethyl)-amino]-butyl}-carbamic acid tert-butyl ester (265 mg, 0.88 mmol) and Et3N (169 μL, 1.21 mmol) in CH3CN (10 mL). The reaction mixture was stirred at 50° C. for 16 hours. The solvent was removed under reduced pressure and the brown oil was purified via column chromatography on silica gel (CH2Cl2:MeOH, 95:5, v/v) to give the product as a pale yellow oil (205 mg, 52%). 1H NMR (CDCl3) δ 1.35 (m, 2H), 1.43 (s, 9H), 1.55 (m, 2H), 2.67 (t, 2H, J=7.5 Hz), 2.98 (m, 2H), 3.98 (s, 4H), 4.86 (s, 1H), 7.11 (dd, 2H, J=9.0, 6.0 Hz), 7.61 (d, 2H, J=9.0 Hz), 8.45 (m, 2H). Conversion to the HBr salt using General Procedure D gave COMPOUND 235 as a white solid. 1H NMR (D2O) δ 1.75 (m, 2H), 1.97 (m, 2H), 3.02 (t, 2H, J=7.5 Hz), 3.52 (t, 2H, J=8.1 Hz), 4.80 (s, 2H), 4.82 (s, 2H), 7.42 (dd, 2H, J=8.4, 4.8 Hz), 7.92 (d, 2H, J=8.1 Hz), 8.45 (m, 2H). 13C NMR (D2O) δ 21.51, 24.37, 39.25, 48.71, 55.98, 126.19, 131.75, 139.55, 147.09, 147.26. ES-MS m/z 339 [M+H]+. Anal. Calcd. for C16H20N4Cl2−.3.5HBr.0.8H2O: C, 30.18, H, 3.97; N, 8.80; Cl, 11.13; Br, 43.91. Found: C, 30.18; H, 4.04; N, 8.72; Cl, 10.77; Br, 44.05.
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