反应详情

To 5-bromo-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 66a (360 mg, 0.95 mmol) was added TFA in CH2Cl2 at 0° C., and the mixture was stirred for 30 minutes. The volatiles were then removed under vacuum. The residue was neutralized with NaHCO3 to pH 8, then extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1 to afford to give the free base of the title compound. The base was converted to the salt by treatment with hydrogen chloride saturated EtOH to give the title compound (224 mg). mp 168-169° C. MS (CI/NH3) m/z 277/279 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.69 (dd, J=7.0, 8.5, 2H), 4.06-4.20 (m, 3H), 4.43 (d, J=4.5, 2H), 4.91-4.99 (m, 1H), 7.94 (d, J=3.0, 1H), 8.17 (d, J=3.0, 1H). Anal. Calcd for C9H10N2OBrCl·0.9 HCl: C, 34.83; H, 3.54; N, 9.03. Found: C, 34.85; H, 3.56; N, 8.82. [α:]25D=-4.81° (c 0.13, MeOH).

1. customThe volatiles were then removed under vacuum
2. extractionextracted with CH2Cl2, which
3. dry with materialwas dried over MgSO4
4. concentrationconcentrated
5. customThe residue was chromatographed on a silica gel column
6. washeluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1
7. customto afford