反应详情

温度

60 °C

5,6-Dichloro-2-(2-(R)-pyrrolidinyl)furo[3,2-b]pyridine from Example 39b (56 mg, 0.22 mmol) was dissolved in an aqueous solution of 37% formaldehyde (excess) and 88% formic acid (excess). The aqueous mixture was heated to 60° C. for 1 hour and then allowed to cool to ambient temperature. The reaction mixture was washed with Et2O, basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The organic phases were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a solid. The solid was dissolved in Et2O (10 mL) and a saturated solution of HCl in Et2O was added dropwise. The solvent was removed and the product recrystallized from MeOH/Et2O to afford a white solid (31 mg, 46%): mp 244-246° C.; 1H NMR (D2O, 300 MHz) δ 2.27-2.37 (m, 2H), 2.47-2.71 (m, 2H), 2.93 (s, 3H), 3.38 (m, 1H), 3.78 (m, 1H), 4.81 (m, partially buried under H2O peak, 1H), 7.27 (s, 1H), 8.26 (s, 1H); MS (CI/NH3) m/z: 271 (M+H)+ ; Anal. Calcd for C12H12Cl2N2O.HCl: C, 46.85; H, 4.26; N, 9.11. Found: C, 46.53; H, 4.21; N, 8.82.

1. temperatureto cool to ambient temperature
2. washThe reaction mixture was washed with Et2O
3. extractionextracted with CH2Cl2 (2×)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customchromatographed (silica gel; CHCl3 /MeOH, 98:2)
7. customto afford a solid
8. customThe solvent was removed
9. customthe product recrystallized from MeOH/Et2O