反应详情

温度

115 °C

The product from Example 68A (40 mg, 0.16 mmol) was treated with octahydro-pyrrolo[1,2-A]pyrazine (31 mg, 0.24 mmol), and to this was added 2-methoxyethanol (0.65 mL) and N,N-diisopropylethylamine (0.20 mL, 1.2 mmol); the reaction was heated at 115° C. for 16 hours, cooled, diluted with CH2Cl2 (25 mL) and washed with 1 M NaOH (10 mL). The aqueous layer was extracted with CH2Cl2 (15 mL). The combined organic layers were dried (MgSO4), filtered, concentrated and purified by chromatography (eluting with 2, 3.5, 5 and 10% (9:1 MeOH:saturated aqueous NH4OH) in CH2Cl2) to provide the title compound. 1H NMR (CDCl3) δ 1.43-1.57 (m, 1H), 1.71-1.94 (m, 3H), 2.13-2.29 (m, 4H), 2.30-2.45 (m, 3H), 2.66 (t, J=6.78 Hz, 2H), 2.81 (dd, J=12.21, 10.17 Hz, 1H), 3.06-3.23 (m, 3H), 3.81-3.89 (m, 1H), 3.98 (dt, J=12.29, 2.33 Hz, 1H), 4.76 (s, 2H), 7.20-7.24 (m, 1H), 7.31-7.39 (m, 2H), 7.71-7.76 (m, 1H); MS (M+H)+ m/z 336.

1. temperaturecooled
2. washwashed with 1 M NaOH (10 mL)
3. extractionThe aqueous layer was extracted with CH2Cl2 (15 mL)
4. dry with materialThe combined organic layers were dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. custompurified by chromatography (eluting with 2, 3.5, 5 and 10% (9:1 MeOH:saturated aqueous NH4OH) in CH2Cl2)