反应详情

A solution of EXAMPLE 10A (300 mg, 0.88 mmol) in acetic acid (10 mL) and water (20 mL) was heated at 70° C. for 20 hours. After cooling, the solution was concentrated to give a light yellow solid. To a solution of the crude aldehyde (80 mg) in dimethyl sulfoxide (2 mL) and methanol (3 mL) was added cyclopropylamine (60 μL) and the mixture stirred at ambient temperature for 1 hour. Sodium cyanoborohydride (54 mg, 0.86 mmol) was added and the mixture heated at 55° C. overnight. Volatiles were removed and the residue purified by HPLC (Zorbax, C-18, 250×2.54 column, Mobile phase A: 0.1% trifluoroacetic acid in water; B: 0.1% trifluoroacetic acid in acetonitrile; 0-100% gradient) to provide 8.8 mg of the title compound as a trifluoroacetate salt. To a solution of this salt in 1:1 methanol/dichloromethane (1 mL) was added 1M HCl in ether (3 mL). Concentration afforded the title compound as a hydrochloride salt. 1H NMR (CD3OD): δ 0.91-1.03 (m, 4H), 2.83-2.89 (m, 1H), 3.23-3.29 (m, 2H), 3.49-3.55 (m, 2H), 7.70-7.79 (m, 3H), 8.03-8.13 (m, 3 H), 8.20 (s, 1H),

1. temperatureAfter cooling
2. concentrationthe solution was concentrated
3. customto give a light yellow solid
4. temperaturethe mixture heated at 55° C. overnight
5. customVolatiles were removed
6. customthe residue purified by HPLC (Zorbax, C-18, 250×2.54 column, Mobile phase A: 0.1% trifluoroacetic acid in water; B: 0.1% trifluoroacetic acid in acetonitrile; 0-100% gradient)