反应详情

To a solution of amide (260) (40 mg, 0.07 mmol)) prepared as described in example 219 in ethyl acetate/methanol (1:1, 80 mL) was added 5% Pd-C (catalytic). The resulting suspension was hydrogenated at 60 psi with stirring for 4 days, with additional portions of Pd-C being added every 24 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure before being chromatographed on silica eluting with methanol/ethyl acetate/triethylamine (1:4:trace), to give amide (330) (6 mg, 16%) as a yellow powder, mp 232–238° C. 1H NMR δ [(CD3)2SO] 10.95 (br s, 1H), 9.33 (br s, 1H), 8.37 (d, J=2.4 Hz, 1H), 8.01 (br s, 1H), 7.69 (s, 1H), 7.54 (d, J=8.9 Hz, 1H), 7.43 (m, 1H), 7.34 (dd, J=7.5, 1.8 Hz, 1H), 7.13–7.05 (m, 3H), 4.67 (t, J=6.2 Hz, 2H), 3.69 (s, 3H), −3.2 (obscured m, 2H), 2.60 (t, J=6.2 Hz, 2H), 2.54–2.49 (obscured m, 8H). FABMS found [M+H]+: 501.2142. C28H28N4O5 requires 501.2138.

1. additionadded every 24 hours
2. filtrationThe reaction mixture was then filtered through celite and
3. concentrationconcentrated under reduced pressure
4. custombefore being chromatographed on silica eluting with methanol/ethyl acetate/triethylamine (1:4:trace)