反应详情

A solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-9-carboxylic acid azetidin-3-ylamide (0.15 g, 0.38 mmol), acetone (84 L, 1.14 mmol), acetic acid (22 L), methanol (1 mL) and DCM (1 mL) was stirred at RT for 1 h. Sodium triacetoxyborohydride (0.2 g, 0.95 mmol) was added and the resultant mixture stirred at RT for 72 h. Further acetone (84 L) and 4 Å molecular sieves were added then stirring continued for 1 h before the addition of further sodium triacetoxyborohydride (0.2 g, 0.95 mmol). The reaction mixture was stirred at RT for 18 h before the addition of saturated aqueous sodium hydrogen carbonate. The resultant mixture was extracted with 10% MeOH in DCM. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% MeOH in DCM) followed by trituration in diethyl ether and recrystallisation in ethyl acetate to give 167 as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J=2.22 Hz, 1H); 7.95 (s, 1H); 7.71 (dd, J=8.44, 2.24 Hz, 1H); 7.23 (d, J=8.43 Hz, 1H); 6.87 (s, 1 H); 5.72-5.64 (m, 1H); 4.74-4.67 (m, 1H); 4.58 (t, J=5.67 Hz, 2H); 3.68 (t, J=7.42 Hz, 2H); 3.22 (t, J=5.69 Hz, 2H); 3.12 (s, 2H); 2.38 (t, J=7.02 Hz, 1H); 1.61 (d, J=6.61 Hz, 6H); 0.98 (d, J=6.21 Hz, 6H). LCMS: RT=6.82 min, M+H+=436

1. extractionThe resultant mixture was extracted with 10% MeOH in DCM
2. dry with materialThe combined extracts were dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customrecrystallisation in ethyl acetate