反应详情

A suspension of 2-(2-isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt (99 mg, 0.18 mmol) in THF (1.8 mL) was treated with 2-bromoacetamide (109 mg, 0.2 mmol) followed by potassium carbonate (56 mg, 0.41 mmol) and the reaction mixture stirred at RT before being diluted with DCM and water. The aqueous layer was extracted twice with DCM and the combined organic extracts washed with saturated aqueous sodium bicarbonate followed by brine then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was dissolved in methanol, the solution cooled to 0° C. and treated with water to form a precipitate which was filtered off and washed with cold methanol/water to give a white solid. The solid was azeotroped with methanol then diethyl ether to give 308 as a white solid (38 mg, 43%). LCMS: RT=2.66 min, [M+H]+=480. 1H NMR 400 MHz (DMSO-d6) δ: 8.39 (1H, d, J=8.32 Hz), 8.16 (1H, s), 7.09-7.08 (1H, m), 6.97 (1H, s), 5.76-5.74 (1H, m), 4.58 (4H, d, J=14.42 Hz), 4.51 (2H, s), 3.96 (2H, s), 3.60 (2H, d, J=11.71 Hz), 3.37 (3H, s), 3.20 (2H, m), 2.86 (1H, m), 2.03 (4H, m), 1.53 (6H, d, J=6.57 Hz)

1. extractionThe aqueous layer was extracted twice with DCM
2. washthe combined organic extracts washed with saturated aqueous sodium bicarbonate
3. dry with materialthen dried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe resultant residue was dissolved in methanol
7. temperaturethe solution cooled to 0° C.
8. additiontreated with water
9. customto form a precipitate which
10. filtrationwas filtered off
11. washwashed with cold methanol/water
12. customto give a white solid
13. customThe solid was azeotroped with methanol