反应详情

To a solution of 3-(3-thienyl)propanoic acid (200 mg, 1.2 mmol) in N,N-dimethylformamide (25 ml) was added 1-hydroxybenzotriazole monohydrate (200 mg, 1.31 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (340 mg, 1.77 mmol). After stirring at room temperature for 10 min the mixture was treated with the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 400 mg, 1.3 mmol) and sodium hydrogen carbonate (220 mg, 2.6 mmol). The reaction mixture was stirred at room temperature for 72 h before concentrating in vacuo. Water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (1×20 ml and 2×15 ml). The combined organic extracts were washed with water (15 ml) and saturated brine (15 ml), dried (MgSO4), and concentrated in vacuo to give a buff solid. The crude product was sonicated in methanol (5 ml) to afford the title compound as an off-white solid (330 mg, 63%, m.p. 179.7° C.).

1. stirringThe reaction mixture was stirred at room temperature for 72 h
2. concentrationbefore concentrating in vacuo
3. additionWater (15 ml) was added
4. extractionthe reaction mixture was extracted with ethyl acetate (1×20 ml and 2×15 ml)
5. washThe combined organic extracts were washed with water (15 ml) and saturated brine (15 ml)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customto give a buff solid