反应详情

Benzo[1,3]dioxole-5-carbonyl chloride (Aldrich, 74 mg, 0.404 mmol) was added into a solution of N-{[1-(4-amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt (as prepared in the previous step 200 mg, 0.404 mmol) and TEA (170 μL, 1.21 mmol) in DCM (5 mL) at 0° C. The reaction was stirred for an additional 2 hours and quenched with saturated sodium bicarbonate. The reaction was then partitioned between DCM and water. The organic layer was separated and the aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compound as white solid.

1. customquenched with saturated sodium bicarbonate
2. customThe reaction was then partitioned between DCM and water
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1
5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give the crude product, which
9. customwas then purified by a CombiFlash® system