反应详情

4-(6-Methoxy-pyridin-3-yl)-cyclohex-3-enone (as prepared in Step C, 1.02 g, 5.02 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt (as prepared in the previous step, 2.54 g, 7.53 mmol) in DCM (15 mL) was treated with TEA (2.80 mL, 20 mmol) for 10 min followed by NaBH(OAc)3 (Aldrich, 3.20 g, 15 mmol) for another 4 hours at room temperature. The reaction was quenched with saturated sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform/IPA “cocktail” (˜3:1, v/v). The combined organic layers were 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 solids.

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