Reaction #2275728

Reaction equation

NaBH(OAc)3

1-(4-oxo-cyclohexyl)-1H-pyridin-2-one

N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt

→

N-({1-[4-(2-Oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Solvents

DCM

Conditions

Workup

1. 1
   OtherThe reaction was quenched with saturated sodium bicarbonate
2. 2
   OtherThe organic layer was separated
3. 3
   Extractionthe aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1
4. 4
   DryingThe combined organic layer was dried over anhydrous Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   Otherto give the crude product, which
8. 8
   Otherwas then purified by a CombiFlash® system
9. 9
   Otherto afford two title compounds as white solids

Procedure

A solution of 1-(4-oxo-cyclohexyl)-1H-pyridin-2-one (as prepared in the previous step, 150 mg, 0.79 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt (as prepared in Example 2 Step C, 400 mg, 1.18 mmol) in DCM (10 mL) was treated with TEA (340 μL, 2.40 mmol) for 10 min followed by NaBH(OAc)3 (Aldrich, 510 mg, 2.40 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 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 two title compounds as white solids: a less polar isomer, and a more polar isomer.

Source