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

HRID 2188546Notes

Reaction equation

HRID 2188546 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH2:4][CH2:3]1.Cl.[NH:16]1[CH2:19][CH:18]([NH:20][C:21]([CH2:23][NH:24][C:25](=[O:36])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)=[O:22])[CH2:17]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[O:14]=[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][N:8]1[CH:5]1[CH2:6][CH2:7][CH:2]([N:16]2[CH2:19][CH:18]([NH:20][C:21]([CH2:23][NH:24][C:25](=[O:36])[C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:33])[F:34])[CH:27]=3)=[O:22])[CH2:17]2)[CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 585626631-(4-Oxo-cyclohexyl)-1H-pyridin-2-oneHCID 66750350N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt

Product 1

HCID 49764566N-({1-[4-(2-Oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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.

Workup

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

Sources & evidence

ORD record
ord-d2e623ab62af4a58b88f9adb01c21475
Source dataset
uspto-grants-2012_12
Patent number
US08324186B2

Reaction notes

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