Sodium triacetoxyborohydride → N-({1-[4-(6-Methoxy-pyridin-3-yl)-cyclohex-3-enyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2388298Notes

Reaction equation

HRID 2388298 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH2:14][CH2:13][C:12](=O)[CH2:11][CH:10]=2)=[CH:5][CH:4]=1.Cl.[NH:17]1[CH2:20][CH:19]([NH:21][C:22]([CH2:24][NH:25][C:26](=[O:37])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=2)=[O:23])[CH2:18]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH2:14][CH2:13][CH:12]([N:17]3[CH2:20][CH:19]([NH:21][C:22]([CH2:24][NH:25][C:26](=[O:37])[C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:34])[F:35])[CH:28]=4)=[O:23])[CH2:18]3)[CH2:11][CH:10]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 595417964-(6-Methoxy-pyridin-3-yl)-cyclohex-3-enoneHCID 66750350N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt

Product 1

HCID 59541823N-({1-[4-(6-Methoxy-pyridin-3-yl)-cyclohex-3-enyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

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 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

Sources & evidence

ORD record
ord-dd626506980549a18e02df939e998123
Source dataset
uspto-grants-2012_09
Patent number
US08269015B2

Reaction notes

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