N-({1-[4-(5-Iodo-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide → N-({1-[4-(5-Cyano-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2188556Notes

Reaction equation

HRID 2188556 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5](=[O:35])[N:6]([CH:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:17][CH:16]([NH:18][C:19]([CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=4)=[O:20])[CH2:15]3)[CH2:10][CH2:9]2)[CH:7]=1.[C:36]([Cu])#[N:37]>CN(C=O)C>[C:36]([C:2]1[CH:3]=[CH:4][C:5](=[O:35])[N:6]([CH:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:15][CH:16]([NH:18][C:19]([CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:31])[F:32])[CH:25]=4)=[O:20])[CH2:17]3)[CH2:10][CH2:9]2)[CH:7]=1)#[N:37]

Participants

4

Reactant 2

HCID 49764697N-({1-[4-(5-Iodo-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamideHCID 178418546HCID 178418546, compound

Product 1

HCID 49764699N-({1-[4-(5-Cyano-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-({1-[4-(5-iodo-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide (as prepared in Example 8, Step C, 300 mg, 0.5 mmol), CuCN (Aldrich, 1 mmol), DMF (4 mL) in a sealed tube was irradiated under microwave at 180° C. for 30 min. The solid was filtered off and the residue was partitioned between water and a chloroform/IPA “cocktail” (˜3:1, v/v). The 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 yellow solid.

Workup

  1. filtrationThe solid was filtered off
  2. customthe residue was partitioned between water
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product, which
  7. customwas then purified by a CombiFlash® system

Sources & evidence

ORD record
ord-580a200aa4ac42599421833a863320e1
Source dataset
uspto-grants-2012_12
Patent number
US08324186B2

Reaction notes

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