Potassium Carbonate → N-(5-bicyclo[2.2.1]heptanyl-methyl)-2-[[3,3-difluoro-3-(4-fluoro-phenyl)-propyl]sulfanyl]-pyridine-3-carboxylic acid amide

HRID 1925551Notes

Reaction equation

HRID 1925551 reaction equation
C([O-])([O-])=O.[K+].[K+].CS(O[CH2:12][CH2:13][C:14]([F:23])([F:22])[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)(=O)=O.[CH:24]12[CH2:30][CH:27]([CH2:28][CH2:29]1)[CH2:26][CH:25]2[CH2:31][NH:32][C:33](=[O:41])[C:34]1[CH:39]=[CH:38][CH:37]=[N:36][C:35]=1[SH:40].CCCCCC.CC(=O)OCC>CN(C=O)C>[CH:27]12[CH2:30][CH:24]([CH:25]([CH2:31][NH:32][C:33]([C:34]3[C:35]([S:40][CH2:12][CH2:13][C:14]([F:22])([F:23])[C:15]4[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=4)=[N:36][CH:37]=[CH:38][CH:39]=3)=[O:41])[CH2:26]1)[CH2:29][CH2:28]2

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 21226206Ethyl acetate hexaneHCID 866453903,3-Difluoro-3-(4-fluorophenyl)-propyl methanesulfonateHCID 178522760N-(bicyclo[2.2.1]heptan-2-ylmethyl)-2-mercapto-nicotinamide

Product 1

HCID 59487304N-(5-bicyclo[2.2.1]heptanyl-methyl)-2-[[3,3-difluoro-3-(4-fluoro-phenyl)-propyl]sulfanyl]-pyridine-3-carboxylic acid amideYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

553 mg (4 mmol) of K2CO3 and 268 mg (1.0 mmol) of 3,3-difluoro-3-(4-fluorophenyl)-propyl methanesulfonate were added in succession to a solution of 262 mg (1.0 mmol) of N-(bicyclo[2.2.1]heptan-2-ylmethyl)-2-mercapto-nicotinamide in DMF (3 ml), and the mixture was heated for 3 h at 60° C. Dilution with water and extraction with EA were then carried out. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. CC (hexane/EA 7:3) of the residue yielded 229 mg (0.5 mmol, 53%) of N-(5-bicyclo[2.2.1]heptanyl-methyl)-2-[[3,3-difluoro-3-(4-fluoro-phenyl)-propyl]sulfanyl]-pyridine-3-carboxylic acid amide. MS: m/z 435.2 [M+H]+.

Workup

  1. extractionDilution with water and extraction with EA
  2. washThe organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69db6f86b5ff4458878ad3b3bca085b0
Source dataset
uspto-grants-2012_05
Patent number
US08178684B2

Reaction notes

Loading…