Acetic Acid → HCID 21906438, compound

HRID 988700Notes

Reaction equation

HRID 988700 reaction equation
F[C:2](F)(F)[C:3](O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:33])[C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:18]=2[NH:24][C:25]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[O:26])=[N:13][CH:14]=1.[C:34](O)(=O)C.C([BH3-])#N.[Na+].[Cl-].[NH4+]>CO.CC(C)=O>[ClH:8].[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:33])[C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:18]=2[NH:24][C:25]([CH:27]2[CH2:32][CH2:31][N:30]([CH:2]([CH3:3])[CH3:34])[CH2:29][CH2:28]2)=[O:26])=[N:13][CH:14]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 5003444Sodium cyanoborohydrideHCID 21906485HCID 21906485, compound

Product 1

HCID 21906438HCID 21906438, compoundYield 175.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

To a stirring suspension of N-(5-chloropyridin-2-yl)-5-methyl-2-[(4-piperidinylcarbonyl)amino]benzamide trifluoroacetate (1.0 g, 2.05 mmol) in methanol (30 mL) was added acetone (15 mL), followed by acetic acid (0.6 mL, 10.5 mmol), and then sodium cyanoborohydride (0.165 g, 2.46 mmol). After stirring overnight, the solution was treated with saturated aqueous ammonium chloride solution, concentrated, and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate, filtered, and concentrated. The crude product was purified by chromatography over silica gel, eluting with a step gradient of 0-10% 2 M solution of ammonia/methanol in dichloromethane. To a stirring solution of the chromatography product in dichloromethane was added 1.0 N hydrochloric acid in diethyl ether until precipitate formed. The mixture was filtered to give 0.81 g (88%) of a white solid.

Workup

  1. concentrationconcentrated
  2. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography over silica gel
  8. washeluting with a step gradient of 0-10% 2 M solution of ammonia/methanol in dichloromethane
  9. additionTo a stirring solution of the chromatography product in dichloromethane was added 1.0 N hydrochloric acid in diethyl ether until precipitate
  10. customformed
  11. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-52700a568a554e71999e02cc75a5d9c1
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

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