Acetic Acid → N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide

HRID 1883042Notes

Reaction equation

HRID 1883042 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]([I: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+].C([O-])(=O)C.[NH4+]>CO>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:33])[C:17]2[CH:22]=[C:21]([I:23])[CH:20]=[CH:19][C:18]=2[NH:24][C:25]([CH:27]2[CH2:28][CH2:29][N:30]([CH:2]([CH3:3])[CH3:34])[CH2:31][CH2:32]2)=[O:26])=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 21906457N-(5-chloropyridin-2-yl)-5-iodo-2-[(4-piperidinylcarbonyl)amino]benzamide trifluoroacetate

Product 1

HCID 21906277N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamideYield 65.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirring suspension of N-(5-chloropyridin-2-yl)-5-iodo-2-[(4-piperidinylcarbonyl)amino]benzamide trifluoroacetate (1.5 g, 2.52 mmol) in methanol (25 mL) was added ac tone (25 mL), followed by acetic acid (0.6 mL, 10 mmol), and then sodium cyanoborohydride (0.67 g, 10 mmol). After stirring overnight, the solution was treated with saturated aqueous ammonium acetate 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 5-15% 2 M solution of ammonia/methanol in dichloromethane. The chromatography product was slurried in diethyl ether and filtered to give 0.87 g (65%) of a white solid.

Workup

  1. additionwas added ac tone (25 mL)
  2. concentrationconcentrated
  3. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography over silica gel
  9. washeluting with a step gradient of 5-15% 2 M solution of ammonia/methanol in dichloromethane
  10. filtrationfiltered

Sources & evidence

ORD record
ord-dfcb3707cd43408d8b6be44f2bca8d34
Source dataset
uspto-grants-2004_07
Patent number
US06759414B2

Reaction notes

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