Acetic Acid → HCID 23438736, compound

HRID 2120177Notes

Reaction equation

HRID 2120177 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]([C:18]2[C:23]([NH:24][C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])=[CH:22][CH:21]=[C:20]([CH3:33])[N:19]=2)=[O:17])=[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]([C:18]2[C:23]([NH:24][C:25]([CH:27]3[CH2:28][CH2:29][N:30]([CH:2]([CH3:3])[CH3:34])[CH2:31][CH2:32]3)=[O:26])=[CH:22][CH:21]=[C:20]([CH3:33])[N:19]=2)=[O:17])=[N:13][CH:14]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 5003444Sodium cyanoborohydrideHCID 23438713HCID 23438713, compound

Product 1

HCID 23438736HCID 23438736, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

To a stirring suspension of N-(5-chloropyridin-2-yl)-6-methyl-3-[ (4-piperidinylcarbonyl)amino]pyridine-2-carboxamide trifluoroacetate (0.75 g, 1.54 mmol) in methanol (11 mL) was added acetone (11 mL), followed by acetic acid (0.45 mL, 7.86 mmol), and then sodium cyanoborohydride (0.51 g, 7.7 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 purified product in dichloromethane was added 1.0 N hydrochloric acid in diethyl ether until precipitate formed. The mixture was filtered to give 0.28 g (40%) 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 purified 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-d5e3c27435634b36ad1e2dc936022943
Source dataset
uspto-grants-2004_02
Patent number
US06689780B1

Reaction notes

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