Water → N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzamide hydrochloride

HRID 1784899Notes

Reaction equation

HRID 1784899 reaction equation
[NH2:1][C:2]1[C:17]([OH:18])=[CH:16][CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][N:8]=1)=[O:5].[CH:19]([N:22]1[CH2:27][CH2:26][CH:25]([CH:28]=O)[CH2:24][CH2:23]1)([CH3:21])[CH3:20].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[ClH:13].[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:14]=[CH:15][CH:16]=[C:17]([OH:18])[C:2]=2[NH:1][CH2:28][CH:25]2[CH2:26][CH2:27][N:22]([CH:19]([CH3:21])[CH3:20])[CH2:23][CH2:24]2)=[N:8][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 521998p-Toluenesulfonic acid monohydrateHCID 178939231-Isopropyl-piperidine-4-carboxaldehydeHCID 180011272-amino-N-(5-chloro-2-pyridinyl)-3-hydroxybenzamide

Product 1

HCID 17964913N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzamide hydrochlorideYield 122.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

2-Amino-N-(5-chloro-2-pyridyl)-3-hydroxybenzamide (100 mg) and 80 mg of 1-isopropylpiperidine-4-carbaldehyde were suspended in 5 ml of toluene, then 10 mg of p-toluenesulfonic acid hydrate were added thereto and the mixture was heated to reflux for 2 hours together with removal of water by an azeotropic operation. After the solvent was evaporated in vacuo, 7 ml of acetic acid and 88 mg of a boran-trimethylamine complex were added to the resulting residue and the mixture was stirred at 70° C. for 15 hours. The solvent was evaporated in vacuo, a saturated aqueous solution of sodium hydrogen carbonate was added to the residue and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated in vacuo and the resulting residue was purified by means of a silica gel column chromatography. After addition of 1N hydrochloric acid and water to the resulting N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[(1-isopropyl-4-piperidyl) methyl]amino}benzamide and the mixture was freeze-dried to give 102 mg of N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzamide hydrochloride.

Workup

  1. temperaturethe mixture was heated
  2. customAfter the solvent was evaporated in vacuo, 7 ml of acetic acid and 88 mg of a boran-trimethylamine complex
  3. additionwere added to the resulting residue
  4. customThe solvent was evaporated in vacuo
  5. additiona saturated aqueous solution of sodium hydrogen carbonate was added to the residue
  6. extractionthe mixture was extracted with chloroform
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated in vacuo
  9. customthe resulting residue was purified by means of a silica gel column chromatography
  10. additionAfter addition of 1N hydrochloric acid and water to the resulting N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[(1-isopropyl-4-piperidyl) methyl]amino}benzamide
  11. customthe mixture was freeze-dried

Sources & evidence

ORD record
ord-a5d779f62c794173830e4dd98530e123
Source dataset
uspto-grants-2009_03
Patent number
US07504417B2

Reaction notes

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