1-(3-chloro-2-fluorobenzoyl)-4-((6-((1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidin-4-ol → HCID 178479674, compound

HRID 1897940Notes

Reaction equation

HRID 1897940 reaction equation
[Cl:1][C:2]1[C:3]([F:38])=[C:4]([CH:35]=[CH:36][CH:37]=1)[C:5]([N:7]1[CH2:12][CH2:11][C:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22]3[CH:26]=[CH:25][N:24](COCC[Si](C)(C)C)[N:23]=3)[N:16]=2)([OH:13])[CH2:9][CH2:8]1)=[O:6]>FC(F)(F)C(O)=O.O>[ClH:1].[Cl:1][C:2]1[C:3]([F:38])=[C:4]([CH:35]=[CH:36][CH:37]=1)[C:5]([N:7]1[CH2:8][CH2:9][C:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22]3[CH:26]=[CH:25][NH:24][N:23]=3)[N:16]=2)([OH:13])[CH2:11][CH2:12]1)=[O:6]

Participants

4

Reactant 1

HCID 668907351-(3-chloro-2-fluorobenzoyl)-4-((6-((1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidin-4-ol

Product 1

HCID 178479674HCID 178479674, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

273 mg of 1-(3-chloro-2-fluorobenzoyl)-4-((6-((1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidin-4-ol was dissolved in 3 ml of trifluoroacetic acid and 0.3 ml of water, followed by stirring the reaction mixture at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo, basified with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The resulting ethyl acetate layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: chloroform to chloroform/methanol=10/1). The obtained free form was dissolved in 5 ml of ethyl acetate. 0.5 ml of 4 M hydrogen chloride in 1,4-dioxane was added to the solution at room temperature, followed by diluting with 5 ml of tert-butyl methyl ether. The precipitate was collected and washed with tert-butyl methyl ether to give the title compound as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionextracted with ethyl acetate
  3. dry with materialThe resulting ethyl acetate layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe resulting residue was purified by a silica gel column chromatography (eluent: chloroform to chloroform/methanol=10/1)
  7. dissolutionThe obtained free form was dissolved in 5 ml of ethyl acetate
  8. addition0.5 ml of 4 M hydrogen chloride in 1,4-dioxane was added to the solution at room temperature
  9. additionby diluting with 5 ml of tert-butyl methyl ether
  10. customThe precipitate was collected
  11. washwashed with tert-butyl methyl ether

Sources & evidence

ORD record
ord-d33cdf8d76794ad1a96ec7ee4e0cd6a1
Source dataset
uspto-grants-2013_08
Patent number
US08519136B2

Reaction notes

Loading…