Trimethylsilylacetylene → 1-(4-Chlorophenyl)-N-[3-ethynyl-4-(4-morpholinopiperidin-1-yl)phenyl]-5-methylpyrazole-4-carboxamide

HRID 1744643Notes

Reaction equation

HRID 1744643 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:20][C:21]([C:23]2[CH:24]=[N:25][N:26]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[C:27]=2[CH3:28])=[O:22])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1.C[Si]([C:40]#[CH:41])(C)C>N1CCCCC1>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([N:26]2[C:27]([CH3:28])=[C:23]([C:21]([NH:20][C:4]3[CH:5]=[CH:6][C:7]([N:8]4[CH2:13][CH2:12][CH:11]([N:14]5[CH2:19][CH2:18][O:17][CH2:16][CH2:15]5)[CH2:10][CH2:9]4)=[C:2]([C:40]#[CH:41])[CH:3]=3)=[O:22])[CH:24]=[N:25]2)=[CH:30][CH:31]=1

Participants

4

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 22227912HCID 22227912, compound

Product 1

HCID 222279551-(4-Chlorophenyl)-N-[3-ethynyl-4-(4-morpholinopiperidin-1-yl)phenyl]-5-methylpyrazole-4-carboxamideYield 3%

Reagents, catalysts & solvents 1

HCID 8082PiperidineSolvent

Procedure

A suspension of N-[3-bromo-4-(4-morpholinopiperidin-1-yl)phenyl]-1-(4-chlorophenyl)-5-methylpyrazole-4-carboxamide (1 g), bistriphenylphosphinepalladium dichloride (0.38 g), cuprous iodide (0.06 g), trimethylsilylacetylene (0.53 g) and piperidine (50 ml) was refluxed under heating for 15 h. The solvent was evaporated and the residue was purified by silica gel column chromatography (mobile phase: ethyl acetate/hexane). The resulting residue was dissolved in methanol (10 ml) and potassium carbonate (170 mg) was added. The mixture was stirred at room temperature for 1 h. After the reaction, potassium carbonate was filtered off. The filtrate was purified by silica gel column chromatography (mobile phase: chloroform/methanol) and recrystallized from a mixed solvent of chloroform-diisopropyl ether to give the title compound (27 mg), melting point: 203–205° C.

Workup

  1. temperaturewas refluxed
  2. temperatureunder heating for 15 h
  3. customThe solvent was evaporated
  4. customthe residue was purified by silica gel column chromatography (mobile phase: ethyl acetate/hexane)
  5. dissolutionThe resulting residue was dissolved in methanol (10 ml)
  6. additionpotassium carbonate (170 mg) was added
  7. customAfter the reaction, potassium carbonate
  8. filtrationwas filtered off
  9. customThe filtrate was purified by silica gel column chromatography (mobile phase: chloroform/methanol)
  10. customrecrystallized from a mixed solvent of chloroform-diisopropyl ether

Sources & evidence

ORD record
ord-15aab6ffd61e4a128093d67afcee3576
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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