Trimethylsilylacetylene → 3-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

HRID 1042654Notes

Reaction equation

HRID 1042654 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[CH3:29])[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([CH2:18][N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:9]=1)=[O:6].C[Si]([C:34]#[CH:35])(C)C>CC#N.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:28]([C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:34]=1[CH3:35])[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:11]=[C:10]([CH2:18][N:19]2[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]2)[CH:9]=1)=[O:6])#[CH:29]

Participants

7

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 594279993-iodo-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

Product 1

HCID 866079783-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 3-iodo-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide (951 mg, 1.84 mmol), PdCl2(PPh3)2 (65 mg, 0.092 mmol) in MeCN (75 mL) and Et3N (20 mL) at room temperature was added trimethylsilylacetylene (0.8 mL, 5.52 mmol) followed by CuI (18 mg, 0.092 mmol). The resulting mixture was allowed to stir at room temperature for 2 h at which time the reaction mixture was concentrated under reduced pressure followed by reconstitution in MeOH (100 mL). To this mixture was added enough K2CO3 to saturate the mixture and the mixture was allowed to stir for about 1.5 h. The mixture was filtered through a pad of Celite. To the filtrate was added silica gel (˜20 mL) and the mixture was concentrated under reduced pressure, and purified via automated flash chromatography (silica gel, 0% to 15% MeOH in CH2Cl2, gradient elution) to afford 3-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionTo this mixture was added enough K2CO3
  3. concentrationto saturate the mixture
  4. stirringto stir for about 1.5 h
  5. filtrationThe mixture was filtered through a pad of Celite
  6. additionTo the filtrate was added silica gel (˜20 mL)
  7. concentrationthe mixture was concentrated under reduced pressure
  8. custompurified
  9. washflash chromatography (silica gel, 0% to 15% MeOH in CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-d27b1910123c4dff97d9e2a786c2b690
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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