Nitrogen → 3-trimethylsilylethynyl-4-methyl-N-[4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl]benzamide

HRID 2059787Notes

Reaction equation

HRID 2059787 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]=[CH:12][C:11]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)=[C:10]([C:22]([F:25])([F:24])[F:23])[CH:9]=1)=[O:6].N#N.C(N(CC)C(C)C)(C)C.[CH3:41][Si:42]([C:45]#[CH:46])([CH3:44])[CH3:43]>[Cu]I.CCOC(C)=O.O.CN(C=O)C>[CH3:29][C:28]1[CH:27]=[CH:26][C:4]([C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]3[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)=[C:10]([C:22]([F:23])([F:25])[F:24])[CH:9]=2)=[O:6])=[CH:3][C:2]=1[C:46]#[C:45][Si:42]([CH3:44])([CH3:43])[CH3:41]

Participants

9

Reactant 4

HCID 947NitrogenHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 468389103-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide

Product 1

HCID 689162413-trimethylsilylethynyl-4-methyl-N-[4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl]benzamideYield 82%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-iodo-4-methyl-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-benzamide (2.59 g, 5 mmol), Pd[(PPh3)]4 (289 mg, 0.25 mmol), CuI (71 mg, 0.375 mmol) was placed in a schlenk flask. The flask was subjected to 3 cycles of vacuum-refilling with N2. To this mixture was added anhydrous N,N-diisopropylethylamine (1.1 mL, 6 mmol), DMF (5 mL), and trimethylsilylacetylene (0.92 mL, 6.5 mmol). This solution was stirred at rt for 24 h. Water and EtOAc were added to the reaction mixture to facilitate the extraction. The combined organic layers were dried over Na2SO4, filtered, and then concentrated on a rotavap and the residue was purified on a silica gel column (eluent: 5% MeOH in CH2Cl2, MeOH was pre-saturated with ammonia gas) to give the desired product as a light yellow solid in 82% yield (2.0 g).

Workup

  1. extractionthe extraction
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated on a rotavap
  5. customthe residue was purified on a silica gel column (eluent: 5% MeOH in CH2Cl2, MeOH was pre-saturated with ammonia gas)

Sources & evidence

ORD record
ord-005e737868844f4389f1bbb475e97e64
Source dataset
uspto-grants-2012_10
Patent number
US08278307B2

Reaction notes

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