Nitrogen → N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(trimethylsilyl)ethynyl]benzamide

HRID 1527885Notes

Reaction equation

HRID 1527885 reaction equation
[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:29])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23](I)[CH:22]=3)=[CH:15][C:14]=2[C:30]([F:33])([F:32])[F:31])[CH2:8][CH2:7]1)([CH3:4])=[O:3].N#N.C(N(CC)C(C)C)(C)C.[CH3:45][Si:46]([C:49]#[CH:50])([CH3:48])[CH3:47]>[Cu]I.CCOC(C)=O.O.CN(C=O)C>[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:29])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:50]#[C:49][Si:46]([CH3:48])([CH3:47])[CH3:45])[CH:22]=3)=[CH:15][C:14]=2[C:30]([F:33])([F:32])[F:31])[CH2:8][CH2:7]1)([CH3:4])=[O:3]

Participants

9

Reactant 4

HCID 947NitrogenHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 68911921N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-iodo-4-methylbenzamide

Product 1

HCID 68911889N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(trimethylsilyl)ethynyl]benzamide

Reagents, catalysts & solvents 4

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

Procedure

N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-iodo-4-methylbenzamide (5 mmol), Pd[(PPh3)]4 (289 mg, 0.25 mmol), CuI (71 mg, 0.375 mmol) is placed in a schlenk flask. The flask is subjected to 3 cycles of vacuum-refilling with N2. To this mixture is added anhydrous N,N-diisopropylethylamine (1.1 mL, 6 mmol), DMF (5 mL), and trimethylsilylacetylene (0.92 mL, 6.5 mmol). This solution is stirred at rt for 24 h. Water and EtOAc are added to the reaction mixture to facilitate the extraction. The combined organic layers are dried over Na2SO4, filtered, and then concentrated on a rotavap and the crude product is purified on a silica gel column (eluent: 5% MeOH in CH2Cl2, MeON is pre-saturated with ammonia gas).

Workup

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

Sources & evidence

ORD record
ord-3df43deea04240a399e6c0476dbef169
Source dataset
uspto-grants-2015_07
Patent number
US09090561B2

Reaction notes

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