3,5-Bis(trifluoromethyl)benzyl bromide → 2''-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide

HRID 1267521Notes

Reaction equation

HRID 1267521 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:24])=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)=[CH:9][CH:10]=1)=[O:4].C[Si](C)(C)[N-][Si](C)(C)C.[K+].[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40]Br>C1COCC1>[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40][N:2]([CH3:1])[C:3]([C:5]1[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:24])=[CH:7][C:8]([N:11]2[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH2:16]2)=[CH:9][CH:10]=1)=[O:4]

Participants

5

Reactant 3

HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 544699872'-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide

Product 1

HCID 98722492''-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amideYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 50 mg (0.15 mmol) 2′-methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide in 2 ml THF 0.2 ml of a 1 M solution (0.2 mmol) of potassium hexamethyldisilazide in THF was added at 0°. After 20 min. 0.028 ml (0.15 mmol) 3,5-bis(trifluoromethyl)benzyl bromide was added dropwise to the resulting suspension. The reaction was quenched with water after 1.5 h. The mixture was diluted with 5 ml 2 N NaOH solution and extracted with 3 5-ml portions of ethyl acetate. The combined organic extracts were dried (Na2SO4) and evaporated. Chromatography (SiO2, CH2Cl2/methanol 19:1) gave 25 mg (29%) 2′-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide, MS (ISP): 550.5 (M+H)+.

Workup

  1. customThe reaction was quenched with water after 1.5 h
  2. additionThe mixture was diluted with 5 ml 2 N NaOH solution
  3. extractionextracted with 3 5-ml portions of ethyl acetate
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-84b765f2009a4c4a8771c5b97e10bcdc
Source dataset
uspto-grants-2003_04
Patent number
US06552088B2

Reaction notes

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