Piperazine → HCID 58914460, compound

HRID 1297067Notes

Reaction equation

HRID 1297067 reaction equation
F[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH3:18])=[CH:12]3)=[O:7])=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CN(C)C=O>[CH3:18][C:13]1[NH:14][C:15]2[C:11]([CH:12]=1)=[CH:10][C:9]([NH:8][C:6](=[O:7])[C:5]1[CH:19]=[CH:20][C:2]([N:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[C:3]([C:21]([F:24])([F:23])[F:22])[CH:4]=1)=[CH:17][CH:16]=2

Participants

4

Reactant 2

HCID 4837PiperazineHCID 69491031HCID 69491031, compound

Product 1

HCID 58914460HCID 58914460, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

Synthesis: 4-Fluoro-3-trifluoromethyl benzoyl chloride (0.42 mL, 2.77 mmol) was added to a solution of 2-methyl-1H-indol-5-ylamine (472 mg, 3.23 mmol) and triethylamine (0.42 mL, 3.01 mmol) in anhydrous dichloromethane at room temperature. The reaction mixture was stirred at room temperature for two hours then diluted with a 1:1 mixture of ethyl acetate and water (80 mL). The organic layer was washed sequentially with 0.5N HCl, saturated NaHCO3, water, saturated NaCl and dried over anhydrous sodium sulfate. The desired 4-fluoro-N-(2-methyl-1H-indol-5-yl)-3-trifluoromethyl-benzamide was obtained as a purple solid in nearly quantitative yield. This material was taken onto the next step without further purification. 4-Fluoro-N-(2-methyl-1H-indol-5-yl)-3-trifluoromethyl-benzamide (1.02 g, 3.03 mmol) and piperazine (1.83 g, 21.21 mmol) was dissolved in N,N-dimethylformamide (10 mL). The reaction mixture was heated in a sealed glass tube at 125° C. for two and a half hours. The crude mixture was then cooled to room temperature, concentrated and the residue chromatographed with 10% MeOH/CH2Cl2+2% triethylamine to afford N-(2-Methyl-1H-indol-5-yl)-4-piperazin-1-yl-3-trifluoromethyl-benzamide, the title compound (86% yield). 1H NMR (400 MHz , CD3OD) δ 8.26 (d, J=2.3 Hz, 1H), 8.18 (dd, J=8.6, 2.3 Hz, 1H), 7.69 (d, J=1.6 Hz, 1H, 7.55 (d, J=8.6 Hz, 1H), 7.28-7.17 (m, 2H), 2.99 (s, 8H), 2.41 (s, 3H).

Workup

  1. customThis material was taken onto the next step without further purification
  2. concentrationconcentrated
  3. customthe residue chromatographed with 10% MeOH/CH2Cl2+2% triethylamine

Sources & evidence

ORD record
ord-c8f03af29ef84d1b923ba9d635066034
Source dataset
uspto-grants-2007_07
Patent number
US07250413B2

Reaction notes

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