Triethylamine → HCID 69491031, compound

HRID 1297066Notes

Reaction equation

HRID 1297066 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[CH3:15][C:16]1[NH:17][C:18]2[C:23]([CH:24]=1)=[CH:22][C:21]([NH2:25])=[CH:20][CH:19]=2.C(N(CC)CC)C>ClCCl.C(OCC)(=O)C.O>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:25][C:21]2[CH:22]=[C:23]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([CH3:15])=[CH:24]3)=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 27339925-Amino-2-methylindole

Product 1

HCID 69491031HCID 69491031, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

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. customSynthesis
  2. washThe organic layer was washed sequentially with 0.5N HCl, saturated NaHCO3, water, saturated NaCl
  3. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-c9f506a9563644cc9550e8a70335aa05
Source dataset
uspto-grants-2007_07
Patent number
US07250413B2

Reaction notes

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