Diisopropylethylamine → 2-[[4-(2,4-Dichlorophenyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine

HRID 1416298Notes

Reaction equation

HRID 1416298 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][N:6]2[CH:15]=1.[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>C1COCC1>[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[N:24]1[CH2:25][CH2:26][N:27]([CH2:2][C:3]2[N:4]=[C:5]3[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][N:6]3[CH:15]=2)[CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27375271-(2,4-Dichlorophenyl)piperazineHCID 140427792-(Chloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine

Product 1

HCID 193671162-[[4-(2,4-Dichlorophenyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridineYield 77.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(chloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine (0.452 g), 1-(2,4-dichlorophenyl)piperazine (Example 31, Step 1; 0.468 g), diisopropylethylamine (Aldrich; 0.299 g), and THF (4 mL) is stirred at reflux for 21 h. After cooling, the mixture is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate, concentrated. and the residue chromatographed on silica gel using methanol/dichloromethane (2.5/97.5) to give 0.64 g of 2-[[4-(2,4-dichlorophenyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine. The methanesulfonate salt is prepared by dissolving 2-[[4-(2,4-dichlorophenyl)-1-piperazinyl]methyl]-6-(trifluoromethyl) imidazo[1,2-a]pyridine in ethyl acetate/hexane and adding methanesulfonic acid (0.143 g) dissolved in methanol. The mixture is concentrated under reduced pressure and the residue is crystallized from ethyl acetate to give 0.691 g of the title compound; mp 161-162° C.; MS m/z 428; IR (mineral oil) 1162, 1225, 1033, 1130, 1142, 1337 cm-1. 1H NMR (CDCl3) δ2.78, 3.09, 3.83, 6.96, 7.18, 7.31, 7.35, 7.66, 7.68, 8.47.

Workup

  1. temperatureat reflux for 21 h
  2. temperatureAfter cooling
  3. customthe mixture is partitioned between dichloromethane and aq. sodium bicarbonate
  4. dry with materialThe organic layers are dried over sodium sulfate
  5. concentrationconcentrated
  6. customand the residue chromatographed on silica gel

Sources & evidence

ORD record
ord-b78a43e1cf9144819f4bef240e320010
Source dataset
uspto-grants-1999_06
Patent number
US05912246

Reaction notes

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