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

HRID 849497Notes

Reaction equation

HRID 849497 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) δ 2.78, 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. customthe residue chromatographed on silica gel

Sources & evidence

ORD record
ord-fc813af1364c423bbac1b65573650499
Source dataset
uspto-grants-2000_01
Patent number
US06013654

Reaction notes

Loading…