Triethylamine → 3-Chloro-4-[4-[(6-chloroimidazo[1,2-a]pyridin-2-yl)methyl]-1-piperazinyl]benzonitrile

HRID 1416270Notes

Reaction equation

HRID 1416270 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11]Cl)[N:10]=2)[CH:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[C:17]#[N:18].C(N(CC)CC)C>C(N(CC)CC)C.C1COCC1>[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:27][CH2:26][N:25]([CH2:11][C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]3[CH:8]=2)[CH2:24][CH2:23]1)[C:17]#[N:18]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 48683896-Chloro-2-(chloromethyl)imidazo[1,2-a]pyridineHCID 193671133-Chloro-4-(piperazin-1-yl)benzonitrile

Product 1

HCID 193671143-Chloro-4-[4-[(6-chloroimidazo[1,2-a]pyridin-2-yl)methyl]-1-piperazinyl]benzonitrileYield 88.5%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (Example 4, Step 1; 0.140 g), 3-chloro-4-(piperazin-1-yl)benzonitrile (0.155 g), triethylamine (0.078 g), and THF (2.5 mL) is heated at reflux for 5.5 h and then stirred overnight at room temperature. A few drops of triethylamine are then added and the mixture is stirred an additional 4 h at reflux. After cooling, the mixture is concentrated and the residue is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate and concentrated. Chromatography of the residue on silica gel using methanol/dichloromethane (4/96) gives 0.238 g of the title compound. A portion of the material is recrystallized from ethyl acetate/ethyl ether/hexane; mp 137-138° C.; MS m/z 385, 387; IR (mineral oil) 1501, 2225, 1130, 1342, 1490 cm-1. 1H NMR (CDCl3) δ2.77, 3.21, 3.79, 7.03, 7.14, 7.47-7.54, 7.61, 8.14.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 5.5 h
  3. stirringthe mixture is stirred an additional 4 h
  4. temperatureat reflux
  5. temperatureAfter cooling
  6. concentrationthe mixture is concentrated
  7. customthe residue is partitioned between dichloromethane and aq. sodium bicarbonate
  8. dry with materialThe organic layers are dried over sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-76e8ca55141b496f8f07aeb99139e7e0
Source dataset
uspto-grants-1999_06
Patent number
US05912246

Reaction notes

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