Triethylamine → 2-(2-cyclopentyl-5,6,7,8-tetrahydro-indolizin-3-yl)-N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-acetamide

HRID 37879Notes

Reaction equation

HRID 37879 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)[CH:3]=1.C(N(CC)CC)C.[CH:29]1([C:34]2[CH:35]=[C:36]3[N:41]([C:42]=2[C:43](=[O:47])[C:44](Cl)=[O:45])[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1>[CH:29]1([C:34]2[CH:35]=[C:36]3[N:41]([C:42]=2[C:43](=[O:47])[C:44]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([N:12]4[CH2:13][CH2:14][N:9]([C:4]5[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[N:5]=5)[CH2:10][CH2:11]4)=[CH:16][CH:17]=2)=[O:45])[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 668513514-[4-(4,6-Dimethyl-2-pyridyl)piperazin-1-yl]anilineHCID 86649693HCID 86649693, compound

Product 1

HCID 251220302-(2-cyclopentyl-5,6,7,8-tetrahydro-indolizin-3-yl)-N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-acetamideYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenylamine (prepared as described in Reference Example 94; 0.20 g, 0.71 mmol) and triethylamine (0.3 mL, 2.1 mmol) in THF (5 mL) was cooled to 0° C. A solution of (2-cyclopentyl-5,6,7,8-tetrahydro-indolizin-3-yl)-oxo-acetyl chloride (prepared as described in Reference Example 22, 0.24 g, 0.85 mmol) in THF (2 mL) was added and the mixture stirred under N2 atmosphere at 0° C. for 1 h and then at room temperature for 1 h. The mixture was quenched with sodium bicarbonate solution and extracted twice with ethyl acetate. The combined organic phases were washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (60-120 mesh) eluting with 12% ethyl acetate/chloroform to afford 2-(2-cyclopentyl-5,6,7,8-tetrahydro-indolizin-3-yl)-N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-acetamide (0.17 g, 46%) as a solid.

Workup

  1. waitat room temperature for 1 h
  2. customThe mixture was quenched with sodium bicarbonate solution
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic phases were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (60-120 mesh)
  8. washeluting with 12% ethyl acetate/chloroform

Sources & evidence

ORD record
ord-1dc97c98f0ad4a21bbec3f5254142165
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Reaction notes

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