Triethylamine → N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-thienylacetyl)piperidin-3-yl]methyl}piperazine-1-carboxamide

HRID 2371190Notes

Reaction equation

HRID 2371190 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].C(N(CC)CC)C.[S:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[CH2:37][C:38](Cl)=[O:39]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([C:38](=[O:39])[CH2:37][C:33]4[S:32][CH:36]=[CH:35][CH:34]=4)[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1623622-Thiopheneacetyl chlorideHCID 57656731N-(3,4-Dichlorophenyl)-4-[(3R)-piperidin-3-ylmethyl]piperazine-1-carboxamide

Product 1

HCID 57656870N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-thienylacetyl)piperidin-3-yl]methyl}piperazine-1-carboxamideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(3,4-dichlorophenyl)-4-[(3R)-piperidin-3-ylmethyl]piperazine-1-carboxamide (150 mg) and triethylamine (0.11 mL) in tetrahydrofuran (5 mL) at room temperature was added 2-thiopheneacetyl chloride under argon at room temperature. The solution was stirred for 30 minutes and then quenched with methanol. The mixture was loaded onto a SCX-2 column and eluted with methanol then 7M NH3 in methanol. The basic fraction was concentrated and the residue purified by silica column chromatography, eluting with a gradient of 0 to 10% methanol in dichloromethane to give the title compound as a yellow oil (150 mg, 75%).

Workup

  1. customquenched with methanol
  2. washeluted with methanol
  3. concentrationThe basic fraction was concentrated
  4. customthe residue purified by silica column chromatography
  5. washeluting with a gradient of 0 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-6efa456038a94b1f9fb0c6d1cabc1883
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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