Dimethylamine → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-dimethylcarbamoylmorpholino)-2-butynyl]piperazine

HRID 584243Notes

Reaction equation

HRID 584243 reaction equation
[CH3:1][NH:2][CH3:3].[F:4][C:5]([F:47])([F:46])[C:6]1[CH:7]=[C:8]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]#[C:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][C@H:22]2[C:27]([OH:29])=O)[CH2:13][C@H:12]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:10].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.O1CCCC1>[F:43][C:42]([F:44])([F:45])[C:40]1[CH:39]=[C:8]([CH:7]=[C:6]([C:5]([F:4])([F:47])[F:46])[CH:41]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]#[C:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][C@H:22]2[C:27](=[O:29])[N:2]([CH3:3])[CH3:1])[CH2:13][C@H:12]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:10]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86588523(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-carboxymorpholino)-2-butynyl]piperazine

Product 1

HCID 86588522(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-dimethylcarbamoylmorpholino)-2-butynyl]piperazine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A tetrahydrofuran solution of dimethylamine (2 M, 0.32 ml) was added to a mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-carboxymorpholino)-2-butynyl]piperazine (0.13 g), 1-hydroxybenzotriazole (85 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g) in N,N-dimethylformamide (5 ml), and the whole was stirred at room temperature for 5 hours. After the solvent was removed by evaporation, dichloromethane and sodium hydrogen carbonate solution were added to the residue. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel with 3% of methanol in dichloromethane as an eluent to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-dimethylcarbamoylmorpholino)-2-butynyl]piperazine. It was dissolved in ethyl acetate (10 ml) and the solution was added 4N hydrogen chloride in ethyl acetate (0.26 ml). The mixture was evaporated in vacuo and the residue was triturated with a mixture of ethyl acetate and isopropyl ether to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-((3S)-3-dimethylcarbamoylmorpholino)-2-butynyl]piperazine dihydrochloride (0.12 g) as a solid.

Workup

  1. customAfter the solvent was removed by evaporation, dichloromethane and sodium hydrogen carbonate solution
  2. additionwere added to the residue
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel with 3% of methanol in dichloromethane as an eluent

Sources & evidence

ORD record
ord-b87016cbf43c49ec84c78dc554f2bafd
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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