Triethylamine → N-[1(S)-Benzyl-2-hydroxy-2-(4-methyl-3-oxopiperazin-2-yl)-ethyl]-acetamide hydrochloride

HRID 732598Notes

Reaction equation

HRID 732598 reaction equation
[NH2:1][C@@H:2]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:3]([CH:5]1[NH:10][CH2:9][CH2:8][N:7]([CH3:11])[C:6]1=[O:12])[OH:4].[ClH:20].CN(C)CCCN=C=N[CH2:29][CH3:30].C(N(CC)CC)C.CN(C1C=CC=CN=1)C.O.[OH:49]N1C2C=CC=CC=2N=N1>ClCCl.Cl.O1CCOCC1.C(O)(=O)C>[ClH:20].[CH2:13]([C@H:2]([NH:1][C:29](=[O:49])[CH3:30])[CH:3]([OH:4])[CH:5]1[C:6](=[O:12])[N:7]([CH3:11])[CH2:8][CH2:9][NH:10]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 579388223-(2-(S)-amino-1-hydroxy-3-phenylpropyl)-1-methylpiperazin-2-one

Product 1

HCID 68815306N-[1(S)-Benzyl-2-hydroxy-2-(4-methyl-3-oxopiperazin-2-yl)-ethyl]-acetamide hydrochlorideYield 10%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Stir overnight at room temperature under a nitrogen atmosphere a solution of acetic acid (25 μl, 0.45), 3-(2-(S)-amino-1-hydroxy-3-phenylpropyl)-1-methylpiperazin-2-one (120 mg, 0.45 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (112 mg, 0.58 mmol), triethylamine (0.12 mL, 0.9 mmol), dimethylaminopyridine (5.5 mg, 0.04 mmol) and 1-hydroxybenzotriazole hydrate (HOBt) (79 mg, 0.58 mmol) in dichloromethane (10 mL/mmol). Dilute with more dichloromethane and wash with, 5% aqueous sodium bicarbonate solution, saturated aqueous sodium chloride. Dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 9:1 dichloromethane:methanol) to provide a white solid. Suspend the solid in 4 M HCl in 1,4-dioxane and stir for 10 min and concentrate the solution to give the title compound as a white solid (15 mg, 10%).

Workup

  1. washwash with, 5% aqueous sodium bicarbonate solution, saturated aqueous sodium chloride
  2. dry with materialDry (magnesium sulfate)
  3. concentrationconcentrate
  4. custompurify
  5. wash(silica gel chromatography, eluting with 9:1 dichloromethane:methanol)
  6. customto provide a white solid
  7. concentrationconcentrate the solution

Sources & evidence

ORD record
ord-99079ce10b38428ba92b84367cf3cee0
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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