Diisopropylethylamine → ((3E)-1,1-dimethyl-5-((2R)-4-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-2-((2-naphthyl)methyl)-5-oxopiperazin-1-yl)-5-oxopent-3-enyl)carbamic acid tert-butyl ester

HRID 366105Notes

Reaction equation

HRID 366105 reaction equation
[CH3:1][C:2]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])([CH3:9])[CH2:3]/[CH:4]=[CH:5]/[C:6]([OH:8])=O.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:40][NH:41][C:42](=[O:69])[C@H:43]([N:51]1[CH2:56][C@@H:55]([CH2:57][C:58]2[CH:67]=[CH:66][C:65]3[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=3)[CH:59]=2)[NH:54][CH2:53][C:52]1=[O:68])[CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.O>[C:14]([O:13][C:11](=[O:12])[NH:10][C:2]([CH3:1])([CH3:9])[CH2:3]/[CH:4]=[CH:5]/[C:6]([N:54]1[CH2:53][C:52](=[O:68])[N:51]([C@@H:43]([C:42](=[O:69])[NH:41][CH3:40])[CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:56][C@H:55]1[CH2:57][C:58]1[CH:67]=[CH:66][C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:59]=1)=[O:8])([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 54574578(2R)-N-methyl-2-((5R)-5-((2-naphthyl)methyl)-2-oxopiperazin-1-yl)-3-phenylpropionamide

Product 1

HCID 59965076((3E)-1,1-dimethyl-5-((2R)-4-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-2-((2-naphthyl)methyl)-5-oxopiperazin-1-yl)-5-oxopent-3-enyl)carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

(2E)-5-Methyl-5-(tert-butyloxycarbonylamino)hex-2-enoic acid was dissolved in methylene chloride (10 ml). 1-Hydroxy-7-azabenzotriazol (60 mg, 0.46 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (100 mg, 0.51 mmol) were added and the mixture was stirred for 15 min. (2R)-N-Methyl-2-((5R)-5-((2-naphthyl)methyl)-2-oxopiperazin-1-yl)-3-phenylpropionamide (185 mg, 0.46 mmol) and diisopropylethylamine (0.08 ml) were added and the mixture was stirred overnight. Water (10 ml) and methylene chloride (10 ml) were added and the mixture was washed with an aqueous solution of sodium hydrogen sulphate (10%, 20 ml), a saturated aqueous solution of sodium hydrogen carbonate (20 ml), dried (magnesium sulfate) and the solvent was removed in vacuo. The residue was chromatographed on silica (3×30 cm) using ethyl acetate/heptane (1:1) as eluent to afford 0.20 g of ((3E)-1,1-dimethyl-5-((2R)-4-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-2-((2-naphthyl)methyl)-5-oxopiperazin-1-yl)-5-oxopent-3-enyl)carbamic acid tert-butyl ester.

Workup

  1. additionwere added
  2. washthe mixture was washed with an aqueous solution of sodium hydrogen sulphate (10%, 20 ml)
  3. dry with materiala saturated aqueous solution of sodium hydrogen carbonate (20 ml), dried (magnesium sulfate)
  4. customthe solvent was removed in vacuo
  5. customThe residue was chromatographed on silica (3×30 cm)

Sources & evidence

ORD record
ord-bf727eaa4a80400c9ec14f081751ed0c
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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