Diisopropylethylamine → ((3E)-1,1-Dimethyl-4-{N-methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamoyl}but-3-enyl)carbamic acid tert-butyl ester

HRID 413493Notes

Reaction equation

HRID 413493 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)C(C)C)C.[CH3:49][N:50]([C@@H:67]([C:75](=[O:86])[N:76]([CH3:85])[CH2:77][CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][N:80]=1)[CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:51](=[O:66])[C@H:52]([NH:64][CH3:65])[CH2:53][C:54]1[CH:63]=[CH:62][C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH:55]=1>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13](=[O:15])[N:64]([CH3:65])[C@@H:52]([C:51](=[O:66])[N:50]([CH3:49])[C@@H:67]([C:75](=[O:86])[N:76]([CH3:85])[CH2:77][CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][N:80]=1)[CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[CH2:53][C:54]1[CH:63]=[CH:62][C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH:55]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 20587656(2R)-N-Methyl-2-(methylamino)-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}-3-(2-naphthyl)propionamide

Product 1

HCID 59063567((3E)-1,1-Dimethyl-4-{N-methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamoyl}but-3-enyl)carbamic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2E)-5-(tert-Butoxycarbonylamino)-5-methylhex-2-enoic acid (2.87 g, 11.8 mmol), 1-hydroxy-7-azabenzotriazole (1.6 g, 11.8 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.26 g, 11.8 mmol) were dissolved in dichloromethane (30 mL). The reaction mixture was stirred for 15 min. Ethyidiisopropylamine (2.0 mL, 11.8 mmol) was added. (2R)-N-Methyl-2-(methylamino)-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}-3-(2-naphthyl)propionamide (6.0 g, 11.8 mmol) dissolved in dichloromethan (10 mL) was added. The reaction mixture was stirred for 16 h. The reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (100 mL). The aqueous phase was extracted with dichloromethane (100 mL). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate as eluent, to give 5.28 g of ((3E)-1,1-Dimethyl-4-{N-methyl-N-[(1R)1-(N-methyl-N{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamoyl}but-3-enyl)carbamic acid tert-butyl ester.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 16 h
  3. washThe reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (100 mL)
  4. extractionThe aqueous phase was extracted with dichloromethane (100 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customThe crude product was purified by flash chromatography on silica (400 g)

Sources & evidence

ORD record
ord-4c00cd920b314a81a4792296d5b1d5e5
Source dataset
uspto-grants-2003_05
Patent number
US06566337B1

Reaction notes

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