Water → (2E)-5-Amino-5-methylhex-2-enoic acid N-methyl-N-[(1R)-1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(2-pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]amide

HRID 413494Notes

Reaction equation

HRID 413494 reaction equation
C(OC(=O)[NH:7][C:8]([CH3:53])([CH3:52])[CH2:9]/[CH:10]=[CH:11]/[C:12](=[O:51])[N:13]([CH3:50])[C@@H:14]([C:26](=[O:49])[N:27]([CH3:48])[C@@H:28]([C:36](=[O:47])[N:37]([CH3:46])[CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+].O>ClCCl>[CH3:50][N:13]([C@@H:14]([C:26](=[O:49])[N:27]([CH3:48])[C@@H:28]([C:36](=[O:47])[N:37]([CH3:46])[CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1)[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1)[C:12](=[O:51])/[CH:11]=[CH:10]/[CH2:9][C:8]([NH2:7])([CH3:52])[CH3:53]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2×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 ester

Product 1

HCID 9809474(2E)-5-Amino-5-methylhex-2-enoic acid N-methyl-N-[(1R)-1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(2-pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]amideYield 70.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

((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 (5.28 g, 7.2 mmol) was dissolved in dichloromethane (50 mL). The solution was cooled to −10° C. Trifluoroacetic acid (50 mL) was added to the stirred solution. The reaction mixture was stirred for 45 min at −10° C. The reaction mixture was added to a solution of ice, sodium hydrogen carbonate and water. The reaction mixture was neutralised with sodium hydrogen carbonate. Dichloromethane (400 mL) was added. The aqueous phase was extracted with dichloromethane (300 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 (40 g), using 15% of a solution, 7% ammonium in ethanole, in dichloromethane as eluent, to give 3.2 g of the title compound.

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane (300 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. customThe solvent was removed in vacuo
  4. customThe crude product was purified by flash chromatography on silica (40 g)

Sources & evidence

ORD record
ord-e7a902ce05504603a3b7f905e8b680cb
Source dataset
uspto-grants-2003_05
Patent number
US06566337B1

Reaction notes

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