Triethylamine → HCID 178501615, compound

HRID 1722908Notes

Reaction equation

HRID 1722908 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:16][C:17](=[O:25])[N:18]([CH3:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:13](O)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.Cl.[NH2:28][C@H:29]([C:36]([NH:38][C@@H:39]([CH2:48][CH:49]([CH3:51])[CH3:50])[CH:40]([OH:47])[C:41]([O:43][CH:44]([CH3:46])[CH3:45])=[O:42])=[O:37])[CH2:30][C:31]1[N:35]=[CH:34][NH:33][CH:32]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[C:1]1([CH2:11][CH:12]([CH2:16][C:17](=[O:25])[N:18]([CH3:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:13]([NH:28][C@H:29]([C:36]([NH:38][C@@H:39]([CH2:48][CH:49]([CH3:51])[CH3:50])[CH:40]([OH:47])[C:41]([O:43][CH:44]([CH3:45])[CH3:46])=[O:42])=[O:37])[CH2:30][C:31]2[N:35]=[CH:34][NH:33][CH:32]=2)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 139595242-(1-naphthylmethyl)-3-(N-methyl-N-methoxycarbonylmethylcarbamoyl)propionic acidHCID 178446017isopropyl (2RS,3S)-3-(L-histidyl)amino-2-hydroxy-5-methylhexanoate dihydrochloride

Product 1

HCID 178501615HCID 178501615, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 50 mg of 2-(1-naphthylmethyl)-3-(N-methyl-N-methoxycarbonylmethylcarbamoyl)propionic acid and 70 mg of isopropyl(2RS,3S)-3-(L-histidyl)amino-2-hydroxy-5-methylhexanoate dihydrochloride in 4 ml of N,N-dimethylformamide were added 0.036 ml of diphenylphosphoryl azide and 0.064 ml of triethylamine with stirring under ice-cooling, and the mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and a 5% aqueous sodium bicarbonate solution was added to the residue. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol=5/1 by volume; Rf2 =0.36) to obtain 10 mg of isopropyl(2RS,3S)-3-{N-[2-(1-naphthylmethyl)-3-(N-methyl-N-methoxycarbonylmethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiona 5% aqueous sodium bicarbonate solution was added to the residue
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe ethyl acetate layer was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol=5/1 by volume; Rf2 =0.36)

Sources & evidence

ORD record
ord-d4eb2a69d4694301857826c2e2ec6f71
Source dataset
uspto-grants-1989_08
Patent number
US04857650

Reaction notes

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