Triethylamine → HCID 10790304, compound

HRID 1647426Notes

Reaction equation

HRID 1647426 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:23])[C@H:5]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)[NH:6][C:7]([C:9]1([NH2:14])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:8].C(N(CC)CC)C.[C:31]([S:34][C@@H:35]([CH:39]([CH3:41])[CH3:40])[C:36](O)=[O:37])(=[O:33])[CH3:32].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2N=CC=CC=2N=N1>ClCCl>[CH3:2][O:3][C:4](=[O:23])[C@H:5]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=1)[NH:6][C:7]([C:9]1([NH:14][C:36](=[O:37])[C@@H:35]([S:34][C:31](=[O:33])[CH3:32])[CH:39]([CH3:41])[CH3:40])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:8]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 181649HOAtHCID 10654866(2S)-2-(acetylsulfanyl)-3-methylbutanoic acidHCID 70266804HCID 70266804, compound

Product 1

HCID 10790304HCID 10790304, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [(1-amino(1-cyclopentyl)carbonyl]-L-tyrosine methyl ester hydrochloride (1.36 g, 3.97 mmol) in dichloromethane (50 mL) is added triethylamine (0.55 mL, 3.97 mmol). The mixture is stirred for 5 minutes and then (S)-2-acetylthio-3-methylbutanoic acid (0.70 g, 3.97 mmol), 1,3-dicyclohexylcarbodiimide (0.82 g, 3.97 mmol) and 1-hydroxy-7-azabenzotriazole (0.54 g, 3.97 mmol) are added. The mixture is stirred for 16 hours and then the solid precipitate is filtered off. The organic phase is washed with a saturated solution of sodium bicarbonate (30 mL), brine, dried over MgSO4, filtered and concentrated under reduced pressure to give a white foam. The foam is purified by flash chromatography on silica gel, eluting with hexane-ethyl acetate (1:1). The pure fractions are concentrated and the resulting foam is crystallized from ethyl acetate-hexane to afford N-[[1-[(2(S)-acetylmercapto-3-methyl-1-oxobutyl)amino]-1-cyclopentyl]carbonyl]-L-tyrosine methyl ester as a white solid, m.p. 157°-158° C., the compound of formula III wherein R1 is 4-hydroxyphenyl, R2 is methyl, R3 is acetyl and R4 is isopropyl.

Workup

  1. stirringThe mixture is stirred for 16 hours
  2. filtrationthe solid precipitate is filtered off
  3. washThe organic phase is washed with a saturated solution of sodium bicarbonate (30 mL), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a white foam
  8. customThe foam is purified by flash chromatography on silica gel
  9. washeluting with hexane-ethyl acetate (1:1)
  10. concentrationThe pure fractions are concentrated
  11. customthe resulting foam is crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-5b9d4073b96b4debb661810624ffab3f
Source dataset
uspto-grants-1995_07
Patent number
US05432186

Reaction notes

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