Triethylamine → (4S)-1-[(2S,3S)-3-(N2-t-Butoxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamide

HRID 1780262Notes

Reaction equation

HRID 1780262 reaction equation
C(N(CC)CC)C.[NH2:8][C@@H:9]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@H:10]([OH:26])[C:11]([N:13]1[CH2:24][C@@H:23]([Cl:25])[CH2:22][C@H:14]1[C:15]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:12].N#N.[C:36]([O:40][C:41]([NH:43][C@H:44]([C:49](O)=[O:50])[CH2:45][C:46](=[O:48])[NH2:47])=[O:42])([CH3:39])([CH3:38])[CH3:37]>CN(C)C=O>[C:36]([O:40][C:41]([NH:43][C@H:44]([C:49]([NH:8][C@@H:9]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@H:10]([OH:26])[C:11]([N:13]1[CH2:24][C@@H:23]([Cl:25])[CH2:22][C@H:14]1[C:15]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:12])=[O:50])[CH2:45][C:46](=[O:48])[NH2:47])=[O:42])([CH3:38])([CH3:39])[CH3:37]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22872716(4S)-1-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamideHCID 86750818N2 t-butoxycarbonyl-L-asparagine

Product 1

HCID 70048547(4S)-1-[(2S,3S)-3-(N2-t-Butoxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4.4 ml (31.4 mmol) of triethylamine were added, whilst ice-cooling, to a solution of 6.0 g (15.7 mmol) of (4S)-1-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamide [prepared as described in Preparation 21(b)] and 10.6 g (30.0 mmol) of the p-nitrophenyl ester of N2 -t-butoxycarbonyl-L-asparagine in 50 ml of dimethylformamide, and the resulting mixture was stirred for 3 days. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the residue was diluted with methylene chloride. The diluted solution was washed with a 5% w/v aqueous solution of citric acid, with a 1N aqueous solution of sodium hydroxide and with a saturated aqueous solution of sodium chloride, in that order, after which it was concentrated by evaporation under reduced pressure. The residue thus obtained was purified by column chromatography, using a 1:30 by volume mixture of methanol and methylene chloride as the eluent, to give 7.6 g of the title compound as a colorless powder, melting at 126°-132° C.

Workup

  1. distillationAt the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure
  2. additionthe residue was diluted with methylene chloride
  3. washThe diluted solution was washed with a 5% w/v aqueous solution of citric acid, with a 1N aqueous solution of sodium hydroxide and with a saturated aqueous solution of sodium chloride, in that order
  4. concentrationafter which it was concentrated by evaporation under reduced pressure
  5. customThe residue thus obtained
  6. customwas purified by column chromatography
  7. additionby volume mixture of methanol and methylene chloride as the eluent

Sources & evidence

ORD record
ord-428422f1780b45eab0f842a300a3d610
Source dataset
uspto-grants-1997_05
Patent number
US05629406

Reaction notes

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