Ethylmorpholine → 1-[3(S)-[[N-(tert.butoxycarbonyl)-L-cysteinyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-2(S)-piperidinecarboxamide

HRID 742901Notes

Reaction equation

HRID 742901 reaction equation
[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C@H:3]([OH:18])[CH2:4][N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[C:26]([O:30][C:31]([NH:33][C@H:34]([C:38](O)=[O:39])[CH2:35][S:36]C)=[O:32])([CH3:29])([CH3:28])[CH3:27].OC1C2N=NNC=2C=CC=1.C(N1CCOCC1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)(=O)C>[C:26]([O:30][C:31]([NH:33][C@H:34]([C:38]([NH:1][C@@H:2]([CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C@H:3]([OH:18])[CH2:4][N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[C:11]([NH:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:12])=[O:39])[CH2:35][SH:36])=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 7018744Boc-cys(ME)-OHHCID 186482391-[3 (S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-2(S)-piperidinecarboxamideHCID 178418300HCID 178418300, compound

Product 1

HCID 867462921-[3(S)-[[N-(tert.butoxycarbonyl)-L-cysteinyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-2(S)-piperidinecarboxamideYield 39.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.02 g of 1-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-2(S)-piperidinecarboxamide and 685 mg of N-(tert.butoxycarbonyl)-S-methyl-L-cysteine in 7 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 394 mg of hydroxybenzotriazole, 335 mg of N-ethylmorpholine and 661 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 3 hours. The mixture was diluted with ethyl acetate and filtered. The filtrate was washed with aqueous sodium bicarbonate solution and with sodium chloride solution and then evaporated. The solvent was removed by evaporation and the residue was chromatographed on silica gel using dichloromethane/methanol (96:4) for the elution to give 630 mg of 1-[3(S)-[[N-(tert.butoxycarbonyl)-L-cysteinyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-2(S)-piperidinecarboxamide in the form of a white solid; MS: m/e 565 [M+H]+.

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with aqueous sodium bicarbonate solution and with sodium chloride solution
  3. customevaporated
  4. customThe solvent was removed by evaporation
  5. customthe residue was chromatographed on silica gel
  6. washfor the elution

Sources & evidence

ORD record
ord-1b716864fcc74c88bb640d0bee411a7a
Source dataset
uspto-grants-1996_09
Patent number
US05554756

Reaction notes

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