Ethylmorpholine → Ro 31-8875

HRID 1614284Notes

Reaction equation

HRID 1614284 reaction equation
[NH2:1][C@@H:2]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C@H:3]([OH:22])[CH2:4][N:5]1[C@H:14]([C:15]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][C@H:12]2[C@H:7]([CH2:8][CH2:9][CH2:10][CH2:11]2)[CH2:6]1.[CH2:30]([O:37][C:38]([NH:40][C@H:41]([C:46](O)=[O:47])[CH2:42][C:43](=[O:45])[NH2:44])=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.OC1C2N=NNC=2C=CC=1.C(N1CCOCC1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)(=O)C>[CH2:30]([O:37][C:38]([NH:40][C@H:41]([C:46]([NH:1][C@@H:2]([CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C@H:3]([OH:22])[CH2:4][N:5]1[C@H:14]([C:15]([NH:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[CH2:13][C@H:12]2[C@H:7]([CH2:8][CH2:9][CH2:10][CH2:11]2)[CH2:6]1)=[O:47])[CH2:42][C:43](=[O:45])[NH2:44])=[O:39])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 75314Benzyloxycarbonyl-asparagineHCID 9865804(3S,4aS,8aS)-2-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-tert-butyldecahydroisoquinoline-3-carboxamideHCID 178418300HCID 178418300, compound

Product 1

HCID 453680Ro 31-8875Yield 47.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 561 mg of 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide and 372 mg of N-(benzyloxycarbonyl)-L-asparagine in 20 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 189 mg of hydroxybenzotriazole, 161 mg of N-ethylmorpholine and 317 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 16 hours. The mixture was then diluted with ethyl acetate and filtered. The filtrate was washed with aqueous sodium bicarbonate solution and sodium chloride solution. The solvent was removed by evaporation and the residue was chromatographed on silica gel using dichloromethane/methanol (9:1) for the elution to give 434 mg of 2-[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide as a white solid from methanol/diethyl ether; MS: m/e 650 [M+H]+, NMR: δ (d4CH3OH, 400 MHz):

Workup

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

Sources & evidence

ORD record
ord-7d27ea9cbfe24eec9c0d02cc4fb30448
Source dataset
uspto-grants-1993_03
Patent number
US05196438

Reaction notes

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