Quinaldic Acid → Saquinavir

HRID 1614285Notes

Reaction equation

HRID 1614285 reaction equation
[NH2:1][C@H:2]([C:7]([NH:9][C@@H:10]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C@H:11]([OH:30])[CH2:12][N:13]1[C@H:22]([C:23]([NH:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:21][C@H:20]2[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]2)[CH2:14]1)=[O:8])[CH2:3][C:4](=[O:6])[NH2:5].[C:38](O)(=[O:49])[C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:40]=1.OC1C2N=NNC=2C=CC=1.C(N1CCOCC1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)(=O)C>[C:26]([NH:25][C:23]([C@@H:22]1[CH2:21][C@H:20]2[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]2)[CH2:14][N:13]1[CH2:12][C@@H:11]([OH:30])[C@@H:10]([NH:9][C:7](=[O:8])[C@H:2]([CH2:3][C:4](=[O:6])[NH2:5])[NH:1][C:38]([C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:40]=1)=[O:49])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:24])([CH3:28])([CH3:29])[CH3:27]

Participants

8

Reactant 5

HCID 7124Quinaldic AcidHCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 100980232-[3(S)-[(L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamideHCID 178418300HCID 178418300, compound

Product 1

HCID 441243SaquinavirYield 25%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 154 mg of 2-[3(S)-[(L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide and 52 mg of quinaldic acid in 6 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 41 mg of hydroxybenzotriazole, 35 mg of N-ethylmorpholine and 68 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 64 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 residue was chromatographed on silica gel using dichloromethane/methanol (9:1) for the elution to give 50 mg of N-tert.butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide as a white solid; MS: m/e 671 [M+H]+, NMR: δ (d4CH3OH, 400 MHz):

Workup

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

Sources & evidence

ORD record
ord-edd25d31946e451db4b4ee7ecf0e65a0
Source dataset
uspto-grants-1993_03
Patent number
US05196438

Reaction notes

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