Dicyclohexylcarbodiimide → Saquinavir

HRID 1899412Notes

Reaction equation

HRID 1899412 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([NH:13][C@H:14]([C:19]([OH:21])=O)[CH2:15][C:16](=[O:18])[NH2:17])=[O:12].[NH2:22][C@@H:23]([CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C@H:24]([OH:43])[CH2:25][N:26]1[C@H:35]([C:36]([NH:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][C@H:33]2[C@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:27]1.ON1C(=O)C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)(=O)C>[C:39]([NH:38][C:36]([C@@H:35]1[CH2:34][C@H:33]2[C@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:27][N:26]1[CH2:25][C@@H:24]([OH:43])[C@@H:23]([NH:22][C:19](=[O:21])[C@H:14]([CH2:15][C:16](=[O:18])[NH2:17])[NH:13][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1)=[O:12])[CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 9865804(3S,4aS,8aS)-2-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-tert-butyldecahydroisoquinoline-3-carboxamideHCID 11044384(S)-4-Amino-4-oxo-2-(((quinolin-2-yl)carbonyl)amino)butanoic acid

Product 1

HCID 441243SaquinavirYield 80.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 287 mg of N-(2-quinolylcarbonyl)-L-asparagine and 401 mg of 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS, 8aS)- isoquinoline-3(S)-carboxamide in 3 ml of tetrahydrofuran was cooled to -10° C. and 163 mg of 3-hydroxy-1,2,3-benzotriazin-4(3H)-one and 220 mg of dicyclohexylcarbodiimide were added. The mixture was stirred at -10° C. for 2 hours and at 20° C. for 16 hours, then diluted with ethyl acetate and filtered. The liltrate was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution and then evaporated. The residue was chromatographed on silica gel using 4% (by volume) methanol in dichloromethane for the elution to give 537 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]+.

Workup

  1. filtrationfiltered
  2. washThe liltrate was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution
  3. customevaporated
  4. customThe residue was chromatographed on silica gel using 4% (by volume) methanol in dichloromethane for the elution

Sources & evidence

ORD record
ord-2f13b0b1cfbb4a1bbfea42932fb94fde
Source dataset
uspto-grants-1996_11
Patent number
US05571920

Reaction notes

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