Dicyclohexylcarbodiimide → Saquinavir

HRID 1614287Notes

Reaction equation

HRID 1614287 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 [prepared as described in Example 1 (i)-(vii)] 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 filtrate 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 which was identical with the product obtained in the first paragraph of Example 2.

Workup

  1. filtrationfiltered
  2. washThe filtrate 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-2d4c0a2267014c31abf895e875ead27b
Source dataset
uspto-grants-1993_03
Patent number
US05196438

Reaction notes

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