3,5-Dichlorobenzoic acid → HCID 70050059, compound

HRID 1647203Notes

Reaction equation

HRID 1647203 reaction equation
[NH2:1][C@H:2]([C:7]([NH:9][C@@H:10]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@H:11]([OH:26])[CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5].[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[C:42]([Cl:44])[CH:43]=1)[C:38](O)=[O:39].O.OC1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[C:42]([Cl:44])[CH:43]=1)[C:38]([NH:1][C@H:2]([C:7]([NH:9][C@@H:10]([CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:11]([OH:26])[CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:19]([NH:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5])=[O:39]

Participants

6

Reactant 4

HCID 58113,5-Dichlorobenzoic acidHCID 10868DicyclohexylcarbodiimideHCID 70050099HCID 70050099, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 70050059HCID 70050059, compoundYield 44.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 60 mg (0.13 mmol) of 2(S)-[3(S)-[[L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-1(R)-cyclohexanecarboxamide, 25 mg (0.13 mmol) of 3,5-dichlorobenzoic acid, 18 mg (0.13 mmol) of hydroxybenzotriazole hydrate and 27 mg (0.13 mmol) of dicyclohexylcarbodiimide in 2 ml of dimethylformamide was stirred at room temperature under nitrogen for 20 hours. The mixture was then filtered and the solid was washed with dichloromethane. The combined filtrate and washings were evaporated to dryness and the residue was partitioned between 50 ml of ethyl acetate and 10 ml of saturated aqueous sodium hydrogen carbonate solution. The separated organic phase was dried over anhydrous magnesium sulphate and evaporated. The residue was chromatographed on silica gel using 5% methanol in dichloromethane for the elution. The product was purified further by recrystallization from a mixture of 2 ml of dichloromethane and 10 ml of n-hexane to give 37 mg of 2(S)-[3(S)-[[N-(3,5-dichlorobenzoyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-1(R)-cyclohexanecarboxamide as a white solid of melting point 220°-226° C.

Workup

  1. filtrationThe mixture was then filtered
  2. washthe solid was washed with dichloromethane
  3. customThe combined filtrate and washings were evaporated to dryness
  4. customthe residue was partitioned between 50 ml of ethyl acetate and 10 ml of saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialThe separated organic phase was dried over anhydrous magnesium sulphate
  6. customevaporated
  7. customThe residue was chromatographed on silica gel using 5% methanol in dichloromethane for the elution
  8. customThe product was purified further by recrystallization from a mixture of 2 ml of dichloromethane and 10 ml of n-hexane

Sources & evidence

ORD record
ord-790971b8b2454603be2198e346c29676
Source dataset
uspto-grants-1995_07
Patent number
US05430041

Reaction notes

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