1,1'-Carbonyldiimidazole → HCID 86645204, compound

HRID 450803Notes

Reaction equation

HRID 450803 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=2)[C:27](O)=[O:28])=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:33])[N:10]1[CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]1[NH:40][S:41]([CH3:44])(=[O:43])=[O:42].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:57][S:58]([NH2:61])(=[O:60])=[O:59].C1CCN2C(=NCCC2)CC1>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24]2[CH:32]=[CH:31][CH:30]=[C:26]([C:27](=[O:28])[NH:61][S:58]([CH3:57])(=[O:60])=[O:59])[CH:25]=2)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:33])[N:10]1[CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]1[NH:40][S:41]([CH3:44])(=[O:43])=[O:42]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 72303363HCID 72303363, compound

Product 1

HCID 86645204HCID 86645204, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 330 mg of 3-{[({[(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]methyl}benzoic acid in 5 ml of DMF was added 122 mg of CDI, followed by stirring at room temperature for 30 minutes. To the reaction solution were added 71 mg of methane sulfonamide and 0.11 ml of DBU, followed by stirring at room temperature for 3 hours. To the reaction solution was added ethyl acetate, followed by washing with 1 M hydrochloric acid and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent was then evaporated. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol) to obtain a crude purified product. This was recrystallized with acetonitrile-water to obtain 273 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-N-({3-[(methylsulfonyl)carbamoyl]benzyl}oxy)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

Workup

  1. stirringby stirring at room temperature for 3 hours
  2. washby washing with 1 M hydrochloric acid
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was then evaporated
  5. customThe residue was purified by silica gel column chromatography (eluent: chloroform-methanol)
  6. customto obtain a crude
  7. custompurified product
  8. customThis was recrystallized with acetonitrile-water

Sources & evidence

ORD record
ord-d4453e2e0b0a4208a4212736207f0b12
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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