1,1'-Carbonyldiimidazole → HCID 72303445, compound

HRID 1747100Notes

Reaction equation

HRID 1747100 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.C(=O)(O)O.[NH2:61][C:62]([NH2:64])=[NH:63]>CN(C=O)C>[NH2:63][C:62](=[N:61][C:27]([C:26]1[CH:25]=[C:24]([CH:32]=[CH:31][CH:30]=1)[CH2:23][O:22][NH:21][C:19]([CH:18]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:33])[N:10]([CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]2[NH:40][S:41]([CH3:44])(=[O:42])=[O:43])[CH:9]1[C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])=[O:20])=[O:28])[NH2:64]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 286947Carbonic acid-guanidine (1:1)HCID 72303363HCID 72303363, compound

Product 1

HCID 72303445HCID 72303445, compoundYield 55.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 590 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, 217 mg of CDI, and 9 ml of DMF was stirred at 50° C. for 1 hour, and 241 mg of guanidine carbonate was then added thereto, followed by stirring at the same temperature for 3 hours. The reaction solution was left to be cooled and the solvent was then evaporated under reduced pressure. The residue was diluted with ethyl acetate, and washed with a saturated aqueous sodium hydrogen carbonate solution and then with a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent:chloroform-methanol) and recrystallized from acetonitrile to obtain 348 mg of (3RS,4RS)—N-({3-[(diaminomethyl ene)carb amoyl]benzyl}oxy)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a colorless solid.

Workup

  1. stirringby stirring at the same temperature for 3 hours
  2. waitThe reaction solution was left
  3. temperatureto be cooled
  4. customthe solvent was then evaporated under reduced pressure
  5. additionThe residue was diluted with ethyl acetate
  6. washwashed with a saturated aqueous sodium hydrogen carbonate solution
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (eluent:chloroform-methanol)
  10. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-ffd4c3ddc6254a8a9720e05546862b42
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

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