1,1'-Carbonyldiimidazole → HCID 72303445, compound

HRID 450828Notes

Reaction equation

HRID 450828 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 stifling 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-[(diaminomethylene)carbamoyl]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. waitby stifling 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-1273e25d4b2040ab87c3a3de600ad1e8
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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