1,1'-Carbonyldiimidazole → HCID 178426901, compound

HRID 2215117Notes

Reaction equation

HRID 2215117 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21]([C:24]([OH:26])=O)=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]([F:36])([F:35])[F:34].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)(O)O.[NH2:53][C:54]([NH2:56])=[NH:55]>CN(C)C=O.O>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21]([C:24]([NH:55][C:54]([NH2:56])=[NH:53])=[O:26])=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]([F:36])([F:35])[F:34]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 286947Carbonic acid-guanidine (1:1)HCID 1027808210-(2-methyl-2'-trifluoromethyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 178426901HCID 178426901, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]4-yl)-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol) and 1,1′-carbonyldiimidazole (0.17 g, 1.05 mmol) were dissolved in anhydrous N,N-dimethylformamide (5 mL). After stirring for 30 minutes, guanidine carbonate (0.19 g, 1.05 mmol) was added, and the reaction was heated to 100° C. for 4 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give an orange oil. Purification was achieved by preparative HPLC on a Primesphere 5 C18 (0.2×15 cm) column using a solvent gradient from 55:45:0.1 to 90:10:0.1 acetonitrile-water-trifluoroacetic acid. After removal of the acetonitrile in vacuo, the aqueous solution was neutralized with saturated aqueous sodium bicarbonate, and then extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 0.25 g of the title compound as a white solid.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an orange oil
  7. customPurification
  8. customAfter removal of the acetonitrile in vacuo
  9. extractionextracted with ethyl acetate
  10. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5631c0a80f55478aa9d3a7ba28964f59
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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