Sodium Chloride → HCID 22707363, compound

HRID 993176Notes

Reaction equation

HRID 993176 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[CH:22]=[C:21]4[N:24]([CH2:30][CH3:31])[C:25](=[O:29])[N:26]([CH2:27][CH3:28])[C:20]4=[CH:19][C:18]=3[C:17](Cl)=[N:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[N+:40]([C:43]1[CH:48]=[CH:47][C:46]([N:49]=C=O)=[CH:45][CH:44]=1)([O-:42])=[O:41].[Cl-].[Na+]>ClCCl.O>[CH2:27]([N:26]1[C:20]2=[CH:19][C:18]3[CH:17]=[N:16][N:15]=[C:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([NH:49][C:46]5[CH:47]=[CH:48][C:43]([N+:40]([O-:42])=[O:41])=[CH:44][CH:45]=5)=[O:5])[CH2:9][CH2:10]4)[C:23]=3[CH:22]=[C:21]2[N:24]([CH2:30][CH3:31])[C:25]1=[O:29])[CH3:28]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 6422Trifluoroacetic acidHCID 66012Benzene, 1-isocyanato-4-nitro-HCID 86585281HCID 86585281, compound

Product 1

HCID 22707363HCID 22707363, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 758.4 mg (1.65 mmol) of 4-(8-chloro-1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo[4,5-g]phthalazin-5-yl)-1-piperazinecarboxylic acid tert-butyl ester obtained in Reference Example 21 (5) in 20 ml of dichloromethane was added 50 ml of trifluoroacetic acid under ice-cooling, followed by stirring at the same temperature for 5 hours. After the solvent was evaporated, the residue was subjected to azeotropic distillation with toluene twice. The obtained residue was dissolved in 20 ml of acetic acid, and a suspension of 300 mg of 10% palladium-carbon in 5 ml of water was added thereto, followed by overnight stirring at room temperature in an atmosphere of hydrogen. After the catalyst was separated by filtration using Celite, the solvent was evaporated, and the residue was subjected to azeotropic distillation with triethylamine. The obtained residue was dissolved in 10 ml of dimethylformamide, and 297.3 mg (1.81 mmol) of 4-nitrophenyl isocyanate was added thereto, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into water, and sodium chloride was added thereto. The precipitated crystals were collected by filtration, washed with water, and dried, followed by purification by silica gel chromatography to give the desired compound as colorless crystals.

Workup

  1. temperaturecooling
  2. customAfter the solvent was evaporated
  3. distillationthe residue was subjected to azeotropic distillation with toluene twice
  4. dissolutionThe obtained residue was dissolved in 20 ml of acetic acid
  5. additiona suspension of 300 mg of 10% palladium-carbon in 5 ml of water
  6. additionwas added
  7. waitfollowed by overnight
  8. stirringstirring at room temperature in an atmosphere of hydrogen
  9. customAfter the catalyst was separated by filtration
  10. customthe solvent was evaporated
  11. distillationthe residue was subjected to azeotropic distillation with triethylamine
  12. dissolutionThe obtained residue was dissolved in 10 ml of dimethylformamide
  13. stirringby stirring at room temperature for 2 hours
  14. additionwas added
  15. filtrationThe precipitated crystals were collected by filtration
  16. washwashed with water
  17. customdried
  18. customfollowed by purification by silica gel chromatography

Sources & evidence

ORD record
ord-490934bf98d84535b9fee3413bf31750
Source dataset
uspto-grants-2002_10
Patent number
US06472391B2

Reaction notes

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