Imidazole → HCID 22707537, compound

HRID 353143Notes

Reaction equation

HRID 353143 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26]CC4C=CC=CC=4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[H][H].N1C=CN=C1.[Si:41](Cl)([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42].[Cl-].[Na+].[N+:51]([C:54]1[CH:59]=[CH:58][C:57]([N:60]=C=O)=[CH:56][CH:55]=1)([O-:53])=[O:52]>C(O)C.O.[C].[Pd]>[Si:41]([O:26][C:20]1[CH:19]=[C:18]2[C:23]([C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:6]([NH:60][C:57]4[CH:58]=[CH:59][C:54]([N+:51]([O-:53])=[O:52])=[CH:55][CH:56]=4)=[O:5])[CH2:13][CH2:12]3)=[N:15][CH:16]=[N:17]2)=[CH:22][C:21]=1[O:24][CH3:25])([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42]

Participants

10

Reactant 6

HCID 795ImidazoleHCID 5234Sodium Chloride2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 66012Benzene, 1-isocyanato-4-nitro-HCID 109064811,1-Dimethylethyl 4-[6-methoxy-7-(phenylmethoxy)-4-quinazolinyl]-1-piperazinecarboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 22707537HCID 22707537, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To a suspension of 162.0 mg (0.36 mmol) of 4-(7-benzyloxy-6-methoxy-4-quinazolinyl)-1-piperazinecarboxylic acid tert-butyl ester obtained in Reference Example 8 (6) in 10 ml of ethanol was added a suspension of 100 mg of 10% palladium-carbon in 5 ml of water, followed by stirring in a stream of hydrogen at room temperature for 7.5 hours. After the catalyst was separated by filtration using Celite, the solvent was evaporated. The residue was dissolved in 5 ml of dichloromethane, and 5 ml of trifluoroacetic acid was added thereto under ice-cooling, followed by stirring at the same temperature for 2 hours. After the solvent was evaporated, the residue was subjected to azeotropic distillation with toluene twice, and the obtained residue was dissolved in 5 ml of dichloromethane. To the resulting solution were added 122.5 mg (1.80 mmol) of imidazole and 108.5 mg (0.72 mmol) of tert-butyldimethylsilyl chloride, followed by stirring at room temperature for 2 hours. To the resulting mixture was further added 500.0 mg (3.32 mmol) of tert-butyldimethylsilyl chloride, followed by overnight stirring. After addition of a saturated aqueous solution of sodium chloride, the resulting mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate. After the solvent was evaporated, the residue was dissolved in 5 ml of dimethylformamide, and 88.6 mg (0.54 mmol) of 4-nitrophenyl isocyanate was added thereto, followed by stirring at room temperature for 40 minutes. 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 45.6 mg (24%) of 4-(7-tert-butyldimethylsilyloxy-6-methoxy-4-quinazolinyl)-N-(4-nitrophenyl)-1-piperazinecarboxamide.

Workup

  1. additionwas added
  2. customAfter the catalyst was separated by filtration
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in 5 ml of dichloromethane
  5. addition5 ml of trifluoroacetic acid was added
  6. temperatureunder ice-cooling
  7. customAfter the solvent was evaporated
  8. distillationthe residue was subjected to azeotropic distillation with toluene twice
  9. dissolutionthe obtained residue was dissolved in 5 ml of dichloromethane
  10. stirringby stirring at room temperature for 2 hours
  11. waitfollowed by overnight
  12. stirringstirring
  13. extractionthe resulting mixture was extracted with chloroform
  14. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  15. customAfter the solvent was evaporated
  16. dissolutionthe residue was dissolved in 5 ml of dimethylformamide
  17. stirringby stirring at room temperature for 40 minutes
  18. additionwas added
  19. filtrationThe precipitated crystals were collected by filtration
  20. washwashed with water
  21. customdried
  22. customfollowed by purification by silica gel chromatography

Sources & evidence

ORD record
ord-64103396c2fd4ebd9edd8f75ccbaa8be
Source dataset
uspto-grants-2004_06
Patent number
US06750218B2

Reaction notes

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