Diethyl 4-(4-chloro-2-aminobenzoyl)-1H-pyrazole-3,5-dicarboxylate → 7-Chloro-3-(ethoxycarbonyl)pyrazolo[3,4-c][1]benzazepine-4,10-(1H,9H)dione

HRID 428413Notes

Reaction equation

HRID 428413 reaction equation
OC1C=CC=CN=1.[Cl:8][C:9]1[CH:31]=[CH:30][C:12]([C:13]([C:15]2[C:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:17][NH:18][C:19]=2[C:20]([O:22]CC)=O)=[O:14])=[C:11]([NH2:32])[CH:10]=1>C1(C)C=CC=CC=1>[Cl:8][C:9]1[CH:31]=[CH:30][C:12]2[C:13](=[O:14])[C:15]3[C:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:17][NH:18][C:19]=3[C:20](=[O:22])[NH:32][C:11]=2[CH:10]=1

Participants

4

Reactant 2

HCID 18358868Diethyl 4-(4-chloro-2-aminobenzoyl)-1H-pyrazole-3,5-dicarboxylateHCID 178516071HCID 178516071, compound

Product 1

HCID 1784704817-Chloro-3-(ethoxycarbonyl)pyrazolo[3,4-c][1]benzazepine-4,10-(1H,9H)dioneYield 38%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
171.5 °C

Procedure

To a solution of 2-hydroxypyridine (1.30 g, 13.69 mmol) in toluene (400 mL) was added diethyl 4-(4-chloro-2-amino-benzoyl)-1H-pyrazole-3,5-dicarboxylate (5 g, 13.69 mmol). The mixture was refluxed for 2 days and then the solvent was distilled off and the residual solid was heated at 171-172° C. for 4 days. The solid was allowed to cool and was continuously chromatographed eluting for 2 hours with dichloromethane to remove starting material. The remaining material on the column was eluted with chloroform:2-propanol (97:3) for 4 days. After each day the solvent in the receiving flask was replaced with fresh solvent. Filtering the solvent from the first two receiving flasks gave the title compound as a white solid (1.65 g, 38%, mp 290° C.). Alternatively, the title compound can preferably be removed from the column by elution with ethanol/chloroform (7:93).

Workup

  1. temperatureThe mixture was refluxed for 2 days
  2. distillationthe solvent was distilled off
  3. temperatureto cool
  4. customwas continuously chromatographed
  5. washeluting for 2 hours with dichloromethane
  6. customto remove
  7. washThe remaining material on the column was eluted with chloroform:2-propanol (97:3) for 4 days
  8. waitAfter each day the solvent in the receiving flask was replaced with fresh solvent
  9. filtrationFiltering the solvent from the first two receiving flasks

Sources & evidence

ORD record
ord-71878da472dd405bbb54e702b3c1c746
Source dataset
uspto-grants-2001_11
Patent number
US06313290B1

Reaction notes

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