Chloroform → 7-amino-4,9-dimethyl-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one, hydrochloride
Reaction equation
C(OC(=O)[NH:10][CH:11]1[C:25](=[O:26])[N:24]([CH3:27])[CH2:23][C:14]2[C:15]3[CH:16]=[N:17][NH:18][C:19]=3[C:20]([CH3:22])=[CH:21][C:13]=2[CH2:12]1)C1C=CC=CC=1.[H][H].C(Cl)(Cl)[Cl:32]>CO.[Pd]>[ClH:32].[NH2:10][CH:11]1[C:25](=[O:26])[N:24]([CH3:27])[CH2:23][C:14]2[C:15]3[CH:16]=[N:17][NH:18][C:19]=3[C:20]([CH3:22])=[CH:21][C:13]=2[CH2:12]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of (4,9-dimethyl-8-oxo-3,6,7,8,9,10-hexahydro-2,3,9-triaza-cyclohepta[e]inden-7-yl)-carbamic acid benzyl ester (50 mg, 0.132 mmol) in methanol and chloroform (0.5 mL) was added 10% palladium on carbon (20 mg) under nitrogen atmosphere. The reaction mixture was brought to hydrogen atmosphere (1 atm) and stirred for 3 h. The catalyst was filtered and the solvent was evaporated to give 7-amino-4,9-dimethyl-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one, hydrochloride in almost quantitative yield. To the amine salt in dichloromethane was added disuccinimidyl carbonate (37 mg, 0.145 mmol) and triethylamine (0.11 mL, 0.8 mmol) at room temperature. After 120 min, 3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one, hydrochloride (39 mg, 0.145 mmol) was added and stirring continued for 12 h. The solvent was evaporated and the crude product was purified by Prep HPLC to give 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid (4,9-dimethyl-8-oxo-3,6,7,8,9,10-hexahydro-2,3,9-triaza-cyclohepta[e]inden-7-yl)-amide in 59% overall yield. MS (ESI) 502 (M+H); Rf=1.31.
Workup
- filtrationThe catalyst was filtered
- customthe solvent was evaporated
Sources & evidence
- ORD record
- ord-287e7e52acbc4230893d0c409c1b6ffa
- Source dataset
- uspto-grants-2009_06
- Patent number
- US07544680B2
Reaction notes
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