Triethylamine → 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

HRID 1985541Notes

Reaction equation

HRID 1985541 reaction equation
Cl.[NH2:2][CH:3]1[C:17](=[O:18])[N:16]([CH3:19])[CH2:15][C:6]2[C:7]3[CH:8]=[N:9][NH:10][C:11]=3[C:12]([CH3:14])=[CH:13][C:5]=2[CH2:4]1.[C:20](=O)(ON1C(=O)CCC1=O)[O:21]N1C(=O)CCC1=O.C(N(CC)CC)C.Cl.[NH:46]1[CH2:51][CH2:50][CH:49]([N:52]2[CH2:61][C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[NH:54][C:53]2=[O:62])[CH2:48][CH2:47]1>ClCCl>[CH3:14][C:12]1[C:11]2[NH:10][N:9]=[CH:8][C:7]=2[C:6]2[CH2:15][N:16]([CH3:19])[C:17](=[O:18])[CH:3]([NH:2][C:20]([N:46]3[CH2:47][CH2:48][CH:49]([N:52]4[CH2:61][C:60]5[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=5)[NH:54][C:53]4=[O:62])[CH2:50][CH2:51]3)=[O:21])[CH2:4][C:5]=2[CH:13]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 676246Di(succinimido) carbonateHCID 183213553-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one hydrochlorideHCID 1317269227-amino-4,9-dimethyl-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one, hydrochloride

Product 1

HCID 247834174-(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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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

  1. waitcontinued for 12 h
  2. customThe solvent was evaporated
  3. customthe crude product was purified by Prep HPLC

Sources & evidence

ORD record
ord-cf43334788334a6b8de30142b544348d
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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