Reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]4[CH2:34][CH2:33][CH2:32][CH2:31][C:25]=4[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11].C(OC(C1C=NN(C2NC(=O)C3C4CCCCC=4C=CC=3N=2)C=1)=O)C.Cl[CH2:61][O:62][CH2:63][CH2:64][O:65][CH3:66]>C1COCC1.CCOC(C)=O>[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:29]([CH2:61][O:62][CH2:63][CH2:64][O:65][CH3:66])[C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]4[CH2:34][CH2:33][CH2:32][CH2:31][C:25]=4[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
DIEA (0.76 mL, 4.4 mmol) was added to a 2:1 mixture of 1-(4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester and 1-(1-oxo-1,2,7,8,9,10-hexahydro-benzo[f]quinazolin-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.500 g, 1.478 mmol) in THF (7.4 mL), followed by 1-chloromethoxy-2-methoxy-ethane (0.186 mL, 1.63 mmol). The reaction mixture was stirred at room temperature for 18 h, diluted with EtOAc (40 mL), and washed with water (30 mL). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers were washed with brine (40 mL), dried (MgSO4), and concentrated. The residue was purified by FCC (5-60% EtOAc/hexanes) to yield the titled compound (0.257 g, 41% yield) and 1-[2-(2-methoxy-ethoxymethyl)-1-oxo-1,2,7,8,9,10-hexahydro-benzo[t]quinazolin-3-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (69.0 mg, 11% yield).
Workup
- washwashed with water (30 mL)
- extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
- washthe combined organic layers were washed with brine (40 mL)
- dry with materialdried (MgSO4)
- concentrationconcentrated
- customThe residue was purified by FCC (5-60% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-92a598e2b034447d9de07f8a71ff93e6
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08937078B2
Linked notes
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