(2-Iodoethyl)cyclopropane → 8-Chloro-10-(2-cyclopropylethyl)-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one
Reaction equation
[CH:1]1([CH2:4][CH2:5]I)[CH2:3][CH2:2]1.C([Li])(C)(C)C.[Cl:12][C:13]1[CH:22]=[CH:21][C:20]2[N:19]=[C:18]3[C:23](=[O:27])[NH:24][CH:25]=[N:26][C:17]3=[C:16]([C:28]([F:31])([F:30])[F:29])[C:15]=2[CH:14]=1>CCOCC.C1COCC1>[Cl:12][C:13]1[CH:22]=[CH:21][C:20]2[NH:19][C:18]3[C:23](=[O:27])[NH:24][CH:25]=[N:26][C:17]=3[C:16]([CH2:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)([C:28]([F:30])([F:29])[F:31])[C:15]=2[CH:14]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of 1-cyclopropyl-2-iodoethane (12.5 g, 63.9 mmol, 5 equiv) in anhydrous Et2O (128 mL) at −78° C. was added tert-butyl lithium (1.7M in pentane, 75 mL, 128 mmol, 10 equiv). The resulting white suspension was stirred at −78° C. for 50 min and added via cannula to a suspension of 7 (3.83 g, 12.8 mmol) in THF (64 mL) at −78° C. The resulting dark yellow mixture was stirred at −78° C. for 30 min and then allowed to warm to 0° C. over 5 h. The reaction was quenched with satd. NH4Cl (100 mL) and H2O (100 mL). The reaction mixture was extracted with EtOAc (3×100 mL) and the combined organic layers washed with brine and dried (MgSO4). Chromatography (SiO2, 40 to 50% EtOAc-hexane) provided the desired product as a yellow solid (2.92 g, 62%). ESI HRMS m/z 370.1735 (M++H, C17H16ClF3N3O requires 370.0934).
Workup
- stirringThe resulting dark yellow mixture was stirred at −78° C. for 30 min
- temperatureto warm to 0° C. over 5 h
- customThe reaction was quenched with satd
- extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
- washthe combined organic layers washed with brine
- dry with materialdried (MgSO4)
Sources & evidence
- ORD record
- ord-70567ce31bc24521bb4b79122be8f65e
- Source dataset
- uspto-grants-2007_03
- Patent number
- US07186830B2
Reaction notes
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