Trifluoroacetic acid → 2-[(1S)-1-Aminopropyl]-5-fluoro-3-phenyl-4(3H)-quinazolinone
Reaction equation
C(OC(=O)[NH:7][C@H:8]([C:11]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:19](=[O:27])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[F:28])[N:12]=1)[CH2:9][CH3:10])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@H:8]([C:11]1[N:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:19](=[O:27])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[F:28])[N:12]=1)[CH2:9][CH3:10]Participants
Procedure
A solution of compound 110 (85 mmol) in dichloromethane (60 mL) was treated with trifluoroacetic acid (60 mL). The reaction mixture was stirred for 1 h, concentrated in vacuo, and partitioned between dichloromethane (150 mL) and 10% K2CO3 (sufficient amount to keep the pH greated than 10). The aqueous layer was extracted with additional dichloromethane (100 mL), and the combined organic layers were washed with water (50 mL) and brine (50 mL). After drying with Mg SO4, the solution was concentrated to provide compound 111 as an off-white solid (22 g, 88%). 1H NMR (300 MHz, CDCl3) δ 7.73-7.65 (m, 1H), 7.62-7.49 (m, 4H), 7.32-7.22, (m, 2H), 7.13-7.06 (m, 1H), 3.42 (dd, J=7.5, 5.2 Hz, 1H), 1.87-1.70 (m, 1H), 1.58-1.43 (m, 1H), 0.80 (t, J=7.4 Hz, 3H), ESI-MS m/z 298.2 (MH+). The reaction described above and compound 111 are shown below.
Workup
- concentrationconcentrated in vacuo
- custompartitioned between dichloromethane (150 mL) and 10% K2CO3 (sufficient amount
- extractionThe aqueous layer was extracted with additional dichloromethane (100 mL)
- washthe combined organic layers were washed with water (50 mL) and brine (50 mL)
- dry with materialAfter drying with Mg SO4
- concentrationthe solution was concentrated
Sources & evidence
- ORD record
- ord-8edf41fa09f04bdeb94264ac2ce269f9
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08980901B2
Reaction notes
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