Trifluoroacetic acid → 6-(2-(2-((3-chloro-4-(difluoromethoxy)phenyl)amino)pyrimidin-5-yl)ethyl)quinolin-2(1H)-one
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[N:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]3[CH:22]=[C:23]4[C:28](=[CH:29][CH:30]=3)[N:27](COCC[Si](C)(C)C)[C:26](=[O:39])[CH:25]=[CH:24]4)=[CH:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([F:11])[F:10].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[N:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]3[CH:22]=[C:23]4[C:28](=[CH:29][CH:30]=3)[NH:27][C:26](=[O:39])[CH:25]=[CH:24]4)=[CH:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([F:10])[F:11]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 6-(2-(2-((3-chloro-4-(difluoromethoxy)phenyl)amino)pyrimidin-5-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one (0.05 g, 0.087 mmol) in DCM (5 mL) was added TFA (0.067 mL, 0.872 mmol) and stirred at room temperature for 12 h. The reaction mixture was concentrated and purified by preparative HPLC on a Symmetry C8 column (19×250 mm, 7 μm) using 0-100% mobile phase B (ACN) in mobile phase A (10 mM ammonium acetate) to give 6-(2-(2-((3-chloro-4-(difluoromethoxy)phenyl)amino)pyrimidin-5-yl)ethyl)quinolin-2(1H)-one as an off white solid (0.017 g, 44% yield). 1HNMR 400 MHz, DMSO-d6: δ 2.83 (t, J=14.80 Hz, 2H), 2.93 (t, J=14.80 Hz, 2H), 6.46-6.49 (m, 1H), 6.95-7.39 (m, 4H), 7.48 (s, 1H), 7.65-7.68 (m, 1H), 7.84 (d, J=9.60 Hz, 1H), 8.09 (d, J=2.40 Hz, 1H), 8.37 (s, 2H), 9.78 (s, 1H), 11.68 (s, 1H). LCMS (ES-API), RT: 2.95 min, m/z 441.0 (M−H)−.
Workup
- concentrationThe reaction mixture was concentrated
- custompurified by preparative HPLC on a Symmetry C8 column (19×250 mm, 7 μm)
Sources & evidence
- ORD record
- ord-6cee78d4a5d74db4a66a923fe66851ac
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08841301B2
Reaction notes
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