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2,4,6-trichloro-8-fluoro-7-(2-fluoro-6-methoxyphenyl)quinazoline[ No CAS ]
(2R,5S)-tert-butyl 4-(2,6-dichloro-8-fluoro-7-(2-fluoro-6-methoxyphenyl)quinazolin-4-yl)-2,5-dimethylpiperazine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
2.1 g
With triethylamine; In dichloromethane; at 0 - 20℃;
To a stirred solution of 2,4,6-trichloro-8-fluoro-7-(2-fluoro-6- methoxyphenyl)quinazoline (2 g, 5.34 mmol) in DCM (2OmL) at 0 °C, TEA (1.08 g, 10.7 mmol) was added and then (2R,5S)-tert-butyl 2,5-dimethylpiperazine-1- carboxylatet (1.15 g, 5.34 mmol) in DCM (20 mL) was added slowly. The mixture was stirred at RT overnight. The mixture was partitioned between water (5OmL) and DCM(lOOmL X 2).The organic layer was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel to afford the desired product 3-2 (2.1 g). ESI-MS m/z: 553 [M+H].
tert-butyl (2S,5S)-4-(bis(4-fluorophenyl)methyl)-2,5-dimethylpiperazine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51.8%
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃;
To a solution of 4,4'-(chloromethylene)bis(fluorobenzene) (200 mg, 0.838 mmol) in acetonitrile (20 mL) at room temperature were added tert-butyl (2S,5S)-2,5- dimethylpiperazine-1-carboxylate (198 mg, 0.922 mmol) and DIPEA (0.439 mL, 2.51 mmol). The reaction mixture was heated to 85 C overnight and concentrated under reduced pressure to yield residue. The residue was dissolved in DCM (100 mL) and washed with water (20 mL), brine (20 mL) and dried over sodium sulfate and (1115) concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography using 24 g flash column, eluting with 30 % EtOAc in petroleum ether. The fractions were concentrated under reduced pressure to yield tert-butyl (2S,5S)-4- (bis(4-fluorophenyl)methyl)-2,5-dimethylpiperazine-1-carboxylate (200 mg, 51.8 % yield); LCMS: m/z = 417.4 (M+H); rt 1.74 min. LCMS Method: Mobile phase A: (1116) Buffer: acetonitrile (95:5) Mobile phase B: Buffer: acetonitrile (5:95) Method: %B: 0 min-20 %:1.1min -90 %: 1.7 min-90 % Column: AQUITY UPLC BEH C18 (3.0 x 50 mm) 1.7 ^m, Flow: 0.7 mL/min.
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