5-Fluoro-2-trifluoromethyl-phenylboronic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following Example 278, Suzuki coupling of tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate and 5-fluoro-2-(trifluoromethyl)phenylboronic acid gave 279 as a brown solid (54 mg, 55% over two steps). 1H NMR (400 MHz, d4-MeOD) 7.94 (dd, J=8.9, 5.4 Hz, 1H), 7.60-7.50 (m, 2H), 7.40 (td, J=8.3, 2.6 Hz, 1H), 3.73 (s, 3H), 3.21-3.09 (m, 4H), 2.63 (d, J=6.6 Hz, 2H), 1.84 (d, J=12.5 Hz, 2H), 1.57-1.48 (m, 1H), 1.38 (qd, J=11.8, 4.7 Hz, 2H). LCMS (ES+) m/z 498 (M+1)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-methyl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 1; 400 mg, 2.74 mmol), 5-fluoro-2-(trifluoromethyl)phenylboronic acid (Cuschem, Inc., Yonkers, N.Y.; 512 mg, 2.46 mmol), copper(II) acetate (497 mg, 2.74 mmol) and triethylamine (380 μL, 2.7 mmol) in 1,2-dichloroethane (18 mL) was heated in an oil bath at 50° C. for 2 h. The mixture was allowed to cool, and it was then adsorbed onto silica gel and purified by chromatography using an ISCO 40 g column, eluting with 10% ethyl acetate/hexanes, to give N′-(5-fluoro-2-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (348 mg, 41%) as a colorless oil that solidified. to cool purified by chromatography eluting with 10% ethyl acetate/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following Example 278, Suzuki coupling of tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate and 5-fluoro-2-(trifluoromethyl)phenylboronic acid gave 279 as a brown solid (54 mg, 55% over two steps). 1H NMR (400 MHz, d4-MeOD) 7.94 (dd, J=8.9, 5.4 Hz, 1H), 7.60-7.50 (m, 2H), 7.40 (td, J=8.3, 2.6 Hz, 1H), 3.73 (s, 3H), 3.21-3.09 (m, 4H), 2.63 (d, J=6.6 Hz, 2H), 1.84 (d, J=12.5 Hz, 2H), 1.57-1.48 (m, 1H), 1.38 (qd, J=11.8, 4.7 Hz, 2H). LCMS (ES+) m/z 498 (M+1)