3-amino-1-[(2-fluoro-6-methoxyphenyl)methyl]piperidin-2-one

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(2-methylpyridin-4-yl)-1H-indazole-5-carboxylic acid (50 mg, 0.154 mmol), 3-amino-1-(2-fluoro-6-methoxybenzyl)piperidin-2-one (148 mg, 0.308 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (44.4 mg, 0.231 mmol) and hydroxybenzo-triazole (23.62 mg, 0.154 mmol) were combined in a sealed vial. DMF (0.8 ml) and N,N-diisopropylethylamine (0.269 ml, 1.542 mmol) were added and the reaction mixture stirred for 16 hours at a temperature of 23° C. The residue was then purified by preparative HPLC Normal phase, eluting with dichloromethane/MeOH (0-20%) to give N-(1-(2-fluoro-6-methoxybenzyl)-2-oxopiperidin-3-yl)-3-(2-methylpyridin-4-yl)-1H-indazole-5-carboxamide as a colorless solid. MS ESI calc'd. for C27H26FN5O3 [M+H]+488, found 488. 1H NMR (600 MHz, CDCl3) δ 10.80-10.49 (m, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.53 (s, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.73 (s, 1H), 7.67 (d, J=4.9 Hz, 1H), 7.52 (d, J=8.7 Hz, 1H), 7.46 (s, 1H), 6.75-6.65 (m, 3H), 5.00 (d, J=14.1 Hz, 1H), 4.51 (d, J=14.2 Hz, 1H), 4.49-4.42 (m, 1H), 3.84 (s, 3H), 3.35-3.21 (m, 2H), 2.65 (s, 3H), 1.95-1.82 (m, 2H), 1.65-1.55 (s, 2H). The residue was then purified by preparative HPLC Normal phase eluting with dichloromethane/MeOH (0-20%)

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

実験手順: The synthetic intermediate from Step 1 (329 mg, 0.934 mmol), dichloromethane (1 ml), and trifluoroacetic acid (1 ml) were combined in an open vial, and the mixture was allowed to stir for 1 hour. The mixture was then diluted with toluene (3 ml) and subsequently concentrated to dryness. Crude (3-amino-1-(2-fluoro-6-methoxybenzyl)piperidin-2-one so obtained was used in the next synthetic transformation without additional purification. subsequently concentrated to dryness