5-amino-1-methylpiperidin-2-one

反応条件: temp:115.01; pressure:0.00; stir:

実験手順: In a 10 ml MW vial, Pd2((dba)3 (10.85 mg, 0.01 mmol), 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (BINAP) (14.56 mg, 0.02 mmol), sodium 2-methylpropan-2-olate (261 mg, 2.71 mmol), 5-amino-1-methylpiperidin-2-one (200 mg, 1.56 mmol) and 2-bromo-3-chloropyridine (300 mg, 1.56 mmol) mixed in toluene (3 mL) to give a brown suspension. The mixture was degassed with N2 bubbling for 5 min, then the vial was capped and the reaction stirred at 115°C in an oil-bath for 1h then to rt for 2h. LC-MS 1h: 15% product. LC-MS o/n: 19% product. The reaction was cooled to rt and the solvent was evaporated. The residue was purified by automated flash chromatography on a 50g column. A gradient from 20% to 100% of EtOAc in heptane over 20CV was used as mobile phase. The product was collected using the wavelength 307 and 241 nm. Product was not found in any of the fractions, reaction discarded.

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

実験手順: The title compound was prepared in analogy to the procedure described for step E2 using 2-bromo-5-[(4-chlorophenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester (intermediate B) and 5-amino-1-methylpiperidin-2-one (ChemBridge, free base was made from the purchased HCl salt) as starting materials. The crude reaction mixture was diluted with EtOAc and washed with aqueous NaHCO3 solution and brine. tr: 1.07 min (LC-MS 2); ESI-MS: 511.1 [M+H]+ (LC-MS 2); 1H-NMR (DMSO-d6, 400 MHz) δ ppm 7.42 (m, 2H), 7.30 (m, 2H), 6.28 (NH, br, 1H), 4.85-5.00 (m, 1 H), 4.25 (quin, 2 H), 3.15-3.05 (m, 2H), 2.84-2.75 (m, 1H), 2.72 (d, 3H), 2.38-1.85 (m, 4H), 1.75-1.58 (m, 1), 1.45 (d, 3 H), 1.24 (t, 3 H), 0.83 (t, 3H). The crude reaction mixture washed with aqueous NaHCO3 solution and brine 1.07 min (LC-MS 2)

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

実験手順: The title compound was prepared in analogy to the procedure described for step E2 using 2-bromo-5-[(4-chlorophenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester (intermediate B) and 5-amino-1-methylpiperidin-2-one (ChemBridge, free base was made from the purchased HCl salt) as starting materials. The crude reaction mixture was diluted with EtOAc and washed with aqueous NaHCO3 solution and brine. tr: 1.07 min (LC-MS 2); ESI-MS: 511.1 [M+H]+ (LC-MS 2); 1H-NMR (DMSO-d6, 400 MHz) δ ppm 7.42 (m, 2H), 7.30 (m, 2H), 6.28 (NH, br, 1H), 4.85-5.00 (m, 1 H), 4.25 (quin, 2 H), 3.15-3.05 (m, 2H), 2.84-2.75 (m, 1H), 2.72 (d, 3H), 2.38-1.85 (m, 4H), 1.75-1.58 (m, 1), 1.45 (d, 3 H), 1.24 (t, 3 H), 0.83 (t, 3H). The crude reaction mixture washed with aqueous NaHCO3 solution and brine 1.07 min (LC-MS 2)

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

実験手順: The title compound was prepared in analogy to the procedure described for Step D2, but 2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester (Step E4) and 5-amino-1-methylpiperidin-2-one [1228838-10-5] (free base was made from the purchased HCl salt) were used instead of 5-bromo-2-[(4-chloro-phenyl)hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester and 3-chloro-4-fluoroaniline respectively to afford the title compound (diastereomeric mixture) as an off-white solid. tR: 4.31 min (HPLC 1); ESI-MS: tR=1.13/1.15 min, [M+H]+ 432/434 (LC-MS 1); TLC: Rf=0.25 (EtOAc). The title compound was prepared in analogy to the procedure

反応条件: temp:115.01; pressure:0.00; stir: