tert-Butyl 4-(4-bromobenzyl)piperazine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a mixture of 4-bromobenzyl bromide (5 g, 20 mmol) and N-Boc piperazine (4.47 g, 24 mmol) in DMF (25 mL), K2CO3 (5.52 g, 40 mmol) was added and the reaction mixture was stirred for 16 h at room temperature. After completion of reaction (monitored by TLC), the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product, V-1-I. This compound was used for next step without purification. was added After completion of reaction (monitored by TLC) extracted with ethyl acetate (30 mL×3) The combined organic layers were washed with brine (100 mL) dried over anhydrous Na2SO4 filtered concentrated under reduced pressure to give crude product, V-1-I This compound was used for next step without purification

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Bromo-4-(bromomethyl)benzene (8.078 g, 32.3 mmol) and tert-butyl piperazine-1-carboxylate (6.625 g, 35.6 mmol) were dissolved in DMF (40 ml) and K2CO3 (8.93 g, 64.6 mmol) was added. The reaction mixture was heated to 60° C. for 4 h and then filtered through a pad of celite. The filtrate was evaporated and the residue was triturated in hexanes to produce compound 451 as white solid (9.46 g, 82% yield). LCMS: 255.0 (M+H)+. filtered through a pad of celite The filtrate was evaporated the residue was triturated in hexanes

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of tert-butyl 4-(4-bromo-benzyl)piperazine-1-carboxylate (371 mg, 1.04 mmol), 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one (300 mg, 1.04 mmol), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (43.2 mg, 41.8 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (79.6 mg, 0.167 mmol) in toluene (2.09 ml) was added sodium tert-butoxide (151 mg, 1.57 mmol) under nitrogen atmosphere. The mixture was stirred at 150° C. for 30 minutes in Biotage Microwave reactor. The mixture was filtered through a pad of Celite, and concentrated in vacuo. The residue was purified by NH-silica gel column chromatography (eluent; hexane/ethyl acetate=1/1) to afford tert-butyl 4-{4-[4-(1-methyl-6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yloxy)piperidin-1-yl]benzyl}piperazine-1-carboxylate as a pale yellow solid (236 mg, 0.420 mmol, 40%). The mixture was filtered through a pad of Celite concentrated in vacuo The residue was purified by NH-silica gel column chromatography (eluent; hexane/ethyl acetate=1/1)

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

実験手順: To a mixture of 4-bromobenzyl bromide (5 g, 20 mmol) and N-Boc piperazine (4.47 g, 24 mmol) in DMF (25 mL), K2CO3 (5.52 g, 40 mmol) was added and the reaction mixture was stirred for 16 h at room temperature. After completion of reaction (monitored by TLC), the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product, V-1-I. This compound was used for next step without purification. was added After completion of reaction (monitored by TLC) extracted with ethyl acetate (30 mL×3) The combined organic layers were washed with brine (100 mL) dried over anhydrous Na2SO4 filtered concentrated under reduced pressure to give crude product, V-1-I This compound was used for next step without purification