1-propan-2-ylimidazolidin-2-one

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

実験手順: 3-Benzyloxy-9-bromo-2-[5-(4-fluoro-benzyl)-thiazol-2-yl]-7-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one (product of example 218, 110 mg, 0.18 mmol), 1-isopropyl-imidazolidin-2-one (30 mg, 0.22 mmol), Pd2(dba)3 (15 mg, 0.02 mmol), Xantphos (15 mg, 0.2 mmol), Cs2CO3 (58.5 mg, 0.18 mmol) were mixed in anhydrous dioxane (5 ml). The mixture was heated at 90° C. under the atmosphere of N2 for 4 h, after which water was added and then extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product (95 mg, yield 81%). extracted with ethyl acetate washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography

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

実験手順: 3-Benzyloxy-9-bromo-2-[5-(4-fluoro-benzyl)-thiazol-2-yl]-7-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one (product of example 218, 110 mg, 0.18 mmol), 1-isopropyl-imidazolidin-2-one (30 mg, 0.22 mmol), Pd2(dba)3 (15 mg, 0.02 mmol), Xantphos (15 mg, 0.2 mmol), Cs2CO3 (58.5 mg, 0.18 mmol) were mixed in anhydrous dioxane (5 ml). The mixture was heated at 90° C. under the atmosphere of N2 for 4 h, after which water was added and then extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product (95 mg, yield 81%). extracted with ethyl acetate washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet was charged with 2-isopropylaminoethylamine (2550 g, 25 moles) and urea (1500 g, 25 moles). The reaction mixture was heated to 125° C. for seven hours and then 170° C. until no more gas releasing was observed. About 3155 g of N-isopropyl-2-imidazolidone was obtained. The reaction is represented as follows: ##STR10## A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet 170° C.

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet was charged with 2-isopropylaminoethylamine (2550 g, 25 moles) and urea (1500 g, 25 moles). The reaction mixture was heated to 125° C. for seven hours and then 170° C. until no more gas releasing was observed. About 3155 g of N-isopropyl-2-imidazolidone was obtained. The reaction is represented as follows: ##STR10## A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet 170° C.

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

実験手順: A 0° C. suspension of 1-(2-chloroethyl)-3-isopropylurea (6.00 g, 36.4 mmol) in THF (60 mL) was treated with NaH (60% in mineral oil, 2.50 g, 104 mmol) and stirred at RT overnight. The mixture was concentrated to dryness, treated with satd. NH4Cl, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford 1-isopropylimidazolidin-2-one (3.21 g, 69%) as a waxy solid. MS (ESI) m/z: 129.1 (M+H+). The mixture was concentrated to dryness treated with satd NH4Cl, extracted with EtOAc (3×) the combined organics were dried over Na2SO4 concentrated to dryness

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

実験手順: 3-Benzyloxy-9-bromo-2-[5-(4-fluoro-benzyl)-thiazol-2-yl]-7-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one (product of example 218, 110 mg, 0.18 mmol), 1-isopropyl-imidazolidin-2-one (30 mg, 0.22 mmol), Pd2(dba)3 (15 mg, 0.02 mmol), Xantphos (15 mg, 0.2 mmol), Cs2CO3 (58.5 mg, 0.18 mmol) were mixed in anhydrous dioxane (5 ml). The mixture was heated at 90° C. under the atmosphere of N2 for 4 h, after which water was added and then extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product (95 mg, yield 81%). extracted with ethyl acetate washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of toluene (8 mL) and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.2 mmol) was degassed with nitrogen for 4 minutes, then heated at 80° C. until the (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl dissolved completely. The solution was allowed to cool to rt and palladium acetate (0.09 mmol) was added. The mixture was stirred until the palladium acetate completely dissolved. The resultant yellow solution was added to a mixture of 6-bromo-3-(1,4-diazabicyclo[3.2.2]non-4-ylcarbonyl)-1,2-benzisothiazole (0.33 mmol), 1-isopropylimidazolidin-2-one (0.5 mmol) and cesium carbonate (0.39 mmol) under a nitrogen atmosphere. The reaction mixture was subjected to microwave radiation at 150° C. for 360 s. The inorganic precipitates were removed by filtration, and the filtrate was concentrated. The residue was purified by preparative HPLC to provide the product in 75% yield. 1H NMR (CD3OD) δ 8.17 (s, 1H), 8.03-7.93 (m, 2H), 4.30-4.05 (m, 2H), 3.92 (t, J=7.14, 2H), 3.70 (t, J=5.7, 2H), 3.54 (t, J=7.1, 2H), 3.20-3.00 (m, 6H), 1.22 (d, J=6.78, 3 6H); LC/MS (EI) tR3.10 min, m/z 415 (M++1). was degassed with nitrogen for 4 minutes dissolved completely to cool to rt completely dissolved at 150° C. for 360 s The inorganic precipitates were removed by filtration the filtrate was concentrated The residue was purified by preparative HPLC to provide the product in 75% yield

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

実験手順: 3-Benzyloxy-9-bromo-2-[5-(4-fluoro-benzyl)-thiazol-2-yl]-7-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one (product of example 218, 110 mg, 0.18 mmol), 1-isopropyl-imidazolidin-2-one (30 mg, 0.22 mmol), Pd2(dba)3 (15 mg, 0.02 mmol), Xantphos (15 mg, 0.2 mmol), Cs2CO3 (58.5 mg, 0.18 mmol) were mixed in anhydrous dioxane (5 ml). The mixture was heated at 90° C. under the atmosphere of N2 for 4 h, after which water was added and then extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product (95 mg, yield 81%). extracted with ethyl acetate washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet was charged with 2-isopropylaminoethylamine (2550 g, 25 moles) and urea (1500 g, 25 moles). The reaction mixture was heated to 125° C. for seven hours and then 170° C. until no more gas releasing was observed. About 3155 g of N-isopropyl-2-imidazolidone was obtained. The reaction is represented as follows: ##STR10## A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet 170° C.