morpholine-3-carboxamide

反応条件: temp:0.00; pressure:0.00; stir:

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: Ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (2.85 g, 6 mmol) was reacted with morpholine-3-carboxamide (0.78 g, 6 mmol) according to the procedure as described in Example 25, Step B to give the title compound as a yellow solid (1.54 g, 49%). The compound was characterized by the following spectroscopic data:

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

実験手順: Ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (2.75 g, 6 mmol) was reacted with morpholine-3-carboxamide (0.78 g, 6 mmol) according to the procedure as described in Example 25, Step B to give the title compound as a yellow solid (1.37 g, 45%). The compound was characterized by the following spectroscopic data:

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

実験手順: Ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (2.75 g, 6 mmol) was reacted with morpholine-3-carboxamide (0.78 g, 6 mmol) according to the procedure as described in Example 25, Step B to give the title compound as a yellow solid (1.37 g, 45%). The compound was characterized by the following spectroscopic data:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (3.02 g, 6 mmol), morpholine-3-carboxamide (0.78 g, 6 mmol) and potassium carbonate (1.66 g, 12 mmol) in anhydrous ethanol (70 mL) was stirred at 25° C. for 12 hours under N2. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=100/1) to give the title compound as a yellow solid (1.66 g, 50%). The compound was characterized by the following spectroscopic data: The reaction mixture was filtered the filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=100/1)

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

実験手順: A mixture of methyl morpholine-3-carboxylate hydrochloride (0.55 g, 3.0 mmol) and a solution of NH3 in methanol (7 mol/L, 20 mL) was stirred at 50° C. for 24 hours in a sealed tube. The mixture was concentrated in vacuo to give the title compound as glutinous semisolid (0.39 g, 99%). The compound was characterized by the following spectroscopic data: The mixture was concentrated in vacuo

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

実験手順: A mixture of methyl morpholine-3-carboxylate hydrochloride (0.55 g, 3.0 mmol) and a solution of NH3 in methanol (7 mol/L, 20 mL) was stirred at 50° C. for 24 hours in a sealed tube. The mixture was concentrated in vacuo to give the title compound as glutinous semisolid (0.39 g, 99%). The compound was characterized by the following spectroscopic data: The mixture was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-morpholinecarboxamide (830 mg, 3.40 mmol), 2-amino-4,6-dichloropyrimidine (502 mg, 3.06 mmol), and Hunig's base (1.6 mL, 9.16 mmol) in CH3CN (12 mL) was stirred at 100° C. in a sealed tube for 40 hours. The mixture was diluted with EtOAc (100 mL), and washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL). The combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL). All of the organic phases were combined, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (394 mg) as a white solid. LC-MS (ES) m/z=258, 260 [M+H]+. washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL) The combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL) dried (Na2SO4) filtered concentrated in vacuo The residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-morpholinecarboxamide (830 mg, 3.40 mmol), 2-amino-4,6-dichloropyrimidine (502 mg, 3.06 mmol), and Hunig's base (1.6 mL, 9.16 mmol) in CH3CN (12 mL) was stirred at 100° C. in a sealed tube for 40 hours. The mixture was diluted with EtOAc (100 mL), and washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL). The combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL). All of the organic phases were combined, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (394 mg) as a white solid. LC-MS (ES) m/z=258, 260 [M+H]+. washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL) The combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL) dried (Na2SO4) filtered concentrated in vacuo The residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient)