1-methyl-1,3-diazinan-2-one

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:

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: A solution of 0.30 g (2.6 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one from step A above in 5 mL of anhydrous DMF was added to a 10 mL round bottom flask containing 0.16 g (4.2 mmol) of a 60% sodium hydride suspension in mineral oil under an atmosphere of nitrogen. After stirring for 10 min 0.62 g (3.2 mmol) of tert-butyl bromoacetate was added in one portion and the reaction mixture was allowed to stir overnight. The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution and then diluted with 20 mL of water. The resulting suspension was extracted with ethyl acetate (3×10 mL) and the combined organics were washed with water (2×3 mL), brine (1×3 mL) and dried over magnesium sulfate. The mixture was filtered, evaporated and purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient to afford the title compound as a clear oil (0.090 g, 15%). 1HNMR (500 MHz, CDCl3) δ: 3.88 (s, 2H), 3.23 (t, J=6 Hz, 2H), 3.20 (t, J=6 Hz, 2H), 2.84 (s, 3H), 1.94-1.89 (m, 2H), 1.37 (s, 9H). LC-MS: m/z (ES) 229 (MH)+. was added in one portion The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution diluted with 20 mL of water The resulting suspension was extracted with ethyl acetate (3×10 mL) the combined organics were washed with water (2×3 mL), brine (1×3 mL) dried over magnesium sulfate The mixture was filtered evaporated purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient

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

実験手順: A solution of 0.30 g (2.6 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one from step A above in 5 mL of anhydrous DMF was added to a 10 mL round bottom flask containing 0.16 g (4.2 mmol) of a 60% sodium hydride suspension in mineral oil under an atmosphere of nitrogen. After stirring for 10 min 0.62 g (3.2 mmol) of tert-butyl bromoacetate was added in one portion and the reaction mixture was allowed to stir overnight. The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution and then diluted with 20 mL of water. The resulting suspension was extracted with ethyl acetate (3×10 mL) and the combined organics were washed with water (2×3 mL), brine (1×3 mL) and dried over magnesium sulfate. The mixture was filtered, evaporated and purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient to afford the title compound as a clear oil (0.090 g, 15%). 1HNMR (500 MHz, CDCl3) δ: 3.88 (s, 2H), 3.23 (t, J=6 Hz, 2H), 3.20 (t, J=6 Hz, 2H), 2.84 (s, 3H), 1.94-1.89 (m, 2H), 1.37 (s, 9H). LC-MS: m/z (ES) 229 (MH)+. was added in one portion The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution diluted with 20 mL of water The resulting suspension was extracted with ethyl acetate (3×10 mL) the combined organics were washed with water (2×3 mL), brine (1×3 mL) dried over magnesium sulfate The mixture was filtered evaporated purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient

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

実験手順: The title compound, light yellow oil, MS: m/e=306.2 (M+H+), can be prepared in accordance with the general method of example 31, step 2 from (5-phenylethynyl-pyridin-2-yl)-methanol (example 31, step 1) and 1-methyl-tetrahydro-pyrimidin-2-one.

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

実験手順: A solution of 0.30 g (2.6 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one from step A above in 5 mL of anhydrous DMF was added to a 10 mL round bottom flask containing 0.16 g (4.2 mmol) of a 60% sodium hydride suspension in mineral oil under an atmosphere of nitrogen. After stirring for 10 min 0.62 g (3.2 mmol) of tert-butyl bromoacetate was added in one portion and the reaction mixture was allowed to stir overnight. The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution and then diluted with 20 mL of water. The resulting suspension was extracted with ethyl acetate (3×10 mL) and the combined organics were washed with water (2×3 mL), brine (1×3 mL) and dried over magnesium sulfate. The mixture was filtered, evaporated and purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient to afford the title compound as a clear oil (0.090 g, 15%). 1HNMR (500 MHz, CDCl3) δ: 3.88 (s, 2H), 3.23 (t, J=6 Hz, 2H), 3.20 (t, J=6 Hz, 2H), 2.84 (s, 3H), 1.94-1.89 (m, 2H), 1.37 (s, 9H). LC-MA: m/z (ES) 229 (MH)+. was added in one portion The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution diluted with 20 mL of water The resulting suspension was extracted with ethyl acetate (3×10 mL) the combined organics were washed with water (2×3 mL), brine (1×3 mL) dried over magnesium sulfate The mixture was filtered evaporated purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient

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

実験手順: A solution of 0.30 g (2.6 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one from step A above in 5 mL of anhydrous DMF was added to a 10 mL round bottom flask containing 0.16 g (4.2 mmol) of a 60% sodium hydride suspension in mineral oil under an atmosphere of nitrogen. After stirring for 10 min 0.62 g (3.2 mmol) of tert-butyl bromoacetate was added in one portion and the reaction mixture was allowed to stir overnight. The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution and then diluted with 20 mL of water. The resulting suspension was extracted with ethyl acetate (3×10 mL) and the combined organics were washed with water (2×3 mL), brine (1×3 mL) and dried over magnesium sulfate. The mixture was filtered, evaporated and purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient to afford the title compound as a clear oil (0.090 g, 15%). 1HNMR (500 MHz, CDCl3) δ: 3.88 (s, 2H), 3.23 (t, J=6 Hz, 2H), 3.20 (t, J=6 Hz, 2H), 2.84 (s, 3H), 1.94-1.89 (m, 2H), 1.37 (s, 9H). LC-MA: m/z (ES) 229 (MH)+. was added in one portion The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution diluted with 20 mL of water The resulting suspension was extracted with ethyl acetate (3×10 mL) the combined organics were washed with water (2×3 mL), brine (1×3 mL) dried over magnesium sulfate The mixture was filtered evaporated purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient

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

実験手順: A solution of 0.30 g (2.6 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one from step A above in 5 mL of anhydrous DMF was added to a 10 mL round bottom flask containing 0.16 g (4.2 mmol) of a 60% sodium hydride suspension in mineral oil under an atmosphere of nitrogen. After stirring for 10 min 0.62 g (3.2 mmol) of tert-butyl bromoacetate was added in one portion and the reaction mixture was allowed to stir overnight. The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution and then diluted with 20 mL of water. The resulting suspension was extracted with ethyl acetate (3×10 mL) and the combined organics were washed with water (2×3 mL), brine (1×3 mL) and dried over magnesium sulfate. The mixture was filtered, evaporated and purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient to afford the title compound as a clear oil (0.090 g, 15%). 1HNMR (500 MHz, CDCl3) δ: 3.88 (s, 2H), 3.23 (t, J=6 Hz, 2H), 3.20 (t, J=6 Hz, 2H), 2.84 (s, 3H), 1.94-1.89 (m, 2H), 1.37 (s, 9H). LC-MS: m/z (ES) 229 (MH)+. was added in one portion The reaction mixture was then quenched with 5 mL of a saturated aqueous ammonium chloride solution diluted with 20 mL of water The resulting suspension was extracted with ethyl acetate (3×10 mL) the combined organics were washed with water (2×3 mL), brine (1×3 mL) dried over magnesium sulfate The mixture was filtered evaporated purified by silica gel chromatography eluting with a 0-5% methanol in ethyl acetate gradient

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

実験手順: 450 mg (3.94 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one in 15 ml of DMF are admixed at 0° C. with 663 mg (5.91 mmol) of potassium tert-butoxide, and the mixture is stirred at room temperature for 30 min. 742 mg (4.33 mmol) of 1-fluoro-2-methoxy-4-nitrobenzene are added and the mixture is stirred at RT. After 2 h, the mixture is admixed with 150 ml of water and 8 ml of saturated aqueous sodium chloride solution, and extracted three times with 30 ml each time of ethyl acetate. The combined organic phases are washed with 30 ml of water and then dried over sodium sulfate. After filtration, the solvents are removed under reduced pressure. The residue is purified by chromatography on silica gel (1:5→1:10 cyclohexane/ethyl acetate). This affords 457 mg (43% of theory) of the desired compound. the mixture is stirred at RT After 2 h extracted three times with 30 ml each time of ethyl acetate The combined organic phases are washed with 30 ml of water dried over sodium sulfate After filtration the solvents are removed under reduced pressure The residue is purified by chromatography on silica gel (1:5→1:10 cyclohexane/ethyl acetate)

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16.1 g (76.1 mmol) of potassium phosphate and 0.362 g (1.90 mmol) of copper(I) iodide are initially charged, and the apparatus is baked out and then flushed with argon. 10.0 g (38.1 mmol) of 1-iodo-2-methyl-4-nitrobenzene, 6.51 g (57.0 mmol) of 1-methyltetrahydropyrimidin-2(1H)-one and 0.394 g (3.80 mmol) of N,N′-dimethylenediamine in 200 ml of dioxane are added, and the mixture is stirred at 110° C. After 19 h, after cooling, the mixture is filtered with suction through kieselguhr and then washed three times with 100 ml of ethyl acetate. The solvent is removed under reduced pressure and the residue is purified by chromatography on silica gel (2:1→1:1 cyclohexane/ethyl acetate). This affords 5.94 g (63% of theory) of the desired compound. flushed with argon after cooling the mixture is filtered with suction through kieselguhr washed three times with 100 ml of ethyl acetate The solvent is removed under reduced pressure the residue is purified by chromatography on silica gel (2:1→1:1 cyclohexane/ethyl acetate)