prop-2-en-1-amine;hydrochloride

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: TO 1-methyl-2-oxo-2-tetrahydro-1-H-1-pyrrolylethyl 2,6-dibromohexanoate (295 mg, 0.75 mmol), NaI (225 mg, 1.5 mmol), triethylamine (303 mg, 3.0 mmol) and tetrahydrofuran (4 mL) were added. Subsequently, allylamine hydrochloride (84.2 mg, 0.9 mmol) and tetrahydrofuran (4 mL) were added thereto. The mixture was stirred at 20° C. for 4 hours and then at 40° C. for 15 hours. It was confirmed with NMR analysis of the reaction solution that the conversion ratio was 100% and the diastereo ratio was 75:25. at 40° C. for 15 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoro-aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and a solution of triphosgene (47 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, allylamine hydrochloride (30 mg) was added to the Be reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution, and the mixture was purified by HPLC by development with chloroform/methanol to give 18 mg (yield 28%) of the title compound. the mixture was further stirred at room temperature overnight the mixture was purified by HPLC by development with chloroform/methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, allylamine hydrochloride (21 mg) was added to the reaction solution, and the mixture was stirred at room temperature for additional 30 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by HPLC by development with chloroform/methanol to give 45 mg (yield 72%) of the title compound. the mixture was stirred at room temperature for additional 30 min the mixture was extracted with chloroform The chloroform layer was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure The residue was purified by HPLC by development with chloroform/methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and a solution of triphosgene (50 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, allylamine hydrochloride (31 mg) was added to the reaction solution, and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the mixture was purified by HPLC by development with chloroform/methanol to give 21 mg (yield 33%) of the title compound. the mixture was stirred at room temperature overnight the mixture was purified by HPLC by development with chloroform/methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Twenty g. of 1-phenyl-3-(3-trifluoromethylphenyl)-2-propanone was reacted with ethyl formate and allylamine hydrochloride as described in Examples 1-3 to obtain 10.8 g. of 1-allyl-3-phenyl-5-(3-trifluoromethylphenyl)-4(1H)-pyridinone, which was reacted with 2 g. of lithium aluminum hydride as described in Examples 1-3. The reaction mixture was worked up and chromatographed as described in the examples above to obtain 1.2 g. of the products of Examples 33 and 34 as a mixture. The compounds were identified by mass spectroscopy, which showed an indicated molecular weight of 357. A yield of 1.0 g. of the compound of Example 35 was obtained, which showed a mass spectroscopy molecular weight of 359. to obtain 10.8 g chromatographed to obtain 1.2 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloroethylsulfonyl chloride (2 g, 12.3 mmol) was is dissolved in 2-propanol (20 mL), pyridine (2.7 mL) was added, and the mixture was stirred at room temperature for 3 hours. Allylamine hydrochloride (1.15 g, 12.3 mmol) and diisopropylethylamine (6.4 mL) was added, and stirred at room temperature for 3 hours. The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (0.5 g, 2.4 mmol, 20%). stirred at room temperature for 3 hours The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue the mixture was extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloroethylsulfonyl chloride (2 g, 12.3 mmol) was is dissolved in 2-propanol (20 mL), pyridine (2.7 mL) was added, and the mixture was stirred at room temperature for 3 hours. Allylamine hydrochloride (1.15 g, 12.3 mmol) and diisopropylethylamine (6.4 mL) was added, and stirred at room temperature for 3 hours. The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (0.5 g, 2.4 mmol, 20%). stirred at room temperature for 3 hours The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue the mixture was extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of allylamine hydrochloride (5.0 g, 53.4 mmol) in tetrahydrofuran (100 mL) was added diisopropylethylamine (10 mL) and bromoacetic acid benzyl ester (3.06 g, 13.3 mmol) at 0° C. and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was added ethyl acetate and 1 N-hydrochloric acid solution, the organic layer was separated, and the aqueous layer was extracted two times with ethyl acetate. The organic layers were combined, washed with sodium thiosulfate solution and brine, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL). The mixture was concentrated under reduced pressure and lyophilized to give the title compound (2.12 g, 8.79 mmol, 66%). The reaction mixture was concentrated under reduced pressure The residue was added ethyl acetate and 1 N-hydrochloric acid solution the organic layer was separated the aqueous layer was extracted two times with ethyl acetate washed with sodium thiosulfate solution and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL) The mixture was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of allylamine hydrochloride (5.0 g, 53.4 mmol) in tetrahydrofuran (100 mL) was added diisopropylethylamine (10 mL) and bromoacetic acid benzyl ester (3.06 g, 13.3 mmol) at 0° C. and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was added ethyl acetate and 1 N-hydrochloric acid solution, the organic layer was separated, and the aqueous layer was extracted two times with ethyl acetate. The organic layers were combined, washed with sodium thiosulfate solution and brine, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL). The mixture was concentrated under reduced pressure and lyophilized to give the title compound (2.12 g, 8.79 mmol, 66%). The reaction mixture was concentrated under reduced pressure The residue was added ethyl acetate and 1 N-hydrochloric acid solution the organic layer was separated the aqueous layer was extracted two times with ethyl acetate washed with sodium thiosulfate solution and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL) The mixture was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloroethylsulfonyl chloride (2 g, 12.3 mmol) was dissolved in 2-propanol (20 mL), pyridine (2.7 mL) was added, and the mixture was stirred at room temperature for 3 hours. Allylamine hydrochloride (1.15 g, 12.3 mmol) and diisopropylethylamine (6.4 ml) was added, and stirred at room temperature for 3 hours. The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (0.5 g, 2.4 mmol, 20%). stirred at room temperature for 3 hours The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue the mixture was extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloroethylsulfonyl chloride (2 g, 12.3 mmol) was dissolved in 2-propanol (20 mL), pyridine (2.7 mL) was added, and the mixture was stirred at room temperature for 3 hours. Allylamine hydrochloride (1.15 g, 12.3 mmol) and diisopropylethylamine (6.4 ml) was added, and stirred at room temperature for 3 hours. The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (0.5 g, 2.4 mmol, 20%). stirred at room temperature for 3 hours The reaction mixture was evaporated under reduced pressure, 5% sodium bicarbonate solution was added to the residue the mixture was extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of allylamine hydrochloride (5.0 g, 53.4 mmol) in tetrahydrofuran (100 mL) was added diisopropylethylamine (10 mL) and bromoacetic acid benzyl ester (3.06 g, 13.3 mmol) at 0° C. and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was added ethyl acetate and 1 N-hydrochloric acid solution, the organic layer was extracted, and the aqueous layer was extracted two times with ethyl acetate. The organic layers were collected, washed with sodium thiosulfate solution and brine, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL). The mixture was concentrated under reduced pressure and lyophilized to give the title compound (2.12 g, 8.79 mmol, 66%). The reaction mixture was concentrated under reduced pressure The residue was added ethyl acetate and 1 N-hydrochloric acid solution the organic layer was extracted the aqueous layer was extracted two times with ethyl acetate The organic layers were collected washed with sodium thiosulfate solution and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography to the obtained oil was added 4N-Hydrogen chloride in 1,4-Dioxane (3.5 mL) The mixture was concentrated under reduced pressure