3,4-dihydro-1H-quinazoline-2-thione

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 bromo-(4-nitrophenyl)acetic acid ethyl ester (0.92 g, 3.2 mmol) in ethanol (15 ml) was added to a suspension of 3,4-dihydro-1H-quinazoline-2-thione (0.5 g, 3.0 mmol) in ethanol (10 ml) and the resulting mixture was heated at reflux for 3 h. A brown solid was filtered, washed with ethanol, and dried under reduced pressure to yield 0.86 g (88%) of a yellowish solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 4.89 (m, 2H) 5.95 (s, 1H) 7.12 (d, J=7.63 Hz, 1H) 7.17 (t, J=7.48 Hz, 1H) 7.26 (m, 2H) 7.82 (d, J=8.85 Hz, 2H) 8.25 (d, J=8.85 Hz, 2H). MS (ESI) m/z 326 (MH+); HPLC (Column YMC Xterra OSD 4.6×33 mm S 7) rt 1.53 min; Purity (93%). the resulting mixture was heated at reflux for 3 h A brown solid was filtered washed with ethanol dried under reduced pressure

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

実験手順: To a solution of 2-aminomethyl-phenylamine (6.35 g, 52 mmol) and triethylamine (16.8 ml, 120 mmol) in ether (150 ml) was added dropwise a solution of thiophosgene (4.6 ml, 60 mmol) in ether (40 mL), at −78° C. over 1 h. After warming to rt a precipitate was filtered, washed thoroughly with ether, dissolved in methanol (200 mL) and treated with solid KOH (6.7 g, 120 mmol). The mixture was stirred for 15 min, filtered, and the filtrate was concentrated under reduced pressure to obtaine a residue which was recrystallized from methanol/water to give an off-white solid 7.43 g (87%). 1H NMR (500 MHz, DMSO-D6) δ 4.35 (s, 1H) 6.92 (d, J=7.93 Hz, 1H) 6.96 (m, 1H) 7.08 (d, J=7.32 Hz, 1H) 7.15 (m, 1H) 8.59 (s, 1H) 10.36 (s, 1H). MS (ESI) m/z 165 (MH+); HPLC (Column YMC Xterra OSD 4.6×33 mm S 7) Rt 0.81 min; Purity (96%). was filtered washed thoroughly with ether dissolved in methanol (200 mL) filtered the filtrate was concentrated under reduced pressure was recrystallized from methanol/water

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 106 Parts of N,N-dimethylformamide were added dropwise to 650 parts of aluminum chloride and the solution was stirred for 15 min at 75° C. There were added portionwise 112 parts of 3,4-dihydro-2(1H)-quinazolinethione and, after stirring for 15 min at 75° C., 136 parts of 3-pyridinylcarbonyl chloride hydrochloride. Stirring at 75° C. was continued overnight and then the mixture was poured into 2500 parts of ice-water. The precipitate was filtered off and stirred for 13 hours in a mixture of ice-water and 1530 parts of a sodium hydroxide solution 50%. The product was filtered off, washed with water and dried, yielding 150 parts (82%) of (3-pyridinyl) (1,2,3,4-tetrahydro-2-thioxo-6-quinazolinyl)methanone; (decomp.) (interm. 54). after stirring for 15 min at 75° C. Stirring at 75° C. was continued overnight The precipitate was filtered off stirred for 13 hours in a mixture of ice-water and 1530 parts of a sodium hydroxide solution 50% The product was filtered off washed with water dried

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1.0 g (0.006 mol) 3,4-dihydro-2(1H)-quinazolinethione (compound II), 0.57 g (0.006 mol) chloroacetic acid, and 0.54 g (0.0065 mol) sodium bicarbonate is mixed in 31.25 ml water, and heated overnight at 90° C. Then, 12.5 ml of dimethylformamide is added, and the reaction mixture is refluxed for 61/2 hours. After cooling, 5H-thiazolo[2,3-b]quinazolin-3(2H)-one, as the precipitated solid, is filtered off and recrystallized from anhydrous ethanol. Replacement of 3,4-dihydro-2(1H)-quinazolinethione by a derivative thereof in which a nuclear hydrogen of the benzene ring has been substituted with lower alkyl, alkoxy, halogen, trifluoromethyl, NO2 or NH2, results in the corresponding derivative of 5H-thiazolo[2,3-b]quinazolin-3(2H)-one. the reaction mixture is refluxed for 61/2 hours After cooling 5H-thiazolo[2,3-b]quinazolin-3(2H)-one, as the precipitated solid, is filtered off recrystallized from anhydrous ethanol

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1.0 g (0.006 mol) 3,4-dihydro-2(1H)-quinazolinethione (compound II), 0.57 g (0.006 mol) chloroacetic acid, and 0.54 g (0.0065 mol) sodium bicarbonate is mixed in 31.25 ml water, and heated overnight at 90° C. Then, 12.5 ml of dimethylformamide is added, and the reaction mixture is refluxed for 61/2 hours. After cooling, 5H-thiazolo[2,3-b]quinazolin-3(2H)-one, as the precipitated solid, is filtered off and recrystallized from anhydrous ethanol. Replacement of 3,4-dihydro-2(1H)-quinazolinethione by a derivative thereof in which a nuclear hydrogen of the benzene ring has been substituted with lower alkyl, alkoxy, halogen, trifluoromethyl, NO2 or NH2, results in the corresponding derivative of 5H-thiazolo[2,3-b]quinazolin-3(2H)-one. the reaction mixture is refluxed for 61/2 hours After cooling 5H-thiazolo[2,3-b]quinazolin-3(2H)-one, as the precipitated solid, is filtered off recrystallized from anhydrous ethanol

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

実験手順: Methyl iodide (11.5 ml, 184 mmol) was added to a solution of 3,4-dihydro-1H-quinazoline-2-thione (7.55 g, 46 mmol) in ethanol (150 ml), and the mixture was heated to reflux (3.5 h). The majority of the solvent was then evaporated under reduced pressure, and the precipitate was collected by filtration and washed with a small amount of cold ethanol. The thus obtained title compound (9.60 g, 68%) was used in the next step without further purification. the mixture was heated to reflux (3.5 h) The majority of the solvent was then evaporated under reduced pressure the precipitate was collected by filtration washed with a small amount of cold ethanol

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

実験手順: A solution of bromo-(4-nitrophenyl)acetic acid ethyl ester (0.92 g, 3.2 mmol) in ethanol (15 ml) was added to a suspension of 3,4-dihydro-1H-quinazoline-2-thione (0.5 g, 3.0 mmol) in ethanol (10 ml) and the resulting mixture was heated at reflux for 3 h. A brown solid was filtered, washed with ethanol, and dried under reduced pressure to yield 0.86 g (88%) of a yellowish solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 4.89 (m, 2H) 5.95 (s, 1H) 7.12 (d, J=7.63 Hz, 1H) 7.17 (t, J=7.48 Hz, 1H) 7.26 (m, 2H) 7.82 (d, J=8.85 Hz, 2H) 8.25 (d, J=8.85 Hz, 2H). MS (ESI) m/z 326 (MH+); HPLC (Column YMC Xterra OSD 4.6×33 mm S 7) rt 1.53 min; Purity (93%). the resulting mixture was heated at reflux for 3 h A brown solid was filtered washed with ethanol dried under reduced pressure

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

実験手順: To a solution of 2-aminomethyl-phenylamine (6.35 g, 52 mmol) and triethylamine (16.8 ml, 120 mmol) in ether (150 ml) was added dropwise a solution of thiophosgene (4.6 ml, 60 mmol) in ether (40 mL), at −78° C. over 1 h. After warming to rt a precipitate was filtered, washed thoroughly with ether, dissolved in methanol (200 mL) and treated with solid KOH (6.7 g, 120 mmol). The mixture was stirred for 15 min, filtered, and the filtrate was concentrated under reduced pressure to obtaine a residue which was recrystallized from methanol/water to give an off-white solid 7.43 g (87%). 1H NMR (500 MHz, DMSO-D6) δ 4.35 (s, 1H) 6.92 (d, J=7.93 Hz, 1H) 6.96 (m, 1H) 7.08 (d, J=7.32 Hz, 1H) 7.15 (m, 1H) 8.59 (s, 1H) 10.36 (s, 1H). MS (ESI) m/z 165 (MH+); HPLC (Column YMC Xterra OSD 4.6×33 mm S 7) Rt 0.81 min; Purity (96%). was filtered washed thoroughly with ether dissolved in methanol (200 mL) filtered the filtrate was concentrated under reduced pressure was recrystallized from methanol/water

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 106 Parts of N,N-dimethylformamide were added dropwise to 650 parts of aluminum chloride and the solution was stirred for 15 min at 75° C. There were added portionwise 112 parts of 3,4-dihydro-2(1H)-quinazolinethione and, after stirring for 15 min at 75° C., 136 parts of 3-pyridinylcarbonyl chloride hydrochloride. Stirring at 75° C. was continued overnight and then the mixture was poured into 2500 parts of ice-water. The precipitate was filtered off and stirred for 13 hours in a mixture of ice-water and 1530 parts of a sodium hydroxide solution 50%. The product was filtered off, washed with water and dried, yielding 150 parts (82%) of (3-pyridinyl) (1,2,3,4-tetrahydro-2-thioxo-6-quinazolinyl)methanone; (decomp.) (interm. 54). after stirring for 15 min at 75° C. Stirring at 75° C. was continued overnight The precipitate was filtered off stirred for 13 hours in a mixture of ice-water and 1530 parts of a sodium hydroxide solution 50% The product was filtered off washed with water dried