3-amino-3,4-dihydro-1H-quinolin-2-one;hydrochloride

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

実験手順: The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328.

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

実験手順: The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328.

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

実験手順: The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328.

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

実験手順: The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328.

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

実験手順: To a suspension of 2.42 gm NaH (50% oil dispersion washed 3 ×hexanes) in 50 ml of THF at 0° C. was added solid 5 gm (0.025 mol) of 3-aminodihydrocarbostyrilhydrochloride (T. J. McCord, Arch. of Biochem. & Biophys. 102 48 (1963)) stirring at 0° C. until the evolution of hydrogen had ceased at which time the reaction mixture was warmed to room temperature and stirred a further 1 hour. To the stirred reaction mixture was added dropwise a solution of 6 gm of t-butyl iodoacetate in 20 ml of THF stirring a further 2 hours at room temperature at which time the reaction was quenched with 20 ml of saturated NaHCO3. The reaction mixture was diluted with 20 ml of H2O and extracted 2×50 ml of 9:1 ethylacetate:acetonitrile. The organic layers were combined, filtered through MgSO4 and concentrated in vacuo to give 5 gm of 1-t-butoxycarbonylmethyl- 3-aminodihydrocarbostyril. NMR (CDCl3, TMS) 1.4 (s, 9H); 2.0-3.2 (m, 4H), 3.4-3.8 (m, 1H); 4.6 (Q, 2H); 6.6-7.2 (m, 4H) IR C=O 1738, 1680 To the stirred reaction mixture was quenched with 20 ml of saturated NaHCO3 The reaction mixture was diluted with 20 ml of H2O extracted 2×50 ml of 9:1 ethylacetate filtered through MgSO4 concentrated in vacuo

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

実験手順: To a suspension of 2.42 gm NaH (50% oil dispersion washed 3 ×hexanes) in 50 ml of THF at 0° C. was added solid 5 gm (0.025 mol) of 3-aminodihydrocarbostyrilhydrochloride (T. J. McCord, Arch. of Biochem. & Biophys. 102 48 (1963)) stirring at 0° C. until the evolution of hydrogen had ceased at which time the reaction mixture was warmed to room temperature and stirred a further 1 hour. To the stirred reaction mixture was added dropwise a solution of 6 gm of t-butyl iodoacetate in 20 ml of THF stirring a further 2 hours at room temperature at which time the reaction was quenched with 20 ml of saturated NaHCO3. The reaction mixture was diluted with 20 ml of H2O and extracted 2×50 ml of 9:1 ethylacetate:acetonitrile. The organic layers were combined, filtered through MgSO4 and concentrated in vacuo to give 5 gm of 1-t-butoxycarbonylmethyl- 3-aminodihydrocarbostyril. NMR (CDCl3, TMS) 1.4 (s, 9H); 2.0-3.2 (m, 4H), 3.4-3.8 (m, 1H); 4.6 (Q, 2H); 6.6-7.2 (m, 4H) IR C=O 1738, 1680 To the stirred reaction mixture was quenched with 20 ml of saturated NaHCO3 The reaction mixture was diluted with 20 ml of H2O extracted 2×50 ml of 9:1 ethylacetate filtered through MgSO4 concentrated in vacuo

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

実験手順: To a suspension of 2.42 gm NaH (50% oil dispersion washed 3×hexanes) in 50 ml of THF at 0° C. was added solid 5 gm (0.025 mol) of 3-aminodihydrocarbostyrilhydrochloride (T. J. McCord, Arch. of Biochem. & Biophys. 102 48, 1963) and the mixture was stirred at 0° C. until the evolution of hydrogen had ceased. When the evolution stopped, the reaction mixture was warmed to room temperature and stirred an additional 1 hour, at which time a solution of 6 gm of t-butyl iodoacetate in 20 ml of THF was added dropwise. After an additional two hours of stirring at room temperature, the reaction was quenched with 20 ml of saturated NaHCO3, and the reaction mixture was diluted with 20 ml of H2O and extracted twice with 50 ml of 9:1 ethylacetate:acetonitrile. The organic layers were combined, filtered through MgSO4 and concentrated in vacuo to give 5 gm of 1-t-butoxycarbonylmethyl-3 -aminodihydrocarbostyril. was added dropwise the reaction was quenched with 20 ml of saturated NaHCO3 the reaction mixture was diluted with 20 ml of H2O extracted twice with 50 ml of 9:1 ethylacetate filtered through MgSO4 concentrated in vacuo

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

実験手順: To a suspension of 2.42 gm NaH (50% oil dispersion washed 3×hexanes) in 50 ml of THF at 0° C. was added solid 5 gm (0.025 mol) of 3-aminodihydrocarbostyrilhydrochloride (T. J. McCord, Arch. of Biochem. & Biophys. 102 48, 1963) and the mixture was stirred at 0° C. until the evolution of hydrogen had ceased. When the evolution stopped, the reaction mixture was warmed to room temperature and stirred an additional 1 hour, at which time a solution of 6 gm of t-butyl iodoacetate in 20 ml of THF was added dropwise. After an additional two hours of stirring at room temperature, the reaction was quenched with 20 ml of saturated NaHCO3, and the reaction mixture was diluted with 20 ml of H2O and extracted twice with 50 ml of 9:1 ethylacetate:acetonitrile. The organic layers were combined, filtered through MgSO4 and concentrated in vacuo to give 5 gm of 1-t-butoxycarbonylmethyl-3 -aminodihydrocarbostyril. was added dropwise the reaction was quenched with 20 ml of saturated NaHCO3 the reaction mixture was diluted with 20 ml of H2O extracted twice with 50 ml of 9:1 ethylacetate filtered through MgSO4 concentrated in vacuo

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

実験手順: The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328.

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

実験手順: To a suspension of 2.42 gm NaH (50% oil dispersion washed 3×hexanes) in 50 ml of THF at 0° C. was added solid 5 gm (0.025 mol) of 3-aminodihydrocarbostyrilhydrochloride (T. J. McCord, Arch. of Biochem. & Biophys. 102 48 (1963)) stirring at 0° C. until the evolution of hydrogen had ceased at which time the reaction mixture was warmed to room temperature and stirred a further 1 hour. To the stirred reaction mixture was added dropwise a solution of 6 gm of t-butyl iodoacetate in 20 ml of THF stirring a further 2 hours at room temperature at which time the reaction was quenched with 20 ml of saturated NaHCO3. The reaction mixture was diluted with 20 ml of H2O and extracted 2×50 ml of 9:1 ethylacetate:acetonitrile. The organic layers were combined, filtered through MgSO4 and concentrated in vacuo to give 5 gm of 1-t-butoxycarbonylmethyl-3 -aminodihydrocarbostyril. To the stirred reaction mixture was quenched with 20 ml of saturated NaHCO3 The reaction mixture was diluted with 20 ml of H2O extracted 2×50 ml of 9:1 ethylacetate filtered through MgSO4 concentrated in vacuo

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

実験手順: Sodium hydride (60% in oil, 191 mg, 4.70 mmol) was added to 3-amino-3,4-dihydroquinolin-2(1H)-one hydrochloride (J. Med. Chem., 28, 1985; 1511–16, 450 mg, 2.27 mmol), in anhydrous DMF (6 mL) at 0° C. over a period of 5 min keeping the internal temperature at <10° C. The reaction was stirred for a further 30 min before addition of [2,2-dimethyl-1,3-dioxolan-4-yl]methyl methanesulfonate (J. Med. Chem. 35, 1992, 1650–62; 528 mg, 2.50 mmol) and the reaction has then heated to 80° C. for a period of 5 hours The reaction was then cooled and evaporated before addition of sat. aqueous NaHCO3 (20 mL) and EtOAc (50 mL). The organic layer was then dried (MgSO4), filtered and evaporated and the residue was purified by column chromatography (MeOH:DCM 1:19) to afford the title compound (330 mg, 53%) as colourless oil. at <10° C was then cooled evaporated before addition of sat. aqueous NaHCO3 (20 mL) and EtOAc (50 mL) The organic layer was then dried (MgSO4) filtered evaporated the residue was purified by column chromatography (MeOH:DCM 1:19)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% in oil, 1.60 g, 39.80 mmol) was added to 3-amino-3,4-dihydroquinolin-2(1H)-one hydrochloride (3.59 g, 18.09 mmol), in anhydrous DMF (50 mL) at 0° C. over a period of 10 min. The reaction was stirred for a further 30 min before addition of (2,2-dimethyl-1,3-dioxan-5-yl)methyl methanesulfonate [CAS registary number 131372-64-0] (4.05 g, 18.09 mmol) and the reaction has then heated to 60° C. for a period of 16 h. The reaction was then cooled and evaporated before addition of sat. aqueous NaHCO3 (200 mL) and EtOAc (500 mL). The organic layer was then dried (MgSO4), filtered and evaporated and the residue was purified by column chromatography (MeOH:DCM, 3:37) to afford the title compound (3.00 g, 57%) as a colourless oil. The reaction was then cooled evaporated before addition of sat. aqueous NaHCO3 (200 mL) and EtOAc (500 mL) The organic layer was then dried (MgSO4) filtered evaporated the residue was purified by column chromatography (MeOH:DCM, 3:37)