(3S,4S)-3-(BOC-氨基)-4-甲基吡咯烷

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidine (1.80 g, 8.97 mmol), ethyl 3-methyl-2,4,5-trifluorobenzoate (2.18 g, 10.0 mmol), and 1,8-diazabicyclo[5.4.0]undeca-7-ene (DBU) (2.24 mL, 15 mmol) in dimethyl sulfoxide (20 mL) was stirred under a nitrogen atmosphere at an external temperature of 60° C. for 70 hours. The temperature of the mixture was cooled to room temperature. The resultant mixture was poured to a 10% aqueous citric acid solution, followed by extraction with ethyl acetate (200 mL×3), washing by water (200 mL), saturated aqueous sodium hydrogencarbonate (150 mL), and saturated brine (150 mL), and dried over anhydrous sodium magnesium. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1), to thereby yield the title compound as colorless crystals (2.51 g, 70.2%). followed by extraction with ethyl acetate (200 mL×3) washing by water (200 mL), saturated aqueous sodium hydrogencarbonate (150 mL), and saturated brine (150 mL) dried over anhydrous sodium magnesium After filtration the filtrate was concentrated under reduced pressure The obtained residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (1.0 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.89 g), DBU (0.62 g) and anhydrous acetonitrile (30 ml) was refluxed for 27 hours. Then, the reacting mixture was treated as described in example 33 and recrystallized from chloroform-methanol-concentrated aqueous ammonia (20:20:1) to give the title compound (0.008 g) as white powder, mp 300~° C. (decompd.). was refluxed for 27 hours Then, the reacting mixture was treated recrystallized from chloroform-methanol-concentrated aqueous ammonia (20:20:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.7 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.62 g), DBU (0.43 g) and anhydrous acetonitrile (30 ml) was refluxed for 52 hours. After cooling, the resulting precipitate was collected by filtration, washed with chilled acetonitrile and this was added to concentrated hydrochloric acid-methanol (1:1, 5 ml) and stirred for 40 minutes at elevated temperature. The reacting mixture was collected by filtration, washed with chilled water sufficiently and recrystallized from chloroform-methanol-concentrated aqueous ammonia (10:10:3) to give the title compound (0.076 g) as pale yellow prisms, mp 268°-270° C. (decompd.). was refluxed for 52 hours After cooling the resulting precipitate was collected by filtration washed with chilled acetonitrile this was added to concentrated hydrochloric acid-methanol (1:1, 5 ml) The reacting mixture was collected by filtration washed with chilled water sufficiently recrystallized from chloroform-methanol-concentrated aqueous ammonia (10:10:3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.7 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.62 g), DBU (0.43 g) and anhydrous acetonitrile (30 ml) was refluxed for 52 hours. After cooling, the resulting precipitate was collected by filtration, washed with chilled acetonitrile and this was added to concentrated hydrochloric acid-methanol (1:1, 5 ml) and stirred for 40 minutes at elevated temperature. The reacting mixture was collected by filtration, washed with chilled water sufficiently and recrystallized from chloroform-methanol-concentrated aqueous ammonia (10:10:3) to give the title compound (0.076 g) as pale yellow prisms, mp 268°-270° C. (decompd.). was refluxed for 52 hours After cooling the resulting precipitate was collected by filtration washed with chilled acetonitrile this was added to concentrated hydrochloric acid-methanol (1:1, 5 ml) The reacting mixture was collected by filtration washed with chilled water sufficiently recrystallized from chloroform-methanol-concentrated aqueous ammonia (10:10:3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (3S)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (0.5 g), anhydrous dimethyl sulfoxide (10 ml) and cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.54 g) was stirred for 2 hours at 90°-100° C. and then concentrated. The resulting residue was dissolved in chloroform and the solution was washed with 10% aqueous citric acid solution further washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The resulting precipitate was triturated in methanol and collected by filtration to give the title compound (0.67 g) as yellowish powder, mp 206°-207° C. concentrated The resulting residue was dissolved in chloroform the solution was washed with 10% aqueous citric acid solution further washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate concentrated The resulting precipitate was triturated in methanol collected by filtration

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (0.5 g), anhydrous dimethyl sulfoxide (10 ml) and cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.54 g) was stirred for 2 hours at 90°-100° C. and then concentrated. To the residue was added methanol and the resulting precipitate was collected by filtration and then washed with cold methanol to give the title compound (0.58 g) as yellowish powder, mp 219°-220° C. concentrated To the residue was added methanol the resulting precipitate was collected by filtration washed with cold methanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6,7,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.5 g), anhydrous acetonitrile (5 ml), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.5 g) and DBU (0.27 g) was refluxed for an hour and then concentrated. The resulting residue was dissolved in chloroform and the solution was washed with 10% aqueous citric acid solution. After concentration of the chloroform layer, the resulting precipitate was triturated in water, and collected by filtration and washed with water, methanol and ether successively to give the title compound (0.51 g) as white powder, mp 217°-219° C. was refluxed for an hour concentrated The resulting residue was dissolved in chloroform the solution was washed with 10% aqueous citric acid solution After concentration of the chloroform layer, the resulting precipitate was triturated in water collected by filtration washed with water, methanol and ether successively

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8-chloro-1-ethyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.25 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.21 g), DBU (0.15 g) and anhydrous acetonitrile (4 ml) was refluxed for 2.5 hours. Then, the reacting mixture was treated as described in example 22 to give the title compound (0.1 g) as white powder, mp 222°-224° C. (decompd.). was refluxed for 2.5 hours Then, the reacting mixture was treated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8-chloro-1-ethyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.25 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.21 g), DBU (0.15 g) and anhydrous acetonitrile (4 ml) was refluxed for 2.5 hours. Then, the reacting mixture was treated as described in example 22 to give the title compound (0.1 g) as white powder, mp 222°-224° C. (decompd.). was refluxed for 2.5 hours Then, the reacting mixture was treated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (1.0 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.89 g), DBU (0.62 g) and anhydrous acetonitrile (30 ml) was refluxed for 2 hours and then concentrated. The resulting residue was dissolved in chloroform (50 ml), washed with 10% aqueous citric acid solution and water successively, dried over anhydrous sodium sulfate and concentrated. To the resulting residue was added hot methanol to crystallize and then cooled. The resulting precipitate was collected by filtration, added to the mixture of concentrated hydrochloric acid-methanol (1:1, 18 ml) and stirred at room temperature for an hour. The reacting mixture was neutralized with concentrated aqueous ammonia and the resulting precipitate was collected by filtration, washed with ice-water sufficiently and recrystallized from dichloromethane-methanol (1:1) to give the title compound (0.41 g) as colorless prisms, mp 232°-234° C. (decompd.). was refluxed for 2 hours concentrated The resulting residue was dissolved in chloroform (50 ml) washed with 10% aqueous citric acid solution and water successively dried over anhydrous sodium sulfate concentrated To the resulting residue was added hot methanol to crystallize cooled The resulting precipitate was collected by filtration added to the mixture of concentrated hydrochloric acid-methanol (1:1, 18 ml) the resulting precipitate was collected by filtration washed with ice-water sufficiently recrystallized from dichloromethane-methanol (1:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8-bromo-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.19 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.14 g), DBU (0.095 g) and anhydrous acetonitrile (5 ml) was refluxed for 2 hours and then concentrated. The resulting residue was dissolved in chloroform (70 ml), washed with 10% aqueous citric acid solution, water successively, dried over anhydrous sodium sulfate and then concentrated. To the resulting oily residue was added hot methanol to crystallize and cooled. The resulting precipitate was collected by filtration, added to the mixture of concentrated hydrochloric acid-methanol (1:1, 3 ml) and stirred for 2.5 hours under elevated temperature. The reaction mixture was neutralized with concentrated aqueous ammonia, the resulting precipitate was collected by filtration, washed with ice-water and recrystallized from dichloromethane-methanol-concentrated aqueous ammonia (10:10:1) to give the title compound (0.06 g) as yellow prisms, mp 225°-226.5° C. (decompd.). was refluxed for 2 hours concentrated The resulting residue was dissolved in chloroform (70 ml) washed with 10% aqueous citric acid solution, water successively dried over anhydrous sodium sulfate concentrated To the resulting oily residue was added hot methanol to crystallize cooled The resulting precipitate was collected by filtration added to the mixture of concentrated hydrochloric acid-methanol (1:1, 3 ml) the resulting precipitate was collected by filtration washed with ice-water recrystallized from dichloromethane-methanol-concentrated aqueous ammonia (10:10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8-bromo-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.19 g), cis-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.14 g), DBU (0.095 g) and anhydrous acetonitrile (5 ml) was refluxed for 2 hours and then concentrated. The resulting residue was dissolved in chloroform (70 ml), washed with 10% aqueous citric acid solution, water successively, dried over anhydrous sodium sulfate and then concentrated. To the resulting oily residue was added hot methanol to crystallize and cooled. The resulting precipitate was collected by filtration, added to the mixture of concentrated hydrochloric acid-methanol (1:1, 3 ml) and stirred for 2.5 hours under elevated temperature. The reaction mixture was neutralized with concentrated aqueous ammonia, the resulting precipitate was collected by filtration, washed with ice-water and recrystallized from dichloromethane-methanol-concentrated aqueous ammonia (10:10:1) to give the title compound (0.06 g) as yellow prisms, mp 225°-226.5° C. (decompd.). was refluxed for 2 hours concentrated The resulting residue was dissolved in chloroform (70 ml) washed with 10% aqueous citric acid solution, water successively dried over anhydrous sodium sulfate concentrated To the resulting oily residue was added hot methanol to crystallize cooled The resulting precipitate was collected by filtration added to the mixture of concentrated hydrochloric acid-methanol (1:1, 3 ml) the resulting precipitate was collected by filtration washed with ice-water recrystallized from dichloromethane-methanol-concentrated aqueous ammonia (10:10:1)