4-bromo-3-fluorobenzoyl chloride

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: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. ##STR38## may be formed

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

実験手順: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. may be formed

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

実験手順: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. may be formed

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

実験手順: To a stirred solution of 4-bromo-3-fluorobenzoyl chloride (5.6 g, CAS 695188-21-7) in acetonitrile (30 ml) and THF (30 ml) at 0-5° C. was added dropwise (trimethylsilyl)diazomethane (13.7 ml, 2 M solution in diethyl ether). The reaction mixture was stirred at room temperature for 30 min TLC analysis showed the reaction was complete. Hydrochloric acid (3.81 ml, 37% aq.) was then added dropwise at 0-5° C. over 10 minutes and the reaction mixture was then stirred at room temperature for a further 20 minutes. The reaction mixture was poured into EtOAc and extracted sequentially with aq. Na2CO3 solution, water and saturated brine. The organic layer was then dried over Na2SO4 and concentrated in vacuo to afford 2-chloro-1-(4-bromo-3-fluoro-phenyl)-ethanone (5.67 g) as a yellow solid which was used in the next step without further purification. MS (EI): 203 ([{81Br}M-CH2Cl]+), 201 ([{79Br}M-CH2Cl]+), 175 ([{81Br}M-CH2Cl—CO]+), 173 ([{79Br}M-CH2Cl—CO]+). the reaction mixture was then stirred at room temperature for a further 20 minutes extracted sequentially with aq. Na2CO3 solution, water and saturated brine The organic layer was then dried over Na2SO4 concentrated in vacuo

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

実験手順: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. ##STR38## may be formed

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

実験手順: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. may be formed

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

実験手順: As an alternative to the quinolone synthesis outlined above, the quinolone nucleus may be formed using the route illustrated in Scheme II. Similar methodology for the preparation of quinolones was first described in German patent application DE3142854. Starting from a 4-bromo-3-fluoro-benzoyl chloride, condensation with malonic acid monoethyl ester monopotassium salt gives a benzoyl acetate that is subsequently reacted with triethyl orthoformate. The resulting ethoxymethylene derivative is reacted with a primary amine and cyclized to the quinolone. may be formed

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-3-fluorobenzoyl chloride (3.00 g, 12.6 mmol) and anisole (1.65 mL, 1.65 g, 15.2 mmol, 1.20 eq) in DCM (30 mL) at −5° C. was added, portion-wise, over 5 minutes, AlCl3 (2.54 g, 19.0 mmol, 1.50 eq) as a powder. The reaction was stirred at −5° C. for 2 h. The reaction was poured onto a mixture of 1 N HCl (100 mL) and ice (200 g) and stirred for 1 h. The DCM layer was washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) and concentrated. The resulting white solid was triturated with ˜100 mL hexanes, filtered and air-dried overnight to afford 3.26 g (83%) of compound 185. 1H NMR (400 MHz, DMSO-d6): δ 3.87 (s, 3H), 7.11 (d, J=8.9 Hz, 2H), 7.45 (d, J=8.9 Hz, 1H), 7.64 (d, J=8.9 Hz, 1H), 7.78 (d, J=8.9 Hz, 2H), 7.91 (t, J=7.1 Hz, 1H). stirred for 1 h The DCM layer was washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) concentrated The resulting white solid was triturated with ˜100 mL hexanes filtered air-dried overnight

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-3-fluorobenzoyl chloride (3.00 g, 12.6 mmol) and anisole (1.65 mL, 1.65 g, 15.2 mmol, 1.20 eq) in DCM (30 mL) at −5° C. was added, portion-wise, over 5 minutes, AlCl3 (2.54 g, 19.0 mmol, 1.50 eq) as a powder. The reaction was stirred at −5° C. for 2 h. The reaction was poured onto a mixture of 1 N HCl (100 mL) and ice (200 g) and stirred for 1 h. The DCM layer was washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) and concentrated. The resulting white solid was triturated with ˜100 mL hexanes, filtered and air-dried overnight to afford 3.26 g (83%) of compound 185. 1H NMR (400 MHz, DMSO-d6): δ 3.87 (s, 3H), 7.11 (d, J=8.9 Hz, 2H), 7.45 (d, J=8.9 Hz, 1H), 7.64 (d, J=8.9 Hz, 1H), 7.78 (d, J=8.9 Hz, 2H), 7.91 (t, J=7.1 Hz, 1H). stirred for 1 h The DCM layer was washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) concentrated The resulting white solid was triturated with ˜100 mL hexanes filtered air-dried overnight

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-3-fluorobenzoyl chloride (3.00 g, 12.6 mmol) and anisole (1.65 mL, 1.65 g, 15.2 mmol, 1.20 eq) in DCM (30 mL) at −5° C. was added, portion-wise, over 5 minutes, AlCl3 (2.54 g, 19.0 mmol, 1.50 eq) as a powder. The reaction was stirred at −5° C. for 2 h. The reaction was poured onto a mixture of 1 N HCl (100 mL) and ice (200 g) and stirred for 1 h. The DCM layer washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) and concentrated. The resulting white solid was triturated with ˜100 mL hexanes, filtered and air-dried overnight to afford 3.26 g (83%) of compound 185. 1H NMR (400 MHz, DMSO-d6): δ 3.87 (s, 3 H), 7.11 (d, J=8.9 Hz, 2 H), 7.45 (d, J=8.9 Hz, 1H), 7.64 (d, J=8.9 Hz, 1 H), 7.78 (d, J=8.9 Hz, 2H), 7.91 (t, J=7.1 Hz, 1H). stirred for 1 h The DCM layer washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) concentrated The resulting white solid was triturated with ˜100 mL hexanes filtered air-dried overnight