4-(bromomethyl)-1-fluoro-2-methylbenzene

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: To a solution of oxepan-2-one (0.562 g, 4.925 mmol) and 4-fluoro-3-methylbenzyl bromide (3.000 g, 14.774 mmol) in 20 mL of toluene, was added KOH (1.382 g, 24.625 mmol). The mixture was refluxed for 86 h. After cooling to room temperature, the reaction mixture was diluted with water (80 mL) and washed with ether. The aqueous layer was acidified with concentrated HCl to pH=2 and extracted with ether (50 mL×3). The combined organic extracts dried (Na2SO4), filtered, and concentrated under reduced pressure to give the title compound as colorless oil which was used directly in the next step without further purification (1.173 g, 94% yield). LC-MS: tR=8.0 min, m/z 277 (M+H)+. The mixture was refluxed for 86 h washed with ether extracted with ether (50 mL×3) The combined organic extracts dried (Na2SO4) filtered concentrated 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 oxepan-2-one (0.562 g, 4.925 mmol) and 4-fluoro-3-methylbenzyl bromide (3.000 g, 14.774 mmol) in 20 mL of toluene, was added KOH (1.382 g, 24.625 mmol). The mixture was refluxed for 86 h. After cooling to room temperature, the reaction mixture was diluted with water (80 mL) and washed with ether. The aqueous layer was acidified with concentrated HCl to pH=2 and extracted with ether (50 mL×3). The combined organic extracts dried (Na2SO4), filtered, and concentrated under reduced pressure to give the title compound as colorless oil which was used directly in the next step without further purification (1.173 g, 94% yield). LC-MS: tR=8.0 min, m/z 277 (M+H)+. The mixture was refluxed for 86 h washed with ether extracted with ether (50 mL×3) The combined organic extracts dried (Na2SO4) filtered concentrated under reduced pressure

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

実験手順: The title compound (0.001 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8-tetrahydro-1H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14; found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.48-7.43 (m, 4H), 7.08-7.06 (m, 1H), 6.99-6.97 (m, 2H), 5.32 (s, 2H), 3.88 (s, 2H), 3.16-3.14 (m, 2H), 2.89-2.86 (m, 2H), 2.22 (d, J=1.6 Hz, 3H), 1.80 (m, 2H).

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

実験手順: The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14; found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.49-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.07-7.01 (m, 1H), 7.00-6.95 (m, 1H), 6.95-6.90 (m, 1H), 5.31 (s, 2H), 2.97-2.91 (m, 4H), 2.89-2.84 (m, 2H), 2.82-2.77 (m, 2H), 2.22 (s, 3H).

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

実験手順: The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14; found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.49-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.07-7.01 (m, 1H), 7.00-6.95 (m, 1H), 6.95-6.90 (m, 1H), 5.31 (s, 2H), 2.97-2.91 (m, 4H), 2.89-2.84 (m, 2H), 2.82-2.77 (m, 2H), 2.22 (s, 3H).

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

実験手順: The title compound (0.001 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8-tetrahydro-1H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C, 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14. found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.48-7.43 (m, 4H), 7.08-7.06 (m, 1H), 6.99-6.97 (m, 2H), 5.32 (s, 2H), 3.88 (s, 2H), 3.16-3.14 (m, 2H), 2.89-2.86 (m, 2H), 2.22 (d, J=1.6 Hz, 3H), 1.80 (m, 2H).

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

実験手順: The title compound (0.001 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8-tetrahydro-1H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C, 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14. found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.48-7.43 (m, 4H), 7.08-7.06 (m, 1H), 6.99-6.97 (m, 2H), 5.32 (s, 2H), 3.88 (s, 2H), 3.16-3.14 (m, 2H), 2.89-2.86 (m, 2H), 2.22 (d, J=1.6 Hz, 3H), 1.80 (m, 2H).

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

実験手順: The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C, 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14. found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.49-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.07-7.01 (m, 1H), 7.00-6.95 (m, 1H), 6.95-6.90 (m, 1H), 5.31 (s, 2H), 2.97-2.91 (m, 4H), 2.89-2.84 (m, 2H), 2.82-2.77 (m, 2H), 2.22 (s, 3H).

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: