2-(2-fluorophenyl)-1,3-dithiane

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:

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 2-(2-fluorophenyl)-1,3-dithiane (2.72 g, 12.7 mmol, 4.4 eq.) in THF (65 mL) under nitrogen at 0° C. was added n-BuLi (1.6M/hexane; 7.4 mL, 11.8 mmol, 4.1 eq.) over 0.5 hr. After another 0.5 hr, the 0° C. bath was removed and replaced by a −78° C. bath. 5-(Chloromethyl)-N-isopropylthiazolo[5,4-b]pyridin-2-amine dihydrochloride (0.90 g, 2.86 mmol, 1.0 eq.) was added in portions after 15 min., and the reaction was stirred for 1.5 hr. Ice, EtOAc and saturated aqueous NaHCO3 were added, and the −78° C. bath was removed. After stirring to room temperature, the layers were separated, and the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel chromatography using CH2Cl2 followed by CH2Cl2:MeOH (40:1) as eluent afforded 5-((2-(2-fluorophenyl)-1,3-dithian-2-yl)methyl)-N-isopropylthiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.95 g, 79% yield). the 0° C. bath was removed replaced by a −78° C. the −78° C. bath was removed After stirring to room temperature the layers were separated the organic layer was dried over Na2SO4 filtered 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 solution of 2-(2-fluorophenyl)-1,3-dithiane (0.820 g, 3.83 mmol) in THF (25 mL) was added n-BuLi (1.6 M in hexane, 2.3 mL, 3.68 mmol) at −10° C. over 10 min. The resulting solution was stirred at −10° C. for 30 min before a solution of 2-(isopropylamino)benzo[d]thiazole-6-carbaldehyde (0.385 g, 1.75 mmol) in THF (5 mL) was added. The mixture was stirred at between −10° C. and 5° C. for 2.5 hr, and then quenched with saturated NH4Cl solution (25 mL). This was extracted with AcOEt (3×20 mL). The combined extract was washed with brine and dried over anhydrous MgSO4. The title compound (0.563 g, 74% yield) was isolated as a pale yellow solid by silica gel chromatography (35% AcOEt/hexane). was added quenched with saturated NH4Cl solution (25 mL) This was extracted with AcOEt (3×20 mL) The combined extract was washed with brine dried over anhydrous MgSO4

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-fluorobenzaldehyde (10.03 g, 80.8 mmol, 1.0 eq.) and NBS (2.16 g, 12.1 mmol, 0.2 eq.) in CH2Cl2 (400 mL) was added 1,3-propanedithiol (9.8 mL, 97.6 mmol, 1.2 eq.). After 0.75 h, the reaction mixture was concentrated in vacuo. The residue was diluted with CH2Cl2 and water, and the layers were separated. The organic layer was dried over Na2SO4, filtered, concentrated in vacuo, and triturated with hexanes to give 2-(2-fluorophenyl)-1,3-dithiane as a white solid (13.55 g, 78% yield). the reaction mixture was concentrated in vacuo The residue was diluted with CH2Cl2 and water the layers were separated The organic layer was dried over Na2SO4 filtered concentrated in vacuo triturated with hexanes

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-(2-fluorophenyl)-1,3-dithiane (2.72 g, 12.7 mmol, 4.4 eq.) in THF (65 mL) under nitrogen at 0° C. was added n-BuLi (1.6M/hexane; 7.4 mL, 11.8 mmol, 4.1 eq.) over 0.5 hr. After another 0.5 hr, the 0° C. bath was removed and replaced by a −78° C. bath. 5-(Chloromethyl)-N-isopropylthiazolo[5,4-b]pyridin-2-amine dihydrochloride (0.90 g, 2.86 mmol, 1.0 eq.) was added in portions after 15 min., and the reaction was stirred for 1.5 hr. Ice, EtOAc and saturated aqueous NaHCO3 were added, and the −78° C. bath was removed. After stirring to room temperature, the layers were separated, and the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel chromatography using CH2Cl2 followed by CH2Cl2:MeOH (40:1) as eluent afforded 5-((2-(2-fluorophenyl)-1,3-dithian-2-yl)methyl)-N-isopropylthiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.95 g, 79% yield). the 0° C. bath was removed replaced by a −78° C. the −78° C. bath was removed After stirring to room temperature the layers were separated the organic layer was dried over Na2SO4 filtered 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 solution of 2-(2-fluorophenyl)-1,3-dithiane (0.820 g, 3.83 mmol) in THF (25 mL) was added n-BuLi (1.6 M in hexane, 2.3 mL, 3.68 mmol) at −10° C. over 10 min. The resulting solution was stirred at −10° C. for 30 min before a solution of 2-(isopropylamino)benzo[d]thiazole-6-carbaldehyde (0.385 g, 1.75 mmol) in THF (5 mL) was added. The mixture was stirred at between −10° C. and 5° C. for 2.5 hr, and then quenched with saturated NH4Cl solution (25 mL). This was extracted with AcOEt (3×20 mL). The combined extract was washed with brine and dried over anhydrous MgSO4. The title compound (0.563 g, 74% yield) was isolated as a pale yellow solid by silica gel chromatography (35% AcOEt/hexane). was added quenched with saturated NH4Cl solution (25 mL) This was extracted with AcOEt (3×20 mL) The combined extract was washed with brine dried over anhydrous MgSO4

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-fluorobenzaldehyde (10.03 g, 80.8 mmol, 1.0 eq.) and NBS (2.16 g, 12.1 mmol, 0.2 eq.) in CH2Cl2 (400 mL) was added 1,3-propanedithiol (9.8 mL, 97.6 mmol, 1.2 eq.). After 0.75 h, the reaction mixture was concentrated in vacuo. The residue was diluted with CH2Cl2 and water, and the layers were separated. The organic layer was dried over Na2SO4, filtered, concentrated in vacuo, and triturated with hexanes to give 2-(2-fluorophenyl)-1,3-dithiane as a white solid (13.55 g, 78% yield). the reaction mixture was concentrated in vacuo The residue was diluted with CH2Cl2 and water the layers were separated The organic layer was dried over Na2SO4 filtered concentrated in vacuo triturated with hexanes