1-chloro-2-(chloromethyl)-3-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 123 g of (0.687 mole) of 6-chloro-2-fluorobenzyl chloride are added dropwise at 20°-40° C. to a suspension of 47 g (0.722 mole) of sodium azide in 400 ml of dimethylsulfoxide. The mixture is stirred for 4 hours at room temperature, then diluted with ice-water and extracted with cyclohexane. The solvent is removed by distillation and the residue is distilled, affording 6-chloro-2-fluorobenzyl azide; bp15 =99°-100° C. extracted with cyclohexane The solvent is removed by distillation the residue is distilled

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The starting material may be prepared as follows: A mixture of 98 g (0.678 mole) of 6-chloro-2-fluorotoluene, 91.5 g (0.678 mole) of sulfuryl chloride and 0.2 g of dibenzoyl peroxide is stirred for 3 hours at 100°-110° C. and then distilled, affording 6-chloro-2-fluorobenzyl chloride with a boiling point in the range from 78°-82° C. The starting material may be prepared distilled

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-chloro-2-(chloromethyl)-3-fluorobenzene and isolated as white solid (6.8 mg, 39%). MS (m/e): 425.4 (MH+).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.34 g (0.015 g atom) of sodium in 70 mL of ethanol was added 2.0 g (0.013 mol) of 2-mercapto-1H-imidazo[4,5-c]pyridine. After stirring at room temperature for 25 minutes, the reaction mixture was evaporated to dryness in a rotary evaporator. To the residue was added 40 mL of DMF. To the resulting solution was added dropwise 2.33 g (0.013 mol) of 2-chloro-6-fluorobenzyl chloride in 3 mL of DMF. The reaction mixture was stirred overnight at room temperature and was then poured into 400 mL of chilled water. The precipitate that formed was collected by filtration and amounted to 3.11 g. An analytical sample (m.p. 224°-226° C.) was obtained by recrystallization from ethanol. the reaction mixture was evaporated to dryness in a rotary evaporator To the residue was added 40 mL of DMF The reaction mixture was stirred overnight at room temperature The precipitate that formed was collected by filtration An analytical sample (m.p. 224°-226° C.) was obtained by recrystallization from ethanol