1-(bromomethyl)-2-methylsulfonylbenzene

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: In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-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-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-(bromomethyl)-2-(methylsulfonyl)benzene and isolated as white solid. MS (m/e): 443.3 (MH+). isolated as white solid

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-difluoropyrrolidin-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-(bromomethyl)-2-(methylsulfonyl)benzene and isolated as white solid. MS (m/e): 451.3 (MH+). isolated as white solid

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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 2; 50 mg, 0.245 mmol) was dissolved in DMF (1.5 mL). K2CO3 (42 mg, 0.30 mmol), tetrabutylammonium iodide (14 mg, 0.038 mmol), and 1-bromomethyl-2-methylsulfonyl-benzene (which is available from Combi-Blocks; 62 mg, 0.25 mmol) were added. The reaction mixture was heated at 40° C. for 13 h. The reaction mixture was cooled to room temperature and partitioned between H2O (5 mL) and EtOAc (5 mL). The organic layer was dried (Na2SO4), filtered, evaporated, and purified twice by chromatography (40-60% EtOAc/hexanes) to give 3-[4-(2-methanesulfonyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (3 mg, 3%) as a white powder. HRMS Calcd. for C18H17N2O5S (M+H)+, 373.0853. Found: 373.0854. The reaction mixture was cooled to room temperature partitioned between H2O (5 mL) and EtOAc (5 mL) The organic layer was dried (Na2SO4) filtered evaporated purified twice by chromatography (40-60% EtOAc/hexanes)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 2; 50 mg, 0.245 mmol) was dissolved in DMF (1.5 mL). K2CO3 (42 mg, 0.30 mmol), tetrabutylammonium iodide (14 mg, 0.038 mmol), and 1-bromomethyl-2-methylsulfonyl-benzene (which is available from Combi-Blocks; 62 mg, 0.25 mmol) were added. The reaction mixture was heated at 40° C. for 13 h. The reaction mixture was cooled to room temperature and partitioned between H2O (5 mL) and EtOAc (5 mL). The organic layer was dried (Na2SO4), filtered, evaporated, and purified twice by chromatography (40-60% EtOAc/hexanes) to give 3-[4-(2-methanesulfonyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (3 mg, 3%) as a white powder. HRMS Calcd. for C18H17N2O5S (M+H)+, 373.0853. Found: 373.0854. The reaction mixture was cooled to room temperature partitioned between H2O (5 mL) and EtOAc (5 mL) The organic layer was dried (Na2SO4) filtered evaporated purified twice by chromatography (40-60% EtOAc/hexanes)

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

Procedure: Use a method similar to the Preparation 177, using 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 1-bromomethyl-2-methanesulfonyl-benzene to give, after deprotection by the General Procedure 1-4, the title compound and as a white solid. MS (APCI+) m/z: 382 (M+H)+. similar to the Preparation 177 to give

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

Procedure: To a stirred solution of (2-methanesulfonyl-phenyl)methanol (735 mg, 3.99 mmol) in dry DCM (2 mL) at 0° C., add a solution of 1M phosphorous tribromide in DCM (6.0 mL, 6.0 mmol) and continue stirring for 1 h. Dilute with saturated aqueous NaHCO3, extract three times with ethyl ether, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (12:1) to provide the title compound as a white solid (950 mg, 97%). extract three times with ethyl ether dry over anhydrous MgSO4 concentrate in vacuo Purify by chromatography on silica gel eluting with hexane/EtOAc (12:1)

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

Procedure: A solution of 36.5 g of 2-(methylsulfonyl)benzyl bromide and 11.4 g of thiourea in 500 ml absolute ethanol was stirred at reflux temperature for 11/2 hours and then allowed to cool to room temperature. Upon standing, the solution yielded white feather-like crystals which were collected by filtration, washed with cold 1-chlorobutane, and dried in vacuo. The yield of 2-(methylsulfonyl)phenylmethyl carbamimidothioate hydrobromide, m.p. 203°-206° C., was 36.3 g. at reflux temperature for 11/2 hours the solution yielded white feather-like crystals which were collected by filtration washed with cold 1-chlorobutane dried in vacuo

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-difluoropyrrolidin-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-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-(bromomethyl)-2-(methylsulfonyl)benzene and isolated as white solid. MS (m/e): 443.3 (MH+). isolated as white solid

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-difluoropyrrolidin-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-(bromomethyl)-2-(methylsulfonyl)benzene and isolated as white solid. MS (m/e): 451.3 (MH+). isolated as white solid