tert-butyl N-(2-bromoethyl)-N-methylcarbamate

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

Procedure: The title compound was prepared from 4-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)phenol and tert-butyl 2-bromoethyl(methyl)carbamate using the method described in Example 41, followed by deprotection using trifluoroacetic acid.

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

Procedure: The title compound was prepared from 4-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)phenol and tert-butyl 2-bromoethyl(methyl)carbamate using the method described in Example 41, followed by deprotection using trifluoroacetic acid.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 83 (87 mg, 0.171 mmol) in DMF (855 μl) was added potassium carbonate (59.1 mg, 0.428 mmol). The mixture was cooled to 0° C., then followed by the addition of tert-butyl 2-bromoethyl(methyl)carbamate (44.8 mg, 0.188 mmol) [made by following the procedure described above for the synthesis of 72 (scheme 10, example 8, step 1), except using tert-butyl 2-hydroxyethyl(methyl)carbamate in place of N-Boc-(R)-3-hydroxypyrrolidine]. The mixture was stirred at room temperature for 16 h, and then more tert-butyl 2-bromoethyl(methyl)carbamate (44.8 mg, 0.188 mmol) was added. The mixture was stirred at room temperature for 30 min, then at 80° C. for 1 hour. The mixture was quenched with water and extracted with ethyl acetate, washed with brine, dried (MgSO4) filtered and concentrated. The residue was purified by silica gel column chromatography with gradient of methanol (0-10%) in dichloromethane to afford 84 (11 mg, 12%) as a white solid. LRMS (ESI): calc. 553.3; found 554.2 (MNa)+. The mixture was stirred at room temperature for 30 min at 80° C. for 1 hour The mixture was quenched with water extracted with ethyl acetate washed with brine dried (MgSO4) filtered concentrated The residue was purified by silica gel column chromatography with gradient of methanol (0-10%) in dichloromethane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Bromo-ethyl)-methyl-carbamic acid tert-butyl ester (0.09 g, 0.38 mmol) is added to a solution of hydroxy-diphenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester (0.265 g, 0.79 mmol) in DMF (10 ml). The resulting mixture is heated at 60° C. for 5 hours and concentrated. This procedure is repeated twice giving the title compound as a mixture containing unreacted hydroxy-diphenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester. concentrated