tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate

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: A solution of 3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (2.5 g, 11.7 mmol) in CH2Cl2 (50 mL) was treated with trimethylsilyl isocyanate (14 mL, 117 mmol). The resultant mixture was stirred at rt for 4 h., concentrated and redissolved in CH2Cl2 (50 mL). To this solution was added HCl (4.0 N in 1,4-dioxane, 12 mL), and the resultant mixture was stirred at rt for 3 h. Concentration afforded the title compound as a white powder (2.4 g, 99%). MS (ESI): mass calcd. for C7H13N3O, 155.1; m/z found, 156.2 [M+H]+. concentrated redissolved in CH2Cl2 (50 mL) To this solution was added HCl (4.0 N in 1,4-dioxane, 12 mL) Concentration

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

Procedure: To a stirred solution of acid VIII (0.00021 mol, 1 eq) in DMF (5 mL), EDCI (0.048 g, 0.00024 mol, 1.1 eq), HOBt (0.038 g, 0.00024 mol, 1.1 eq) and DIPEA (0.15 mL, 0.00078 mol, 2.5 eq) were added at 0° C. and stirred for 15 minutes. A solution of amine LXXI (0.00021 mol, 1 eq) was then added at 0° C. and then the resulting mixture was allowed to stir at room temperature for overnight. After completion of the reaction, water (20 mL) was added and extracted with ethyl acetate (2×30 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 60-120 mess, 70% ethyl acetate in hexane) to give compound in 49-55% yield. to stir at room temperature for overnight was added extracted with ethyl acetate (2×30 mL) The combined organic layer was dried over anhydrous Na2SO4 concentrated under reduced pressure The crude product was purified by column chromatography (silica gel, 60-120 mess, 70% ethyl acetate in hexane) to give compound in 49-55% yield

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

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