tert-butyl 2,2-dimethylpiperazine-1-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:; See reaction.notes.procedure_details.

Procedure: Using synthetic method analoguous to that of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(2,4-dimethylpiperazin-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide, the title compound was prepared from tert-butyl 2,2-dimethylpiperazine-1-carboxylate. LCMS (Method 25) [M+H]+=573.2, RT=0.97 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.2, 6.9 Hz), 8.69-8.68 (m, 2H), 8.27 (s, 1H), 7.62 (dd, 1H, J=2.7, 8.7 Hz), 7.56 (d, 1H, J=2.4 Hz), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.5, 6.9 Hz), 7.03 (t, 1H, 73.1 Hz), 5.17 (s, 2H), 3.48-3.42 (m, 2H), 2.28-2.22 (m, 2H), 2.17 (s, 3H), 2.08 (s, 2H), 1.39 (s, 6H).

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

Procedure: Using synthetic method analoguous to that of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(2,4-dimethylpiperazin-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide, the title compound was prepared from tert-butyl 2,2-dimethylpiperazine-1-carboxylate. LCMS (Method 25) [M+H]+=573.2, RT=0.97 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.2, 6.9 Hz), 8.69-8.68 (m, 2H), 8.27 (s, 1H), 7.62 (dd, 1H, J=2.7, 8.7 Hz), 7.56 (d, 1H, J=2.4 Hz), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.5, 6.9 Hz), 7.03 (t, 1H, 73.1 Hz), 5.17 (s, 2H), 3.48-3.42 (m, 2H), 2.28-2.22 (m, 2H), 2.17 (s, 3H), 2.08 (s, 2H), 1.39 (s, 6H).

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

Procedure: To a solution of formaldehyde (0.044 mL, 0.584 mmol) in methanol (2 mL) was added 1,1-dimethylethyl 2,2-dimethyl-1-piperazinecarboxylate (125 mg, 0.584 mmol, commercially available, for example from ChemPacific Corp., Baltimore, USA). The reaction mixture was stirred at room temperature for 1 hour before the addition of 4-(trifluoromethyl)phenylisocyanide (100 mg, 0.584 mmol, Fluorochem, Old Glossop, UK) and trimethylsilyl azide (0.092 mL, 0.701 mmol). The resulting reaction mixture was stirred at room overnight. The resulting reaction mixture

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

Procedure: To a solution of formaldehyde (0.044 mL, 0.584 mmol) in methanol (2 mL) was added 1,1-dimethylethyl 2,2-dimethyl-1-piperazinecarboxylate (125 mg, 0.584 mmol, commercially available, for example from ChemPacific Corp., Baltimore, USA). The reaction mixture was stirred at room temperature for 1 hour before the addition of 4-(trifluoromethyl)phenylisocyanide (100 mg, 0.584 mmol, Fluorochem, Old Glossop, UK) and trimethylsilyl azide (0.092 mL, 0.701 mmol). The resulting reaction mixture was stirred at room overnight. The resulting reaction mixture

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(chloromethyl)-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole (440 mg, 1.68 mmol, commercially available from Otava, Kiev, Ukraine) in acetonitrile (8 mL) was added 1,1-dimethylethyl 2,2-dimethyl-1-piperazinecarboxylate (359 mg, 1.68 mmol, commercially available, for example from ChemPacific Corp., Baltimore, USA) and triethylamine (0.701 mL, 5.03 mmol). The mixture was then heated to 120° C. for 20 minutes in a microwave reactor.

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(chloromethyl)-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole (440 mg, 1.68 mmol, commercially available from Otava, Kiev, Ukraine) in acetonitrile (8 mL) was added 1,1-dimethylethyl 2,2-dimethyl-1-piperazinecarboxylate (359 mg, 1.68 mmol, commercially available, for example from ChemPacific Corp., Baltimore, USA) and triethylamine (0.701 mL, 5.03 mmol). The mixture was then heated to 120° C. for 20 minutes in a microwave reactor.

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

Procedure: To a solution of 2.20 g of 2,2-Dimethyl-piperazine-1-carboxylic acid tert-butyl ester in 50 ml DCM was added 1.15 ml of benzaldehyde, followed by the addition of 2.61 g of sodium triacetoxyborohydride in small portions. The reaction was stirred at r.t. overnight. To the reaction was then added water. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. 3.30 g (100%) of the title compound were obtained and used without further purification. The layers were separated the organic layer was washed with brine dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 2.20 g of 2,2-Dimethyl-piperazine-1-carboxylic acid tert-butyl ester in 50 ml DCM was added 1.15 ml of benzaldehyde, followed by the addition of 2.61 g of sodium triacetoxyborohydride in small portions. The reaction was stirred at r.t. overnight. To the reaction was then added water. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. 3.30 g (100%) of the title compound were obtained and used without further purification. The layers were separated the organic layer was washed with brine dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 2.20 g of 2,2-Dimethyl-piperazine-1-carboxylic acid tert-butyl ester in 50 ml DCM was added 1.15 ml of benzaldehyde, followed by the addition of 2.61 g of sodium triacetoxyborohydride in small portions. The reaction was stirred at r.t. overnight. To the reaction was then added water. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. 3.30 g (100%) of the title compound were obtained and used without further purification. The layers were separated the organic layer was washed with brine dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 2.20 g of 2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester in 50 ml DCM was added 1.15 ml of benzaldehyde, followed by the addition of 2.61 g of sodium triacetoxyborohydride in small portions. The reaction was stirred at r.t. overnight. To the reaction was then added water. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. 3.30 g (100%) of the title compound were obtained and used without further purification. The layers were separated the organic layer was washed with brine dried over Na2SO4 filtered concentrated in vacuo