2-(4-aminopiperidin-1-yl)-N-methylacetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 2-(4-aminopiperidin-1-yl)-N-methylacetamide. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.86 (m, 11H) 1.95 (d, J=4.29 Hz, 2H) 2.15 (t, J=10.61 Hz, 2H) 2.62 (s, 3H) 2.81 (d, J=11.37 Hz, 2H) 2.90 (s, 2H) 3.33 (s, 3H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.77 (t, J=8.46 Hz, 1H) 7.43-7.53 (m, 2H) 7.57-7.69 (m, 1H) 7.97 (s, 1H) 8.14 (d, J=7.58 Hz, 1H) 8.20-8.35 (m, 2H) [M+H] calc'd for C29H38F2N8O4, 601. found 601. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 2-(4-aminopiperidin-1-yl)-N-methylacetamide. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.86 (m, 11H) 1.95 (d, J=4.29 Hz, 2H) 2.15 (t, J=10.61 Hz, 2H) 2.62 (s, 3H) 2.81 (d, J=11.37 Hz, 2H) 2.90 (s, 2H) 3.33 (s, 3H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.77 (t, J=8.46 Hz, 1H) 7.43-7.53 (m, 2H) 7.57-7.69 (m, 1H) 7.97 (s, 1H) 8.14 (d, J=7.58 Hz, 1H) 8.20-8.35 (m, 2H) [M+H] calc'd for C29H38F2N8O4, 601. found 601. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.0 g (10 mmoles) of piperidine, which as dissolved in DMF, anhydrous, 100 mL, was added 2.8 g (20 mmoles) K2CO3, and 1.2 g (11 mmoles) 2-chloro-N-methylacetamide. After stirring at 50° C. for overnight, the mixture was diluted with 500 mL of EtOAc, washed with brine (3×500 mL), dried over Na2SO4, and solvent was evaporated in vacuum. The resulting residue was treated with 50% TFA/DCM and was stirred at r.t. for 2 hrs, and solvent was evaporated in vacuum. The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%). [M+H] calc'd for C8H17N3O, 172. found 172. washed with brine (3×500 mL) dried over Na2SO4, and solvent was evaporated in vacuum The resulting residue was treated with 50% TFA/DCM was stirred at r.t. for 2 hrs solvent was evaporated in vacuum The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 2-(4-aminopiperidin-1-yl)-N-methylacetamide. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.86 (m, 11 H) 1.95 (d, J=4.29 Hz, 2 H) 2.15 (t, J=10.61 Hz, 2 H) 2.62 (s, 3 H) 2.81 (d, J=11.37 Hz, 2 H) 2.90 (s, 2 H) 3.33 (s, 3 H) 3.94 (s, 3 H) 4.05 (t, J=14.02 Hz, 2 H) 4.77 (t, J=8.46 Hz, 1 H) 7.43-7.53 (m, 2 H) 7.57-7.69 (m, 1 H) 7.97 (s, 1 H) 8.14 (d, J=7.58 Hz, 1 H) 8.20-8.35 (m, 2 H) [M+H] calc'd for C29H38F2N8O4, 601; found 601. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.0 g (10 mmoles) of piperidine, which as dissolved in DMF, anhydrous, 100 mL, was added 2.8 g (20 mmoles) K2CO3, and 1.2 g (11 mmoles) 2-chloro-N-methylacetamide. After stirring at 50° C. for overnight, the mixture was diluted with 500 mL of EtOAc, washed with brine (3×500 mL), dried over Na2SO4, and solvent was evaporated in vacuum. The resulting residue was treated with 50% TFA/DCM and was stirred at r.t. for 2 hrs, and solvent was evaporated in vacuum. The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%). [M+H] calc'd for C8H17N3O, 172; found 172. washed with brine (3×500 mL) dried over Na2SO4, and solvent was evaporated in vacuum The resulting residue was treated with 50% TFA/DCM was stirred at r.t. for 2 hrs solvent was evaporated in vacuum The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 2-(4-aminopiperidin-1-yl)-N-methylacetamide. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.86 (m, 11H) 1.95 (d, J=4.29 Hz, 2H) 2.15 (t, J=10.61 Hz, 2H) 2.62 (s, 3H) 2.81 (d, J=11.37 Hz, 2H) 2.90 (s, 2H) 3.33 (s, 3H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.77 (t, J=8.46 Hz, 1H) 7.43-7.53 (m, 2H) 7.57-7.69 (m, 1H) 7.97 (s, 1H) 8.14 (d, J=7.58 Hz, 1H) 8.20-8.35 (m, 2H) [M+H] calc'd for C29H38F2N8O4, 601. found 601. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.0 g (10 mmoles) of piperidine, which as dissolved in DMF, anhydrous, 100 mL, was added 2.8 g (20 mmoles) K2CO3, and 1.2 g (11 mmoles) 2-chloro-N-methylacetamide. After stirring at 50° C. for overnight, the mixture was diluted with 500 mL of EtOAc, washed with brine (3×500 mL), dried over Na2SO4, and solvent was evaporated in vacuum. The resulting residue was treated with 50% TFA/DCM and was stirred at r.t. for 2 hrs, and solvent was evaporated in vacuum. The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%). [M+H] calc'd for C8H17N3O, 172. found 172. washed with brine (3×500 mL) dried over Na2SO4, and solvent was evaporated in vacuum The resulting residue was treated with 50% TFA/DCM was stirred at r.t. for 2 hrs solvent was evaporated in vacuum The resulting mixture was purified by prep HPLC to give yellow oil, yield 1.5 g (88%)