spiro[3.5]nonan-7-ylmethanamine

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]-6-chloro-2-cyanopyrimidine-5-carboxylic acid allyl ester (1.1 mmol) and C-Spiro[3.5]non-7-yl-methylamine (1.4 mmol) in C2H5CN (10 mL) is added triethylamine (2.8 mmol) at room temperature. After stirring at 80° C. for 1 h, the reaction mixture is cooled to room temperature and diluted with AcOEt. The organic layer is washed with H2O and aq. KHSO4 and brine. The organic layer is dried over MgSO4 and evaporated in vacuo, which is directly used for the next reaction without further purification. To a solution of the crude 4-[2-(1-tert-butoxy carbonylpiperidin-4-yl)ethoxy]-2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid allyl ester (1.1 mmol) in THF (5 mL) are added morpholine (3.4 mmol) and Pd(PPh3)4 (0.06 mmol) successively. After stirring at the same temperature for 0.5 h, the reaction mixture is diluted with AcOEt. The organic layer is washed with H2O and evaporated in vacuo. The residue is purified by silica gel column chromatography to give a 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid as yellow pale solid; 1H-NMR (CDCl3), δ: 0.97-1.08 (2H, m), 1.15-1.29 (5H, m), 1.48 (9H, s), 1.48-1.86 (15H, m), 2.69 (2H, t), 3.39 (2H, t), 4.11 (2H, m), 4.66 (2H, t), 9.42 (1H, br t). the reaction mixture is cooled to room temperature The organic layer is washed with H2O and aq. KHSO4 and brine The organic layer is dried over MgSO4 evaporated in vacuo, which is directly used for the next reaction without further purification After stirring at the same temperature for 0.5 h The organic layer is washed with H2O evaporated in vacuo The residue is purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]-6-chloro-2-cyanopyrimidine-5-carboxylic acid allyl ester (1.1 mmol) and C-Spiro[3.5]non-7-yl-methylamine (1.4 mmol) in C2H5CN (10 mL) is added triethylamine (2.8 mmol) at room temperature. After stirring at 80° C. for 1 h, the reaction mixture is cooled to room temperature and diluted with AcOEt. The organic layer is washed with H2O and aq. KHSO4 and brine. The organic layer is dried over MgSO4 and evaporated in vacuo, which is directly used for the next reaction without further purification. To a solution of the crude 4-[2-(1-tert-butoxy carbonylpiperidin-4-yl)ethoxy]-2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid allyl ester (1.1 mmol) in THF (5 mL) are added morpholine (3.4 mmol) and Pd(PPh3)4 (0.06 mmol) successively. After stirring at the same temperature for 0.5 h, the reaction mixture is diluted with AcOEt. The organic layer is washed with H2O and evaporated in vacuo. The residue is purified by silica gel column chromatography to give a 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid as yellow pale solid; 1H-NMR (CDCl3), δ: 0.97-1.08 (2H, m), 1.15-1.29 (5H, m), 1.48 (9H, s), 1.48-1.86 (15H, m), 2.69 (2H, t), 3.39 (2H, t), 4.11 (2H, m), 4.66 (2H, t), 9.42 (1H, br t). the reaction mixture is cooled to room temperature The organic layer is washed with H2O and aq. KHSO4 and brine The organic layer is dried over MgSO4 evaporated in vacuo, which is directly used for the next reaction without further purification After stirring at the same temperature for 0.5 h The organic layer is washed with H2O evaporated in vacuo The residue is purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[2-(6-chloro-2-cyanopyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester (0.82 mmol) and C-spiro[3.5]non-7-ylmethylamine (0.86 mmol) in CH3CN (10 mL) is added K2CO3 (2.2 mmol) at room temperature. After stirring at 80° C. for 12 h, the reaction mixture is cooled to room temperature and diluted with AcOEt. The organic layer is washed twice with H2O and dried over MgSO4 and evaporated in vacuo to give a crude 4-(2-{2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidin-4-yloxy}ethyl)piperidine-1-carboxylic acid tert-butyl ester. the reaction mixture is cooled to room temperature The organic layer is washed twice with H2O dried over MgSO4 evaporated in vacuo

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]-6-chloro-2-cyanopyrimidine-5-carboxylic acid allyl ester (1.1 mmol) and C-Spiro[3.5]non-7-yl-methylamine (1.4 mmol) in C2H5CN (10 mL) is added triethylamine (2.8 mmol) at room temperature. After stirring at 80° C. for 1 h, the reaction mixture is cooled to room temperature and diluted with AcOEt. The organic layer is washed with H2O and aq. KHSO4 and brine. The organic layer is dried over MgSO4 and evaporated in vacuo, which is directly used for the next reaction without further purification. To a solution of the crude 4-[2-(1-tert-butoxy carbonylpiperidin-4-yl)ethoxy]-2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid allyl ester (1.1 mmol) in THF (5 mL) are added morpholine (3.4 mmol) and Pd(PPh3)4 (0.06 mmol) successively. After stirring at the same temperature for 0.5 h, the reaction mixture is diluted with AcOEt. The organic layer is washed with H2O and evaporated in vacuo. The residue is purified by silica gel column chromatography to give a 4-[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid as yellow pale solid; 1H-NMR (CDCl3), δ: 0.97-1.08 (2H, m), 1.15-1.29 (5H, m), 1.48 (9H, s), 1.48-1.86 (15H, m), 2.69 (2H, t), 3.39 (2H, t), 4.11 (2H, m), 4.66 (2H, t), 9.42 (1H, br t). the reaction mixture is cooled to room temperature The organic layer is washed with H2O and aq. KHSO4 and brine The organic layer is dried over MgSO4 evaporated in vacuo, which is directly used for the next reaction without further purification After stirring at the same temperature for 0.5 h The organic layer is washed with H2O evaporated in vacuo The residue is purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[2-(6-chloro-2-cyanopyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester (0.82 mmol) and C-spiro[3.5]non-7-ylmethylamine (0.86 mmol) in CH3CN (10 mL) is added K2CO3 (2.2 mmol) at room temperature. After stirring at 80° C. for 12 h, the reaction mixture is cooled to room temperature and diluted with AcOEt. The organic layer is washed twice with H2O and dried over MgSO4 and evaporated in vacuo to give a crude 4-(2-{2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidin-4-yloxy}ethyl)piperidine-1-carboxylic acid tert-butyl ester. the reaction mixture is cooled to room temperature The organic layer is washed twice with H2O dried over MgSO4 evaporated in vacuo