N-(2-methoxyethyl)-N-methylpiperidin-4-amine

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: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carbaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using the general reductive amination procedure to yield [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl-amine, which was reacted with 2-aminopyrimidine-5-boronic acid, pinacol ester in General Procedure A. Purification on silica yielded 397. NMR (CDCl3); 1.55-1.58 (2H, m), 1.71-1.74 (2H, m), 2.02-2.05 (2H, m), 2.30 (3H, s), 2.41-2.43 (1H, m), 2.62 (2H, t), 3.00 (2H, d), 3.39 (3H, s), 3.46 (2H, t), 3.75 (2H, s), 3.85-3.89 (4H, m), 3.92-3.96 (4H, m), 5.23 (2H, s, br.), 7.12 (1H, s), 9.30 (2H, s). MS ESI m/z 499 (MH+, 100%)

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with methyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-yl]-carbamic acid tert-butyl ester according to General Procedure A. The resulting solid was purified by mass directed chromatography to give 368 as an off white solid (14% yield). NMR (CDCl3, 400 MHz), 1.59-1.62 (2H, m), 1.64-1.67 (2H, m), 2.04-2.07 (2H, m), 2.34 (3H, s), 2.37-2.42 (1H, m), 2.66-2.69 (2H, m), 3.02-3.05 (2H, m), 3.10 (3H, d, J=4.8), 3.37 (3H, s), 3.48-3.51 (2H, m), 3.74 (2H, s), 3.87-3.89 (4H, m), 3.93-3.95 (4H, m), 5.33-5.34 (1H, m), 7.10 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=513

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with methyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-carbamic acid tert-butyl ester according to General Procedure A. The resulting solid was triturated with diethyl ether to give 367 as an off white solid (35% yield). NMR (DMSO, 400 MHz), 1.38-1.50 (2H, m), 1.60-1.66 (2H, m), 1.97-2.03 (2H, m), 2.09 (2H, s), 2.19 (3H, s), 2.24-2.33 (1H, m), 2.55 (2H, dd, J=7.8 and 6.2), 2.84 (3H, d, J=4.8), 2.88-2.94 (2H, m), 3.31-3.36 (2H, m), 3.71 (2H, s), 3.75-3.79 (4H, m), 3.86-3.89 (4H, m), 6.50 (1H, d, J=8.8), 6.90-6.94 (1H, m), 7.43 (1H, s), 8.26 (1H, dd, J=8.8 and 2.3), 9.00 (1H, d, J=2.1). MS: (ESI+): MH+=512

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

実験手順: (2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde) was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethyl ether and methanol to give 366 as an off white solid (53% yield). NMR (CDCl3, 400 MHz), 1.59-1.70 (2H, m), 1.78-1.81 (2H, m), 2.10 (2H, t, J=12.3), 2.37 (3H, s), 2.42-2.48 (1H, m), 2.70 (2H, t, J=5.9), 3.07 (2H, d, J=11.3), 3.41 (3H, s), 3.49-3.54 (2H, m), 3.78 (2H, s), 3.92-3.94 (4H, m), 3.97-4.00 (4H, m), 4.67 (2H, br s), 6.60 (1H, d, J=8.9), 7.13 (1H, s), 8.51 (1H, dd, J=8.6 and 2.2), 9.20 (1H, d, J=1.6). MS: (ESI+): MH+=498

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

実験手順: Reaction between 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde 10 (Example 3) and (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine (Example 187) using General Procedure B-3 yielded 1-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N-(2-methoxyethyl)-N-methylpiperidin-4-amine.

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

実験手順: Reaction between 2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carbaldehyde (General Procedure D-2) and (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using General Procedure B-3 yielded 1-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)-N-(2-methoxyethyl)-N-methylpiperidin-4-amine.

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carbaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using the general reductive amination procedure to yield [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl-amine, which was reacted with 2-aminopyrimidine-5-boronic acid, pinacol ester in General Procedure A. Purification on silica yielded 397. NMR (CDCl3); 1.55-1.58 (2H, m), 1.71-1.74 (2H, m), 2.02-2.05 (2H, m), 2.30 (3H, s), 2.41-2.43 (1H, m), 2.62 (2H, t), 3.00 (2H, d), 3.39 (3H, s), 3.46 (2H, t), 3.75 (2H, s), 3.85-3.89 (4H, m), 3.92-3.96 (4H, m), 5.23 (2H, s, br.), 7.12 (1H, s), 9.30 (2H, s). MS ESI m/z 499 (MH+, 100%)

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carbaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using the general reductive amination procedure to yield [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl-amine, which was reacted with 2-aminopyrimidine-5-boronic acid, pinacol ester in General Procedure A. Purification on silica yielded 397. NMR (CDCl3); 1.55-1.58 (2H, m), 1.71-1.74 (2H, m), 2.02-2.05 (2H, m), 2.30 (3H, s), 2.41-2.43 (1H, m), 2.62 (2H, t), 3.00 (2H, d), 3.39 (3H, s), 3.46 (2H, t), 3.75 (2H, s), 3.85-3.89 (4H, m), 3.92-3.96 (4H, m), 5.23 (2H, s, br.), 7.12 (1H, s), 9.30 (2H, s). MS ESI m/z 499 (MH+, 100%)

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with methyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-yl]-carbamic acid tert-butyl ester according to General Procedure A. The resulting solid was purified by mass directed chromatography to give 368 as an off white solid (14% yield). NMR (CDCl3, 400 MHz), 1.59-1.62 (2H, m), 1.64-1.67 (2H, m), 2.04-2.07 (2H, m), 2.34 (3H, s), 2.37-2.42 (1H, m), 2.66-2.69 (2H, m), 3.02-3.05 (2H, m), 3.10 (3H, d, J=4.8), 3.37 (3H, s), 3.48-3.51 (2H, m), 3.74 (2H, s), 3.87-3.89 (4H, m), 3.93-3.95 (4H, m), 5.33-5.34 (1H, m), 7.10 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=513

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

実験手順: 2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with methyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-carbamic acid tert-butyl ester according to General Procedure A. The resulting solid was triturated with diethyl ether to give 367 as an off white solid (35% yield). NMR (DMSO, 400 MHz), 1.38-1.50 (2H, m), 1.60-1.66 (2H, m), 1.97-2.03 (2H, m), 2.09 (2H, s), 2.19 (3H, s), 2.24-2.33 (1H, m), 2.55 (2H, dd, J=7.8 and 6.2), 2.84 (3H, d, J=4.8), 2.88-2.94 (2H, m), 3.31-3.36 (2H, m), 3.71 (2H, s), 3.75-3.79 (4H, m), 3.86-3.89 (4H, m), 6.50 (1H, d, J=8.8), 6.90-6.94 (1H, m), 7.43 (1H, s), 8.26 (1H, dd, J=8.8 and 2.3), 9.00 (1H, d, J=2.1). MS: (ESI+): MH+=512

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

実験手順: (2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde) was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethyl ether and methanol to give 366 as an off white solid (53% yield). NMR (CDCl3, 400 MHz), 1.59-1.70 (2H, m), 1.78-1.81 (2H, m), 2.10 (2H, t, J=12.3), 2.37 (3H, s), 2.42-2.48 (1H, m), 2.70 (2H, t, J=5.9), 3.07 (2H, d, J=11.3), 3.41 (3H, s), 3.49-3.54 (2H, m), 3.78 (2H, s), 3.92-3.94 (4H, m), 3.97-4.00 (4H, m), 4.67 (2H, br s), 6.60 (1H, d, J=8.9), 7.13 (1H, s), 8.51 (1H, dd, J=8.6 and 2.2), 9.20 (1H, d, J=1.6). MS: (ESI+): MH+=498