1-(2-methylpropyl)piperidin-4-one

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol

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

Procedure: (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with 1-(2-methylpropyl)-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-isobutyl-piperidin-4-yl)-methyl-amine as a solid (48% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethylether and methanol to give 346 as a solid (60% yield). NMR (CDCl3, 400 MHz), 0.91 (6H, d, J=6.6), 1.587-1.70 (2H, m), 1.71-1.79 (3H, m), 1.89 (2H, t, J=11.7), 2.07 (2H, d, J=7.3), 2.37 (3H, s), 2.48-2.54 (1H, m), 2.96 (2H, d, J 11.6), 3.88-3.90 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.22 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=497 The resulting crude solid was triturated with diethyl ether and methanol