1-ethylpiperidin-4-one

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

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

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

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

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

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

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

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-bromo-3-(1-methylethoxy)benzene (5.0 g, 23 mmol) in anhydrous tetrahydrofuran (50 ml) at −78° C. under an atmosphere of nitrogen was added n-butyllithium (1.6M in hexane, 13.7 ml, 22 mmol) dropwise. The reaction mixture was stirred for 1 h at −78° C., before N-ethyl-4-piperidone (2.95 ml, 22 mmol) was added dropwise at −78° C. over 15 minutes, and the reaction mixture was then warmed to −20° C. over 30 minutes. The solution was poured onto 2N aqueous hydrochloric acid (35 ml) and this was further acidified to pH 1 with concentrated hydrochloric acid. Hexane (50 ml) was added and the two layers were separated. The organic layer was discarded and the pH of the aqueous layer was adjusted to 14 using sodium hydroxide pellets. The basic aqueous layer was extracted with hexane:diethyl ether (1:1, 5×50 ml) and the combined extracts were dried (MgSO4) and concentrated to give the title compound as a crude oil (4.2 g, 73% crude yield) which was used without further purification. was added dropwise at −78° C. over 15 minutes the two layers were separated The basic aqueous layer was extracted with hexane:diethyl ether (1:1, 5×50 ml) the combined extracts were dried (MgSO4) concentrated

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

Procedure: A solution of 100 g (0.789 mol) of 1-ethyl-4-oxopiperidine in 1000 mL of acetone was stirred at rt in a water bath. To this was added 62.2 mL (142 g, 1 mol) of methyl iodide, dropwise at such a rate to keep the temperature below 30 degrees. A precipitate developed within minutes and the mixture was stirred at rt for 4 h. The mixture was filtered and the precipitate washed with acetone and dried to afford the title compound as a white solid. Mass spectrum (ESI) 142 (M+). the temperature below 30 degrees A precipitate developed within minutes The mixture was filtered the precipitate washed with acetone dried

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-ethyl-4-piperidone using standard reductive amination conditions. The resulting crude solid was triturated with a small amount of diethyl ether and methanol to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-(1-ethyl-piperidin-4-yl)-methyl-amine as a solid (50% 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 347 as a solid (75% yield). NMR (CDCl3, 400 MHz), 1.10 (3H, t, J=7.2), 1.56-1.73 (2H, m), 1.84-1.95 (4H, m), 2.38 (3H, s), 2.42 (2H, q, J=7.0), 2.51-2.58 (1H, m), 3.06 (2H, d, J=11.8), 3.88-3.91 (4H, m), 3.93 (2H, s), 4.03-4.06 (4H, m), 5.21 (2H, br s), 7.27 (1H, s), 9.30 (2H, s). MS: (ESI+): MH+=469 The resulting crude solid was triturated with a small amount of diethyl ether and methanol

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

Procedure: 1-Ethyl-4-piperidone (500 mg, 3.93 mmol) was mixed with 1-methyl-3,5-dinitro-2-pyridone (392 mg, 1.97 miol) in 1M methanolic ammonia (40 mL, 40 mmol) and heated at reflux for 3 h. The solvent was evaporated off and the residue was suspended in CHCl3 and flash chromatographed over silica gel (32 g) eluting with EtOAc to afford an orange solid (379 mg, 93% yield). heated at reflux for 3 h The solvent was evaporated off flash chromatographed over silica gel (32 g) eluting with EtOAc

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