2-bromo-N,N-diethylethanamine

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:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of Example 21 (780 mg, 1.67 mmol) in THF (25 ml) is added sodium hydride (60% dispersion in mineral oil; 653 mg, 2.53 mmol). The mixture is stirred for 1 hour at room temperature, then 2-bromo-N,N-diethylethanamine (653 mg, 2.53 mmol) is added, and the solution is stirred overnight (16 h) at room temperature. The reaction mixture is quenched with methanol (10 ml), concentrated, and the crude product is purified by preparative HPLC. the solution is stirred overnight (16 h) at room temperature The reaction mixture is quenched with methanol (10 ml) concentrated the crude product is purified by preparative HPLC

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

Procedure: To a solution of 4,4,5,5-tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (250 mg, 1.29 mmol) and sodium hydride (61.8 mg, 2.58 mmol) in tetrahydrofuran at 0° C. was added 2-bromo-N,N-diethylethanamine (558 mg, 2.58 mmol). The reaction was allowed to warm up to room temperature and was monitored by LCMS. After 90 minutes there was still no reaction and potassium iodide (1.71 g, 10.3 mmol) was added and the reaction was heated at 50° C. overnight. The reaction mixture was diluted with a large volume of ethyl acetate and water and partitioned. The organic layer containing the product was washed with brine and concentrated in vacuo to give clear thick oil confirmed by LCMS to be 100% pure N,N-diethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethanamine (340 mg, yield 90%, M+1 294.2) was added the reaction was heated at 50° C. overnight partitioned The organic layer containing the product was washed with brine concentrated in vacuo to give clear thick oil

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

Procedure: From 2-chloro-5-[5-(3-chlorothiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamine (0.100 g, 0.320 mmol), anhydrous EtOH (1.3 mL), 2-bromo-N,N-diethylethylamine.HBr (0.334 g, 1.28 mmol) and Et3N (0.230 mL, 1.60 mmol) was obtained 0.006 g (5%) of the title compound as a white solid. 1H NMR (acetone-d6): 8.08 (d, 1H, J=5.5 Hz), 7.48–7.37 (m, 3H), 7.34 (d, 1H, J=5.2 Hz), 2.82–2.80 (m, 4H), 2.62–2.58 (m, 4H), 1.07 (t, 6H, J=7.0 Hz).

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

Procedure: From 2-chloro-5-[5-(3-chlorothiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamine (0.100 g, 0.320 mmol), anhydrous EtOH (1.3 mL), 2-bromo-N,N-diethylethylamine.HBr (0.334 g, 1.28 mmol) and Et3N (0.230 mL, 1.60 mmol) was obtained 0.006 g (5%) of the title compound as a white solid. 1H NMR (acetone-d6): 8.08 (d, 1H, J=5.5 Hz), 7.48–7.37 (m, 3H), 7.34 (d, 1H, J=5.2 Hz), 2.82–2.80 (m, 4H), 2.62–2.58 (m, 4H), 1.07 (t, 6H, J=7.0 Hz).

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

Procedure: To a solution of 5-[2-(3-aminophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrile (20 mg, 45.91 micromol) and N,N-diethyl-2-amino-bromoethane.HBr (12 mg, 45.91 micromol) in THF was added sodium t-butoxide (9 mg, 91.82 micromol) and the eaction was stirred at ambient temperature overnight. TLC indicated conversion to product (10% MeOH:CH2Cl2). The reaction was partitioned between EtOAc and water, the organics were dried over sodium sulfate then concentrated in vacuo. The crude product was purified by chromatography (silica gel, 5% MeOH:CH2Cl2) to afford VI-26 in 33% yield. δ0.95 (bs, 6H), 1.0-1.8 (m, 10H), 2.0 (s, 3H), 2.6 (s, 3H), 2.75 (bs, 2H), 3.4 (s, 1H), 3.6 (bs, 2H), 4.0 (bs, 2H), 5.2 (s, 1H), 6.5 (d, 1H), 6.55 (s, 1H) , 6.6 (d, 1H) , 7.0 (t, 1H) , 8.1 (s, 1H). The reaction was partitioned between EtOAc and water the organics were dried over sodium sulfate then concentrated in vacuo The crude product was purified by chromatography (silica gel, 5% MeOH:CH2Cl2) to afford VI-26 in 33% yield

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

Procedure: To a stirred solution of Example 21 (780 mg, 1.67 mmol) in THF (25 ml) is added sodium hydride (60% dispersion in mineral oil; 653 mg, 2.53 mmol). The mixture is stirred for 1 hour at room temperature, then 2-bromo-N,N-diethylethanamine (653 mg, 2.53 mmol) is added, and the solution is stirred overnight (16 h) at room temperature. The reaction mixture is quenched with methanol (10 ml), concentrated, and the crude product is purified by preparative HPLC. the solution is stirred overnight (16 h) at room temperature The reaction mixture is quenched with methanol (10 ml) concentrated the crude product is purified by preparative HPLC