2-methyl-4-methylsulfonylbutan-2-amine

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

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

Procedure: A solution of 1-(3-fluoro-2-methylquinoxalin-5-yl)ethanone (126g, 300 mg, 1.469 mmol), 2-methyl-4-(methylsulfonyl)butan-2-amine (338b, 486 mg, 2.94 mmol), and N-ethyl-N-isopropylpropan-2-amine (1.02 mL, 5.88 mmol) in NMP (2.94 mL) was stirred at 120° C. for 16 h when product and a small amount of hydrolysis were observed via lcms. The reaction mixture was diluted with DCM (150 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (3×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM to 2% 2 M NH3 in MeOH/DCM to give 1-(2-methyl-3-((2-methyl-4-(methylsulfonyl)butan-2-yl)amino)quinoxalin-5-yl)ethanone (338c, 513 mg, 1.47 mmol, 100% yield) as a red oil contaminated with NMP. 1H NMR (400 MHz, CDCl3) δ ppm 1.56 (s, 6H) 2.56 (s, 3H) 2.62-2.68 (m, 2H) 2.78 (s, 3H) 2.83 (s, 3H) 2.94-3.01 (m, 2H) 4.82 (s, 1H) 7.40 (dd, J=8.12, 7.34 Hz, 1H) 7.70 (dd, J=7.34, 1.47 Hz, 1H) 7.92 (dd, J=8.12, 1.47 Hz, 1H). MS (ESI, pos. ion) m/z: 350.2 (M+1). a small amount of hydrolysis added to a separatory funnel washed with saturated aq. NaHCO3 (3×100 mL) the organic layer was separated dried over Na2SO4 concentrated was purified

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

Procedure: A solution of 1-(3-fluoro-2-methylquinoxalin-5-yl)ethanone (126g, 300 mg, 1.469 mmol), 2-methyl-4-(methylsulfonyl)butan-2-amine (338b, 486 mg, 2.94 mmol), and N-ethyl-N-isopropylpropan-2-amine (1.02 mL, 5.88 mmol) in NMP (2.94 mL) was stirred at 120° C. for 16 h when product and a small amount of hydrolysis were observed via lcms. The reaction mixture was diluted with DCM (150 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (3×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM to 2% 2 M NH3 in MeOH/DCM to give 1-(2-methyl-3-((2-methyl-4-(methylsulfonyl)butan-2-yl)amino)quinoxalin-5-yl)ethanone (338c, 513 mg, 1.47 mmol, 100% yield) as a red oil contaminated with NMP. 1H NMR (400 MHz, CDCl3) δ ppm 1.56 (s, 6H) 2.56 (s, 3H) 2.62-2.68 (m, 2H) 2.78 (s, 3H) 2.83 (s, 3H) 2.94-3.01 (m, 2H) 4.82 (s, 1H) 7.40 (dd, J=8.12, 7.34 Hz, 1H) 7.70 (dd, J=7.34, 1.47 Hz, 1H) 7.92 (dd, J=8.12, 1.47 Hz, 1H). MS (ESI, pos. ion) m/z: 350.2 (M+1). a small amount of hydrolysis added to a separatory funnel washed with saturated aq. NaHCO3 (3×100 mL) the organic layer was separated dried over Na2SO4 concentrated was purified

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

Procedure: At RT, Pd/C (1.262 g of 10% wt., 10.65 mmol) was added to a solution of 3-methyl-1-(methylsulfonyl)-3-nitrobutane (338a, 2.08 g, 10.65 mmol) in EtOH (53.3 mL) and DCM (53.3 mL). The reaction mixture was placed under hydrogen (46 psi) in a carbonate jacketed reaction vessel at RT for 16 h when the pressure had reduced to ambient pressure. The reaction vessel was pressurized again to 50 psi hydrogen for 3 d when the pressure had reduced to 40 psi. The mixture was filtered through a pad of Celite, covered with sand, and washed with DCM then MeOH. The filtrate was distilled to first remove the DCM and MeOH before a white solid was observed; this was filtered, washed with DCM, and dried in vacuo to give 2-methyl-4-(methylsulfonyl)butan-2-amine (338b, 1.62 g, 9.80 mmol, 92% yield) as a crystalline white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (s, 6H) 2.00 (d, J=17.21 Hz, 1H) 2.00 (t, J=4.11 Hz, 1H) 3.02 (s, 3H) 3.29 (d, J=17.21 Hz, 1H) 3.29 (t, J=4.50 Hz, 1H) 8.20 (br. s., 2H). MS (ESI, pos. ion) m/z: 166.2 (M+1). reaction vessel at RT for 16 h when the pressure The mixture was filtered through a pad of Celite washed with DCM The filtrate was distilled to first remove the DCM and MeOH before a white solid this was filtered washed with DCM dried in vacuo

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethyloxy-pyridine-2-carboxylic acid (Example 42a) and 2-methyl-4-(methylsulfonyl)-2-butanamine (CAN 1250515-16-2) as starting materials; LC-MS (UV peak area/ESI) 95%, 381.1843 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethyloxy-pyridine-2-carboxylic acid (Example 42a) and 2-methyl-4-(methylsulfonyl)-2-butanamine (CAN 1250515-16-2) as starting materials; LC-MS (UV peak area/ESI) 95%, 381.1843 (M+H)+.

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

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

Procedure: A solution of 1-(3-fluoro-2-methylquinoxalin-5-yl)ethanone (126g, 300 mg, 1.469 mmol), 2-methyl-4-(methylsulfonyl)butan-2-amine (338b, 486 mg, 2.94 mmol), and N-ethyl-N-isopropylpropan-2-amine (1.02 mL, 5.88 mmol) in NMP (2.94 mL) was stirred at 120° C. for 16 h when product and a small amount of hydrolysis were observed via lcms. The reaction mixture was diluted with DCM (150 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (3×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM to 2% 2 M NH3 in MeOH/DCM to give 1-(2-methyl-3-((2-methyl-4-(methylsulfonyl)butan-2-yl)amino)quinoxalin-5-yl)ethanone (338c, 513 mg, 1.47 mmol, 100% yield) as a red oil contaminated with NMP. 1H NMR (400 MHz, CDCl3) δ ppm 1.56 (s, 6H) 2.56 (s, 3H) 2.62-2.68 (m, 2H) 2.78 (s, 3H) 2.83 (s, 3H) 2.94-3.01 (m, 2H) 4.82 (s, 1H) 7.40 (dd, J=8.12, 7.34 Hz, 1H) 7.70 (dd, J=7.34, 1.47 Hz, 1H) 7.92 (dd, J=8.12, 1.47 Hz, 1H). MS (ESI, pos. ion) m/z: 350.2 (M+1). a small amount of hydrolysis added to a separatory funnel washed with saturated aq. NaHCO3 (3×100 mL) the organic layer was separated dried over Na2SO4 concentrated was purified

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

Procedure: At RT, Pd/C (1.262 g of 10% wt., 10.65 mmol) was added to a solution of 3-methyl-1-(methylsulfonyl)-3-nitrobutane (338a, 2.08 g, 10.65 mmol) in EtOH (53.3 mL) and DCM (53.3 mL). The reaction mixture was placed under hydrogen (46 psi) in a carbonate jacketed reaction vessel at RT for 16 h when the pressure had reduced to ambient pressure. The reaction vessel was pressurized again to 50 psi hydrogen for 3 d when the pressure had reduced to 40 psi. The mixture was filtered through a pad of Celite, covered with sand, and washed with DCM then MeOH. The filtrate was distilled to first remove the DCM and MeOH before a white solid was observed; this was filtered, washed with DCM, and dried in vacuo to give 2-methyl-4-(methylsulfonyl)butan-2-amine (338b, 1.62 g, 9.80 mmol, 92% yield) as a crystalline white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (s, 6H) 2.00 (d, J=17.21 Hz, 1H) 2.00 (t, J=4.11 Hz, 1H) 3.02 (s, 3H) 3.29 (d, J=17.21 Hz, 1H) 3.29 (t, J=4.50 Hz, 1H) 8.20 (br. s., 2H). MS (ESI, pos. ion) m/z: 166.2 (M+1). reaction vessel at RT for 16 h when the pressure The mixture was filtered through a pad of Celite washed with DCM The filtrate was distilled to first remove the DCM and MeOH before a white solid this was filtered washed with DCM dried in vacuo

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethyloxy-pyridine-2-carboxylic acid (Example 42a) and 2-methyl-4-(methylsulfonyl)-2-butanamine (CAN 1250515-16-2) as starting materials; LC-MS (UV peak area/ESI) 95%, 381.1843 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethyloxy-pyridine-2-carboxylic acid (Example 42a) and 2-methyl-4-(methylsulfonyl)-2-butanamine (CAN 1250515-16-2) as starting materials; LC-MS (UV peak area/ESI) 95%, 381.1843 (M+H)+.

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