2-methyl-2-(methylamino)propanamide

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: Compound 20 was synthesized from 4h (251 mg, 0.60 mmol) and 5a (130 mg, 1.08 mmol) as a white solid (176 mg, 60%) in a manner similar to that described in Example 36. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, 2H), 7.46 (d, 1H), 7.28 (m, 3H), 7.22 (d, 1H), 3.49 (s, 3H), 2.42 (s, 3H), 1.42 (s, 6H); ESMS m/z: 495.1 (M+1).

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

Procedure: Compound 19 was synthesized from 4g (248 mg, 0.68 mmol) and 5a (130 mg, 1.08 mmol) as a white solid (121 mg, 39%) in a manner similar to that described in Example 36. 1H NMR (400 MHz, CDCl3) δ 7.39 (d, 1H), 7.20 (dd, 1H), 7.13 (d, 1H), 7.06 (dd, 2H), 6.97 (dd, 2H), 3.43 (s, 3H), 2.33 (s, 3H), 1.36 (s, 6H); ESMS m/z: 445.0 (M+1).

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

Procedure: Compound 14 was synthesized from 4b (249 mg, 0.68 mmol) and 5a (130 mg, 1.08 mmol) as a white solid (152 mg, 49%) in a manner similar to that described in Example 36. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, 1H), 7.30-7.28 (m, 3H), 7.21 (d, 2H), 7.04 (d, 2H), 3.48 (s, 3H), 1.36 (s, 6H); ESMS m/z: 447.0 (M+1)

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

Procedure: To a solution of 4a (1.0 g, 2.62 mmol) in toluene (30 mL) at 0° C. were sequentially added DMF (0.2 mL) and oxalyl chloride (1.48 g, 11.66 mmol) dropwise. The resulting mixture was allowed to warm to room temperature and stirred for 1 h, then transferred slowly to a mixture of 5a (0.50 g, 4.30 mmol) and triethylamine (0.42 g, 4.16 mmol) in THF (30 mL) at 0° C. After the mixture was warmed and stirred at room temperature for 15 h, the reaction was quenched with water and extracted with ethyl acetate (2×30 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude residue (1.22 g), which without purification, underwent intramolecular cyclization by treatment with sodium methoxide (270 mg, 5.00 mmol) in methanol (30 mL) at 60° C. for 4 h. After the reaction was complete, the reaction mixture was concentrated and poured into ice water and the resulting mixture was extracted with ethyl acetate (2×30 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with hexanes/ethyl acetate (1:1) to afford the desired product 6 (0.67 g, 55%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, 1H), 7.25 (d, 2H), 7.22 (dd, 1H), 7.12 (d, 1H), 7.01 (d, 2H), 3.42 (s, 3H), 2.35 (s, 3H), 1.37 (s, 6H); ESMS m/z: 461.0 (M+1). at 0° C. After the mixture was warmed stirred at room temperature for 15 h the reaction was quenched with water extracted with ethyl acetate (2×30 mL) The combined extracts were washed with brine dried over anhydrous sodium sulfate filtered concentrated to give the crude residue (1.22 g), which the reaction mixture was concentrated poured into ice water the resulting mixture was extracted with ethyl acetate (2×30 mL) The combined extracts were washed with brine dried over anhydrous sodium sulfate filtered concentrated The residue was purified by flash chromatography on silica gel with hexanes/ethyl acetate (1:1)