2-cyclohexylacetamide

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

Procedure: Cyclohexylacetyl chloride (1 mL, 6.52 mmol) was added to solution of NH4OH (˜15M, 5 mL, ˜75 mmol) in EtOAc (5 mL) and satd. NaHCO3 (5 mL) and stirred at RT for 20 minutes. The layers were separated, the aqueous layer extracted with EtOAc (2×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford 2-cyclohexylacetamide (481 mg, 52%) as a white solid. The layers were separated the aqueous layer extracted with EtOAc (2×) the combined organics were dried over Na2SO4 concentrated to dryness

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution 2-cyclohexylacetamide (0.104 g, 0.737 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 70° C. overnight. The mixture was concentrated to dryness, added to a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.154 mL, 1.105 mmol) in THF (3 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The resulting residue was suspended in 60% EtOAc/Hex, sonicated and the solid collected via filtration and dried to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamide (77 mg, 51%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.83 (s, 1H), 10.56 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 2.27 (d, J=7.0 Hz, 2H), 2.02 (s, 3H), 1.73-1.56 (br m, 5H), 1.18-1.13 (m, 4H), 0.97-0.94 (m, 2H); MS (ESI) m/z: 412.2 (M+H+). The mixture was concentrated to dryness extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness sonicated the solid collected via filtration dried

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution 2-cyclohexylacetamide (0.104 g, 0.737 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 70° C. overnight. The mixture was concentrated to dryness, added to a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.154 mL, 1.105 mmol) in THF (3 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The resulting residue was suspended in 60% EtOAc/Hex, sonicated and the solid collected via filtration and dried to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamide (77 mg, 51%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.83 (s, 1H), 10.56 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 2.27 (d, J=7.0 Hz, 2H), 2.02 (s, 3H), 1.73-1.56 (br m, 5H), 1.18-1.13 (m, 4H), 0.97-0.94 (m, 2H); MS (ESI) m/z: 412.2 (M+H+). The mixture was concentrated to dryness extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness sonicated the solid collected via filtration dried

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

Procedure: Aqueous ammonia was added to solution of 2-cyclohexylacetyl chloride (500 mg, 3.11 mmol) in CHCl3 (10 ml). After completion of reaction, the reaction mixture was diluted with CHCl3 (2×30 ml). The organic layer was washed with saturated sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. The organic layer was concentrated under vacuum, crude compound was washed with hexane (2×8 ml) and dried to afford 400 mg (87.8%) of 2-cyclohexylacetamide. After completion of reaction The organic layer was washed with saturated sodium bicarbonate solution, brine dried over anhydrous sodium sulfate The organic layer was concentrated under vacuum, crude compound was washed with hexane (2×8 ml) dried

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

Procedure: Aqueous ammonia was added to solution of 2-cyclohexylacetyl chloride (500 mg, 3.11 mmol) in CHCl3 (10 ml). After completion of reaction, the reaction mixture was diluted with CHCl3 (2×30 ml). The organic layer was washed with saturated sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. The organic layer was concentrated under vacuum, crude compound was washed with hexane (2×8 ml) and dried to afford 400 mg (87.8%) of 2-cyclohexylacetamide. After completion of reaction The organic layer was washed with saturated sodium bicarbonate solution, brine dried over anhydrous sodium sulfate The organic layer was concentrated under vacuum, crude compound was washed with hexane (2×8 ml) dried

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

Procedure: Cyclohexylacetyl chloride (1 mL, 6.52 mmol) was added to solution of NH4OH (˜15M, 5 mL, ˜75 mmol) in EtOAc (5 mL) and satd. NaHCO3 (5 mL) and stirred at RT for 20 minutes. The layers were separated, the aqueous layer extracted with EtOAc (2×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford 2-cyclohexylacetamide (481 mg, 52%) as a white solid. The layers were separated the aqueous layer extracted with EtOAc (2×) the combined organics were dried over Na2SO4 concentrated to dryness

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution 2-cyclohexylacetamide (0.104 g, 0.737 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 70° C. overnight. The mixture was concentrated to dryness, added to a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.154 mL, 1.105 mmol) in THF (3 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The resulting residue was suspended in 60% EtOAc/Hex, sonicated and the solid collected via filtration and dried to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamide (77 mg, 51%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.83 (s, 1H), 10.56 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 2.27 (d, J=7.0 Hz, 2H), 2.02 (s, 3H), 1.73-1.56 (br m, 5H), 1.18-1.13 (m, 4H), 0.97-0.94 (m, 2H); MS (ESI) m/z: 412.2 (M+H+). The mixture was concentrated to dryness extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness sonicated the solid collected via filtration dried