1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one

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

Procedure: To an ice cold solution of 4-(trifluoromethyl)phenyl isocyanate (56.1 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (64 mg, 55%) as a white solid. Mp 207.9-209.3° C. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.57 (m, 4H), 6.40 (d, J=7.6 Hz, 1H), 4.28 (brd, J=12.4 Hz, 1H), 3.96 (brd, J=13.6 Hz, 1H), 3.78-3.70 (m, 1H), 3.18 (t, J=11.6 Hz, 1H), 2.82 (t, J=11.0 Hz, 1H), 2.67-2.60 (m, 1H), 1.89 (d, J=10.8 Hz, p 1H), 1.83 (d, J=10.4 Hz, 1H), 1.56-1.42 (m, 2H), 1.42-1.31 (m, 2H), 1.31-1.16 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 M Hz, DMSO-d6) −60.324 (s). followed by extraction with EtOAc Flash chromatography eluted with 50:1 DCM MeOH followed by recrystallization from acetone

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

Procedure: To an ice cold solution of 4-(trifluoromethyl)phenyl isocyanate (56.1 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (64 mg, 55%) as a white solid. Mp 207.9-209.3° C. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.57 (m, 4H), 6.40 (d, J=7.6 Hz, 1H), 4.28 (brd, J=12.4 Hz, 1H), 3.96 (brd, J=13.6 Hz, 1H), 3.78-3.70 (m, 1H), 3.18 (t, J=11.6 Hz, 1H), 2.82 (t, J=11.0 Hz, 1H), 2.67-2.60 (m, 1H), 1.89 (d, J=10.8 Hz, p 1H), 1.83 (d, J=10.4 Hz, 1H), 1.56-1.42 (m, 2H), 1.42-1.31 (m, 2H), 1.31-1.16 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 M Hz, DMSO-d6) −60.324 (s). followed by extraction with EtOAc Flash chromatography eluted with 50:1 DCM MeOH followed by recrystallization from acetone

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

Procedure: To an ice cold solution of 4-(trifluoromethoxy)phenyl isocyanate (60.9 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (65 mg, 54%) as a white solid. Mp 167.0-167.4° C. 1H NMR (600 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 6.28 (d, J=7.8 Hz, 1H), 4.27 (brd, J=13.2 Hz, 1H), 3.95 (brd, J=15.6 Hz, 1H), 3.75-3.69 (m, 1H), 3.18 (t, J=11.1 Hz, 1H), 2.81 (t, J=10.8 Hz, 1H), 2.68-2.60 (m, 1H), 1.88 (d, J=10.8 Hz, 1H), 1.82 (d, J=10.8 Hz, 1H), 1.51-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.10 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 MHz, DMSO-d6) −57.545 (s). followed by extraction with EtOAc Flash chromatography eluted with 50:1 DCM MeOH followed by recrystallization from acetone

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

Procedure: To an ice cold solution of 4-(trifluoromethyl)phenyl isocyanate (56.1 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (64 mg, 55%) as a white solid. Mp 207.9-209.3° C. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.57 (m, 4H), 6.40 (d, J=7.6 Hz, 1H), 4.28 (brd, J=12.4 Hz, 1H), 3.96 (brd, J=13.6 Hz, 1H), 3.78-3.70 (m, 1H), 3.18 (t, J=11.6 Hz, 1H), 2.82 (t, J=11.0 Hz, 1H), 2.67-2.60 (m, 1H), 1.89 (d, J=10.8 Hz, p 1H), 1.83 (d, J=10.4 Hz, 1H), 1.56-1.42 (m, 2H), 1.42-1.31 (m, 2H), 1.31-1.16 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 M Hz, DMSO-d6) −60.324 (s). followed by extraction with EtOAc Flash chromatography eluted with 50:1 DCM MeOH followed by recrystallization from acetone

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

Procedure: To an ice cold solution of 4-(trifluoromethoxy)phenyl isocyanate (60.9 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (65 mg, 54%) as a white solid. Mp 167.0-167.4° C. 1H NMR (600 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 6.28 (d, J=7.8 Hz, 1H), 4.27 (brd, J=13.2 Hz, 1H), 3.95 (brd, J=15.6 Hz, 1H), 3.75-3.69 (m, 1H), 3.18 (t, J=11.1 Hz, 1H), 2.81 (t, J=10.8 Hz, 1H), 2.68-2.60 (m, 1H), 1.88 (d, J=10.8 Hz, 1H), 1.82 (d, J=10.8 Hz, 1H), 1.51-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.10 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 MHz, DMSO-d6) −57.545 (s). followed by extraction with EtOAc Flash chromatography eluted with 50:1 DCM MeOH followed by recrystallization from acetone