3-(fluoromethyl)azetidine-3-carbonitrile

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 an 8 mL scintillation vial equipped for stirring was added (R)-3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (80 mg, 0.293 mmol) under nitrogen. DMF (0.5 mL), 3-(fluoromethyl)azetidine-3-carbonitrile (93 mg, 0.439 mmol), HOBt (67.2 mg, 0.439 mmol), EDC (84 mg, 0.439 mmol) and N,N-dimethylpyridin-4-amine (53.6 mg, 0.439 mmol) were added and the solution was stirred at 25° C. for 4 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected and lyophilized to afford the title compound as a white solid (34.5 mg, 25.3%). 1H NMR (400 MHz, DMSO-d6) δ 0.78 (dd, J=6.57, 3.79 Hz, 3 H) 0.97 (dd, J=12.88, 6.32 Hz, 3 H) 2.30-2.41 (m, 1 H) 3.99 (dd, J=9.98, 4.42 Hz, 1 H) 4.22 (d, J=9.35 Hz, 2 H) 4.36 (s, 1 H) 4.62-4.71 (m, 1 H) 4.76-4.88 (m, 2 H) 4.87-5.03 (m, 1 H) 5.02-5.09 (m, 1 H) 7.09 (t, J=4.80 Hz, 1 H) 7.88 (dd, J=5.56, 2.27 Hz, 1 H) 8.27 (t, J=5.31 Hz, 1 H) 12.25 (d, J=8.84 Hz, 1 H). [M+H] calc'd for C19H20FN5O2, 370; found, 370.5. To an 8 mL scintillation vial equipped the solution was stirred at 25° C. for 4 h The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%) The fractions were collected

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

Procedure: To an 8 mL scintillation vial equipped for stirring was added (R)-3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (80 mg, 0.293 mmol) under nitrogen. DMF (0.5 mL), 3-(fluoromethyl)azetidine-3-carbonitrile (93 mg, 0.439 mmol), HOBt (67.2 mg, 0.439 mmol), EDC (84 mg, 0.439 mmol) and N,N-dimethylpyridin-4-amine (53.6 mg, 0.439 mmol) were added and the solution was stirred at 25° C. for 4 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected and lyophilized to afford the title compound as a white solid (34.5 mg, 25.3%). 1H NMR (400 MHz, DMSO-d6) δ 0.78 (dd, J=6.57, 3.79 Hz, 3 H) 0.97 (dd, J=12.88, 6.32 Hz, 3 H) 2.30-2.41 (m, 1 H) 3.99 (dd, J=9.98, 4.42 Hz, 1 H) 4.22 (d, J=9.35 Hz, 2 H) 4.36 (s, 1 H) 4.62-4.71 (m, 1 H) 4.76-4.88 (m, 2 H) 4.87-5.03 (m, 1 H) 5.02-5.09 (m, 1 H) 7.09 (t, J=4.80 Hz, 1 H) 7.88 (dd, J=5.56, 2.27 Hz, 1 H) 8.27 (t, J=5.31 Hz, 1 H) 12.25 (d, J=8.84 Hz, 1 H). [M+H] calc'd for C19H20FN5O2, 370; found, 370.5. To an 8 mL scintillation vial equipped the solution was stirred at 25° C. for 4 h The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%) The fractions were collected

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