4-Methylmorpholine → 6-Fluoro-7-(2-fluoro-4-iodophenylamino)-8-(3-hydroxyazetidine-1-carbonyl)-2,3-dihydroindolizin-5(1H)-one

Participants

Reaction Conditions

Reaction Steps

Example 1 (100 mg, 0.23 mmol) was added to a suspension of 3-hydroxyazetidine hydrochloride (50 mg, 0.46 mmol), HATU (132 mg, 0.35 mmol), and N-methylmorpholine (0.13 mL, 1.15 mmol) in DMF (3 mL). The reaction was heated to 75° C. for 5 hours and then concentrated in vacuo. The residue was taken up in DMSO (1.5 mL) and methanol (1.5 mL) and purified via preparative HPLC (25/70 acetonitrile/water) to give 74 mg (76%) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 8.11 (s, 1H), 7.59 (dd, 1H, J=10.6, 1.8 Hz), 7.72 (dd, 1H, J=8.6, 1.7 Hz), 6.88 (t, 1H, J=8.3 Hz), 5.32 (s, 1H), 4.31-4.48 (m, 2H), 4.05-4.15 (m, 1H), 3.98 (t, 2H, J=6.6 Hz), 3.83-3.94 (m, 1H), 3.72 (m, 1H), 3.50 (m, 1H), 2.89-3.06 (m, 2H), 2.06-2.12 (m, 2H). MS (ES) [m+H] calc'd for C18H16F2IN3O3, 488. found 488.

Provenance & Evidence