2-Fluoro-4-iodoaniline → 6-Fluoro-7-(2-fluoro-4-iodophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid

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Reaction Steps

Compound 1d (240 mg, 1.04 mmol) and 2-fluoro-4-iodoaniline (493 mg, 2.08 mmol) stirred in dry THF (10 ml) at 0° C. under nitrogen. LiHMDS (1M in THF, 3.11 mL, 3.11 mmol) was added dropwise, and the reaction stirred 4 h while warming to RT. The solution was quenched with 1N HCl and extracted with 10% MeOH/CH2Cl2 (3×). Organics were dried (MgSO4) and concentrated in vacuo. Purification by silica gel chromatography (10% to 16% MeOH/CH2Cl2) gave 238 mg (53%) of Example 1 as a tan solid. 1H NMR (400 MHz, MeOD-d4): δ 7.22-7.31 (m, 2H), 6.67 (t, 1H, J=8.0 Hz), 4.06 (t, 2H, J=7.6 Hz), 3.45 (t, 2H, J=7.6 Hz), 2.05-2.15 (m, 2H). MS (ES) [m+H] calc'd for C15H11F2IN2O3, 433. found 433.

Provenance & Evidence