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

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Reaction Steps

Compound 8d (183 mg, 1.04 mmol) and 2-fluoro-4-iodoaniline (384 mg, 1.62 mmol) stirred in dry THF (8 ml) at 0° C. under nitrogen. LiHMDS (1M in THF, 2.4 mL, 2.4 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 20% MeOH/CH2Cl2) gave 76 mg (22%) of compound 8e as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ7.57 (d, 1H, J=9.1 Hz), 7.37 (d, 1H, J=8.3 Hz), 6.38 (t, 1H, J=9.0 Hz), 4.00 (t, 2H, J=7.6 Hz), 3.41 (t, 2H, J=8.1 Hz), 2.06-2.09 (m, 2H), 1.61 (s, 3H). MS (ES) [m+H] calc'd for C16H14FIN2O3, 429. found 429.

Provenance & Evidence