1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(4-Morpholinyl)-4H-1-benzopyran-4-one

Participants

Reaction Steps

EDCI (102 mg, 0.53 mmol) was added in one portion to 8-(1-(3,5-difluorophenylamino) ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (200 mg, 0.35 mmol, enantiomer 2 ([α]D20°-102°, described as a starting material in Example 7.0a), (S)-pyrrolidin-3-ol (0.043 mL, 0.53 mmol) and HOPO (47.1 mg, 0.42 mmol) dissolved in DCM (2 mL) in a screwcap vial. The resulting solution was stirred at RT for 5 min then 50° C. for 30 min. More EDCI (˜50 mg) was added to complete the reaction. The solution was washed with a 10% aq. citric acid solution, water, brine and dried over magnesium sulfate. The solvent was evaporated and the crude product purified by flash chromatography on silica gel (40 g) eluting with 0 to 10% MeOH in DCM. The solvent was evaporated to dryness to afford 8-(1-(3,5-difluorophenylamino)ethyl)-6-(S)-3-hydroxypyrrolidine-1-carbonyl)-2-morpholino-4H-chromen-4-one (95%) as a off-white foam. Mass Spectrum: M+H+ 500. NMR Spectrum (CDCl3): 1.60 (d, 3H), 1.89-2.11 (m, 1H), 2.54 (bs, 0.5H), 2.81 (bs, 0.5H), 3.29-3.43 (m, 2H), 3.51 (bs, 4H), 3.64-3.78 (m, 2H), 3.79-3.91 (m, 5H), 4.42 (bs, 0.5H), 4.54 (bs, 0.5H), 4.59 (bs, 0.5H), 4.70 (bs, 0.5H), 4.87-4.95 (m, 1H), 5.54 (bs, 1H), 5.89-6.01 (m, 2H), 6.09 (dd, 1H), 7.85 (s, 0.5H), 7.87 (s, 0.5H), 8.18 (bs, 0.5H), 8.25 (bs, 0.5H).

Provenance & Evidence