Acetic Anhydride → (S)-N-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)-N-(1-methoxypropan-2-yl)acetamide

Participants

Reaction Steps

A suspension of urea 334 (66 mg, 0.127 mmol) in acetic anhydride (2 ml) was stirred at rt for 2 days. The reaction mixture was quenched by addition of methanol and water, and partitioned with AcOEt. After separation, the organic layer was collected, washed with water, 1N NaOH (×4), water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude solid was purified by flash column chromatography on silica gel (eluent 2% of ammonium hydroxyde in MeOH/DCM: 05/90 to 10/90) to afford the title compound 335 (46 mg, 0.08 mmol, 64% yield) as an off-white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): mixture of rotamers, 8.70 (s, 1H), 8.58-8.48 (m, 2H), 8.34 and 8.30 (2s, 1H), 8.27 and 8.19 (2d, J=8.3 Hz, 1H), 7.85-7.69 (m, 2H), 7.38 (t, J=9.0 Hz, 1H), 7.20 (bd, J=9.0 Hz, 1H), 6.67-6.54 (m, 2H), 4.74-4.16 (m, 3H), 3.41-3.22 (m, 2H), 3.15 and 3.13 (2s, 3H), 2.59-2.52 (m, 1H), 2.16 and 1.96 (2s, 3H), 1.09 and 1.04 (2d, J=6.9 Hz, 3H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H). MS (m/z): 564.4 (M+H).

Provenance & Evidence