2-Fluoroaniline → HCID 10309468, compound

Participants

Reaction Steps

A mixture of 3-(2-chloro-phenyl)-4-oxo-3,4-dihydro-thieno[3,2-d]pyrimidine-2-carboxaldehyde (0.435 g, 1.5 mmol), 2-fluoroaniline (0.121 mL, 1.25 mmol), and anhydrous sodium sulfate (2.1 g 15 mmol) in glacial acetic acid (10 mL) was stirred overnight at ambient temperature. Sodium triacetoxyborohydride (0.795 g, 3.75 mmol) was added in one portion and the reaction was stirred for four hours. The reaction was carefully poured into saturated aqueous sodium bicarbonate and repeatedly extracted with methylene chloride. The combined organic phase was washed with water and brine, dried over sodium sulfate and concentrated. The residue was flash chromatographed on silica gel eluting with 2:1 hexane/ethyl acetate. After elution of a 50 mL forerun, 15 mL fractions were collected. Fractions 3-12 were combined and concentrated to afford 0.190 g (39%) of 3-(2-chloro-phenyl)-2-[(2-fluoro-phenylamino)-methyl]-3H-thieno[3,2-d]pyrimidin-4-one as a tan solid which had: mp 175-176° C.; 1H NMR δ 7.84 (d, J=5.5 Hz, 1 H), 7.66 (dd, J=1.5, 8 Hz, 1 h), 7.53 (sym m, 2 H), 7.42 (d, J=5.5 Hz, 1 H), 7.37 (dd, J=2, 7 Hz, 1 H), 6.97 (ddd, J=1.5, 8, 11.5 Hz, 1 H), 6.90 (t, J=7.5 Hz, 1 H), 6.63 (sym m, 1 H), 6.40 (dt, J=1.5, 9 Hz, 1 H), 5.17 (br s, 1 H), 3.96 (dd, J=5.5, 17 Hz, 1 H), 3.87 (dd, J=5, 17 Hz, 1 H). Analysis calculated for C19H13ClFN3OS: C, 59.15; H, 3.40; N, 10.89. Found: C, 58.96; H, 3.41; N, 11.17.

Provenance & Evidence