4-Fluoro-3-(trifluoromethyl)aniline → HCID 66823611, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (93) (4.90 g, 29.68 mmol) in SOCl2 (250 mL), CH2Cl2 (50 mL) and DMF (8 drops) was heated under reflux for 3 h. The solvents were then removed by vacuum distillation and the residue was evaporated to dryness. The resulting crude 4-chloro-6-fluoropyrido[3,4-d]pyrimidine was dissolved in CH2Cl2 (50 mL) and iPrOH (120 mL), to which 4-fluoro-3-(trifluoromethyl)aniline (5.85 g, 32.66 mmol) was added before the solution was heated under reflux at 84° C. for 30 min using an air condenser. During reflux the CH2Cl2 was evaporated and the crude product precipitated from the remaining iPrOH as a pale yellow solid. The mixture was cooled to the room temperature, poured into an ice-cold beaker of 5% aqueous Na2CO3 and stirred for 15 min at 0° C. The solid was collected by filtration, washed several times with water and then hexane before being dried in a vacuum oven (45° C.) overnight to give 6-fluoro-N-(4-fluoro-3-(trifluoromethyl)phenyl)pyrido[3,4-d]pyrimidin-4-amine (163) (9.68 g, 100%) as a yellow solid, m.p. 247-249° C. 1H NMR [(CD3)2SO] δ 10.25 (s, 1H), 8.99 (s, 1H), 8.75 (s, 1H), 8.34 (dd, J=6.5, 2.7 Hz, 1H), 8.26-8.30 (m, 1H), 8.24 (s, 1H), 7.60 (t, J=9.7 Hz, 1H). Anal. Calcd for C14H7F5N4: C, 51.54; H, 2.16; N, 17.17%. found: C, 51.37; H, 2.30; N, 16.93%.

Provenance & Evidence