Diisopropylethylamine → [(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-pyrido[3,2-d]pyrimidin-4-yl-amine

Participants

Reaction Steps

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.082 g, 0.25 mmol), 4-chloropyrido[3,2-d]pyrimidine (J. Med Chem, 1833, 1996) (0.035 g, 0.21 mmol) and DIPEA (0.174 mL, 1.0 mmol) in IPA (1 mL) was heated to 70° C. in a sealed tube under argon for 1 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with water (2 mL). The aqueous was extracted with EtOAc (10 mL). The combined organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-8% (9:1 MeOH/0.880 NH3) in DCM). Product containing fractions were evaporated and freeze dried to give 317 as an off white solid, (15 mg, 18%). LCMS (Method C): RT 3.55 min [M+H]+ 385.05. 1H NMR δ (ppm) (DMSO-d6): 8.83 (1H, dd, J=4.24, 1.57 Hz), 8.63 (1H, d, J=7.55 Hz), 8.40 (1H, s), 8.11 (1H, dd, J=8.46, 1.57 Hz), 7.84 (1H, dd, J=8.47, 4.24 Hz), 7.74 (1H, dd, J=8.81, 4.85 Hz), 7.59 (2H, d, J=7.53 Hz), 7.50-7.50 (3H, m), 7.12 (1H, ddd, J=9.87, 8.81, 2.53 Hz), 6.86 (1H, dd, J=8.92, 2.51 Hz), 5.59 (1H, dq, J=7.09 Hz), 1.59 (3H, d, J=6.81 Hz)

Provenance & Evidence