Diisopropylethylamine → (S)-N-(1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethyl)-9H-purin-6-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of (5)-1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethylamine (48.5 mg, 0.221 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (52.9 mg, 0.221 mmol), and DIPEA (0.113 mL, 0.663 mmol) in n-butanol (1 mL) was stirred in a sealed vial at 90° C. for 16 h. After cooling to RT, volatiles were removed under reduced pressure. The residue was dissolved in MeOH (3 mL) and the resulting solution was cooled in an ice bath. HCl in isopropanol (1.25 M, 2 mL) was added and the mixture stirred at 0° C. for 1 h and then concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-14% 2M NH3/MeOH in DCM) afforded 398 as a white solid (43.4 mg, 58%). LCMS (Method J): RT 4.80 min [M+H]+ 338.2. 1H NMR ((CD3)2SO, 400 MHz): 12.81 (1H, bs), 8.23 (1H, s), 8.15 (1H, s), 7.96 (1H, d, J=7.8 Hz), 7.37 (1H, dd, J=8.8, 4.2 Hz), 6.92 (1H, dd, J=10.5, 8.8 Hz), 5.80 (1H, bs), 4.29-4.16 (2H, m), 2.87 (2H, t, J=6.1 Hz), 2.16-2.05 (2H, m), 1.68 (3H, d, J=6.8 Hz)

Provenance & Evidence