Diisopropylethylamine → HCID 178422875, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-1-(7-fluoro-4-methyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethylamine (15.8 mg, 0.0677 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (17.8 mg, 0.0745 mmol), and DIPEA (0.0346 mL, 0.20 mmol) in n-butanol (0.5 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 (1.5 mL) and cooled in an ice bath. HCl in isopropanol (1.25 M, 1 mL) was added and the mixture stirred at 0° C. for 90 min 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 2-12% 2M NH3/MeOH in DCM) afforded 407 as a white solid (8 mg, 34%). Analytical data shows the product to be a mixture of diastereomers (ratio ˜1:1) which could be separated. LCMS (Method K): RT 2.59 & 2.62 min [M+H]+ 352. 1H NMR (CD3OD, 400 MHz): 8.25 & 8.24 (1H, 2 s), 8.10 & 8.08 (1H, 2 s), 7.39-7.35 (1H, m), 6.96-6.91 (1H, m), 5.93 & 5.82 (1H, 2 bs), 5.26-5.21 & 4.93-4.87 (1H, 2 m), 3.09-3.03 (1H, m), 2.97-2.88 (1H, m), 2.27-2.21 (1H, m), 2.15-2.03 (1H, m), 1.83 & 1.78 (3H, 2 d, J=6.9 Hz), 1.45 & 1.41 (3H, 2 d, J=6.7 Hz)

Provenance & Evidence