Hydrochloric Acid → HCID 178461932, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[2-((S)-1-aminoethyl)-6-fluorobenzoimidazol-1-yl]cyclohexanecarbonitrile (100 mg, 0.35 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (91 mg, 0.38 mmol) and DIPEA (0.10 mL, 0.72 mmol) in n-butanol (0.7 mL) was heated for 48 h at 105° C. After cooling to RT, the crude reaction mixture was treated with 4N HCl in dioxane (0.5 mL) and stirred for 1 h at RT. The crude mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-8% MeOH in DCM), then triturated with hot EtOAc and purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 0-40%, 0.1% HCO2H in acetonitrile/water) to afford 174 as a white solid (26 mg, 18%). LCMS (Method K): RT 2.93 min [M+H]+ 405.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.45 (1H, s), 8.34-7.94 (3H, m), 7.71-7.56 (2H, m), 7.05-6.96 (1H, m), 5.96 (1H, bs), 4.62-4.59 (1H, m), 3.09-2.95 (1H, m), 2.38-2.25 (1H, m), 2.21-2.07 (2H, m), 1.93 (1H, bd, J=12.75 Hz), 1.84 (1H, bd, J=12.00 Hz), 1.73-1.65 (5H, m), 1.02 (1H, bs). Broad signals due to presence of rotamers/tautomers

Provenance & Evidence