Sodium Carbonate → N3'-(2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)-[4,4'-bipyridine]-2,3'-diamine

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with a 1:1 mixture of N-(4-bromopyridin-3-yl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine and N-(4-chloropyridin-3-yl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine (Example 29, step 1, 85 mg), (2-aminopyridin-4-yl)boronic acid (44 mg, 0.31 mmol, CombiPhos Catalysis, Inc., Princeton, N.J.), Pd(PPh3)4 (12 mg, 10.6 μmol) and 2 M Na2CO3 (0.33 mL) in dioxane (1.5 mL). The reaction was stirred and heated in a microwave at 130° C. for 25 min. The mixture was diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over anh. Na2SO4, filtered and concentrated. The crude material was purified by prep HPLC method 4. The desired fractions were collected and concentrated. The residue was partitioned between 30 mL of EtOAc and 5 mL of 0.5 M NaOH. The organic solution was washed with brine (5 mL), dried over Na2SO4 and concentrated to afford N3′-(2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)-[4,4′-bipyridine]-2,3′-diamine (15 mg, 17% yield) as an orange solid. MS (ESI, pos. ion) m/z: 415.9 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 9.88 (s, 1 H), 8.34 (d, J=4.89 Hz, 1 H), 8.16 (d, J=5.09 Hz, 1 H), 7.75 (d, J=9.39 Hz, 1 H), 7.39 (m, 2 H), 7.34 (s, 1 H), 7.14 (d, J=4.89 Hz, 1 H), 7.05 (t, J=8.22 Hz, 2 H), 6.78-6.85 (m, 1 H), 6.63 (s, 1 H), 6.53 (dt, J=9.39, 1.76 Hz, 1 H), 4.55 (br., 2 H).

Provenance & Evidence