Water → HCID 68291749, compound

Participants

Reaction Conditions

Reaction Steps

(R)-4-((4-amino-3,3-dimethyl-4-oxobutane-2-yl)amino)-6-bromopyrrolo[1,2-b]pyridazine-3-carboxamide (50 mg, 0.136 mmol) was taken in a sealed tube contained in acetonitrile (8 mL) and water (0.8 ml) mixture was added 4-methoxyphenylboronic acid (37.1 mg, 0.204 mmol), sodium carbonate (43.2 mg, 0.407 mmol). The reaction was degassed for 10 min. Next, PdCl2(TPP)2 (14.90 mg, 0.020 mmol) was added and the reaction mixture was heated to 100° C. and stirred for 30 min. After completion of reaction, it was then quenched with water (30 ml) and extracted into EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and solvent was removed under vacuum. Crude product was purified by prep HPLC purification to get desired product as an off white solid (16 mg, 29.8% yield). 1HNMR (400 MHz, DMSO) δ ppm: 1.16-1.19 (d, J=12 Hz, 6H), 1.23-1.24 (d, J=4.0 Hz, 3H), 3.79 (s, 3H), 4.69-4.73 (t, J=16 Hz, 1H), 6.95-7.01 (m, 3H), 7.214-7.263 (d, J=19.6 Hz, 4H), 7.67-7.70 (d, J=12 Hz, 2H), 8.08 (s, 1H), 8.198 (s, 1H), 10.827-10.851 (d, J=9.6 Hz, 1H). column: Purospherstar RP-18 (4×55) mm, 3 μm. Buffer: 20 mM NH4OAc in Water, Mobile Phase: A-Buffer+ACN (90+10), B-Buffer+ACN (10+90); Flow: 2.5 mL/min, Retention Time: 1.520 min, Purity: 99.46%. HPLC: Column: SUNFIRE C18 (4.6×150) mm, 3.5 micron Buffer: 0.05% TFA in water pH 2.5 Mobile phase: A: Buffer:Acetonitrile (95:5) B: Acetonitrile:buffer (95:5) Flow: 1.0 mL/min Retention Time: 8.269 min Enantioselectivity: 98.66%.

Provenance & Evidence