Nitrogen → HCID 86696343, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of N-(3-((3-bromoimidazo[1,2-b]pyridazin-6-yl)amino)propyl)-N-isopropylacetamide (219.2 mg, 0.6 mmol), (5-acetylthiophen-2-yl)boronic acid [206551-43-1] (128.4 mg, 0.8 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (266.5 mg, 1.3 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), complex with dichloromethane [95464-05-4] (53.6 mg, 0.1 mmol) contained in a 25 mL round bottomed flask was added a solution of 30% (v/v) water in 1,2-dimethoxyethane (13 mL) and a magnetic stir bar. The reaction pot was fitted to a reflux condenser, lowered into an ambient temperature oil bath, and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated to an oil bath temperature of 85° C. for 17 h then cooled and partitioned between brine and ethyl acetate. The phase separated extract was dried (MgSO4) and evaporated to yield a dark brown solid. Product was purified by preparative RP-HPLC. Purified chromatography fractions were combined and partitioned between aqueous saturated sodium bicarbonate and ethyl acetate. The organic extract dried (CaSO4) and evaporated to provide N-(3-((3-(5-acetylthiophen-2-yl)imidazo[1,2-b]pyridazin-6-yl)amino)propyl)-N-isopropylacetamide as 45.7 mg of yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.05-1.20 (m, 4H) 1.24 (br. s., 1H) 1.86-2.03 (m, 4H) 2.49-2.56 (m, 6H) 3.24-3.48 (m, 5H) 6.76 (dd, J=9.73, 1.14 Hz, 1H) 7.33-7.43 (m, 1H) 7.79-7.84 (m, 1H) 7.97 (d, J=4.04 Hz, 1H) 8.14 (d, J=5.05 Hz, 1H). LRMS (ESI) m/z 400.2 [(M+H)]+, calc'd for C20H25N5O2S: 399.52.

Provenance & Evidence