Nitrogen → HCID 86696416, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of [2-(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-phenyl-carbamic acid ethyl ester (354.7 mg, 0.9 mmol), (4-carbamoylphenyl)boronic acid [123088-59-5] (174.2 mg, 1.1 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (368.8 mg, 1.6 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (74.4 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), evaporated, flash chromatographed (silica gel eluted with 10% (v/v) methanol/ethyl acetate) and further purified by preparative RP-HPLC to provide {2-[3-(4-carbamoyl-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-ethyl}-phenyl-carbamic acid ethyl ester as a white powder, mp. 227-228° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03 (t, J=7.07 Hz, 2H) 2.51 (dt, J=3.73, 1.80 Hz, 2H) 3.31 (s, 1H) 3.48 (q, J=6.23 Hz, 2H) 3.91-4.04 (m, 3H) 6.69 (d, J=9.85 Hz, 1H) 7.18-7.35 (m, 5H) 7.76 (d, J=9.85 Hz, 1H) 7.91-8.01 (m, 3H) 8.21 (d, J=8.59 Hz, 2H). 13C NMR (100 MHz, DMSO-d6) δ ppm 14.25, 48.18, 60.95, 112.37, 124.91, 125.75, 126.00, 126.35, 127.18, 127.79, 128.77, 130.81, 131.93, 132.15, 137.57, 141.78, 153.40, 154.85, 167.49. LRMS (ESI) m/z 445.1 [(M+H)]+, calc'd for C24H24N6O3: 444.50.

Provenance & Evidence