Nitrogen → HCID 86696420, compound

Participants

Reaction Steps

A solution of 10% (v/v) water in THF (25 mL) was added to a mixture of [2-(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-isopropyl-carbamic acid isopropyl ester (515.1 mg, 1.34 mmol), potassium cyclopropyltrifluoroborate [1065010-87-1] (396.8 mg, 2.7 mmol), cesium carbonate [534-17-8] (1.3 g, 4.0 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (110.4 mg, 0.1 mmol) contained in a 50 mL round bottomed flask. The reaction pot was fitted to a reflux condenser and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated reflux for 4d then cooled and filtered. The filtrate was partitioned between brine and ethyl acetate and the phase separated organic extract dried (MgSO4) and evaporated to give a black oil which was purified by preparatory RP-HPLC to provide 41.6 mg of [2-(3-cyclopropyl-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-isopropyl-carbamic acid isopropyl ester as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.77-0.84 (m, 2H) 0.98-1.06 (m, 2H) 1.20-1.32 (m, 14H) 2.08-2.19 (m, 1H) 3.43-3.50 (m, 2H) 3.50-3.59 (m, 2H) 6.61 (d, J=9.70 Hz, 1H) 7.08 (s, 1H) 7.52 (d, J=9.70 Hz, 1H). LRMS (ESI) m/z 346.2 [(M+H)]+, calc'd for C18H27N6O2: 345.45.

Provenance & Evidence