Nitrogen → HCID 89802612, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of [4-(3-bromo-pyrazolo[1,5-a]pyrimidin-5-yl)-piperazin-1-yl]-pyrrolidin-1-yl-methanone (381.0 mg, 01.0 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine [874186-98-8] (512.7 mg, 2.5 mmol), copper chloride [7758-89-6] (99.4 mg, 1.0 mmol), cesium carbonate [534-17-8] (651.8 mg, 2.0 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (82.1 mg, 0.1 mmol) contained in a 25 mL round bottomed flask was added anhydrous DMF 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 100° C. for 17 h then cooled and partitioned between brine and ethyl acetate. The phase separated extract was dried (MgSO4) and evaporated to afford a brown oil which was purified by preparative RP-HPLC. Isolated product was dissolved in methanol, diluted with concentrated hydrochloric acid, evaporated to dryness, redissolved in methanol and precipitated by the addition of diethyl ether. Filtration of the precipitate yielded 83.2 mg of [4-(3-pyridin-2-yl-imidazo[1,2-b]pyridazin-6-yl)-piperazin-1-yl]-pyrrolidin-1-yl-methanone dihydrochloride salt as a light yellow powder, mp. 202-203° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.73-1.84 (m, 4H) 3.33 (t, J=6.44 Hz, 4H) 3.36-3.43 (m, 4H) 3.62-3.72 (m, 4H) 7.45-7.52 (m, 1H) 7.66 (d, J=10.11 Hz, 1H) 8.08 (td, J=7.83, 1.77 Hz, 1H) 8.18 (d, J=10.10 Hz, 1H) 8.54 (s, 1H) 8.60 (d, J=8.08 Hz, 1H) 8.72 (d, J=4.55 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 25.04, 45.05, 45.27, 47.84, 114.83, 121.12, 123.43, 123.55, 126.59, 127.01, 134.87, 138.20, 145.21, 149.07, 155.74, 161.49. LRMS (ESI) m/z 378.2 [(M+H)]+, calc'd for C20H23N7O: 377.45.

Provenance & Evidence