Nitrogen → 4-[3-(3-Methoxy-pyridin-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-piperazine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-(3-bromo-imidazo[1,2-b]pyridazin-6-yl)-piperazine-1-carboxylic acid tert-butyl ester (524.4 mg, 1.4 mmol), 3-methoxypyridine-4-boronic acid hydrate [1072952-50-1] (253.1 mg, 1.7 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (632.2 mg, 2.8 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (117.6 mg, 0.1 mmol) contained in a 50 mL round bottomed flask was added a solution of 30% (v/v) water in 1,2-dimethoxyethane (25 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 (pH adjusted to 10 with 3N aqueous sodium hydroxide) and ethyl acetate. The phase separated extract was dried (CaSO4) and evaporated to afford a brown oil which was purified by preparative RP-HPLC to obtain a white powder, mp. 205-206° C. (dec.). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (s, 9H) 3.46-3.55 (m, 8H) 4.02 (s, 3H) 7.30 (d, J=10.10 Hz, 1H) 8.00 (d, J=9.85 Hz, 1H) 8.13 (s, 1H) 8.35 (d, J=5.05 Hz, 1H) 8.41 (d, J=5.05 Hz, 1H) 8.51 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 28.04, 45.53, 56.33, 79.10, 111.13, 120.39, 120.75, 124.25, 126.24, 134.48, 135.69, 137.20, 142.26, 151.08, 153.85, 154.60. LRMS (ESI) m/z 411.3 [(M+H)]+, calc'd for C21H26N6O3: 410.48.

Provenance & Evidence