Nitrogen → HCID 86696436, compound

Participants

Reaction Steps

1.6 M n-butyl lithium in hexanes (5.8 mL, 9.3 mmol) was rapidly syringed into a stirred, colorless, N2 blanketed solution of (S)-2-[(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.8 g, 4.6 mmol) in anhydrous THF (100 mL) held at −73° C. The reaction solution immediately turned brown in color and was allowed to stir for 5 minutes. The generated aryl lithium was quenched by the careful addition of saturated aqueous NH4Cl (2 mL). The reaction solution was partitioned between brine and ethyl acetate, the extract dried (CaSO4), and the crude product flash chromatographed (silica gel, eluted with 10% (v/v methanol/ethyl acetate) and crystallized from ethyl acetate/heptane to provide S)-2-(imidazo[1,2-b]pyridazin-6-ylaminomethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as 1.5 g of off white powder, mp. 161-162° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40 (s, 9H) 1.72-1.95 (m, 4H) 3.10-3.22 (m, 1H) 3.28 (br. s., 2H) 3.41-3.53 (m, 1H) 3.92-4.05 (m, 1H) 6.65 (d, J=9.60 Hz, 1H) 6.96 (br. s., 1H) 7.36 (d, J=0.76 Hz, 1H) 7.66 (d, J=9.60 Hz, 2H). 13C NMR (100 MHz, DMSO-d6) δ ppm 23.15, 28.13, 43.14, 45.96, 46.36, 55.57, 56.15, 78.30, 112.50, 116.01, 125.26, 130.32, 135.78, 153.75. LRMS (ESI) m/z 318.3 [(M+H)]+, calc'd for C16H23N6O2: 317.36.

Provenance & Evidence