p-Toluenesulfonic acid → 5-(3H-Imidazo[4,5-c]pyridin-6-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile

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A mixture of tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.016 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (18 mg, 0.031 mmol) in toluene (1.5 mL) was degassed under a stream of nitrogen gas with stirring for 10 minutes. After addition of 1-(4-methoxybenzyl)-6-bromo-1H-imidazo[4,5-c]pyridine (50 mg, 0.157 mmol), 5-amino-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile in DMF (0.5 mL) (38 mg, 0.173 mmol) and caesium carbonate (102 mg, 0.314 mmol), the mixture was degassed for a further 5 minutes and then heated at 120° C. for 30 minutes in a microwave reactor. Upon cooling, the mixture was diluted with methanol and isolated by SPE using a MP-TsOH cartridge, washing with methanol and then eluting with 2 M ammonia in methanol. The combined basic fractions were concentrated in vacuo. Preparative HPLC gave the title compound (10.8 mg, 0.032 mmol, 20%). 1H NMR (d6-DMSO, 400 MHz) δ 10.82 (br s, 1H), 8.75 (d, 1H, J=1.0 Hz), 8.36 (br s, 1H), 8.28 (br s, 1H), 8.21 (s, 1H), 8.15 (br s, 1H), 5.48-5.41 (m, 1H), 2.62 (dd, 1H, J=13.1, 7.1 Hz), 2.5-2.46 (m, partly obscured by DMSO, 1H), 2.19 (s, 6H), 1.41 (d, 3H, J=6.3 Hz). LC-MS (2) Rt=1.78 min; m/z (ESI−) 337 (M−H).

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