C1COCCN1.CC(C)(C)OC(=O)Nc1cncc(I)c1>C1COCCO1.CC(=O)O.CC(=O)O.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C([O-])[O-].[Cs+].[Cs+].[Pd]>Nc1cncc(N2CCOCC2)c1morpholine (0.272 mL, 3.12 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.07 mmol), tert-butyl 5-iodopyridin-3-ylcarbamate (200 mg, 0.62 mmol), diacetoxypalladium (7.01 mg, 0.03 mmol) and cesium carbonate (407 mg, 1.25 mmol) were suspended in 1,4-dioxane (4 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford the boc protected product. HCl in dioxane (4M, 5mL) was added to the product . The resulting suspension was stirred at room temperature for 3 hours. The product was evaporated to dryness to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH plus 1% aqueous ammonia in DCM. Pure fractions were evaporated to dryness to afford 5-morpholinopyridin-3-amine (31.0 mg, 27.7 %) as a cream solid.
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