Morpholine → 6-Morpholin-4-ylimidazo[1,2-a]pyridine

Temperature

90 °C

6-bromoimidazo[1,2-a]pyridine (299 mg, 1.52 mmol), dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (35.4 mg, 0.08 mmol), RuPhos 2nd generation (58.9 mg, 0.08 mmol), morpholine (0.159 ml, 1.82 mmol) and cesium carbonate (1483 mg, 4.55 mmol) were dissolved in degassed 1,4-dioxane (15.100 ml). Reaction mixture was purged with nitrogen for 2-3 minutes before heating to 90 °C and stirred under nitrogen overnight. The reaction was incomplete, therefore additional morpholine (0.159 ml, 1.82 mmol), RuPhos 2nd generation (58.9 mg, 0.08 mmol) and dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (35.4 mg, 0.08 mmol) were added and the reaction mixture washeated for a further 6.5 hours at 105°C. The reaction was still only ~20% complete therefore additional morpholine (0.318 ml), RuPhos 2nd generation (117.8 mg) and dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (70.8 mg) were added and the reaction heated for a further 24 hours at 105°C and then allowed to cool to RT. The residue partitioned between EtOAc and water, the organic phase was separated and the aq. rextracted with more EtOAc. The combined organic extracts were washed with brine, dried over magnesium sulfate filtered and evaporated. The crude material was purified by flash silica (12g, grace) chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-(imidazo[1,2-a]pyridin-6-yl)morpholine (98 mg, 31.8 %) as a white solid.

ORD record

ord-c4c5eb3c12504ceeb83c5886c7e20d94

Source dataset

750 AstraZeneca ELN dataset

Original link

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