Example 49
Synthesis of AM362-A.
To a degassed mixture of tert-butyl 5-bromoisoindoline-2-carboxylate (1 g, 3.3 mmol), 1-methyl-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (1.12 g, 5.031 mmol) and Cs2CO3 (3.2 g, 9.9 mmol) in 1,4-dioxane (10 mL) was added Pd(dppf)Cl2 under N2 atmosphere and the mixture was heated at 95° C. overnight. The reaction mixture was diluted with DCM (25 mL) and the catalyst was removed by filtration through the celite. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (PE:EtOAc=80:20˜60:40) to give AM362-A (0.8 g, 76%) as a brown gum.
Compound AM362 (450 mg, 95%, a brown solid) was synthesized in a similar procedure used for AM351 from AM351-D.
Compound AM403 (250 mg, 96%, a yellow solid) was synthesized in a similar manner using the appropriately substituted boronic acid pinacol ester variant of AM362.
