Potassium Phosphate, Tribasic → HCID 53329356, compound

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.236 g, 0.664 mmol, prepared as in Example 2, Step 1-2), potassium phosphate (0.564 g, 2.66 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.063 g, 0.133 mmol), Pd2(dba)3 (0.030 g, 0.033 mmol), and 3-(2-iodo-3-methylphenyl)imidazo[1,5-a]pyridine (0.222 g, 0.664 mmol). The vessel was evacuated and flushed with nitrogen three times before dioxane (4.43 mL) and water (2.215 mL) (each degassed by bubbling nitrogen gas through the solution for 10 min prior to addition) were added. The reaction mixture was stirred and heated in a microwave reactor at 140° C. for 15 min. The reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide and extracted with EtOAc. The combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, water, saturated sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:20 2M NH3 in MeOH/DCM. The fractions containing the product (with some impurities) were combined and concentrated. The solid was dissolved in MeOH and filtered to remove some of the impurity. The remainder of the sample was purified by reverse-phase preparative HPLC with 0.1% TFA in CH3CN/H2O, gradient 5-70% over 20 min to provide 6-(2-(imidazo[1,5-a]pyridin-3-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine. The purified compound was partitioned between DCM and saturated sodium bicarbonate. The layers were separated and the aqueous layer was extracted with DCM. The combined organic extracts were washed with saturated sodium chloride and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give 6-(2-(imidazo[1,5-a]pyridin-3-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine as a white solid. MS (ESI, pos. ion) m/z: 436 (M+1).

Provenance & Evidence