Lithium Hexamethyldisilazide → 5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one

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Reaction Steps

A mixture of 4-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (463 mg, 2162 μmol) and 5-amino-6-methylisoquinolin-1(2H)-one (377 mg, 2162 μmol) in THF (1.5 mL) was sonicated for 5 min until all the solid was mixed well. Lithium bis(trimethylsilyl)amide (9.7 mL, 9.72 mmol; 1 M in THF) was added via a syringe and the reaction tube was sonicated and stirred at RT for 5 min. The reaction was heated to 120° C. in a microwave for 20 min. The reaction mixture was cooled to rt and partitioned between DCM and NaHCO3. The aqueous layer was washed with DCM three times. The combined organic layers were washed with brine and dried over Na2SO4, then concentrated in vacuo. The residue was purified via flash column on silica (MeOH-DCM=0.5-6%) to give a light brown solid 5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one (550 mg, 69% yield). MS (ESI, pos. ion) m/z: 369

Provenance & Evidence