Lithium diisopropylamide → (E)-Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1-fluorovinylphosphonate

Participants

Reaction Steps

To a stirred solution of tetraethyl fluoromethylenediphosphonate (2.5 equiv.) in THF (0.27 M) cooled at −78° C. was added LDA solution (1.8 M in ethylbenzene/pentane/hexane, 2.0 equiv.). The resulting reaction mixture was warmed up to room temperature and stirred for 30 minutes, before it was cooled back down to −78° C. A solution of 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (2-2) (Example 9−Step 1) (1.0 equiv.) in THF (0.18 M) was added, and the reaction mixture was allowed to warm up to room temperature slowly. The reaction was quenched with saturated NH4Cl solution. Aqueous phase was extracted with DCM (3×). The combined organic phases were combined and concentrated in vacuo. The residue was purified by a COMBIFLASH® system (ISCO) using a gradient of 0-5% MeOH/DCM to provide (E)-Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1-fluorovinylphosphonate (3-2) as a colorless solid.

Provenance & Evidence