Trimethylaluminum → (R)-3,3-dimethyl-2-(6-methyl-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid

Participants

Reaction Conditions

Reaction Steps

(R)-Benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate (10 mg, 0.018 mmol), Pd(Ph3P)4 (10 mg, 0.009 mmol), and dioxane (1 mL) were combined in a 2 mL microwave vial. The mixture was purged with nitrogen, and trimethylaluminum (2.0M/toluene, 0.053 mL, 0.11 mmol) was added. The vial was sealed and the reaction mixture was heated in a Biotage Initiator™ microwave for 1 h at 120° C. The reaction was repeated three times with an increased amount of (R)-benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate (30 mg) in each reaction. The reaction mixtures were combined and the resulting mixture was concentrated and purified by preparative HPLC (30-70% AcCN/H2O with 0.035% TFA) to afford the title compound as a yellow oil (36 mg, 44%). 1H NMR (500 MHz, CD3OD) δ 1.21 (s, 9H), 2.30 (s, 3H), 2.36 (s, 3H), 4.94 (s, 1H), 5.07 (d, J=18.6 Hz, 1H), 5.21 (d, J=19.0 Hz, 1H), 7.36 (d, J=8.3 Hz, 2H), 8.04 (d, J=4.9 Hz, 2H), 8.10 (s, 1H), 8.22 (s, 1H). [M+H] calc'd for C23H25N3O5S, 456; found, 456

Provenance & Evidence