Dimethyl Sulfoxide → Methyl 2-[(1-{bis[(tert-butoxy)carbonyl]amino}isoquinolin-6-yl)amino]-15,15-difluoro-4,17,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaene-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a pressured-bottle charged with 4B (177 mg, 0.215 mmol), palladium(II) acetate (24.09 mg, 0.107 mmol), TEA (0.089 mL, 0.644 mmol) and DMSO (5 mL)/MeOH (2.500 mL) was added dppp (44.3 mg, 0.107 mmol). The resulting mixture was charged with carbon monoxide at 25 psi and stirred at 80° C. under an atmosphere of CO overnight. The reaction mixture was cooled to rt, filtered though CELITE® and concentrated to about ½ original volume. Water (50 mL) was added to the mixture and then extracted using 50% EtOAc/hexanes (3×). The combined organics were washed with water, dried with NaSO4 then filtered and concentrated. The residue was purified on Isco (40 g) eluting with 0 to 30% EtOAc/dichloromethane to give 4C (130 mg, 0.162 mmol, 75% yield) as a white solid. MS and 1H NMR are consistent with the desired product.

Provenance & Evidence