Potassium Phosphate, Tribasic → HCID 86689241, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 3-chloro-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine 2,2,2-trifluoroacetate (43 mg, 0.077 mmol, step 3), 2-fluoropyridine-4-boronic acid (27.0 mg, 0.192 mmol, Aldrich), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (5.43 mg, 7.67 μmol, Aldrich) and potassium phosphate (48.8 mg, 0.230 mmol, Aldrich). The vial was evacuated and backfilled with N2 gas (2×). Dioxane (0.6 mL) and water (0.2 mL) were added, and the vial was heated in the microwave for 30 min at 100° C. The reaction mixture was partitioned between EtOAc and water. The organic phase was separated and the solvent was removed under reduced pressure. The residue was purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 20 min to obtain the title product (23 mg, 0.037 mmol, 48.3% yield) as a light-yellow solid. MS m/z=508.1 [M+H]+. Calculated for C29H16F3N5OC2HF3O2: 621.49 (TFA salt). 1H-NMR (300 MHz, MeOH) δ ppm 7.14 (t, J=1.61 Hz, 1H) 7.30-7.39 (m, 1H) 7.39-7.48 (m, 1H) 7.53-7.70 (m, 3H) 7.72-7.86 (m, 4H) 7.92 (ddd, J=9.94, 7.75, 1.90 Hz, 1H) 8.16 (d, J=4.97 Hz, 1H) 8.22 (d, J=5.41 Hz, 1H) 8.26-8.37 (m, 1H).

Provenance & Evidence