Cesium carbonate → HCID 68183096, compound

Participants

Reaction Conditions

Reaction Steps

In a 10-mL microwave vial, a suspension of 3-bromo-4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (69.5 mg, 0.162 mmol, single enantiomer of unknown configuration), cesium carbonate (0.146 g, 0.448 mmol) and phenylacetylene (0.107 mL, 0.975 mmol) in N,N-dimethylformamide (0.750 mL) was degassed by bubbling argon balloon for 5-10 min., then 2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (12.6 mg, 0.0265 mmol) and bis(acetonitrile)palladium(II) chloride (2.11 mg, 0.00812 mmol) was added. The vial was sealed, and the mixture was heated at 50° C. for 16 h. The r×n was cooled to rt, and combined with a previous r×n of same scale. The reaction was transferred to a separatory funnel with EA. Water was added, and the layers were separated. The aqueous layer was extracted w/EA. The organic layers were combined, washed w/brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude mixture was purified using column chromatography on silica gel (40 g ISCO column, gradient 100% hexanes to 100% EtOAc over 60 minutes to obtain impure product (51 mg). Final purification by HPLC gave the title product as an off-white solid (10 mg, 7%). LCMS: (FA) ES+ 449, 451. 1H NMR (400 MHz, DMSO) δ 7.47 (d, J=4.2 Hz, 1H), 7.40-7.32 (m, 5H), 7.27-7.23 (m, 2H), 7.21-7.17 (m, 2H), 4.31-4.29 (m, 1H), 3.91 (dd, J=12.9, 5.6 Hz, 1H), 3.79-3.76 (m, 4H), 3.57-3.52 (m, 2H), 3.49-3.44 (m, 2H), 3.30-3.27 (m, 1H).

Provenance & Evidence