Cesium carbonate → HCID 60164039, compound

Participants

Reaction Conditions

Reaction Steps

A 2 mL microwave vial equipped with a magnetic stirrer was charged under N2 with 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-yl trifluoromethanesulfonate CCH 42040-1 (13 mg, 23 μmol), t-butyl carbamate (5 mg, 43 μmol), dry powdered cesium carbonate (15 mg, 46 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (4 mg, 7 μmol) and tris(dibenzylideneacetone)dipalladium(0) (4 mg, 4 μmol). Dry THF (1.5 mL) was then added and the mixture was stirred for 45 min at 140° C. under microwave irradiation. After cooling to RT, the mixture was diluted with EtOAc (30 mL), then filtered through celite. The solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. The residue was then dissolved in CH2Cl2 (10 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of TFA (1 mL) and the mixture was stirred overnight at RT then concentrated to dryness under vacuum. The residue was basified with a saturated NaHCO3 solution (10 mL) before extraction with CH2Cl2 (40 mL). The organic phase was isolated, washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50) gave 4 mg of 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-amine. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (0.5 mL) and the solution was stirred for 5 min at RT, and concentrated at 40° C. under vacuum to afford 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-amine hydrochloride 65 as a pale brown solid (4 mg, 38% yield).

Provenance & Evidence