Potassium Carbonate → Tert-butyl 3-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1h)-yl)propanoate

Participants

Reaction Steps

3-(3-chloro-4-isopropoxyphenyl)-5-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1,2,4-oxadiazole (0.1088 g, 0.294 mmol) in DMF (2.94 ml) (briefly heated to 40° C. for complete dissolution). K2CO3 (0.081 g, 0.588 mmol) and tert-butyl 3-bromopropanoate (0.046 ml, 0.276 mmol) was added and the mixture stirred at ambient temperature for 2 hrs. Additional tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol) was added and the reaction was stirred at 60° C. over the weekend. Additional tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol) was added and the reaction continued heated at 60° C. overnight. Additional K2CO3 (0.041 g, 0.294 mmol) was added, followed by tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol). The reaction was heated at 60° C. overnight. The reaction mixture was filtered and the filtrate concentrated in vacuo to give ˜179 mg of crude yellow oil. The crude residue was purified via Analogix system using RediSep RS 12 g column, with a gradient of 0-45% EtOAc/Heptane over 35 min. at 15 mL/min. Fractions 23-28 were combined and concentrated to yield tert-butyl 3-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)propanoate (91 mg, 0.183 mmol) as light yellow oil. LCMS (Table 1, Method c) Rt=3.39 min, m/z 500.72 (M+H)+.

Provenance & Evidence