Proton sponge → HCID 49806735, compound

Participants

Reaction Steps

To a solution of 4-(4-chlorophenyl)-2-methyl-7-(6-(trifluoromethyl)pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline (69 mg, 0.17 mmol) in 1,2-dichloroethane (5 mL) at 0° C. was added proton sponge (37 mg, 0.17 mmol) and 1-chloroethyl chloroformate (56 μL, 0.51 mmol) dropwise. The resultant mixture was stirred at 0° C. for one hour and then heated at reflux for 1.5 hours. After concentrating the mixture in vacuo, the crude intermediate was taken up in methanol (5.0 mL) and heated at reflux for 1 hour. After concentrating in vacuo, the crude product obtained was purified by preparative thin layer chromatography using 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide as eluent to give 4-(4-chlorophenyl)-7-(6-(trifluoromethyl)pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline (22 mg, 33%) as a light yellow oil: [α]23D +7.5° (c 0.08, methanol). To a solution of the newly obtained tetrahydroisoquinoline (20 mg, 0.051 mmol) in acetonitrile (1 mL) was added L-tartaric acid (8 mg, 0.051 mmol) followed by slow addition of water (4 mL). The resultant solution was lyophilized for two days to give the correspondent L-tartrate salt (>99% AUC HPLC) as an off-white solid: 1H NMR (CD3OD, 500 MHz) δ 8.39 (d, J=9.0 Hz, 1H), 8.17 (d, J=9.0 Hz, 1H), 8.17 (s, 1H), 8.03 (dd, J=8.0, 2.0 Hz, 1H), 7.41 (d, J=8.5 Hz, 2H), 7.28 (d, J=8.5 Hz, 2H), 7.11 (d, J=8.5 Hz, 1H), 4.65-4.53 (m, 3H), 4.42 (s, 2H), 3.80-3.76 (m, 1H), 3.47-3.43 (m, 1H); ESI MS m/z 390 [M+H]+.

Provenance & Evidence