Triethylamine → (R)-6-methoxy-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole dihydrochloride

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-1-(pyrrolidin-3-yl)piperidine (freebase of Reference Example 5C, 0.721 g, 4.668 mmol), 2-chloro-6-methoxybenzo[d]thiazole (0.848 g, 4.244 mmol), and triethylamine (1.77 mL, 12.73 mmol) in N,N-dimethylformamide (10 mL) was heated to 150° C. under microwave irradiation for 1.5 hours. The reaction mixture was diluted with water (350 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (2×200 mL) then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Analogix SF40-120 g, 98:2 ethyl acetate/methanol). Fractions containing product were combined and concentrated under reduced pressure to give a solid. The solid was dissolved in hot ethyl acetate, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and a crystallization attempt was set up with ethyl acetate and diethyl ether. A gummy solid formed. The remaining solution was decanted free of this solid and the decant was treated with excess 4 M HCl in dioxane to provide the title compound as a precipitate that was collected by filtration. 1H NMR (300 MHz, CD3OD) δ ppm 7.53 (d, J=5.8 Hz, 1H), 7.52 (s, 1H), 7.16 (dd, J=2.5, 9.0 Hz, 1H), 4.36-4.21 (m, 2H), 4.20-3.99 (m, 2H), 3.93-3.79 (m, 1H), 3.86 (s, 3H), 3.74-3.51 (m, 2H), 3.25-3.06 (m, 2H), 2.84-2.55 (m, 2H), 2.07-1.82 (m, 5H), 1.68-1.49 (m, 1H); MS (DCI/NH3) m/z 318 (M+H)+.

Provenance & Evidence