Chloride → (R)-ethyl 2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxylate

Participants

Reaction Steps

A mixture of ethyl 2-chlorobenzo[d]thiazole-6-carboxylate (1.62 g, 6.72 mmol), (R)-1-(pyrrolidin-3-yl)piperidine dihydrochloride (Reference Example 5c, 1.80 g, 7.94 mmol), and triethylamine (5.11 mL, 36.66 mmol) in N,N-dimethylformamide (19 mL) was stirred at ambient temperature for 17 hours. According to TLC (100% ethyl acetate) the spot for starting chloride was replaced by a much lower Rf, ninhydrin-positive spot. The reaction mixture was diluted with water (400 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, 99:1 ethyl acetate/methanol). Fractions containing product were combined and concentrated under reduced pressure to provide the title compound. 1H NMR (300 MHz, CD3OD) δ ppm 8.34 (d, J=1.7 Hz, 1H), 7.96 (dd, J=1.7 Hz, 8.5, 1H), 7.49 (d, J=8.6 Hz, 1H), 4.36 (q, J=7.1 Hz, 2H), 3.82 (dt, J=8.8, 18.3 Hz, 2H), 3.63-3.50 (m, 1H), 3.41 (t, J=9.3 Hz, 1H), 3.16-3.02 (m, 1H), 2.67-2.43 (m, 4H), 2.43-2.30 (m, 1H), 2.11-1.93 (m, 1H), 1.72-1.59 (m, 4H), 1.58-1.45 (m, 2H), 1.39 (t, J=7.1 Hz, 3H); MS (DCI/NH3) m/z 360 (M+H)+.

Provenance & Evidence