Diisopropylethylamine → trans-(4-Cyclobutylpiperazin-1-yl)-[2-(6-(trifluoromethyl)pyridin-3-yl)cyclopropyl]methanone

Participants

Reaction Steps

To a stirring solution of 26C (16 mg, 0.070 mmol) in DMF (0.5 mL) at ambient temperature was added DIPEA (0.050 mL, 0.28 mmol) and TBTU (23 mg, 0.070 mmol). After stirring for 2 min, 4A (16 mg, 0.08 mmol) was added in one portion. After stirring for 19 h, the reaction was concentrated under reduced pressure. The residue was diluted with EtOAc (15 mL) then washed successively with dilute aq. K2CO3 (5 mL), H2O (2 mL), and brine (3 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was subjected to flash chromatography (basic alumina-8 g; gradient elution: 5% EtOAc/Hexane for 1 min then 5-100% EtOAc/Hexane over 13 min at 18 mL/min) to afford 8.7 mg 26D (36% yield). m/z (ES+) M+1=285.2; HPLC tR=0.75 min. 1H NMR (500 MHz, CDCl3) δ 8.53 (dd, J=2.1, 0.6 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.55 (dd, J=8.2, 2.1 Hz, 1H), 3.69-3.59 (m, 4H), 2.74 (quintet, J=7.9 Hz, 1H), 2.60 (ddd, J=9.0, 6.3, 4.0 Hz, 1H), 2.36-2.29 (m, 4H), 2.05 (m, 3H), 1.93-1.82 (m, 2H), 1.79-1.66 (m, 3H), 1.35 (ddd, J=8.7, 6.3, 4.6 Hz, 1H).

Provenance & Evidence