*2.2. Synthesis of ENR-d3*

The reaction was performed according to the synthesis route in Figure 2, which was optimized by a reported method [35]. To a solution of CIP (1.80 g, 5.4 mmol) in DMF (50 mL), Et3N (1.20 g, 11.9 mmol) and 1-bromoethane-2,2,2-*d3* (0.78 g, 7.0 mmol) were added at room temperature. The reaction mixture was heated to 80 °C and further stirred for 2 h under an N2 atmosphere. After cooling to room temperature, DMF was removed by a rotatory evaporator under reduced pressure at ca. 80 ◦C for about 30 min [36], and the residue was purified on a silica gel column using CH2Cl2:EA = 20:1 as the eluent, yielding the desired product (1.66 g, 85%) as a yellow solid. 1H NMR spectra were obtained using a Bruker AM 400 MHz spectrometer (Bruker, Massachusetts, USA) at 298 K using tetramethylsilane (TMS) as the internal standard. HRMS measurements were performed using a Q-Orbitrap mass spectrometer (Q-exactive, Thermo Fisher, USA). 1H NMR (400 MHz, D2O): δ 8.47 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 4.8 Hz, 1H), 3.65–3.59 (m, 1 H), 3.38–3.24 (m, 4H), 2.82–2.66 (m, 4H), 2.51–2.46 (m, 8H), 1.35–1.29 (m, 2H), 1.15–1.09 (m, 2H), 0.99–0.96 (m, 9H). HRMS (ESI, m/z): calcd for C19H20D3FN3O3 ([M + H]+), 363.1912; found, 363.1887.

**Figure 2.** Synthetic route for the target compound.

The purity of ENR-*d3* was determined by LC–UV [37]. The LC–UV equipment consisted of an Agilent 1100 series with an autosampler injector (Agilent Technologies Inc., State of California, USA). UV detection was performed by a diode array detector (DAD) at a wavelength of 280 nm for ENR-*d3*. The ENR was separated by chromatography on a Zorbax Eclipse XDB-C18 (150 mm × 4.6 mm i.d.; Agilent Technologies).
