Diisopropylethylamine → HCID 118116343, compound

Participants

Reaction Steps

A solution of Example 1G and DIPEA (0.182 M and 0.52 M in DMA, respectively, 221 μL, 0.40 mmol Example 1G (1.0 equivalent) and 1.21 mmol DIPEA (3.0 equivalents)), HATU (0.182 M in DMA, 221 μL, 0.40 mmol, 1 equivalent) and 2-(2-chloro-5-fluorophenyl)acetic acid (0.40 M in DMA, 151 μL, 0.60 mmol, 1.5 equivalents) were mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100° C., and passed through the reactor at 180 μL min−1 (10 minute residence time). Upon exiting the reactor, the solution was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm), eluting with a gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6 5 min linear gradient 5-100% A, 6.5-8.5 min 100% A, 8.5-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to provide the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 10.37 (s, 1H), 7.59-7.46 (m, 4H), 7.37-7.27 (m, 2H), 7.18 (td, J=8.5, 3.1 Hz, 1H), 7.14-6.93 (m, 2H), 6.90 (d, J=8.7 Hz, 1H), 5.82 (s, 1H), 3.92 (q, J=7.0 Hz, 2H), 3.85 (s, 2H), 3.36 (s, 3H), 1.14 (t, J=7.0 Hz, 3H). MS (APCI+) m/z 543.0 (M+H)+.

Provenance & Evidence