Diisopropylethylamine → HCID 118117060, compound

Participants

Reaction Steps

A solution of Example 1G and DIPEA (0.15 M and 0.43 M in DMA, respectively, 257 μL, 0.04 mmol Example 1G (1.0 equivalent) and 0.12 mmol DIPEA (3.0 equivalents)), HATU (0.2 M in DMA, 257 μL, 0.052 mmol, 1.3 equivalents), and 2-(1H-pyrazol-1-yl)acetic acid (0.40 M in DMA, 121 μL, 0.048 mmol, 1.2 equivalents) were aspirated from their respective source vials, 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 reaction 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). A gradient of acetonitrile (A) and 0.1% ammonium acetate in water (B) was used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6.5 min linear gradient 5-60% A, 6.5-7.0 min linear gradient 60-100% A, 7.0-8.9 min 100% A, 8.9-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to yield the title compound (7.33 mg, 39% yield). 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.76 (d, J=2.3 Hz, 1H), 7.60-7.45 (m, 4H), 7.37-7.28 (m, 1H), 7.07-6.87 (m, 3H), 6.31 (t, J=2.1 Hz, 1H), 5.82 (s, 1H), 5.00 (s, 2H), 3.93 (q, J=6.9 Hz, 2H), 3.36 (s, 3H), 1.14 (t, J=6.9 Hz, 3H). MS (ESI) m/z 481.1 (M+H+).

Provenance & Evidence