Diisopropylethylamine → HCID 118116343, compound

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)+.

1. customset at 100° C.
2. custompassed through the reactor at 180 μL min−1 (10 minute residence time)
3. custompurified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm)
4. washeluting 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)

ORD record

ord-ea5f3d086c944027bd14c405e9537c27

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428514B2