Toluene → 5,6-Disubstituted anthranilic acid sulfonamide, 9e

Temperature

100 °C

A mixture of Example 225A (123 mg, 0.26 mmol), potassium phosphate (192 mg, 0.9 mmol), butylboronic acid (34 mg, 0.33 mmol), bis(tricyclohexylphosphino)palladium dichloride (19 mg, 0.03 mmol), toluene (4 mL), and water (0.2 mL) was purged with argon and shaken at 100° C. for 36 hours in a sealed container. The mixture was diluted with ethyl acetate (10 mL), washed with water (2×10 mL) and brine, dried (Na2SO4), filtered, concentrated and passed through a silica gel cartridge (20 g) with 15% ethyl acetate/hexanes. The isolated solid was substituted for Example 108C in Example 108D and purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/0.1% aqueous TFA over 8 minutes (10 minute run time) at a flow rate of 40 mL/min to provide the desired-product. MS (ESI(+)) m/e 383 (M+NH4)+; (ESI(−)) m/e 364 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 13.09 (br s, 1H), 9.74 (br s, 1H), 7.78 (m, 2H), 7.39 (m, 2H), 7.08 (d, 1H), 6.71 (d, 1H), 2.55 (q, 2H), 2.18 (s, 3H), 1.44 (m, 2H), 1.32 (m, 2H), 0.91 (t, 3H).

1. washwashed with water (2×10 mL) and brine
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated
5. custompurified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)
6. customover 8 minutes
7. custom(10 minute run time)
8. customto provide the desired-product

ORD record

ord-ae1c384e886e4e6883cc58838382736c

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07491718B2