Potassium Phosphate, Tribasic → 2-(4-(difluoromethoxy)-N-(1-(4-(pyrimidin-5-yl)phenyl)cyclobutyl)phenylsulfonamido) acetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(N-(1-(4-bromophenyl)cyclobutyl)-4-(difluoromethoxy)phenylsulfonamido) acetic acid (20 mg, 0.041 mmol) in n-butanol (2 mL) was added pyrimidin-5-ylboronic acid (7.58 mg, 0.061 mmol), followed by potassium phosphate (17.32 mg, 0.082 mmol) and Pd2 dba3 (2.345 mg, 4.08 μmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (3.89 mg, 8.16 μmol). The mixture was degassed and flushed with argon and then shook at 100° C. for 3 h. The resultant mixture was filtered and the filtrate purified using Shimadzu prep HPLC employing an ACN/water and 0.1% TFA buffer with a Xterra column, 30 mm×100 mm, Gradient over 15 min; Starting conc: 10% B; Ending conc: 100% B. The solvent was removed in vacuo to give 3.3 mg (16% yield, 95% pure) of the title compound as a light gray solid. ESI-MS m/z 490 (MH+), 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.67 (q, J=10.07 Hz, 1H), 1.78-1.92 (m, 1H), 2.63 (t, J=8.70 Hz, 2H), 2.86 (d, J=2.44 Hz, 2H), 4.21 (s, 3H), 6.58 (t, J=75.00 Hz, 1H), 7.09 (d, J=8.55 Hz, 2H), 7.54 (d, J=8.24 Hz, 2H), 7.67 (dd, J=14.80, 8.70 Hz, 4H), 9.10 (s, 2H), 9.31 (s, 1 H).

Provenance & Evidence