Reaction #73392

Reaction equation

methyl 1-((6-(1-(4-fluoro-3-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)pyrimidin-4-yl)methyl)piperidine-4-carboxylate

→

title compound

1-((6-(1-(4-fluoro-3-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)pyrimidin-4-yl)methyl)piperidine-4-carboxylic acid

Solvents

THF H2O

LiOH

Conditions

Workup

1. 1
   Concentrationbefore being concentrated
2. 2
   Otherpurified by semi-prep HPLC (12-48% CAN/H2O with 0.1% TFA)

Procedure

To a solution of methyl 1-((6-(1-(4-fluoro-3-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)pyrimidin-4-yl)methyl)piperidine-4-carboxylate (0.13 g, 0.228 mmol) in 40 mL of THF/H2O (3:1), 2 M aq LiOH solution (0.23 mL) is added. The mixture is stirred at rt for 3.5 h before being concentrated and purified by semi-prep HPLC (12-48% CAN/H2O with 0.1% TFA) to give the title compound. MS (ESI) m/z 558.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.43 (s, 1 H), 9.93-10.12 (m, 1 H), 8.88 (s, 1 H), 8.32 (d, J=9.1 Hz, 1 H), 8.08-8.17 (m, 2 H), 7.96-8.06 (m, 1 H), 7.58 (t, J=9.9 Hz, 1 H), 7.52 (d, J=2.5 Hz, 1 H), 7.25 (br. S., 1 H), 7.17 (dd, J=9.0, 2.4 Hz, 1 H), 6.83 (d, J=3.5 Hz, 1 H), 4.39-4.60 (m, 2 H), 3.45-3.57 (m, 2 H), 2.98-3.17 (m, 2 H), 1.95-2.14 (m, 3 H), 1.73-1.91 (m, 2 H)

Source