Triphenylphosphine → HCID 59451383, compound

Participants

Reaction Steps

In a 24-well Bohdan block, ethyl 5-hydroxy-1H-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(4-morpholinyl)ethanol (0.160 g, 1.22 mmol) and PS-triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 mL). Di-tert-butyl azodicarboxylate (1.22 M in THF, 1 mL) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCl (1 mL) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 μL, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.003 g, 1%) as a glass. 1H NMR (400 MHz, CDCl3): δ ppm 9.05-9.11 (m, 1H), 7.35-7.37 (m, 1H), 7.34 (s, 1H), 7.27-7.31 (m, 2H), 7.15-7.18 (m, 1H), 7.05 (d, 1H), 7.02 (dd, 1H), 6.99 (dd, 1H), 6.79 (d, 1H), 6.50-6.57 (m, 1H), 4.73 (d, 2H), 4.13-4.18 (m, 2H), 3.72-3.79 (m, 4H), 2.82-2.90 (m, 2H), 2.60-2.69 (m, 4H). LCMS m/z 583.1 (M+1).

Provenance & Evidence