Triphenylphosphine → HCID 59451559, compound

Participants

Reaction Steps

In a 24-well Bohdan block, ethyl 5-hydroxy-1H-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(1-methyl-2-pyrrolidinyl)ethanol (0.157 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 (0.007 g, 2%) as a glass. 1H NMR (400 MHz, CDCl3): δ ppm 9.50 (br. s., 1H), 7.22-7.39 (m, 4H), 7.13-7.18 (m, 1H), 7.05-7.12 (m, 1H), 6.95-7.03 (m, 2H), 6.84-6.91 (m, 2H), 4.66-4.75 (m, 2H), 4.07-4.17 (m, 1H), 3.91-4.00 (m, 1H), 3.27-3.41 (m, 1H), 2.76-2.91 (m, 4H), 2.39-2.51 (m, 1H), 2.24-2.36 (m, 1H), 2.16 (br. s., 2H), 1.91-2.08 (m, 3H). LCMS m/z 581.1 (M+1).

Provenance & Evidence