Triphenylphosphine → HCID 59451520, compound

Participants

Reaction Steps

In a 24-well Bohdan block, ethyl 5-hydroxy-1H-indole-2-carboxylate (0.100 g, 0.487 mmol), 3-(dimethylamino)-1-propanol (0.126 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 (0.008 g, 3%) as a glass. 1H NMR (400 MHz, CDCl3-d): δ ppm 9.26 (br. s., 1H), 7.30-7.36 (m, 2H), 7.25-7.27 (m, 1H), 7.22-7.24 (m, 1H), 7.13 (t, 1H), 6.95-7.00 (m, 2H), 6.88 (dd, 1H), 6.79 (d, 1H), 6.73-6.78 (m, 1H), 4.69 (d, 2H), 4.01 (t, 2H), 3.68-3.75 (m, 2H), 3.00-3.08 (m, 2H), 2.68 (s, 6H). LCMS m/z 555.2 (M+1).

Provenance & Evidence