Hydrochloric Acid → HCID 67365092, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of N—((S)-1-{5-bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carbonyl}-3-methylbutyl)-2-(9H-fluoren-9-yl)-acetamide (150.0 mg, 0.212 mmol) and aq 5M NaOH (0.42 mL, 1.1 mmol) in THF (5 mL) was cooled to 0° C. and stirred for 1 h. The organic solvent was removed in vacuo, and the material was transferred to a separatory funnel, extracting with DCM and water. The organic layer was concentrated in vacuo, and [4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)pyrazol-1-yl]-acetic acid ethyl ester (89.1 mg, 0.318 mmol), Pd(PPh3)4 (20 mg, 0.02 mmol), potassium fluoride (61.6 mg, 1.06 mmol) and 4:1 dioxane/H2O were added, and the mixture was heated to 90° C. for 2 h. The organic solvent was removed in vacuo, and the material was transferred to a separatory funnel and extracted with DCM and water. The organic layer was dry-loaded onto silica gel, and purified via column chromatography, eluting with 2% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo, redissolved in EtOH/H2O (8 mL), and LiOH (44.5 mg, 1.06 mmol) was added at 0° C. and stirred for 20 min. The pH of the solution was lowered to pH 5 by addition of 2M HCl, and the organic solvent was removed in vacuo. The material was transferred to a separatory funnel and extracted with DCM and brine. The organic layer was concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=7.1 Hz, 3 H), 4.83 (s, 2 H), 5.29 (q, J=7.1 Hz, 1 H), 7.19 (t, J=8.6 Hz, 1 H), 7.36 (d, J=1.5 Hz, 1 H), 7.39-7.53 (m, 2 H), 7.57 (s, 1 H), 7.82 (s, 1H), 8.34 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 433.00 (100) [MH+]. HPLC: tR=3.53 min (ZQ3, polar—5 min).

Provenance & Evidence