Hydrochloric Acid → 3-(4-fluoro-7-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid

HRID 1512883Notes

Reaction equation

[OH-].[Na+].[F:3][C:4]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][C:21]([O:28][CH:29]([CH3:31])[CH3:30])=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=3)[O:15][N:14]=2)=[C:9]2[C:5]=1[C:6]([CH2:32][CH2:33][C:34]([O:36]CC)=[O:35])=[CH:7][NH:8]2.Cl>C1COCC1.O>[F:3][C:4]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][C:21]([O:28][CH:29]([CH3:30])[CH3:31])=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=3)[O:15][N:14]=2)=[C:9]2[C:5]=1[C:6]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[CH:7][NH:8]2

Participants

Conditions

Temperature: 90 °C

Procedure

Sodium hydroxide (30 mg) was added to a solution of ethyl 3-(4-fluoro-7-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D49) (161 mg) in THF (3 mL) and water (3 mL). The reaction mixture was stirred at 90° C. for 1 hour. Then 0.5 M HCl was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by Mass Directed Auto Prep to afford 3-(4-fluoro-7-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid (E24) (93 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.62 (2H, t), 3.05 (2H, t), 5.54 (1H, m), 6.98 (1H, dd), 7.26 (1H, d), 7.92 (1H, dd), 8.74 (1H, d), 9.32 (1H, d), 11.12 (1H, s), 12.14 (1H, br s). δF (DMSO-d6, 376 MHz): −118.6, −62.8. MS (ES): C22H18F4N4O4 requires 478; found 479.1 (M+H+).

Workup

concentrationThe solvent was concentrated
dissolutionthe residue was dissolved in water
customThe precipitated solid was purified by Mass Directed Auto Prep

Sources & evidence

ORD record: ord-00842306d03f4939adf7bf15baee4a3a
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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