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

HRID 1512884Notes

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:26][CH:27]([CH3:29])[CH3:28])=[C:22]([O:24][CH3:25])[CH:23]=3)[O:15][N:14]=2)=[C:9]2[C:5]=1[C:6]([CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[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:26][CH:27]([CH3:29])[CH3:28])=[C:22]([O:24][CH3:25])[CH:23]=3)[O:15][N:14]=2)=[C:9]2[C:5]=1[C:6]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[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-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D50) (157 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-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid (E25) (110 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 2.62 (2H, t), 3.06 (2H, t), 3.95 (3H, s), 5.42 (1H, m), 6.99 (1H, dd), 7.26 (1H, d), 7.92 (2H, m), 8.67 (1H, d), 11.07 (1H, s), 12.14 (1H, br s). δF (DMSO-d6, 376 MHz): −118.8. MS (ES): C22H21FN4O5 requires 440; found 441.2 (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-d1d2cf0db7f14aa9be7dc8db9045654e
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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