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

HRID 1512881Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

Sodium hydroxide (35 mg) was added to a solution of ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D48) (222 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-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoic acid (E22) (137 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.40 (6H, d), 2.62 (2H, t), 3.07 (2H, t), 5.46 (1H, m), 6.98 (1H, dd), 7.26 (1H, d), 7.91 (1H, dd), 8.72 (1H, d), 9.04 (1H, d), 11.09 (1H, s), 11.71 (1H, br s). δF (DMSO-d6, 376 MHz): −118.7. MS (ES): C21H18ClFN4O4 requires 444; found 445.1 (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-3a8ea6dfd8f54a26a5cdd3b9aabfa723
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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