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

HRID 1512955Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

Sodium hydroxide (25 mg) was added to a solution of ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D148) (875 mg) in THF (4 mL) and water (4 mL). The reaction mixture was stirred at 90° C. for 1 hour, and then at RT for another 24 hours. Then 0.5 M HCl was added until pH was about 6. The solvent was removed, and the residue was dissolved in water. The precipitated solid was purified by MDAP to afford 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoic acid (E105) (101.6 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 2.63 (2H, t), 2.99 (2H, t), 4.98-5.04 (1H, m), 7.10 (1H, dd), 7.30 (1H, s), 7.56 (1H, d), 7.81 (1H, dd), 8.56 (1H, dd), 8.90 (1H, d), 11.11 (1H, s), 12.14 (1H, br s); δF (DMSO-d6, 376 MHz): −115.5; MS (ES): C23H19FN4O4 requires 434; found 435.2 (M+H+).

Workup

waitat RT for another 24 hours
customThe solvent was removed
dissolutionthe residue was dissolved in water
customThe precipitated solid was purified by MDAP

Sources & evidence

ORD record: ord-74004252ecc04a4d949c49e10ec607d7
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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