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

HRID 1512948Notes

Reaction equation

HRID 1512948 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([F:35])=[C:22]4[C:26]=3[N:25]([CH3:27])[CH:24]=[C:23]4[CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+].Cl>O1CCCC1.C(O)(C)C.O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([F:35])=[C:22]4[C:26]=3[N:25]([CH3:27])[CH:24]=[C:23]4[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146068Ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoate

Product 1

HCID 582224213-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoic acidYield 62.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoate (D130) (349 mg) in tetrahydrofuran (THF) (10 mL), Isopropanol (5 mL) and water (2 mL), was added sodium hydroxide (293 mg). The reaction mixture was stirred at room temperature overnight. LCMS showed the reaction was complete. The reaction mixture was neutralized with 2 M HCl till pH ˜6.0. After removing part of organic solvent, the residue was purified by MDAP to give 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E96) (204 mg). δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.61 (2H, t), 3.04 (2H, t), 3.63 (3H, s), 4.95-5.01 (1H, m), 6.96 (1H, dd), 7.23 (1H, s), 7.43 (1H, dd), 7.55 (1H, d), 8.42 (1H, dd), 8.53 (1H, d), 12.15 (1H, s); δF (DMSO-d6, 376 MHz): −120.5; MS (ES): C24H21FN4O4 requires 448; found 449.2 (M+H+).

Workup

  1. customAfter removing part of organic solvent
  2. customthe residue was purified by MDAP

Sources & evidence

ORD record
ord-550dedf727cc4b89928ab591fb5466a3
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

Loading…