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

HRID 1512945Notes

Reaction equation

HRID 1512945 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]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([CH3:28])[C:23]([CH2:29][CH2:30][C:31]([O:33]C)=[O:32])=[CH:22]4)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12].Cl>C1COCC1.C(O)(C)C.O>[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([CH3:28])[C:23]([CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[CH:22]4)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:12])[CH3:13]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67025220Methyl 3-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-2-yl]propanoate

Product 1

HCID 591460403-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-2-yl]propanoic acidYield 17.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide (63 mg) was added to a solution of methyl 3-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-2-yl]propanoate (D116) (72 mg) in THF (5 mL), isopropanol (5 mL) and water (2.5 mL). The reaction mixture was stirred at room temperature overnight. The mixture was neutralized with 2 M HCl till pH ˜6.0. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by Mass Directed Auto Prep to afford 3-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-2-yl]propanoic acid (E91) (12 mg). δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 2.71 (2H, t), 3.03 (2H, t), 3.75 (3H, s), 5.46 (1H, m), 6.40 (1H, s), 7.60 (1H, d), 7.82 (1H, dd), 8.24 (1H, d), 8.56 (1H, d), 8.93 (1H, d), 12.33 (1H, s); MS (ES): C22H21ClN4O4 requires 440; found 441.1 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-3112a4e2cf5249319a280ac9a5b8a736
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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