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

HRID 1512946
Notes
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Reaction equation

HRID 1512946 reaction equation
[OH-].[Na+].[CH3:3][CH:4]([O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[NH:23][C:22]([CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[CH:21]4)[N:14]=2)=[CH:9][C:8]=1[C:34]([F:37])([F:36])[F:35])[CH3:5].Cl>C1COCC1.C(O)(C)C.O>[CH3:5][CH:4]([O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[NH:23][C:22]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[CH:21]4)[N:14]=2)=[CH:9][C:8]=1[C:34]([F:36])([F:37])[F:35])[CH3:3]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146129ethyl 3-(5-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoate

Product 1

HCID 591461083-(5-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoic acidYield 47.7%

Reagents, catalysts & solvents 3

HCID 962
Water
Solvent
HCID 3776IsopropanolSolvent
HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide (36 mg) was added to a solution of ethyl 3-(5-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoate (D117) (89 mg) in THF (1 mL), isopropanol (1 mL) and water (0.5 mL). The mixture was stirred at room temperature until LCMS showed no starting material. The mixture was neutralized with 2 M HCl till pH ˜6.0. The crude product was purified by Mass Directed Auto Prep to afford of 3-(5-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoic acid (E92) (40 mg). δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 2.70 (2H, t), 2.99 (2H, t), 5.55 (1H, m), 6.35 (1H, s), 7.46 (1H, d), 7.77 (1H, dd), 8.23 (1H, s), 8.64 (1H, d), 9.22 (1H, d), 11.36 (1H, s), 12.25 (1H, s); MS (ES): C22H19F3N4O4 requires 460; found 461.2 (M+H+).

Workup

  1. customThe crude product was purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-0d339e637155413db8ff64de32adddf1
Source dataset
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08217028B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes