Sodium Hydroxide → 3-[5-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoic acid

HRID 2189811Notes

Reaction equation

HRID 2189811 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]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])[N:22]=[CH:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+]>C(O)C.C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])[N:22]=[CH:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59316802Ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoate

Product 1

HCID 250625593-[5-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoic acidYield 28.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoate (D58) (523 mg, 1.17 mmol) was dissolved in mixture of ethanol (20 ml) and THF (10 ml) by warming at 50° C. Cooled to RT and added 2N NaOH (1 ml, 2 mmol) and left standing at RT for 30 minutes. Evaporated off the solvent, added water (50 ml) and washed with EtOAc (50 ml). Acidified aqueous layer and extracted product into EtOAc (50 ml). The EtOAc layer was dried (MgSO4) and the solvent evaporated. Triturating with diethyl ether gave the title compound (139 mg) as a beige solid. δH (d6-DMSO, 400 MHz): 1.39 (6H, d), 2.90 (2H, t), 4.66 (2H, t), 4.94-5.03 (1H, m), 7.57 (1H, d), 7.90 (1H, d), 8.07 (1H, dd), 8.28 (1H, d), 8.42 (1H, dd), 8.54 (2H, dd), 12.35 (1H, broad s). MS (ES): C22H19N5O4 requires 417; found (MH+) 418.

Workup

  1. temperatureCooled to RT
  2. waitleft
  3. customEvaporated off the solvent
  4. additionadded water (50 ml)
  5. washwashed with EtOAc (50 ml)
  6. extractionAcidified aqueous layer and extracted product into EtOAc (50 ml)
  7. dry with materialThe EtOAc layer was dried (MgSO4)
  8. customthe solvent evaporated
  9. customTriturating with diethyl ether

Sources & evidence

ORD record
ord-1c3015aebecb419790a75b2d39763f32
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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