Hydrochloric Acid → 2-(5-p-tolyl-1H-pyrazol-1-yl)isonicotinic acid

HRID 878498Notes

Reaction equation

HRID 878498 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=C(C#N)[CH:16]=[CH:15][N:14]=3)[N:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[OH-:21].[Na+].Cl.[CH3:24][CH2:25][OH:26]>>[C:2]1([CH3:1])[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[C:24]([CH:16]=[CH:15][N:14]=3)[C:25]([OH:21])=[O:26])[N:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14798Sodium HydroxideHCID 867254852-[5-(4-Methylphenyl)-1H-pyrazol-1-yl]pyridine-4-carbonitrile

Product 1

HCID 769012472-(5-p-tolyl-1H-pyrazol-1-yl)isonicotinic acidYield 47%

Conditions

Temperature
90 °C

Procedure

To a solution of 2-[5-(4-methylphenyl)-1H-pyrazol-1-yl]pyridine-4-carbonitrile (120 mg, 0.46 mmol) in EtOH (1 mL) was added 10 M NaOH (1 mL) at rt, then stirred at 90° C. for 1 h. The reaction mixture was cooled, acidified with 1N HCl to pH=3, extracted with EtOAc (20 mL), and washed with water and brine. The organic phase was dried, concentrated, triturated with EA/PE (1:1, 5 mL), filtered, and dried to give the title compound (60 mg, 47%) as a brown solid. 1H NMR (400 MHz, DMSO-d6): δ 2.30 (3H, s), 6.65 (1H, d, J=2.0 Hz), 7.13 (4H, s), 7.77 (1H, dd, J=4.8, 1.2 Hz), 7.82 (1H, d, J=1.2 Hz), 8.44 (1H, d, J=4.8 Hz), 13.97 (1H, br s). [M+H] Calc'd for C16H13N3O2, 280; Found, 280.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with EtOAc (20 mL)
  3. washwashed with water and brine
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customtriturated with EA/PE (1:1, 5 mL)
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-cbfa890c201e456b9dd0a54245f571fa
Source dataset
uspto-grants-2015_03
Patent number
US08987461B2

Reaction notes

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