Sodium Hydroxide → 4-(5-Cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylic acid

HRID 874934Notes

Reaction equation

HRID 874934 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:31])[C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]4[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[O:24][N:23]=4)[CH:17]=3)[CH:11]([C:32]([O:34]C)=[O:33])[CH2:10]2)=[N:7][CH:8]=1)#[N:2].[OH-].[Na+]>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:31])[C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]4[N:26]=[C:25]([C:27]([F:29])([F:28])[F:30])[O:24][N:23]=4)[CH:17]=3)[CH:11]([C:32]([OH:34])=[O:33])[CH2:10]2)=[N:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67325316Methyl 4-(5-cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylate

Product 1

HCID 533277884-(5-Cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylic acidYield 24%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 4-(5-cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylate (130 mg, 0.3 mmol) was dissolved in MeOH (4 mL) and cooled to 0° C. 1N NaOH solution (0.3 mL) was added and the reaction mixture was slowly warmed to room temperature and stirred at 50° C. for 1 h. The MeOH was removed under reduced pressure and the aqueous layer was washed with EtOAc. The aqueous layer was acidified to pH 2-3 using 1.5N HCl, extracted with EtOAc, dried over anhydrous sodium sulfate and concentrated over reduced pressure. The crude product was purified by preparative TLC (eluent petroleum ether/EtOAc/AcOH 4:6:0.1 v/v) to get 4-(5-cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylic acid (30 mg, yield 24%). 1H NMR (400 MHz, DMSO-d6) δ 8.49-8.47 (m, 1H), 8.20-8.12 (m, 1H), 8.07 (br s, 1H), 7.89-7.83 (m, 1H), 7.75-7.71 (m, 2H), 6.91 (d, J=7.6 Hz, 1H), 5.00-4.89 (m, 1H), 4.72-4.54 (m, 1H), 4.33-4.23 (m, 1H), 3.62-3.47 (m, 2H), 3.17-3.12 (m, 2H). MS (ESI) m/z: Calculated for C21H15F3N6O4: 472.11. found: 473.2 (M+H)+.

Workup

  1. temperaturethe reaction mixture was slowly warmed to room temperature
  2. customThe MeOH was removed under reduced pressure
  3. washthe aqueous layer was washed with EtOAc
  4. extractionextracted with EtOAc
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated over reduced pressure
  7. customThe crude product was purified by preparative TLC (eluent petroleum ether/EtOAc/AcOH 4:6:0.1 v/v)

Sources & evidence

ORD record
ord-1c5c408183174410aac255438e394d03
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

Loading…