Triethylamine → methyl 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acid

HRID 877439Notes

Reaction equation

HRID 877439 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]([OH:15])=O)=[CH:11][C:10]([C:16]([O:18]C)=[O:17])=[N:9]1.[CH3:20][S:21]([C:24]1[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=1)[C:27]([NH:29][NH2:30])=O)(=[O:23])=[O:22].[Cl-].[NH2+]1CCN=[CH:36]1.C(N(CC)CC)C>ClCCl.O>[CH3:36][C:11]1[C:10]([C:16]([OH:18])=[O:17])=[N:9][N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[C:12]=1[C:13]1[O:15][C:27]([C:26]2[CH:31]=[CH:32][CH:33]=[C:24]([S:21]([CH3:20])(=[O:23])=[O:22])[CH:25]=2)=[N:29][N:30]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 167825273-(Methylsulfonyl)benzohydrazideHCID 57455650Imidazolinium chlorideHCID 897828401-(2-chlorophenyl)-3-(methoxycarbonyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 117962551methyl 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acidYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice cooled stirred solution of compound 7 from Example 2 (750 mg, 2.67 mmol) and 3-(methylsulfonyl)benzohydrazide 3 from Example 1 (575 mg, 2.67 mmol) in dichloromethane (25 mL) was added imidazolinium chloride (902 mg, 5.34 mmol) and stirred for 30 min. Triethyl amine (1.5 mL, 10.68 mmol) was added to the reaction mixture slowly over a period of 30 min, allowed to attain room temperature and stirring continued for over night. Water (50 mL) added to the reaction mixture and extracted with 10% methanol in dichloromethane (50 mL×3). The combined organic layer was washed saturated sodium bicarbonate solution, brine, dried over sodium sulphate and concentrated. The crude reaction mixture on column chromatographic purification using 2% methanol in dichoromethane afforded the title compound 11 (350 mg, 50%). LCMS: 459.25 (M+1)+; HPLC: 93.72% (@210 nm-370 nm) (Rf; 6.704; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 m/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (CDCl3, 400 MHz) δ 8.28 (s, 1H), 8.26 (d, 1H), 8.11 (d, 1H, J=7.6 Hz), 7.75-7.71 (m, 2H), 7.62-7.50 (m, 4H), 4.02 (s, 3H), 3.09 (s, 3H).

Workup

  1. customto attain room temperature
  2. stirringstirring
  3. extractionextracted with 10% methanol in dichloromethane (50 mL×3)
  4. washThe combined organic layer was washed saturated sodium bicarbonate solution, brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe crude reaction mixture
  8. customon column chromatographic purification

Sources & evidence

ORD record
ord-491f6d77feee41e6aa1d57cb40a0da9c
Source dataset
uspto-grants-2015_03
Patent number
US08987318B2

Reaction notes

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