1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-(4-(1,3-dioxolan-2-yl)phenyl)-5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazole

HRID 1941887Notes

Reaction equation

HRID 1941887 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=O)[CH:9]=[N:8]1.CC[N:21]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[O:40]1[CH2:44][CH2:43][O:42][CH:41]1[C:45]1[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][CH:46]=1>CN(C=O)C>[O:40]1[CH2:44][CH2:43][O:42][CH:41]1[C:45]1[CH:52]=[CH:51][C:48]([C:49]2[N:21]=[C:16]([C:10]3[CH:9]=[N:8][N:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[C:11]=3[C:12]([F:13])([F:14])[F:15])[O:18][N:50]=2)=[CH:47][CH:46]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27784284-(1,3-Dioxolan-2-yl)benzonitrileHCID 167877231-(2-Pyridinyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 669966503-(4-(1,3-dioxolan-2-yl)phenyl)-5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (31.46 g, 122 mmol) in DMF (200 mL) was added EDCI (23.34 g, 134 mmol) and HOBt (16.53 g, 122 mmol). After the reaction was stirred for 30 min. at room temperature 4-(1,3-dioxolan-2-yl)benzonitrile, Int.6-A, (16.53 g, 122 mmol) was added. The reaction mixture was stirred at 140° C. for 4 hr. The reaction mixture was concentrated under reduced pressure to remove the volatiles. The residue was partitioned between water and ethyl acetate and the organic layer was washed with aq. HCl solution, NaHCO3 solution, water, and brine before being dried over Na2SO4 and concentrated to provide 3-(4-(1,3-dioxolan-2-yl)phenyl)-5-(1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazole (25 g, 58 mmol). The compound had an HPLC retention time=6.15 min. −Column: HYPERSIL® BDS C18 (4.6×50 mm) Flow rate=0.8 mL/min. Solvent A=, 0.1% TFA in water; Solvent B=acetonitrile. 5%-100% B (0-6 min), 100% B (6-9 min), 100%-5% B (9-11 min). LC/MS M+1=430.0.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto remove the volatiles
  4. customThe residue was partitioned between water and ethyl acetate
  5. washthe organic layer was washed with aq. HCl solution, NaHCO3 solution, water, and brine
  6. dry with materialbefore being dried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-52e85c73cce64fa2971456a0772dae4b
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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