Pyridine → 3-{4-[4-butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-trifluoromethyl-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2233583Notes

Reaction equation

HRID 2233583 reaction equation
[CH2:1]([C:5]1[N:6]=[C:7]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[S:8][C:9]=1[CH2:10][O:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([NH:18][OH:19])=[NH:17])=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.[C:42]1([O:48]C(Cl)=O)C=CC=CC=1>ClCCl>[CH2:1]([C:5]1[N:6]=[C:7]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=2)[S:8][C:9]=1[CH2:10][O:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]2[NH:17][C:42](=[O:48])[O:19][N:18]=2)=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 178441583HCID 178441583, compound

Product 1

HCID 1359619803-{4-[4-butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-trifluoromethyl-phenyl}-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 89.3 mg of 4-[4-butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-N-hydroxy-2-trifluoromethyl-benzamidine in 2 ml of anhydrous dichloromethane were added 92 μl pyridine followed by 21.6 μl phenylchloroformate dropwise. The resulting mixture was stirred at room temperature for 1 h. The solvent was removed in vacuo. To a solution of the resulting residue in 2.5 ml of acetonitrile was added 88 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene. The mixture was stirred under microwave heating at 180° C. for 10 minutes (or stirred at room temperature overnight). The solvent was removed in vacuo and the crude product was purified by column chromatography on silica gel (heptane 1/ethyl acetate 1 then dichloromethane 95/methanol 5 followed by another column with dichloromethane 90/acetone 10) to give 65 mg of 3-{4-[4-butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-trifluoromethyl-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. customThe solvent was removed in vacuo
  2. additionTo a solution of the resulting residue in 2.5 ml of acetonitrile was added 88 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene
  3. stirringThe mixture was stirred under microwave
  4. temperatureheating at 180° C. for 10 minutes
  5. stirring(or stirred at room temperature overnight)
  6. customThe solvent was removed in vacuo
  7. customthe crude product was purified by column chromatography on silica gel (heptane 1/ethyl acetate 1

Sources & evidence

ORD record
ord-b0835dc2feac44908f863676fff34caa
Source dataset
uspto-grants-2010_05
Patent number
US07709509B2

Reaction notes

Loading…