Reaction #474645

Reaction equation

4-chloro-2-pyridine-carboxamide

potassium bis(trimethylsilyl)amide

4-(5-{[4-chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol

K2CO3

→

title product

Yield 79.8%

4-[4-(5-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-1,3,4-oxadiazol-2-yl)phenoxy]-N-methylpyridine-2-carboxamide trifluoroacetate salt

Yield 79.8%

Solvents

MeOH

DMF

Conditions

Workup

1. 1
   OtherThe reaction mixture was microwaved at 200 C for 15 min
2. 2
   Filtrationfiltered through 0.22 um syringe
3. 3
   Filtrationfilter
4. 4
   Otherpurified by preparative reverse-phase chromatography
5. 5
   Otherwas collected
6. 6
   Othersolvent was removed in vacuo

Procedure

4-(5-{[4-chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol (100 mg, 0.281 mmol) was dissolved in ca. 2 mL of anhydrous DMF under argon. Solid potassium bis(trimethylsilyl)amide (140.2 mg, 0.702 mmol) was added and the resulting yellow solution was heated at 80° C. for 15 min. Then solid K2CO3 (19.4 mg, 0.140 mmol) was added, followed by 4-chloro-2-pyridine-carboxamide (52.7 mg, 0.309 mmol). The reaction mixture was microwaved at 200 C for 15 min. Then it was diluted with 1 mL of MeOH, filtered through 0.22 um syringe filter and purified by preparative reverse-phase chromatography using acetonitrile/water gradient with 0.1% TFA. The major peak having the mass of the product was collected; solvent was removed in vacuo to give the title product as a white solid (67.5 mg).

Source