Potassium Carbonate → 4-[4-(5-{[4-Chloro-3-(trifluoromethyl)phenyl]amino}-1,3,4-oxadiazol-2-yl)phenoxy]-n-methylpyridine-2-carboxamide trifluoroacetate salt

HRID 1994036Notes

Reaction equation

HRID 1994036 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)=[N:11][N:10]=2)=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].[CH3:25][Si]([N-][Si](C)(C)C)(C)C.[K+].[C:35]([O-:38])([O-])=[O:36].[K+].[K+].Cl[C:42]1[CH:47]=[CH:46][N:45]=[C:44]([C:48]([NH2:50])=[O:49])[CH:43]=1>CN(C=O)C.CO>[F:22][C:21]([F:24])([F:23])[C:35]([OH:38])=[O:36].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:13][C:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:42]4[CH:47]=[CH:46][N:45]=[C:44]([C:48]([NH:50][CH3:25])=[O:49])[CH:43]=4)=[CH:18][CH:19]=3)=[N:11][N:10]=2)=[CH:4][C:3]=1[C:21]([F:22])([F:23])[F:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 3035434-Chloropyridine-2-carboxamideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1361796924-(5-{[4-Chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol

Product 1

HCID 866042894-[4-(5-{[4-Chloro-3-(trifluoromethyl)phenyl]amino}-1,3,4-oxadiazol-2-yl)phenoxy]-n-methylpyridine-2-carboxamide trifluoroacetate saltYield 79.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

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).

Workup

  1. customThe reaction mixture was microwaved at 200 C for 15 min
  2. filtrationfiltered through 0.22 um syringe
  3. filtrationfilter
  4. custompurified by preparative reverse-phase chromatography
  5. customwas collected
  6. customsolvent was removed in vacuo

Sources & evidence

ORD record
ord-b87d2a6400e943688289050d5549394f
Source dataset
uspto-grants-2010_01
Patent number
US07652051B2

Reaction notes

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