Methyl iodide → HCID 22031538, compound

HRID 1792589Notes

Reaction equation

HRID 1792589 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([C:19]([C:22]([NH:24][NH2:25])=[O:23])=[CH:20][N:21]=4)[CH:18]=3)=[CH:11][N:10]([C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].[Cl-].[NH4+].C(=O)([O-])[O-].[K+].[K+].[CH3:55]I.[C:57](=[S:59])=S>O.C(OCC)(=O)C.CN(C)C=O.O1CCCC1.C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([C:19]([C:22]5[O:23][C:55]([S:59][CH3:57])=[N:25][N:24]=5)=[CH:20][N:21]=4)[CH:18]=3)=[CH:11][N:10]([C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[N:9]=2)=[CH:6][CH:7]=1

Participants

12

Reactant 6

HCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 23537391HCID 23537391, compound

Product 1

HCID 22031538HCID 22031538, compound

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 283 mg 6-[3-(4-fluorophenyl)-1-trityl-1H-pyrazol-4-yl]imidazo[1,2-a]pyridine-3-carboxylic acid hydrazide (compound in Production Example 274), 38 mg carbon disulfide, 20 mg sodium hydroxide, 5 mL ethanol and 5 mL water was heated for 4 hours under reflux. Ethyl acetate, tetrahydrofuran and an aqueous saturated ammonium chloride solution were added to the reaction solution, and the organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The drying agent was filtered off, and the filtrate was evaporated. 285 mg crude product of 5-{6-[3-(4-fluorophenyl)-1-trityl-1H-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl}[1,3,4]oxadiazol-2-thiol was obtained as pale yellow crystals. To a mixture of this thiol derivative, 128 mg potassium carbonate and 10 mL N,N-dimethylformamide under ice-coolingd water in a stream of nitrogen was added 32 μL methyl iodide, and the mixture was stirred for 10 minutes. Ethyl acetate and water were added to the reaction solution, and the organic layer was separated, washed twice with water and then with brine and dried over anhydrous sodium sulfate. The drying agent was filtered off, and the filtrate was evaporated. The resulting residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 148 mg of the title compound as a colorless amorphous.

Workup

  1. temperaturewas heated for 4 hours
  2. temperatureunder reflux
  3. customthe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe drying agent was filtered off
  7. customthe filtrate was evaporated
  8. custom285 mg crude product of 5-{6-[3-(4-fluorophenyl)-1-trityl-1H-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl}[1,3,4]oxadiazol-2-thiol was obtained as pale yellow crystals
  9. customthe organic layer was separated
  10. washwashed twice with water
  11. dry with materialwith brine and dried over anhydrous sodium sulfate
  12. filtrationThe drying agent was filtered off
  13. customthe filtrate was evaporated
  14. customThe resulting residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9f9a04dd3f434f1c9a3c9edb8338bd2d
Source dataset
uspto-grants-2006_07
Patent number
US07074801B1

Reaction notes

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