Potassium Fluoride → HCID 58497205, compound

HRID 1254069Notes

Reaction equation

HRID 1254069 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12](I)=[N:11][C:10]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.[Sn].[S:27]1[CH:31]=[CH:30][CH:29]=[CH:28]1.[F-].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:28]3[S:27][CH:31]=[CH:30][CH:29]=3)=[N:11][C:10]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 58497179HCID 58497179, compoundHCID 70095885HCID 70095885, compound

Product 1

HCID 58497205HCID 58497205, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of Example 133 compound (34 mg, 0.067 mmol), thiophene tin reagent (22.34 μl, 0.0704 mmol) and Pd(PPh3)4 (77.42 mg, 0.067 mmol) in dioxane (1 ml) was vacuumed and purged to N2 for 3 times, then reaction mixture was heated at 110° C. for 4 hrs. The reaction mixture was cooled to rt, added KF (sat, 1 ml), stirred at rt for one hour, filtered, washed with EtOAc, and separated to two layers. The organic layer was washed with brine, dried, filtered, concentrated, and separated by prep TLC (CH2Cl2:Hex:EtOAc=3:3:1) to afford 5-[(4-chlorophenyl)sulfanyl]-1-methyl-4-[4-(methylsulfonyl)phenyl]-2-(thiophen-2-yl)-1H-imidazole (25 mg). 1H NMR (500 MHz), [CDCl3]: 8.38 (m, 2H), 7.95 (m, 2H), 7.50 (m, 2H), 7.40 (m, 2H), 7.15 (m, 1H), 7.10 (m, 2H), 3.82 (s, 3H), 3.05 (s, 3H). LCMS: [M+1]+=461.0. Human FAAH lysate assay: IC50=16.5 nM.

Workup

  1. custompurged to N2 for 3 times
  2. customreaction mixture
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered
  5. washwashed with EtOAc
  6. customseparated to two layers
  7. washThe organic layer was washed with brine
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customseparated by prep TLC (CH2Cl2:Hex:EtOAc=3:3:1)

Sources & evidence

ORD record
ord-75b010c60eb84bd0b9862bb7ca510a5d
Source dataset
uspto-grants-2013_06
Patent number
US08455528B2

Reaction notes

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