Sodium hydride → Methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate

HRID 625671Notes

Reaction equation

HRID 625671 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[S:9][C:10]([Cl:13])=[CH:11][CH:12]=2)=[CH:6][CH:5]=[C:4]([Cl:14])[C:3]=1[CH2:15][C:16]([NH:18][C:19]1[N:20]=[CH:21][S:22][C:23]=1[C:24]([O:26][CH3:27])=[O:25])=[O:17].[H-].[Na+].FC(F)(F)S(O[CH2:36][CH:37]([F:39])[F:38])(=O)=O>O1CCCC1>[Cl:1][C:2]1[C:7]([C:8]2[S:9][C:10]([Cl:13])=[CH:11][CH:12]=2)=[CH:6][CH:5]=[C:4]([Cl:14])[C:3]=1[CH2:15][C:16]([N:18]([CH2:36][CH:37]([F:39])[F:38])[C:19]1[N:20]=[CH:21][S:22][C:23]=1[C:24]([O:26][CH3:27])=[O:25])=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 89826309HCID 89826309, compound

Product 1

HCID 89826349Methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an atmosphere of argon, 300 mg (0.65 mmol) of methyl 4-({[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}amino)-1,3-thiazole-5-carboxylate were dissolved in 15 ml of tetrahydrofuran, and 23 mg (0.97 mmol) of sodium hydride were added at room temperature. The reaction mixture was stirred at RT for 5 min, and a solution of 167 mg (0.78 mmol) of 2,2-difluoroethyl trifluoromethanesulfonate in 6 ml of THF was then added over a period of 10 min. The mixture is then stirred at RT for 12 h. The THF is removed under reduced pressure and the residue is taken up in water. The aqueous phase is extracted with dichloromethane and the organic phase is dried and concentrated by evaporation. The residue is chromatographed (acetonitrile/water (0.05% trifluoroacetic acid 20/80 to 100/0)). This gave 120 mg of methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate.

Workup

  1. stirringThe mixture is then stirred at RT for 12 h
  2. customThe THF is removed under reduced pressure
  3. extractionThe aqueous phase is extracted with dichloromethane
  4. customthe organic phase is dried
  5. concentrationconcentrated by evaporation
  6. customThe residue is chromatographed (acetonitrile/water (0.05% trifluoroacetic acid 20/80 to 100/0))

Sources & evidence

ORD record
ord-ff7f5a849e64479db44b0a381f2613d2
Source dataset
uspto-grants-2016_04
Patent number
US09307767B2

Reaction notes

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