Sodium hydride → 6-[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]-4-(2,2-difluoroethyl)-7-hydroxy[1,3]thiazolo[4,5-b]pyridin-5(4H)-one

HRID 625672Notes

Reaction equation

HRID 625672 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]([N:18]([CH2:28][CH:29]([F:31])[F:30])[C:19]1[N:20]=[CH:21][S:22][C:23]=1[C:24]([O:26]C)=O)=[O:17].[H-].[Na+]>C1COCC1>[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[C:15]1[C:16](=[O:17])[N:18]([CH2:28][CH:29]([F:30])[F:31])[C:19]2[N:20]=[CH:21][S:22][C:23]=2[C:24]=1[OH:26]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 89826349Methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate

Product 1

HCID 898260626-[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]-4-(2,2-difluoroethyl)-7-hydroxy[1,3]thiazolo[4,5-b]pyridin-5(4H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

120 mg (0.23 mmol) of methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate were dissolved in 10 ml of THF, and 6.6 mg (0.27 mmol) of sodium hydride were added under an atmosphere of argon. The reaction mixture was stirred at RT for 4 h. The THF was then removed under reduced pressure and the residue was taken up in water. The aqueous phase was extracted with dichloromethane, the organic phase was dried and concentrated by evaporation, the aqueous phase was acidified with 1N hydrochloric acid. After extraction with dichloromethane, the organic phase was dried and concentrated by evaporation. The product-containing residues were chromatographed (acetonitrile/water (0.05% trifluoroacetic acid) 20/80 to 100/0)). This gave 50 mg of 6-[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]-4-(2,2-difluoroethyl)-7-hydroxy[1,3]thiazolo[4,5-b]pyridin-5(4H)-one.

Workup

  1. customThe THF was then removed under reduced pressure
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. customthe organic phase was dried
  4. concentrationconcentrated by evaporation
  5. extractionAfter extraction with dichloromethane
  6. customthe organic phase was dried
  7. concentrationconcentrated by evaporation
  8. customThe product-containing residues were chromatographed (acetonitrile/water (0.05% trifluoroacetic acid) 20/80 to 100/0))

Sources & evidence

ORD record
ord-544b55a91be6467d86a10ea037d1b2fe
Source dataset
uspto-grants-2016_04
Patent number
US09307767B2

Reaction notes

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