Potassium Carbonate → HCID 69586224, compound

HRID 723149Notes

Reaction equation

HRID 723149 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([S:23][CH3:24])=[C:8]([S:10]([C:13]2[CH:21]=[C:20]([Cl:22])[C:16]3[NH:17][CH:18]=[N:19][C:15]=3[CH:14]=2)(=[O:12])=[O:11])[CH:9]=1)=[O:4].Br[CH2:26][C:27]1[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=1[F:34].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[NH3:17].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([S:23][CH3:24])=[C:8]([S:10]([C:13]2[CH:21]=[C:20]([Cl:22])[C:16]3[N:17]=[CH:18][N:19]([CH2:26][C:27]4[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=4[F:34])[C:15]=3[CH:14]=2)(=[O:11])=[O:12])[CH:9]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([S:23][CH3:24])=[C:8]([S:10]([C:13]2[CH:21]=[C:20]([Cl:22])[C:16]3[N:17]([CH2:26][C:27]4[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=4[F:34])[CH:18]=[N:19][C:15]=3[CH:14]=2)(=[O:11])=[O:12])[CH:9]=1)=[O:4]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 5814352-(Bromomethyl)-1,3-difluorobenzeneHCID 178498675HCID 178498675, compound

Product 3

HCID 222AmmoniaHCID 69586224HCID 69586224, compoundYield 115.9%HCID 69586394HCID 69586394, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-(7-chloro-1H-benzoimidazole-5-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxylic acid methyl ester ((from above step c) 0.201 g, 0.499 mmol) in DMF (4 mL) was treated with α-bromo-2,6-difluorotoluene (0.114 g, 0.549 mmol) and solid K2CO3 (0.152 g, 1.10 mmol). The reaction was stirred at room temperature 17 h, diluted with EtOAc and washed well with water (5×150 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (2% MeOH with 2 M NH3 in CH2Cl2) afforded the products 4-[7-chloro-3-(2,6-difluoro-benzyl)-3H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid methyl ester and 4-[7-chloro-1-(2,6-difluoro-benzyl)-1H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid methyl ester (0.102 g, 38%). These isomers were not separable by silica gel chromatography, but they were carried on together into the next reaction.

Workup

  1. washwashed well with water (5×150 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-70af8efd1d0f4fd8b580ddd96fbd25ac
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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