Methanol → Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate

HRID 1176867Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])=[C:12]([F:22])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].CO.CC1C=CC(S(O)(=O)=O)=CC=1.O.C1C(=O)N([Br:44])C(=O)C1>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:44])=[CH:17][C:16]=2[Cl:21])=[C:12]([F:22])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

6-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 7b (55 mg, 0.172 mmol) is dissolved in 1:1 THF:MeOH (2 mL) and cooled to −78° C. under an atmosphere of nitrogen. TsOH.H2O (49 mg, 0.258 mmol) is added followed by NBS (31 mg, 0.174 mmol). After 10 minutes, the reaction mixture is warmed to 0° C. and then 2 hours later warmed to rt. After 16 hours, the reaction mixture is quenched by the addition of 10% Na2S2O3 and diluted with ethyl acetate and water. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extract are dried (MgSO4) and concentrated under reduced pressure. The product is triturated with methylene chloride to dive 58 mg (85%) of pure desired product as a tan solid.

Workup

temperature2 hours later warmed to rt
waitAfter 16 hours
customthe reaction mixture is quenched by the addition of 10% Na2S2O3
additiondiluted with ethyl acetate and water
customThe layers are separated
extractionthe aqueous layer is extracted with ethyl acetate
extractionThe combined organic extract
dry with materialare dried (MgSO4)
concentrationconcentrated under reduced pressure
customThe product is triturated with methylene chloride

Sources & evidence

ORD record: ord-fc7db0c7646b428486ba8898632930c3
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842816B2

Reaction notes

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