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

HRID 1767795Notes

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 extracts are dried (MgSO4) and concentrated under reduced pressure. The crude product is triturated with methylene chloride to give 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
dry with materialThe combined organic extracts are dried (MgSO4)
concentrationconcentrated under reduced pressure
customThe crude product is triturated with methylene chloride

Sources & evidence

ORD record: ord-853894c37d1a4f21bb2c403ac21b2cf5
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07235537B2

Reaction notes

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