Methanol → HCID 178497006, compound

HRID 1176927Notes

Reaction equation

HRID 1176927 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[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4].CO.C1C(=O)N([I:32])C(=O)C1.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1COCC1.C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([I:32])=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 887Methanol2×HCID 120273N-IodosuccinimideHCID 521998p-Toluenesulfonic acid monohydrateHCID 178497005HCID 178497005, compound

Product 1

HCID 178497006HCID 178497006, compoundYield 69.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

7-Fluoro-6-o-tolylamino-1H-benzoimidazole-5-carboxylic acid methyl ester 7a (1.47 g, 4.92 mmol) is suspended in 1:1 THF:MeOH mixture (44 mL) and cooled to −78° C. under a nitrogen atmosphere. A solution of NIS (1.66 g, 7.39 mmol) in THF (2 mL) is added followed by a MeOH (2 mL) solution of TsOH.H2O (1.87 g, 9.84 mmol). After 30 minutes, the reaction mixture is warmed to 0° C. and 1 mL methylene chloride is added. The reaction is slowly allowed to warm to room temperature with stirring over 16 hours. The reaction mixture is quenched by the addition of 10% Na2S2O4 solution. The reaction mixture is then diluted with water and ethyl acetate and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. The recovered solid is triturated with MeOH to give 1.45 g (69%) pure desired product: MS ESI (+) m/z 426 (M+1) detected; MS ESI (−) m/z 424 (M−1) detected.

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction mixture is quenched by the addition of 10% Na2S2O4 solution
  3. additionThe reaction mixture is then diluted with water and ethyl acetate
  4. customthe layers separated
  5. extractionThe aqueous layer is extracted with ethyl acetate
  6. dry with materialThe combined organic extracts are dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe recovered solid is triturated with MeOH

Sources & evidence

ORD record
ord-97eabb6cee8e439e9db59c09b8a95a90
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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