Hydrochloric Acid → 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-(3-oxo-3-pyrrolidin-1-yl-propyl)-3H-benzoimidazole-5-carboxylic acid

HRID 217035Notes

Reaction equation

HRID 217035 reaction equation
C[O:2][C:3]([C:5]1[C:22]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=2[Cl:31])=[C:21]([F:32])[C:8]2[N:9]=[CH:10][N:11]([CH2:12][CH2:13][C:14](=[O:20])[N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:7]=2[CH:6]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1.O.CCOC(C)=O>[Br:30][C:27]1[CH:28]=[CH:29][C:24]([NH:23][C:22]2[C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]3[N:11]([CH2:12][CH2:13][C:14](=[O:20])[N:15]4[CH2:19][CH2:18][CH2:17][CH2:16]4)[CH:10]=[N:9][C:8]=3[C:21]=2[F:32])=[C:25]([Cl:31])[CH:26]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66885285HCID 66885285, compound

Product 1

HCID 211142056-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-(3-oxo-3-pyrrolidin-1-yl-propyl)-3H-benzoimidazole-5-carboxylic acidYield 104.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-(3-oxo-3-pyrrolidin-1-yl-propyl)-3H-benzoimidazole-5-carboxylic acid methyl ester (41 mg, 0.079 mmol) in THF/H2O (1.5 mL/0.75 mL) is added 0.20 mL (0.20 mmol) of 1 N aqueous LiOH at room temperature. The resulting solution is stirred 16 hours. The reaction mixture is acidified with 1 N aqueous HCl (pH ˜2 to 3) and diluted with EtOAc. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give a crude product (42 mg) which is directly used without further purification.

Workup

  1. dry with materialThe organic layer is dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-01bff00181174b57a6843bc644c0b254
Source dataset
uspto-grants-2012_06
Patent number
US08193231B2

Reaction notes

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