Hydrochloric Acid → 4-((5-Chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-(difluoromethoxy)benzoic acid

HRID 2403472Notes

Reaction equation

HRID 2403472 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][CH3:24])=[N:4][C:5]([NH:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=[O:14])=[CH:11][C:10]=2[O:19][CH:20]([F:22])[F:21])=[N:6][CH:7]=1.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[C:3]([NH:23][CH3:24])=[N:4][C:5]([NH:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=2[O:19][CH:20]([F:21])[F:22])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 58539120Methyl 4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(difluoromethoxy)benzoate

Product 1

HCID 585391254-((5-Chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-(difluoromethoxy)benzoic acidYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(difluoromethoxy)benzoate (500 mg) was dissolved in 5 mL of THF and 5 mL of water. After dissolution, 234 mg of lithium hydroxide was added and the reaction was stirred at room temperature over night. The mixture was checked by LCMS and then carefully acidified with 1N HCl and partitioned with ethyl acetate. The organic layer was concentrated and purified by silica gel chromatography to give 250 mg of 4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(difluoromethoxy)benzoic acid.

Workup

  1. additionwas added
  2. custompartitioned with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-1b8455a556d34d2ab1035d77c7270a47
Source dataset
uspto-grants-2014_08
Patent number
US08802674B2

Reaction notes

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