Hydrochloric Acid → HCID 131735817, compound

HRID 2205567Notes

Reaction equation

HRID 2205567 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([NH:17][C:18]3[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=3[F:25])=[O:16])=[CH:10][CH:9]=2)=[CH:6][C:5]([B:26]2[O:30]C(C)(C)C(C)(C)[O:27]2)=[CH:4][N:3]=1.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([B:26]([OH:27])[OH:30])=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=2[F:25])=[O:16])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 131735816HCID 131735816, compound

Product 1

HCID 131735817HCID 131735817, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 1-(4-(2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea (AGN-227971, 108 mg, 0.234 mmol, 1 eq) in anhydrous tetrahydrofuran (2 mL) was added aq HCl (3N, 2 mL) and the reaction was first stirred at room temperature for two hours. Additional conc. HCl (0.5 mL) was dropwise added to the reaction and the mixture was stirred at 50° C. for further four hours. The reaction was then poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was isolated, washed with brine, and dried with anhydrous sodium sulfate. The upper clear solution was decanted, concentrated to lesser amount, and the solid crashed-out was filtered. This solid was further purified by a reversed phase chromatography (from WATER-CH3CN 9:1 to CH3CN) to give (6-amino-5-(4-(3-(2-fluoro-5-methylphenyl)ureido)phenyl)pyridin-3-yl)boronic acid as a grey solid in amount of 7 mg.

Workup

  1. stirringthe mixture was stirred at 50° C. for further four hours
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was isolated
  4. washwashed with brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. customThe upper clear solution was decanted
  7. concentrationconcentrated to lesser amount
  8. filtrationthe solid crashed-out was filtered
  9. customThis solid was further purified by a reversed phase chromatography (from WATER-CH3CN 9:1 to CH3CN)

Sources & evidence

ORD record
ord-7ac4e97dad7242ee9e1c4976cdee4669
Source dataset
uspto-grants-2016_06
Patent number
US09371314B2

Reaction notes

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