Hydrochloric Acid → Vadadustat

HRID 1797992Notes

Reaction equation

HRID 1797992 reaction equation
C[O:2][C:3](=[O:22])[CH2:4][NH:5][C:6]([C:8]1[C:13]([OH:14])=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:10][N:9]=1)=[O:7].[OH-].[Na+].Cl>C1COCC1>[Cl:21][C:17]1[CH:16]=[C:15]([C:11]2[CH:12]=[C:13]([OH:14])[C:8]([C:6]([NH:5][CH2:4][C:3]([OH:22])=[O:2])=[O:7])=[N:9][CH:10]=2)[CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24891582HCID 24891582, compound

Product 1

HCID 23634441VadadustatYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {[5-(3-chloro-phenyl)-3-hydroxy-pyridine-2-carbonyl]-amino}-acetic acid methyl ester, 6, (0.163 g, 0.509 mmol) in THF (5 mL) is added 1M NaOH (1.5 ml, 1.27 mmol) and the reaction mixture stirred at room temperature for 1 hour. The solution is acidified using 1M HCl (3 mL), the solvent removed under reduced pressure and the resulting solid suspended in CHCl3:iso-propanol (1:1), filtered and the filtrate dried (MgSO4), filtered and re-concentrated under reduced pressure. The crude material is triturated with a small amount of MeOH to afford 0.10 g (64% yield) of the desired product as a colorless solid. 1H NMR (400 MHz, MeOD) δppm 8.31 (1H, d, J=1.8 Hz), 7.47 (2 H, d, J=1.8 Hz), 7.30-7.65 (4H, m), 4.07 (2H, s). HPLC-MS: m/z 307 [M+H]+.

Workup

  1. customthe solvent removed under reduced pressure
  2. filtrationfiltered
  3. dry with materialthe filtrate dried (MgSO4)
  4. filtrationfiltered
  5. concentrationre-concentrated under reduced pressure
  6. customThe crude material is triturated with a small amount of MeOH

Sources & evidence

ORD record
ord-21fbba636a9047e7b8b199f6675e1cde
Source dataset
uspto-grants-2013_01
Patent number
US08343952B2

Reaction notes

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