Methanol → 3-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid

HRID 1411025Notes

Reaction equation

HRID 1411025 reaction equation
C([O:3][C:4](=[O:43])[C:5]([CH3:42])([CH3:41])[CH2:6][NH:7][C:8]([C:10]1[C:11]([OH:40])=[C:12]2[C:17](=[C:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[N:19]=1)[N:16]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:15](=[O:33])[C:14]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[CH:13]2)=[O:9])C.[OH-].[Na+].CO.C1COCC1>C([O-])(O)=O.[Na+]>[CH2:26]([N:16]1[C:17]2[C:12](=[C:11]([OH:40])[C:10]([C:8]([NH:7][CH2:6][C:5]([CH3:42])([CH3:41])[C:4]([OH:43])=[O:3])=[O:9])=[N:19][C:18]=2[C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:13]=[C:14]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:15]1=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 682974583-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl ester

Product 1

HCID 682975313-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acidYield 29.4%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl ester (30 mg, 0.052 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. for 16 h, then concentrated to approximately one-third of its original volume. 1 M HCl was added to acidify the mixture, and the resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4, and the resulting precipitate was isolated by filtration to give 8.4 mg of the title compound as a light yellow solid. MS: (+) m/z 549.56 (M+1).

Workup

  1. concentrationconcentrated to approximately one-third of its original volume
  2. addition1 M HCl was added
  3. extractionthe resulting suspension was extracted with EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH)
  7. customThe product isolated
  8. washwashed several times with ether
  9. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-5ca5abc7f8444f349e7cf0e291f73e1c
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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