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

HRID 920024Notes

Reaction equation

HRID 920024 reaction equation
C([O:3][C:4]([C:6]1([NH:9][C:10]([C:12]2[C:13]([OH:42])=[C:14]3[C:19](=[C:20]([C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)[N:21]=2)[N:18]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:17](=[O:35])[C:16]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:15]3)=[O:11])[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].CO.C1COCC1>C([O-])(O)=O.[Na+]>[CH2:28]([N:18]1[C:19]2[C:14](=[C:13]([OH:42])[C:12]([C:10]([NH:9][C:6]3([C:4]([OH:5])=[O:3])[CH2:7][CH2:8]3)=[O:11])=[N:21][C:20]=2[C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:15]=[C:16]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:17]1=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 682976101-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 682976571-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acidYield 56.8%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acid ethyl ester (24 mg, 0.043 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 (10-100% 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 13 mg of the title compound as a light yellow solid. MS: (+) m/z 533.37 (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 (10-100% 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-d89251b171d14055b4e4f53743f8a261
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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