Tetrahydrofuran → 3-{[1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid

HRID 919926Notes

Reaction equation

HRID 919926 reaction equation
C[O:2][C:3](=[O:37])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:10]([OH:36])=[C:11]2[C:16](=[CH:17][N:18]=1)[N:15]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14](=[O:26])[C:13]([C:27]1[CH:28]=[N:29][C:30]([N:33]([CH3:35])[CH3:34])=[N:31][CH:32]=1)=[CH:12]2)=[O:8].[OH-].[Na+].C1COCC1>CO>[CH2:19]([N:15]1[C:16]2[C:11](=[C:10]([OH:36])[C:9]([C:7]([NH:6][CH2:5][CH2:4][C:3]([OH:37])=[O:2])=[O:8])=[N:18][CH:17]=2)[CH:12]=[C:13]([C:27]2[CH:32]=[N:31][C:30]([N:33]([CH3:35])[CH3:34])=[N:29][CH:28]=2)[C:14]1=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 682975973-{[1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid methyl ester

Product 1

HCID 601518213-{[1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acidYield 54.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-{[1-benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid methyl ester (30 mg, 0.060 mmol), 2 M NaOH (2 mL), THF (2 mL) and MeOH (2 mL) was stirred at r.t. overnight. The mixture was concentrated to approximately one-third of its original volume. 1 M HCl was added until pH was about 4, and the resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The residue was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 4 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 16 mg of the title compound as a pale yellow solid. MS: (+) m/z 489.29 (M+1).

Workup

  1. concentrationThe mixture was concentrated to approximately one-third of its original volume
  2. addition1 M HCl was added until pH was about 4
  3. extractionthe resulting suspension was extracted with EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in saturated NaHCO3
  7. washwashed several times with ether
  8. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-f41eb3454f4f4ca5bba74bc45d1d6759
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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