1,2-Dichloroethane → HCID 86714171, compound

HRID 1411017Notes

Reaction equation

HRID 1411017 reaction equation
CO[C:3]([C:5]1[C:6]([OH:31])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11](CC1C=CC=CC=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1)=[CH:8]2)=[O:4].[OH-].[Na+].[CH:34]1[CH:35]=[CH:36][C:37]2N(O)N=N[C:38]=2[CH:39]=1.[CH2:44](Cl)CCl.Cl.[CH2:49]([O:51][C:52](=[O:57])[CH2:53][CH2:54][CH2:55][NH2:56])[CH3:50].CCN(C(C)C)C(C)C>CCOC(C)=O.C(Cl)Cl.C1COCC1.CO>[CH2:49]([O:51][C:52](=[O:57])[CH2:53][CH2:54][CH2:55][NH:56][C:3]([C:5]1[N:14]([CH2:44][C:38]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:39]=2)[CH:13]=[C:12]2[C:7](=[CH:8][CH:9]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)[C:10](=[O:22])[NH:11]2)[C:6]=1[OH:31])=[O:4])[CH3:50]

Participants

11

Reactant 6

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 126496614-Aminobutyrate ethyl hydrochlorideHCID 68297520HCID 68297520, compound

Product 1

HCID 86714171HCID 86714171, compoundYield 52.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-3-(3-methoxy-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.14 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. overnight, 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. To the residue were then added HOBt (32 mg, 0.23 mmol), CH2Cl2 (3 mL), and EDC (50 mg, 0.26 mmol), and the resulting mixture was stirred for 10 min. 4-Amino-butyric acid ethyl ester HCl salt (39 mg, 0.23 mmol) and Hunig's base (0.1 mL, 0.52 mmol) were added, and the mixture was stirred for 48 h. The mixture was diluted with EtOAc and washed with 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH) to give 38 mg of the title compound. MS: (+) m/z 516.37 (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. stirringthe mixture was stirred for 48 h
  7. washwashed with 0.1 M HCl
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-1c4446dbb7bc4ec0951cb264914175f0
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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