1,2-Dichloroethane → HCID 68297375, compound

HRID 1411019Notes

Reaction equation

HRID 1411019 reaction equation
CO[C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].[OH-].[Na+].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:47]([O:49][C:50]([C:52]1([NH2:55])[CH2:54][CH2:53]1)=[O:51])[CH3:48].CCN(C(C)C)C(C)C>CCOC(C)=O.C(Cl)Cl.C1COCC1.CO>[CH2:47]([O:49][C:50]([C:52]1([NH:55][C:3]([C:5]2[C:6]([OH:29])=[C:7]3[C:12](=[CH:13][N:14]=2)[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10](=[O:22])[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:8]3)=[O:4])[CH2:54][CH2:53]1)=[O:51])[CH3:48]

Participants

11

Reactant 6

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 682973581-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297375HCID 68297375, compoundYield 51.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.16 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 (34 mg, 0.25 mmol), CH2Cl2 (3 mL), and EDC (54 mg, 0.28 mmol), and the resulting mixture was stirred for 10 min. 1-Amino-cyclopropanecarboxylic acid ethyl ester HCl salt (41 mg, 0.25 mmol) and Hunig's base (0.1 mL, 0.56 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 (5-45% EtOAc/hexanes+1% AcOH) to give 40 mg of the title compound. MS: (+) m/z 484.37 (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 (5-45% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-b31a967bd8d64fa4a5bf96f6bc1a07c1
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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