1,2-Dichloroethane → HCID 86714188, compound

HRID 920089Notes

Reaction equation

HRID 920089 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4].[OH-].[Na+].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:41]([O:43][C:44]([C:46]1([NH2:49])[CH2:48][CH2:47]1)=[O:45])[CH3:42].CCN(C(C)C)C(C)C>CCOC(C)=O.[Cl-].[Na+].O.Cl.C(Cl)Cl.C1COCC1.CO>[CH2:41]([O:43][C:44]([C:46]1([NH:49][C:3]([C:5]2[N:6]=[CH:7][C:8]3[C:9](=[O:23])[N:10]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:11]=[CH:12][C:13]=3[C:14]=2[OH:15])=[O:4])[CH2:48][CH2:47]1)=[O:45])[CH3:42]

Participants

13

Reactant 6

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 682977357-Benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester

Product 1

HCID 86714188HCID 86714188, compoundYield 33.2%

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (53 mg, 0.17 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. for 16 h, then concentrated to dryness. The residue was dissolved in water and acidified to pH about 2 with 1 M HCl. The resulting precipitate was isolated by filtration. To the crude solid were added CH2Cl2 (3 mL), HOBt (29 mg, 0.22 mmol), and EDC (47 mg, 0.24 mmol), and the resulting mixture was stirred for 10 min. 1-Amino-cyclopropanecarboxylic acid ethyl ester HCl salt (36 mg, 0.22 mmol) and Hunig's base (0.086 mL, 0.49 mmol) were added, and the mixture was stirred for 16 h. The mixture was diluted with EtOAc and brine, and 1 M HCl was added until pH was about 2. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-40% EtOAc/hexanes+1% AcOH) to give 23 mg of the title compound. MS: (+) m/z 408.29 (M+1).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in water
  3. customThe resulting precipitate was isolated by filtration
  4. stirringthe resulting mixture was stirred for 10 min
  5. stirringthe mixture was stirred for 16 h
  6. additionwas added until pH was about 2
  7. extractionThe aqueous layer was extracted with additional EtOAc
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel chromatography (5-40% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-575d19e02dc44f95b86bf31c8152144a
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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