Trifluoroacetic acid → 1-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (2-formylamino-ethyl)-amide

HRID 1410841Notes

Reaction equation

HRID 1410841 reaction equation
C([O:5][C:6](=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[C:14]([OH:37])=[C:15]2[C:20](=[CH:21][N:22]=1)[N:19]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18](=[O:30])[C:17]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[CH:16]2)=[O:12])(C)(C)C.FC(F)(F)C(O)=O.C(N(CC)CC)C.C(OCC)=O>C(Cl)Cl.C1COCC1>[CH:6]([NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[C:14]([OH:37])=[C:15]2[C:20](=[CH:21][N:22]=1)[N:19]([CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:18](=[O:30])[C:17]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[CH:16]2)=[O:12])=[O:5]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8025Ethyl formateHCID 8471TriethylamineHCID 68297633{2-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 867141321-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (2-formylamino-ethyl)-amideYield 37.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

{2-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-ethyl}-carbamic acid tert-butyl ester (35 mg, 0.068 mmol) was dissolved in CH2Cl2 (2 mL). Trifluoroacetic acid (1 mL) was added, and the mixture was stirred for 2 h. Solvent and excess TFA was removed by evaporation, and to the residue were added THF (3 mL), triethylamine (0.050 mL, 0.34 mmol), and ethyl formate (3 mL). The resulting mixture was refluxed for 4 days. After cooling to r.t., solvent was evaporated. The residue was partitioned between EtOAc and 0.1 M HCl. 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 (0-5% MeOH/CH2Cl2) to give 11.4 mg of the title compound as a light yellow solid. MS: (+) m/z 443.37 (M+1)

Workup

  1. customSolvent and excess TFA was removed by evaporation
  2. temperatureThe resulting mixture was refluxed for 4 days
  3. customsolvent was evaporated
  4. customThe residue was partitioned between EtOAc and 0.1 M HCl
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a0927bf4d051435d9d62c4f9bd0bf24f
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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