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

HRID 919826Notes

Reaction equation

HRID 919826 reaction equation
C(O[C:6](=[O:38])[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.[F:39][C:40]([F:45])([F:44])C(O)=O.C(N(CC)CC)C.FC(F)(F)C(OCC)=O>C(Cl)Cl.C1COCC1>[F:39][C:40]([F:45])([F:44])[C: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:38]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9794Ethyl trifluoroacetateHCID 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 900739721-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(2,2,2-trifluoro-acetylamino)-ethyl]amide

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 (25 mg, 0.049 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 (0.034 mL, 0.24 mmol), and ethyl trifluoroacetate (2 mL). The resulting mixture was refluxed overnight, then concentrated to dryness. The residue was dissolved in EtOAc and washed with 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated, and the crude product was purified by silica gel chromatography (0-5% MeOH/CH2Cl2) to give 12.7 mg of the title compound as a light yellow solid. MS: (+) m/z 511.33 (M+1).

Workup

  1. customSolvent and excess TFA was removed by evaporation
  2. temperatureThe resulting mixture was refluxed overnight
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with 0.1 M HCl
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customthe crude product was purified by silica gel chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-2584487813a94760b5691d1839960fbd
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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