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

HRID 1410833Notes

Reaction equation

HRID 1410833 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.FC(F)(F)C(O)=O.[CH2:46]([N:48](CC)CC)[CH3:47].C(N=C=O)C.Cl>C(Cl)Cl.CCOC(C)=O>[CH2:46]([NH:48][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])[CH3:47]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8022Ethyl isocyanateHCID 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 867141281-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(3-ethyl-ureido)-ethyl]-amideYield 71.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

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 CH2Cl2 (3 mL), triethylamine (0.068 mL, 0.49 mmol), and ethyl isocyanate (17 mg, 0.24 mmol). The resulting mixture was stirred overnight. EtOAc (50 mL) and 0.1 M HCl (20 mL) were added, and the aqueous layer was extracted with additional EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (0-8% MeOH/CH2Cl2) to give 17 mg of the title compound as a pale yellow solid. MS: (+) m/z 486.39 (M+1).

Workup

  1. customSolvent and excess TFA was removed by evaporation
  2. stirringThe resulting mixture was stirred overnight
  3. extractionthe aqueous layer was extracted with additional EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (0-8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-268de624da5f4063b3d86463aebe35ac
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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