Pyridine → HCID 60151267, compound

HRID 919816Notes

Reaction equation

HRID 919816 reaction equation
[C:1]([O:5][C:6](=[O:33])[N:7]([CH2:9][CH2:10][NH:11][C:12]([C:14]1[N:15]=[CH:16][C:17]2[C:18](=[O:32])[N:19]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:20]=[CH:21][C:22]=2[C:23]=1[OH:24])=[O:13])[CH3:8])(C)(C)C.FC(F)(F)C(O)=O.N1C=CC=CC=1.ClC(OC)=O>C(Cl)Cl>[CH3:1][O:5][C:6](=[O:33])[N:7]([CH2:9][CH2:10][NH:11][C:12]([C:14]1[N:15]=[CH:16][C:17]2[C:18](=[O:32])[N:19]([CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:20]=[CH:21][C:22]=2[C:23]=1[OH:24])=[O:13])[CH3:8]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 68297219HCID 68297219, compound

Product 1

HCID 60151267HCID 60151267, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

{2-[(7-Benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethyl}-methyl-carbamic acid tert-butyl ester (25 mg, 0.055 mmol) was dissolved in CH2Cl2 (2 mL). Trifluoroacetic acid (1 mL) was added, and the mixture was stirred at r.t. for 1 h. Solvent and excess TFA were removed in vacuo. To the residue were added CH2Cl2 (2 mL), pyridine (0.072 mL, 0.88 mmol), and methyl chloroformate (0.034 mL, 0.44 mmol), and the resulting mixture was stirred for 16 h. The mixture was diluted with CH2Cl2 and washed with 1 M HCl. The organic layer was dried over MgSO4 and concentrated. The crude product was dissolved in 5 mL of 0.5 M NaOMe solution and refluxed for 1 h. After cooling to r.t., the mixture was acidified to pH about 2 and extracted with EtOAc. The combined organic layer was dried over MgSO4 and concentrated. The residue was chromatographed (0-5% MeOH/CH2Cl2) to give the desired product and an impurity. The crude product was then treated with a mixture of 1 M NaOH and MeOH (1:1 v/v) for 16 h at r.t. The mixture was acidified to pH about 2 and extracted with EtOAc. The organic layer was dried over MgSO4, concentrated, and the crude product was purified by chromatography (0-5% MeOH/CH2Cl2) to give 6.3 mg of the title compound. MS: (+) m/z 411.25 (M+1).

Workup

  1. customSolvent and excess TFA were removed in vacuo
  2. stirringthe resulting mixture was stirred for 16 h
  3. washwashed with 1 M HCl
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in 5 mL of 0.5 M NaOMe solution
  7. temperaturerefluxed for 1 h
  8. temperatureAfter cooling to r.t.
  9. extractionextracted with EtOAc
  10. dry with materialThe combined organic layer was dried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was chromatographed (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9d444c9b5b4546e8957fd0a36cf59187
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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