2,6-Lutidine → (S)-tert-butyl (1-((9-formyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398404Notes

Reaction equation

HRID 1398404 reaction equation
[CH3:1][CH:2]([CH3:33])[CH2:3][C@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:5][O:6][C:7]1[C:8]([CH:23]=C)=[CH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[CH:22]=1.CC1C=CC=C(C)N=1.I([O-])(=O)(=O)=[O:43].[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[CH:23]([C:8]1[C:7]([O:6][CH2:5][C@@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])[CH2:3][CH:2]([CH3:1])[CH3:33])=[CH:22][C:11]2[N:12]([CH3:21])[C:13](=[O:20])[C:14]3[C:19]([C:10]=2[CH:9]=1)=[CH:18][CH:17]=[N:16][CH:15]=3)=[O:43]

Participants

7

Reactant 3

HCID 79372,6-LutidineHCID 23667635Sodium periodateHCID 86710388(S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

Product 1

HCID 86710392(S)-tert-butyl (1-((9-formyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateYield 53.2%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (300 mg, 0.664 mmol) (prepared as described in Example 46, Part A) osmium tetroxide (2.5% in 2-methyl-2-propanol) (4.17 μl, 0.013 mmol), and 2,6-dimethylpyridine (0.155 mL, 1.329 mmol) in 1,4-dioxane (5 mL) and water (2 mL), cooled to 0° C., was stirred for 15 min. Sodium metaperiodate (568 mg, 2.66 mmol) was added and the reaction was warmed to room temperature and stirred for 2 h. The reaction mixture was filtered through diatomaceous earth (Celite®), eluting with EtOAc. The EtOAc layer was washed with saturated aqueous NaHCO3, H2O, then brine. The organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc/petroleum ether) to afford (S)-tert-butyl (1-((9-formyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (160 mg, 0.353 mmol, 53% yield) as a gummy solid. LC/MS (ESI) m/e 454.1, [(M+H)+, calcd for C25H32N3O5, 454.2].

Workup

  1. customprepared
  2. temperaturethe reaction was warmed to room temperature
  3. stirringstirred for 2 h
  4. filtrationThe reaction mixture was filtered through diatomaceous earth (Celite®)
  5. washeluting with EtOAc
  6. washThe EtOAc layer was washed with saturated aqueous NaHCO3, H2O
  7. dry with materialThe organic layer was dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-6028fdf9e99b40eda4a2bc8153fc9377
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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