Cesium carbonate → (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

HRID 1398291Notes

Reaction equation

HRID 1398291 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH3:16])[C:6]=2[CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:24]([NH:31][C@H:32]([CH2:37][OH:38])[CH2:33][CH:34]([CH3:36])[CH3:35])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:35][CH:34]([CH3:36])[CH2:33][C@H:32]([NH:31][C:24](=[O:25])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:37][O:38][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH3:16])[C:6]=2[CH:17]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 867103058-chloro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one

Product 1

HCID 86710306(S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamateYield 19%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-chloro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (440 mg, 1.80 mmol) in toluene (8 mL) at room temperature, was added cesium carbonate (879 mg, 2.70 mmol) and di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (458 mg, 1.079 mmol) and the mixture was degassed for 5 min. The mixture was then treated with N-Boc L-Leucinol (1160 mg, 5.39 mmol) followed by palladium(II)acetate (121 mg, 0.54 mmol) and the mixture degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. After overnight stirring the reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford the crude product which was purified by combi flash (gradient of ethyl acetate and petroleum ether) to afford (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (190 mg, 0.34 mmol, 19% yield) as an off-white solid. LC/MS (ESI) m/e 426.2 [(M+H)+, calcd for C24H32N3O4426.2]; LC/MS retention time (method C): tR=2.10 min.

Workup

  1. customthe mixture was degassed for 5 min
  2. customthe mixture degassed for another 10 min
  3. customThe reaction mixture was sealed
  4. temperaturewas cooled to room temperature
  5. filtrationfiltered through diatomaceous earth (Celite®)
  6. washThe bed was washed with ethyl acetate
  7. concentrationthe combined filtrate was concentrated under reduced pressure
  8. customto afford the crude product which
  9. customwas purified by combi flash (gradient of ethyl acetate and petroleum ether)

Sources & evidence

ORD record
ord-9a36ed1fea2f42eb85a867ff1ba3878f
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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