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

HRID 1398313Notes

Reaction equation

HRID 1398313 reaction equation
[CH2:1]([N:8]1[C:17]2[CH:18]=[C:19](Cl)[CH:20]=[CH:21][C:16]=2[C:15]2[C:10](=[CH:11][N:12]=[CH:13][CH:14]=2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:30]([NH:37][C@H:38]([CH2:43][OH:44])[CH2:39][CH:40]([CH3:42])[CH3:41])([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[C:17]2[CH:18]=[C:19]([O:44][CH2:43][C@@H:38]([NH:37][C:30](=[O:31])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35])[CH2:39][CH:40]([CH3:42])[CH3:41])[CH:20]=[CH:21][C:16]=2[C:15]2[C:10](=[CH:11][N:12]=[CH:13][CH:14]=2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 867103196-benzyl-8-chlorobenzo[c][2,7]naphthyridin-5(6H)-one

Product 1

HCID 86710320(S)-tert-butyl (1-((6-benzyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateYield 37%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution 6-benzyl-8-chlorobenzo[c][2,7]naphthyridin-5(6H)-one (640 mg, 2.00 mmol) in toluene (12 mL) at room temperature, was added cesium carbonate (975 mg, 2.99 mmol) and N-Boc L-Leucinol (1287 mg, 5.99 mmol) and the mixture was degassed with nitrogen for 5 min. The mixture was then treated with di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (508 mg, 1.197 mmol) followed by palladium(II)acetate (448 mg, 2.00 mmol) and 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 crude product which was purified by combi flash (ethyl acetate/petroleum ether) to afford (S)-tert-butyl (1-((6-benzyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (500 mg, 0.738 mmol, 37% yield) as an off-white solid. LC/MS (ESI) m/e 502.3 [(M+H)+, calcd for C30H36N3O4 502.4]; LC/MS retention time (method D): tR=1.26 min.

Workup

  1. customthe mixture was degassed with nitrogen for 5 min
  2. customdegassed 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 crude product which
  9. customwas purified by combi flash (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-0841a6c91bd74374a3165140bea1e7b3
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…