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

HRID 1398295Notes

Reaction equation

HRID 1398295 reaction equation
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.[CH3:33]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:15][N:6]1[C:5]2[CH:16]=[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:21][CH:22]([CH3:24])[CH3:23])[C:2]([CH3:33])=[CH:3][C:4]=2[C:13]2[C:8](=[CH:9][N:10]=[CH:11][CH:12]=2)[C:7]1=[O:14]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 574072TrimethylboroxineHCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 86710308(S)-tert-butyl (1-((6,9-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateYield 38%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In a 10 mL round-bottomed flask, (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (as prepared in Ex. 3, Part A) (150 mg, 0.297 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (41.1 mg, 0.327 mmol), Cs2CO3 (291 mg, 0.892 mmol) and PdCl2(dppf) (21.76 mg, 0.030 mmol) were taken up in a mixture of 1,4-dioxane (2 mL) and water (0.1 mL). The reaction mixture was purged with nitrogen for 5 min and heated at 90° C. for 15 h. 1,4-dioxane was removed under reduced pressure and the residue was dissolved in ethyl acetate (20 mL). The ethyl acetate layer was washed with water (10×2 mL) and dried over sodium sulfate. Removal of the solvent gave crude product (0.08 g), which was filtered through silica-gel column (24 g silica-gel, MeOH—CHCl3 mixture). The product was isolated as off-white solid (0.05 g, 0.11 mmol, 38% yield). LC/MS (ES-API) m/e 440.2 [(M+H)+, calcd for C25H34N3O4, 440.3]; LC/MS retention time (method B): tR=1.95 min.

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. custom1,4-dioxane was removed under reduced pressure
  3. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  4. washThe ethyl acetate layer was washed with water (10×2 mL)
  5. dry with materialdried over sodium sulfate
  6. customRemoval of the solvent
  7. customgave crude product (0.08 g), which
  8. filtrationwas filtered through silica-gel column (24 g silica-gel, MeOH—CHCl3 mixture)

Sources & evidence

ORD record
ord-b6449dfc66454a07b731bfa97fb0b17f
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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