Dichloromethane → 1,1-Dimethylethyl (2-(5-[6-(methyloxy)-1,5-naphthyridin-4-yl]-2-pyridinyl}ethyl)carbamate

HRID 1435878Notes

Reaction equation

HRID 1435878 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2OS(C(F)(F)F)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].ClCCl.C(=O)([O-])[O-].[K+].[K+].Br[C:54]1[CH:55]=[CH:56][C:57]([CH2:60][CH2:61][NH:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[N:58][CH:59]=1>[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2].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]>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[C:54]1[CH:55]=[CH:56][C:57]([CH2:60][CH2:61][NH:62][C:63](=[O:69])[O:64][C:65]([CH3:67])([CH3:66])[CH3:68])=[N:58][CH:59]=1

Participants

9

Reactant 6

HCID 6344Dichloromethane2×HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 112552656-Methoxy-1,5-naphthyridin-4-yl trifluoromethanesulfonateHCID 579386341,1-Dimethylethyl [2-(5-bromo-2-pyridinyl)ethyl]carbamate

Product 1

HCID 579386301,1-Dimethylethyl (2-(5-[6-(methyloxy)-1,5-naphthyridin-4-yl]-2-pyridinyl}ethyl)carbamateYield 62%

Reagents, catalysts & solvents 2

HCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalyst2×HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 1,1,1-trifluoromethanesulfonic acid 6-methoxy[1,5]naphthyridin-4-yl ester (2.0 g, 8.42 mmole) in dry dioxane,(75 mL) at RT was added bis(pinacolato)diboron (2.14 g, 8.43 mmole), potassium acetate (1.91 g, 19.4 mmole), 1,1-bis(diphenylphosphino)ferrocene (0.18 g, 0.32 mmole) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (0.26 g, 0.32 mmole). The reaction contents were heated to 80° C. for 24 h under nitrogen gas and then 1,1-bis(diphenylphosphino)ferrocene (0.18 g, 0.32 mmole), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (0.26 g, 0.32 mmole), potassium carbonate (2.68 g, 19.44 mmole) and 1,1-dimethylethyl [2-(5-bromo-2-pyridinyl)ethyl]carbamate (1.94 g, 6.48 mmole) were added to the reaction pot. After 24 h of vigorous stirring at 80° C., the reaction contents were filtered through a scinter-glass funnel containing a bed of celite (EtOAc). The filtrate was concentrated under vacuum and purified on silica (EtOAc) to afford the title compound (1.52 g, 62%) as a tan solid: LC-MS (ES) m/e 381 (M+H)+.

Workup

  1. customThe reaction contents
  2. additionwere added to the reaction pot
  3. customthe reaction contents
  4. filtrationwere filtered through a scinter-glass funnel
  5. additioncontaining a bed of celite (EtOAc)
  6. concentrationThe filtrate was concentrated under vacuum
  7. custompurified on silica (EtOAc)

Sources & evidence

ORD record
ord-b6fe0b99b4e6467a95b214ba9b0e44bb
Source dataset
uspto-grants-2009_11
Patent number
US07618959B2

Reaction notes

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