Potassium Carbonate → Tert-butyl 7-(5-fluoro-4-methylpyridin-3-yl)-5-methyl-2,6-naphthyridin-3-ylcarbamate

HRID 1502474Notes

Reaction equation

HRID 1502474 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:19])[C:17]=2[CH3:18])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[N:6]=[CH:7]2.[CH3:28]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:19][C:16]1[C:17]([CH3:18])=[C:12]([C:10]2[CH:9]=[C:8]3[C:3]([CH:4]=[C:5]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[N:6]=[CH:7]3)=[C:2]([CH3:28])[N:11]=2)[CH:13]=[N:14][CH:15]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86674985Tert-butyl 5-chloro-7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate

Product 1

HCID 67976737Tert-butyl 7-(5-fluoro-4-methylpyridin-3-yl)-5-methyl-2,6-naphthyridin-3-ylcarbamateYield 50.4%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 5-chloro-7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate (230 mg, 0.592 mmol), trimethylboroxine (225 mg, 1.78 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (42 mg, 0.059 mmol), and potassium carbonate (165 mg, 1.18 mmol) in dioxane (3 mL) was heated at 100° C. for 2 hours. The reaction mixture was diluted with ethyl acetate (75 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as pale yellow solid (110 mg, 50%), which was used in the next step without further purification.

Workup

  1. washwashed with water (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-b934e7be71184e498692d79fd9730134
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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