Sodium Carbonate → Tert-butyl 7-(4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate

HRID 468962Notes

Reaction equation

HRID 468962 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[N:8]=[CH:9]2)=[CH:4][N:3]=1.[CH3:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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>[CH3:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[N:8]=[CH:9]2)=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 86674971Tert-butyl 7-chloro-2,6-naphthyridin-3-ylcarbamate

Product 1

HCID 71115140Tert-butyl 7-(4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamateYield 34.2%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of tert-butyl N-(7-chloro-2,6-naphthyridin-3-yl)carbamate (460 mg, 1.65 mmol), (4-methyl-3-pyridyl)boronic acid (450 mg, 3.3 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (117 mg, 0.165 mmol) and saturated aqueous sodium carbonate solution (0.5 mL) in acetonitrile (5 mL) was heated under microwave irradiation (Biotage) at 130° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (150 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 (12 g, Silica, 0-10% methanol in dichloromethane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (190 mg, 34%), 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 (12 g, Silica, 0-10% methanol in dichloromethane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-63225d69af554168b3b300a00ac16dcb
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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