Sodium Carbonate → 3-Chloro-8-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 1479602Notes

Reaction equation

HRID 1479602 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]([NH:8]C(=O)OC(C)(C)C)[CH:7]=1.Br[C:26]1[C:27]([C:33]#[N:34])=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.O>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]2[C:27](=[C:33]([NH2:34])[N:8]=[C:6]3[CH:7]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]3=2)[N:28]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 441196673-Bromo-6-chloropyridine-2-carbonitrileHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

Product 1

HCID 582135893-Chloro-8-methylbenzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21863594Toluene ethanolSolvent

Procedure

A solution of tert-butyl 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.0 eq.) and 3-bromo-6-chloropicolinonitrile (from Example 20/Step 2) (1.0 eq.), tetrakis(triphenyl-phosphine)palladium (5 mol %), and 2N aqueous sodium carbonate solution (2.0 eq.) in toluene/ethanol (2:1, 0.03 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% EtOAc/Hexanes to give 3-chloro-8-methylbenzo[f][1,7]naphthyridin-5-amine as a pale yellow solid.

Workup

  1. customwas stirred at 100° C. overnight
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vaccuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-823345f95266436dabfb012ed73d1323
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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