Sodium Carbonate → 8-Methyl-2-(p-tolylethynyl)benzo[f][1,7]naphthyridin-5-amine

HRID 340282Notes

Reaction equation

HRID 340282 reaction equation
Cl[C:2]1[C:3]([C:17]#[N:18])=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[CH:7]=1.[CH3:19][C:20]1[CH:21]=[CH:22][C:23](B2OC(C)(C)C(C)(C)O2)=[C:24]([NH:26]C(=O)OC(C)(C)C)[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CO.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][C:20]1[CH:21]=[CH:22][C:23]2=[C:2]3[C:3](=[C:17]([NH2:18])[N:26]=[C:24]2[CH:25]=1)[N:4]=[CH:5][C:6]([C:8]#[C:9][C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1)=[CH:7]3

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 668757343-Chloro-5-(p-tolylethynyl)picolinonitrile

Product 1

HCID 668750168-Methyl-2-(p-tolylethynyl)benzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21863594Toluene ethanolSolvent

Procedure

A solution of 3-chloro-5-(p-tolylethynyl)picolinonitrile (from the previous step) (1.0 eq.), tert-butyl 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.2 eq.), tetrakis(triphenylphosphine)palladium (10 mol %), and 2N sodium carbonate aqueous solution (4.0 eq.) in toluene/ethanol (2:1, 0.2 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with 2% MeOH in DCM. The two phases were separated, and the aqueous layer was extracted with 2% MeOH in DCM twice. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in toluene to give 8-methyl-2-(p-tolylethynyl)benzo[f][1,7]naphthyridin-5-amine.

Workup

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

Sources & evidence

ORD record
ord-f641a89745d4449ba5ee82e6f08021af
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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