Potassium Carbonate → Ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate

HRID 340289Notes

Reaction equation

HRID 340289 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:10]#[C:11][C:12]2[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][C:13]=2[CH3:23])[CH:5]=[N:6][C:7]=1[C:8]#[N:9].[CH3:24][C:25]1[CH:26]=[CH:27][C:28](B2OC(C)(C)C(C)(C)O2)=[C:29]([NH:31]C(=O)OC(C)(C)C)[CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>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>[NH2:9][C:8]1[C:7]2[N:6]=[CH:5][C:4]([C:10]#[C:11][C:12]3[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][C:13]=3[CH3:23])=[CH:3][C:2]=2[C:28]2[CH:27]=[CH:26][C:25]([CH3:24])=[CH:30][C:29]=2[N:31]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 66875033Ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate

Product 1

HCID 66892595Ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate

Reagents, catalysts & solvents 4

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

Procedure

A solution of ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate (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) (1.1 eq.), tetrakis(triphenylphosphine)palladium (8 mol %), and potassium carbonate (3.0 eq.) in toluene/ethanol (9:1, 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. 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 ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate.

Workup

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

Sources & evidence

ORD record
ord-1bb0700d4afb4af2abd03f27cc8fab58
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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