Sodium Carbonate → Ethyl 5-amino-8-methylbenzo[f][1,7]naphthyridine-2-carboxylate

HRID 340247Notes

Reaction equation

HRID 340247 reaction equation
CC1C=CC(B2OC(C)(C)C(C)(C)O2)=C([NH:8]C(=O)OC(C)(C)C)C=1.Cl[C:26]1[C:27]([C:37]#[N:38])=[N:28][CH:29]=[C:30]([CH:36]=1)[C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[Na+].[Na+].[C:45]1([CH3:51])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(O)C>CO>[NH2:8][C:37]1[C:27]2[N:28]=[CH:29][C:30]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:36][C:26]=2[C:48]2[CH:47]=[CH:46][C:45]([CH3:51])=[CH:50][C:49]=2[N:38]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 21863594Toluene ethanolHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 66875248Ethyl 5-chloro-6-cyanonicotinate

Product 1

HCID 58213495Ethyl 5-amino-8-methylbenzo[f][1,7]naphthyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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 ethyl 5-chloro-6-cyanonicotinate (from the previous step) (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 stiffed at 100° C. overnight. After cooling to ambient temperature, the reaction content was diluted with methanol. The insoluble solids were filtered off, and the filtrate was concentrated en vacuo to obtain a crude residue. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% ethyl acetate in hexane to give ethyl 5-amino-8-methylbenzo[f][1,7]naphthyridine-2-carboxylate.

Workup

  1. customwas stiffed at 100° C. overnight
  2. filtrationThe insoluble solids were filtered off
  3. concentrationthe filtrate was concentrated en vacuo
  4. customto obtain a crude residue
  5. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-0a2ce5a7b8994d76afc20305b6ccc0b3
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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