Sodium Carbonate → Benzo[c][1,8]naphthyridin-6-amine

HRID 1259110Notes

Reaction equation

HRID 1259110 reaction equation
CC1(C)C(C)(C)OB(C2[C:10]([NH:15][C:16](=O)OC(C)(C)C)=[N:11][CH:12]=[CH:13][CH:14]=2)O1.BrC1C=CC=CC=1C#[N:28].C(=O)([O-])[O-].[Na+].[Na+].[C:39]1([CH3:45])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(O)C>CO>[CH:14]1[CH:13]=[CH:12][N:11]=[C:10]2[C:45]=1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:16]([NH2:28])=[N:15]2

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 162722-BromobenzonitrileHCID 21863594Toluene ethanolHCID 45925650Tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamate

Product 1

HCID 58213704Benzo[c][1,8]naphthyridin-6-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ylcarbamate (1.0 eq.) and 2-bromobenzonitrile (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 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 product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% ethyl acetate in hexane to give benzo[c][1,8]naphthyridin-6-amine as a white solid. 1H NMR (methanol-d4): δ 8.88 (dd, 1H), 8.67-8.63 (m, 2H), 8.30 (d, 1H), 7.90 (dt, 1H), 7.74 (dt, 1H), 7.36 (dd, 1H). LRMS [M+H]=196.1

Workup

  1. filtrationThe insoluble solids were filtered off
  2. concentrationthe filtrate was concentrated en vacuo
  3. customto obtain a crude residue
  4. customThe crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-e2bee887b5ae48d2bbf66c867e371017
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

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