Sodium Carbonate → Pyrido[3,2-f][1,7]naphthyridin-6-amine

HRID 340243Notes

Reaction equation

HRID 340243 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:10]([NH:15]C(=O)OC(C)(C)C)=[N:11][CH:12]=[CH:13][CH:14]=2)O1.Br[C:25]1[C:26]([C:31]#[N:32])=[N:27][CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CO>[CH:14]1[C:9]2=[C:25]3[C:26](=[C:31]([NH2:32])[N:15]=[C:10]2[N:11]=[CH:12][CH:13]=1)[N:27]=[CH:28][CH:29]=[CH:30]3

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 45925650Tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamate

Product 1

HCID 58213553Pyrido[3,2-f][1,7]naphthyridin-6-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21863594Toluene ethanolSolvent

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 3-bromopicolinonitrile (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 pyrido[3,2-f][1,7]naphthyridin-6-amine as a white solid. 1H NMR (dmso-d6): δ 9.14 (dd, 1H), 8.98 (dd, 1H), 8.90 (dd, 1H), 7.93 (dd, 1H), 7.60 (bs, 2H), 7.30 (dd, 1H). LRMS [M+H]=197.

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-f338615e2893429da2635a556f9bf838
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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