Sodium Carbonate → 3-Chloro-1-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 340240Notes

Reaction equation

HRID 340240 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.Br[C:19]1[C:20]([C:27]#[N:28])=[N:21][C:22]([Cl:26])=[CH:23][C:24]=1[CH3:25].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CO>[Cl:26][C:22]1[CH:23]=[C:24]([CH3:25])[C:19]2[C:20](=[C:27]([NH2:28])[N:8]=[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]3=2)[N:21]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2773226(2-BOC-aminophenyl)boronic acidHCID 866523473-Bromo-6-chloro-4-methylpyridine-2-carbonitrile

Product 1

HCID 866523483-Chloro-1-methylbenzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21863594Toluene ethanolSolvent

Procedure

A solution of 2-(tert-butoxycarbonylamino)phenylboronic acid (1.0 eq.) and 3-bromo-6-chloro-4-methylpicolinonitrile (from step 2) (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 3-chloro-1-methylbenzo[f][1,7]naphthyridin-5-amine as a white solid. 1H NMR (dmso-d6): δ 8.44 (d, 1H), 7.83 (s, 1H), 7.50-7.58 (m, 2H), 7.02 (bs, 2H), 2.98 (s, 3H). LRMS [M+H]=244.1.

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-5e72b744d74940eea82a59d833b9a411
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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