Potassium Carbonate → 8-(3-Methoxy-phenyl)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029077Notes

Reaction equation

HRID 1029077 reaction equation
[NH2:1][C:2]1[C:11](Br)=[CH:10][C:5](C(OC)=O)=[CH:4][N:3]=1.CO[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O)=[O:16].C1(P(C2CCCCC2)C2C=CC=CC=2[C:39]2[C:44]([O:45][CH3:46])=[CH:43][CH:42]=[CH:41][C:40]=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:46][O:45][C:44]1[CH:43]=[C:42]([C:21]2[CH:20]=[CH:19][C:18]3[C:11]4[C:2](=[N:3][CH:4]=[CH:5][CH:10]=4)[NH:1][C:15](=[O:16])[C:17]=3[CH:22]=2)[CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2764099Methyl 6-amino-5-bromonicotinateHCID 27734962-(Methoxycarbonyl)benzeneboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 581683028-(3-Methoxy-phenyl)-5H-benzo[c][1,8]naphthyridin-6-oneYield 116.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

Methyl 6-amino-5-bromonicotinate (500 mg, 2.16 mmol), 2-methoxycarbonylphenylboronic acid (580 mg, 3.25 mmol), palladium(II) acetate (20 mg, 0.09 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (70 mg, 0.17 mmol), and potassium carbonate (900 mg, 6.50 mmol) were dissolved in dioxane/H2O (11 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was diluted with MeOH, filtered through a membrane plug, and purified via prep-LC-MS to provide 21 (60 mg, 11% yield) as a white solid. LC-MS (M+H=241, obsd.=241). 1H NMR (400 MHz, d6-DMSO): δ 8.98 (d, 1H), 8.87 (d, 1H), 8.48 (d, 1H), 8.32 (dd, 1H), 7.88 (t, 1H), 7.65 (t, 1H).

Workup

  1. filtrationfiltered through a membrane plug
  2. custompurified via prep-LC-MS

Sources & evidence

ORD record
ord-b53774d3b2f6418d930a376177ed1b31
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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