Potassium Phosphate, Tribasic → 2-((4-Methoxy-2-methylphenyl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 2167634Notes

Reaction equation

HRID 2167634 reaction equation
Cl[C:2]1[C:3]([C:19]#[N:20])=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[CH3:18])[CH:7]=1.[CH3:21][C:22]1[CH:23]=[CH:24][C:25](B2OC(C)(C)C(C)(C)O2)=[C:26]([NH:28]C(=O)OC(C)(C)C)[CH:27]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C(O)CCC>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:9]#[C:8][C:6]2[CH:5]=[N:4][C:3]3[C:2]([CH:7]=2)=[C:25]2[CH:24]=[CH:23][C:22]([CH3:21])=[CH:27][C:26]2=[N:28][C:19]=3[NH2:20])=[C:11]([CH3:18])[CH:12]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 581665223-Chloro-5-[2-(4-methoxy-2-methylphenyl)ethynyl]-2-pyridinecarbonitrile

Product 1

HCID 581665112-((4-Methoxy-2-methylphenyl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a round bottom flask with refluxing condenser were added 3-chloro-5-((4-methoxy-2-methylphenyl)ethynyl)picolinonitrile (B-1) (1 eq.), tert-butyl 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (A-1) (1.25 eq.), K3PO4 (2 eq.), tris(dibenzylideneacetone)dipalladium(0) (0.05 eq.), and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (Sphos) (0.1 eq.). n-butanol and water (5:2, 0.2 M) were added, and the content was degas sed (vacuum followed by nitrogen flush) for three times. The reaction mixture was stirred vigorously under nitrogen at 100° C. overnight in an oil bath. The content was cooled and taken up in 200 mL of water followed by extraction with methylene chloride. Combined organic layers were dried (Na2SO4) and concentrated. Flash chromatography (silica gel, 0-50% EtOAc in CH2Cl2) afforded the product 2-((4-methoxy-2-methylphenyl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine (B-2).

Workup

  1. temperatureTo a round bottom flask with refluxing condenser
  2. customthe content was degas
  3. custom(vacuum followed by nitrogen flush) for three times
  4. temperatureThe content was cooled
  5. extractionfollowed by extraction with methylene chloride
  6. dry with materialCombined organic layers were dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e645a265b2c64ab38867b6999e5217fa
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

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