Potassium Phosphate, Tribasic → 2-((1H-indol-5-yl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 1479541Notes

Reaction equation

HRID 1479541 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[C:11][C:12]3[CH:13]=[C:14](Cl)[C:15]([C:18]#[N:19])=[N:16][CH:17]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CC1(C)C(C)(C)OB([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH:35]C(=O)OC(C)(C)C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:52]1(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>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[C:11][C:12]3[CH:17]=[N:16][C:15]4[C:14]([CH:13]=3)=[C:31]3[CH:32]=[CH:33][C:34]([CH3:52])=[CH:29][C:30]3=[N:35][C:18]=4[NH2:19])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2773231tert-Butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 668923115-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile

Product 1

HCID 668930492-((1H-indol-5-yl)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 5-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile (from the previous step) (1 eq.), tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.25 eq.), K3PO4 (2 eq.), tris(dibenzylideneacetone)dipalladium(0) (0.05 eq.), and 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.1 eq.). n-Butanol and water (5:2, 0.2 M) were added, and the content were degassed (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 were cooled down and were 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-((1H-indol-5-yl)ethynyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine as a yellow solid.

Workup

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

Sources & evidence

ORD record
ord-05d6fc82a44e4e55a1bec43913ddfb90
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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