Potassium Phosphate, Tribasic → 8-((Tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[f][1,7]naphthyridin-5-amine

HRID 2167638Notes

Reaction equation

HRID 2167638 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.[Si:21]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][C:33](B2OC(C)(C)C(C)(C)O2)=[C:34]([NH:36]C(=O)OC(C)(C)C)[CH:35]=1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].[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>[Si:21]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][C:33]2=[C:2]3[C:3](=[C:19]([NH2:20])[N:36]=[C:34]2[CH:35]=1)[N:4]=[CH:5][C:6]([C:8]#[C:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=1[CH3:18])=[CH:7]3)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 581665223-Chloro-5-[2-(4-methoxy-2-methylphenyl)ethynyl]-2-pyridinecarbonitrileHCID 66890509Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate

Product 1

HCID 670655328-((Tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[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 (from the step 3) (1 equiv.), tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from step 2) (1.25 equiv.), K3PO4 (2 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.05 equiv.), and 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.1 equiv.). 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 contents were cooled down and were taken up in 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 8-((tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[f][1,7]naphthyridin-5-amine as a 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 contents 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-858c35fa3ada4ddda326d08076cd0e21
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

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