Triethylamine → (Z)-7-(2-ethoxyvinyl)-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79446Notes

Reaction equation

HRID 79446 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([Sn](CCCC)(CCCC)/[CH:60]=[CH:61]\[O:62][CH2:63][CH3:64])CCC.C(N(CC)CC)C>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].CN(C)C=O>[CH2:63]([O:62]/[CH:61]=[CH:60]\[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1)[CH3:64]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 5706773cis-1-Ethoxy-2-(tri-n-butylstannyl)ethyleneHCID 672595577-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 70814943(Z)-7-(2-ethoxyvinyl)-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 75.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A round bottom flask was charged with 7-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (330 mg, 0.674 mmol), trio-tolylphosphine (41 mg, 0.135 mmol), tris(dibenzylideneacetone)dipalladium (62 mg, 0.067 mmol) To the flask were added 10 mL of anhydrous dimethylformamide, followed by (Z)-tributyl(2-ethoxyvinyl)stannane (0.34 ml, 1.01 mmol), and triethylamine (0.11 mL, 0.81 mmol). The reaction mixture was degassed under nitrogen, and stirred at 100° C. for 10 hours. The reaction mixture was cooled, diluted with water, and extracted thoroughly with DCM and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, and concentrated. The crude product was subjected to preparative thin-layer chromatography on silica with 5% MeOH-DCM as eluent to afford 246 mg of product as a yellow, foamy solid.

Workup

  1. customThe reaction mixture was degassed under nitrogen
  2. temperatureThe reaction mixture was cooled
  3. additiondiluted with water
  4. extractionextracted thoroughly with DCM and EtOAc
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a0cab07e01ee48f2bc5e7ba0d3813171
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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