Thionyl Chloride → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyridin-2-yl)cyclopropanecarboxamide

HRID 39465Notes

Reaction equation

HRID 39465 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.S(Cl)(Cl)=O.[Br:20][C:21]1[CH:22]=[CH:23][C:24]([NH2:27])=[N:25][CH:26]=1>CN(C=O)C.N1C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:27][C:24]4[CH:23]=[CH:22][C:21]([Br:20])=[CH:26][N:25]=4)=[O:15])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 706222-Amino-5-bromopyridineHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 591661631-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyridin-2-yl)cyclopropanecarboxamideYield 81.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolvent2×

Conditions

Temperature
60 °C

Procedure

To 1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (9.50 g, 46.00 mmol), thionyl chloride (10.00 mL, 138.00 mmol) and DMF (4 drops) were added and the reaction mixture was stirred and heated at 60° C. for thirty minutes. The excess thionyl chloride was evaporated under reduced pressure. A portion of the acid chloride (14.4 mmol) was dissolved in pyridine (10 mL) and was slowly added to 5-bromopyridin-2-amine (14.4 mmol) in pyridine (10 mL). The reaction mixture was stirred at 110° C. for one hour and thirty minutes. The pyridine was evaporated under reduced pressure. The resulting mixture was dissolved in dichloromethane (100 mL) and washed with 1N NaOH (3×25 mL). The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to yield 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyridin-2-yl)cyclopropanecarboxamide (4.20 g, 11.7 mmol, 81%).

Workup

  1. customThe excess thionyl chloride was evaporated under reduced pressure
  2. stirringThe reaction mixture was stirred at 110° C. for one hour and thirty minutes
  3. customThe pyridine was evaporated under reduced pressure
  4. dissolutionThe resulting mixture was dissolved in dichloromethane (100 mL)
  5. washwashed with 1N NaOH (3×25 mL)
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-af36d083591b43ee914efcef6980fcd8
Source dataset
uspto-grants-2013_09
Patent number
US08524910B2

Reaction notes

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