Oxalyl chloride → HCID 178436770, compound

HRID 1865135Notes

Reaction equation

HRID 1865135 reaction equation
[C:1]([C:3]1[C:4]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]#[N:27])=[CH:16][CH:15]=2)=[C:5]([C:11]([OH:13])=O)[N:6]([CH3:10])[C:7]=1[CH2:8][CH3:9])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:34][C:35]1[NH:36][CH:37]=[N:38][N:39]=1>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[NH:38]1[CH:37]=[N:36][C:35]([NH:34][C:11]([C:5]2[N:6]([CH3:10])[C:7]([CH2:8][CH3:9])=[C:3]([C:1]#[N:2])[C:4]=2[C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]#[N:27])=[CH:18][CH:19]=2)=[O:13])=[N:39]1

Participants

7

Reactant 3

HCID 65578Oxalyl chloride2×HCID 112912124-Cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylic acidHCID 178509196HCID 178509196, compound

Product 1

HCID 178436770HCID 178436770, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

prepare a solution of 4-cyano-3-(2′-cyano-biphenyl-4-yl)-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid (200 mg, 0.57 mmol, prepared in example A-75) in 5 mL of methylene chloride and stir under nitrogen. Add 2 drops of dry DMF and cool the mixture to 0° C. Next, add oxalyl chloride (1.10 mmol) dropwise over five minutes. Remove the icebath and stir the reaction for one hour. Add another 1.10 mmol of oxalyl chloride and continue stirring for one hour. Then concentrate the reaction mixture under vacuum to provide the crude acid chloride. Dissolve the crude acid chloride in 3.5 mL of dry pyridine and add 2-amino-1,3,4-triazole (5.9 mmol) and stir overnight at room temperature. Pour into 100 mL of ice-water and extract with methylene chloride (3×50 mL). Dry the combined organic layers over anhydrous Na2SO4, filter and evaporate. Chromatograph the residue over silica gel (100/0-3/1 toluene/EtOAc) to give the title compound (110 mg, 46% yield). MS(ES+, m/e)=422 (M++1).

Workup

  1. customRemove the icebath
  2. stirringstir
  3. customthe reaction for one hour
  4. stirringcontinue stirring for one hour
  5. concentrationThen concentrate the reaction mixture under vacuum
  6. customto provide the crude acid chloride
  7. stirringstir overnight at room temperature
  8. extractionextract with methylene chloride (3×50 mL)
  9. dry with materialDry the combined organic layers over anhydrous Na2SO4
  10. filtrationfilter
  11. customevaporate

Sources & evidence

ORD record
ord-106fde827bd34dbf89398e1a9c13adb8
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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