Oxalyl chloride → HCID 69655137, compound

HRID 1611970Notes

Reaction equation

HRID 1611970 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.C(Cl)(=O)C(Cl)=O.[CH2:20]([O:22][C:23](=[O:37])[C:24]([C:27]1[CH:28]=[N:29][C:30]([NH2:36])=[C:31]([O:33][CH2:34][CH3:35])[CH:32]=1)([CH3:26])[CH3:25])[CH3:21]>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[CH2:20]([O:22][C:23](=[O:37])[C:24]([C:27]1[CH:28]=[N:29][C:30]([NH:36][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)=[O:13])=[C:31]([O:33][CH2:34][CH3:35])[CH:32]=1)([CH3:26])[CH3:25])[CH3:21]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 23593810HCID 23593810, compound

Product 1

HCID 69655137HCID 69655137, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a slurry of 0.31 mmol of 5-chloro-1H-indole-2-carboxylic acid in methylene chloride (1.5 mL) was added 0.4 mL of 1M oxalyl chloride solution in methylene chloride. A solution of DMF (0.031 mL) in methylene chloride (1 mL) was then added dropwise to the slurry. After shaking for 45 min., the acid chloride solution was added dropwise to a solution of 2-(6-amino-5-ethoxy-pyridin-3-yl)-2-methyl-propionic acid ethyl ester in DMF (0.5 mL) and pyridine (0.25 mL). The reaction mixture was then shaken overnight. The reaction mixture was partitioned between EtOAc and 1N aqueous hydrochloric acid, and the phases were separated. The organic phase was washed with 1N aqueous sodium hydroxide, brine, and dried over sodium sulfate. After filtration and evaporation, the residue was further purified on a 2 mm silica gel preparative plate, developing with 9:1 methylene chloride/methanol. The product band was extracted and evaporated to afford 22 mg (7% yield) of the title compound as an amorphous solid. AP/MS+=430, AP/MS−=428.

Workup

  1. stirringThe reaction mixture was then shaken overnight
  2. customThe reaction mixture was partitioned between EtOAc and 1N aqueous hydrochloric acid
  3. customthe phases were separated
  4. washThe organic phase was washed with 1N aqueous sodium hydroxide, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration and evaporation
  7. customthe residue was further purified on a 2 mm silica gel preparative plate
  8. extractionThe product band was extracted
  9. customevaporated

Sources & evidence

ORD record
ord-ba066aae051749d4867830189e447a1b
Source dataset
uspto-grants-2006_01
Patent number
US06992092B2

Reaction notes

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