Ethyl Acetate → 4-Methoxy-7-pyrazinyl-6-azaindol-3-yl-oxoacetic acid methyl ester

HRID 606744Notes

Reaction equation

HRID 606744 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][O:6][C:7]1[CH:15]=[N:14][C:13]([C:16]2[CH:21]=[N:20][CH:19]=[CH:18][N:17]=2)=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2.C([O-])(=[O:24])C.[NH4+].C[CH2:28][O:29][C:30]([CH3:32])=[O:31]>C(Cl)Cl.C[N+]([O-])=O>[CH3:28][O:29][C:30](=[O:31])[C:32]([C:9]1[C:8]2[C:12](=[C:13]([C:16]3[CH:21]=[N:20][CH:19]=[CH:18][N:17]=3)[N:14]=[CH:15][C:7]=2[O:6][CH3:5])[NH:11][CH:10]=1)=[O:24]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 517165Ammonium AcetateHCID 6451240Aluminum(III) ChlorideHCID 207912514-Methoxy-7-(pyrazin-2-YL)-1H-pyrrolo[2,3-C]pyridine

Product 1

HCID 670462744-Methoxy-7-pyrazinyl-6-azaindol-3-yl-oxoacetic acid methyl esterYield 68%

Reagents, catalysts & solvents 1

HCID 23431834Dichloromethane nitromethaneSolvent

Procedure

To a mixture of AlCl3 (3.09 g, 23.2 mmol) in 20 mL of CH2Cl2-MeNO2 (4:1) was added 4-methoxy-7-pyrazinyl-6-azaindole (0.525 g, 2.32 mmol) as a solid. To the resulting burgundy solution was added methyl oxalyl chloride (0.853 mL, 9.28 mmol) dropwise and then the mixture was stirred at room temperature for 1.5 h. The reaction mixture was then carefully poured into cold 20% aqueous ammonium acetate and EtOAc was added. The resulting emulsion was filtered and the residue was washed with additional EtOAc. The organic phase was separated and the aqueous phase was again extracted with EtOAc. The combined organic phase was dried (MgSO4) and evaporated to give 4-methoxy-7-pyrazinyl-6-azaindol-3-yl-oxoacetic acid methyl ester (0.494 g, 68%) as a brownish solid: LCMS m/e 313 (M+H)+. This material (0.456 g, 1.46 mmol) was taken up in 20 mL of MeOH, 1M K2CO3 (5.84 mL, 5.84 mmol) was added and the mixture was stirred at room temperature for 30 min. The solution was then diluted with water (4 mL) and concentrated in vacuo. The resulting aqueous solution was cooled at 0° C. and acidified to pH 1-2 with 6N HCl. This gave a bright yellow precipitate which was filtered, washed with cold 0.1N HCl and ether and dried in vacuo to give the title compound (0.309 g, 71%) as a yellow solid:

Workup

  1. additionwas added
  2. filtrationThe resulting emulsion was filtered
  3. washthe residue was washed with additional EtOAc
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was again extracted with EtOAc
  6. dry with materialThe combined organic phase was dried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-ccd74fd4e3534916bae17c604218cb87
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

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