Dimethylformamide → 6-amino-5-cyano-1H-indazole-7-carboxylic acid methyl ester

HRID 245611Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:6]([NH2:15])=[C:7](Br)[CH:8]=[C:9]2[C:13]=1[NH:12][N:11]=[CH:10]2)=[O:4].C(OCC)(=O)C.C(OC)(C)(C)C.[CH3:28][N:29](C)C=O>[Cl-].[Na+].O.[C-]#N.[Zn+2].[C-]#N>[CH3:1][O:2][C:3]([C:5]1[C:6]([NH2:15])=[C:7]([C:28]#[N:29])[CH:8]=[C:9]2[C:13]=1[NH:12][N:11]=[CH:10]2)=[O:4]

Participants

Conditions

Temperature: 180 °C

Procedure

To a solution of 500 mg (1.85 mmol) of 6-amino-5-bromo-1H-indazole-7-carboxylic acid methyl ester, prepared as in step a in example 16, in 10 mL of N,N-dimethylformamide under an atmosphere of argon is added 135 mg (1.15 mmol) of zinc cyanide and 206 mg (0.185 mmol) of tetrakis(triphenylphsophine)palladium. The reaction mixture is stirred in a microwave oven at 180° C. for 5 minutes. Then, a 1:1 v/v mixture of ethyl acetate and tertbutylmethyl ether and brine are added to the reaction and the phases are separated. The aqueous layer is extracted with tert-butylmethylether. The organic extracts are washed twice with brine, dried over MgSO4 and concentrated in vacuo. The residue is purified by flash chromatography (SiO2, hexane/ethyl acetate 2:1 to 1:1, gradient) to afford 380 mg of product (94%) as a yellowish solid; LC/MS:217/218 (M+H)+.

Workup

additionare added to the reaction
customthe phases are separated
extractionThe aqueous layer is extracted with tert-butylmethylether
washThe organic extracts are washed twice with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue is purified by flash chromatography (SiO2, hexane/ethyl acetate 2:1 to 1:1, gradient)

Sources & evidence

ORD record: ord-8a16bf11ec1f4453a35bc11e4fc6c72a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658801B2

Reaction notes

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