Reaction equation
N1C2C(=CC=CC=2)C=C1C(NN)=O.[CH3:14][O:15][C:16](=[O:26])[C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:18]=1[O:24][CH3:25].[Br:27]NC(=O)CCC(N)=O>C(O)C>[CH3:14][O:15][C:16](=[O:26])[C:17]1[CH:22]=[C:21]([Br:27])[C:20]([NH2:23])=[CH:19][C:18]=1[O:24][CH3:25]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
An indole hydrazide can also be prepared by treating a solution of 2-methoxy-4-amino-benzoic acid methyl ester (xvii) in ethanol with N-bromosuccinamide to form 2-methoxy-4-amino-5-bromo-benzoic acid methyl ester (xviii) (see Scheme VIII). A solution of 2-methoxy-4-amino-5-bromo-benzoic acid methyl ester (xviii) in DMF is then reacted with trimethyl-prop-1-ynyl silane (xix) in the presence of with palladium acetate, Na2CO3, triphenylphosphine and tetrabutylaminium iodide to form 6-methoxy-3-methyl-2-trimethylsilanyl-1H-indole-5-carboxylic acid methyl ester (xx). Compound (xx) is then treated with an aqueous HCl solution to remove the trimethylsilanyl group and form 6-methoxy-3-methyl-1H-indole-5-carboxylic acid methyl ester (xxi). Compound (xxi) is treated with NaOH in a THF/H2O solution to convert the ester to a carboxylic acid. The carboxylic acid is then activated by treating it with oxalyl chloride in dichloromethane and a catalytic amount of DMF, then the activated carboxylic acid is converted to a hydrazide by treating it with hydrazine hydrate in dichloromethane to form 6-methoxy-3-methyl-1H-indole-5-carboxylic acid hydrazide (xxii). Hydrazide (xxii) can be used in the method of Scheme Vor VI to form a compound of the invention
Sources & evidence
- ORD record
- ord-7c3557b0aabf4944bffc27566264d34f
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835464B2
Linked notes
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