N-alkylation of indole derivatives

Details N-alkylation of indole derivatives N-alkylation of indole derivatives

2006-06-27

2006-06-27

Saeed, Kamal A. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

07067676

ABSTRACT:
The present invention provides methods for the efficient preparation of indole derivatives of the formulawherein X is methyl or benzyl; and R1, R2, R3and R4are independently hydrogen, halogen, cyano, nitro, hydroxy, optionally substituted alkyl, alkoxy, aralkoxy, carboxy, alkoxycarbonyl, aryl or heteroaryl; or R1and R2combined together with the carbon atoms to which they are attached form a fused 6-membered aromatic ring; by reacting indoles of the formulawherein R1, R2, R3and R4have meanings as defined for formula I, with dimethyl carbonate when X is methyl, or with dibenzyl carbonate when X is benzyl, in the presence of a catalytic amount of a base at an ambient temperature to afford compounds of formula I wherein X, R1, R2, R3and R4have meanings as defined herein above. In particular, the present invention provides methylation and benzylation of the indole nitrogen in nearly quantitative yields using 1,4-diazabicyclo[2.2.2]octane as the base in a catalytic amount under mild conditions, wherein the alkylations may be conducted in the absence or the presence of an ionic liquid, under microwave irradiation or utilizing conventional heat, or combinations thereof.

REFERENCES:
patent: WO 01/81305 (2001-11-01), None
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