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Synthesis of 6‐substituted 1‐alkoxy‐5‐alkyluracils
Author(s) -
Kim DaeKee,
Kim YoungWoo,
Kim Key H.
Publication year - 1997
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570340148
Subject(s) - chemistry , methanesulfonic acid , sodium azide , alkoxy group , alkyl , acetic acid , medicinal chemistry , azide , uracil , organic chemistry , dna , biochemistry
Synthesis of 6‐substituted 1‐alkoxy‐5‐alkyluracils 2a‐c have been achieved from readily accessible 2‐alkyl‐3,3‐di(methylthio)acryloyl chlorides 4a,b in high overall yields. Treatment of 4a,b with silver cyanate followed by reaction of the resulting isocyanates 5a,b with an appropriate alkoxyamine afforded N ‐alkoxy‐ N ′‐[2‐alkyl‐3,3‐di(methylthio)acryloyl]ureas 6a,b in 85–88% yields. Cyclization of 6a,b in acetic acid containing methanesulfonic acid followed by oxidation with 3‐chloroperoxybenzoic acid gave high yields of 1‐alkoxy‐5‐alkyl‐6‐(methylsulfonyl)uracils 9a,b. Nucleophillic addition‐elimination reaction of 9a,b with sodium azide, phenylthiol, or phenylselenol produced 6‐azido‐1‐butoxythymine ( 2a , 98%), 5‐ethyl‐1‐(2‐phenoxyethoxy)‐6‐(phenylthio)uracil ( 2b , 95%), or 5‐ethyl‐1‐(2‐phenoxyethoxy)‐6‐(phenylselenenyl)uracil ( 2c , 91%).