Preparation of 5-deazariboflavins

Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system

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544310, 544311, 2603409R, 424251, C07D47104

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active

042776031

ABSTRACT:
This invention relates generally to a novel process for preparing 5-deazariboflavins by the cyclization of the corresponding 6-(N-substituted arylamino)uracils with trialkylorthoformate in the presence of a strong acid catalyst. An improved process for preparing the uracil intermediate is also disclosed. More particularly, it is concerned with the process for preparing 5-deazariboflavin by cyclizing 6-[3,4-dimethyl-N-(D-ribityl)anilino[uracil with trialkylorthoformate in the presence of a strong acid catalyst and hydrolyzing the resulting alkoxymethylene derivative. The corresponding uracil intermediate is prepared by reacting 6-chlorouracil with N-D-ribityl-3,4-xylidine.
5-Deazariboflavins having the general Formula (I) herein below: ##STR1## wherein R.sub.7 is hydrogen or methyl, R.sub.8 is methyl, hydroxy or acyloxy and R.sub.10 is a ribityl group and the corresponding acyl and alkoxymethylene derivatives are useful as riboflavin antagonists with particular utility for the chemotherapy of coccidiosis in chickens or as intermediates for the preparation of said antagonists. The bis(alkoxymethylene) derivatives described herein are useful as prodrug forms of 5-deazariboflavins.
When used for the treatment of coccidiosis, such compounds are administered to the animals by way of the feed and are effective in preventing coccidiosis when administered at levels of from about 0.0005% to about 0.05% by weight of the total feed consumed, the amount required for optimum prevention or control of the disease varying with the particular compound employed.

REFERENCES:
Yoneda, et al., "J. C. S., Chem. Comm.," 1976, pp. 203-204.
O'Brien, et al., "Chem. Industry", 1967, pp. 2024-2045.
O'Brien, et al., "J. Heterocyclic Chem.," vol. 17, 1970, pp. 99-105.
Yoneda, et al., "J. Chem. Soc.," Perkin. Trans. I, No. 16, 1976, pp. 1804-1808.
Janda, et al., "Agnew Chem.," Int. Ed. (Engl.), vol. 15, 1976, pp. 443-444.

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