Synthesis of Mitomycin C Analogues. 1. Introduction of the Urethane Function at C-10 of the Pyrroloindole Skeleton

Article abstract of DOI:10.1021/jo00220a023

α-(Alkoxymethylene)-2-(1-pyrrolidinyl)benzeneacetonitriles 5b-e, prepared by condensation of 2-(1-pyrrolidinyl)benzeneacetonitrile with ethyl formate and subsequent alkylation of the sodium salt formed, cyclize thermally to the trans- and cis-9-(alkoxymethyl)pyrrolo<1,2-a>indoles 6b-e and 7b-e, respectively.Treatment of the sodium salt of 5a with acetyl chloride or acetic anhydride affords the 1-alkylindoles 8a and 8b, respectively.The mechanisms of both types of reaction, which are examples of the "tertiary amino effect", are discussed.The CH2OR group of the pyrrolo <1,2-a>indoles 6b, d, e and 7b, d, e is deprotected, dependent on the nature of R, by boron tribromide (R=CH3), hydrobromic acid in acetic acid, and subsequent hydrolysis of the acetate formed (R=CH2Ph) and by concentrated hydrochloric acid in methanol (R=CH2OCH3) to give the corresponding alcohols 6a and 7a, respectively.Treatment of the pyrrolo<1,2-a>indole 7b with sodium in liquid ammonia yields a mixture of isomers of the 9-methylpyrrolo<1,2-a>indole 12b; in addition to the cyano group at C-9 also the methoxy group has been removed.Under these conditions the alcohol 7a affords a mixture of 12b and the decyanated alcohols cis-12c and trans-12c.The alcohols 7a and trans-12c are transformed to the corresponding urethanes 7g and 12d, respectively.