title: One-pot synthesis of 4-substituted 3-amino-2-cyanothiophenes involving O-ethyl thioformate.
abstract: An efficient one-pot synthesis of 4-substituted 3-amino-2-cyanothiophenes is described. Treatment of 2-alkyl or aryl substituted acetonitrile sequentially with 2.1 equiv of LDA, 1.1 equiv of O-ethyl thioformate, and 1.2 equiv of 2-chloroacetonitrile afforded the thiophenes in moderate to good yields. The thiophene core can be readily incorporated into more elaborate pharmaceutically relevant structures as demonstrated by converting 3-amino-2-cyano-4-phenylthiophene (1g) to various functionalized thieno[3,2-d]pyrimidines in only two steps.
authors.affiliation: Chemical Development, Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, New Jersey 08540, United States.
authors.forename: Haiming
authors.initials: H
authors.lastname: Zhang
authors.forename: Mark S
authors.initials: MS
authors.lastname: Bednarz
authors.forename: Ngiap-Kie
authors.initials: NK
authors.lastname: Lim
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Hernandez
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wu
mesh_terms: D005561:Formates / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005561:Formates; D009570:Nitriles; C000591792:O-ethyl thioformate; D013876:Thiophenes