title: One-Step Synthesis of 2-Chloropyrimidin-4-ol Derivatives: An Unusual Reactivity of Thiophosgene.
abstract: A novel, high-yielding, one-step synthesis of 2-chloroquinazolin-4-ols and analogous bicycles from 2-aminoamides using thiophosgene is described. The scope of the reaction includes aminothioamides, amino acids, and fused heterocycle derivatives, furnishing quinazolines, oxazinones, and substituted fused pyrimidine bicycles, respectively. On the basis of observed results with substituted analogues, a mechanism for this transformation is thought to occur via an isothiocyanate intermediate followed by an unexpected chemoselective reaction of thiophosgene on the thiol intermediate.
authors.affiliation: CRT Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Callingham
authors.affiliation: CRT Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Blum
authors.affiliation: CRT Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Pavé
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis* / Q000737:chemistry; D017879:Isothiocyanates / Q000737:chemistry; D015394:Molecular Structure; D010705:Phosgene / Q000031:analogs & derivatives* / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D006843:Hydrocarbons, Chlorinated; D017879:Isothiocyanates; D011743:Pyrimidines; D011799:Quinazolines; C016145:thiophosgene; D010705:Phosgene; C037152:isothiocyanic acid