Saturated heterocycles, 75. Preparation of tetracyclic thiophene derivatives with bridgehead nitrogen. Synthesis of polymethylenethieno[2,3—d]dihydropyrrolo-, tetrahydropyrido- and tetrahydroazepino[1,2—a]pyrimidin-4-ones and -4-thiones

Abstract

The following tetracyclic ring systems and their derivatives have been synthesized for pharmacological investigations: Trimethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 a, 5 a); Tetramethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 b, 1 j, 5 b); Pentamethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and-4-thione (1 c, 5 c); Trimethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 d, 5 d); Tetramethylenethieno[2,3—d]tetrahydropyrido[1,2,—a]pyrimidin-4-one and -4-thione (1 e, 5 e); Pentamethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 f, 5 f); Trimethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 g, 5 g); Tetramethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on and -4-thione (1 h, 5 h); Pentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 i, 5 i); Tentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one (7 b); Pentamethylenethieno-[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one (7 c).

Compounds1 a–i were synthesized from 2-amino-3-ethoxycarbonyl-4,5-polymethylenethiophene2 a–c with the corresponding lactim ethers (3 a–c) in chlorobenzene in the presence of polyphosphoric acid (PPA). Compounds7 b and7 c were obtained in the reaction of β-amino acid esters2 b and2 c with 2-bromopyridine (6). The thione derivatives (5 a–i) were prepared from compounds1 a–i with phosphorus(V) sulphide.

Zusammenfassung

Für pharmakologische Untersuchungen synthetisierten wir die folgenden tetracyclischen Ringsysteme und deren Derivate: Trimethylen-thieno-[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-on und -4-thion (1 a, 5 a); Tetramethylen-thieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-on und 4-thion (1 b, 1 j, 5 b); Pentamethylen-thieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-on und-4-thion (1 c, 5 c); Trimethylen-thieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-on und -4-thion (1 d, 5 d); Tetramethylen-thieno[2,3—d]tetrahydropyrido-[1,2–a]pyrimidin-4-on und -4-thion (1 e, 5 e); Pentamethylen-thieno[2,3—d]tetrahydropyrido[1,2–a]pyrimidin-4-on und -4-thion (1 f, 5 f); Trimethylenthieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on und -4-thion (1 g, 5 g); Tetramethylen-thieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on und -4-thion (1 h, 5 h); Pentamethylen-thieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on und -4-thion (1 i, 5 i); Tetramethylen-thieno[2,3—d]-tetrahydropyrido[1,2—a]pyrimidin-4-on (7 b); Pentamethylen-thieno[2,3—d]-tetrahydropyrido[1,2—a]pyrimidin-4-on (7 c).

Die Verbindungen1 a–i wurden aus 2-Amino-3-(ethoxycarbonyl)-4,5-polymethylenthiophenen (2 a–c) mit den entsprechenden Lactimethern in Chlorbenzol mit Polyphosphorsäure-Katalysator dargestellt. Die Verbindungen7 b und7 c wurden aus β-Aminosäureestern2 b–c und 2-Brompyridin (6) synthetisiert. Die Thionderivate (5 a–i) erhielten wir durch die Reaktion der Verbindungen1 a–i mit Phosphor(V)-sulfid.