Isolation, identification and characterization of two novel process-related impurities in olanzapine.

Olanzapine is a marketed antipsychotic agent for treatment of both positive and negative symptoms of schizophrenia. The chemical synthesis of olanzapine drug substance involved the reaction of thienobenzodiazepine hydrochloride with N-methylpiperazine. During the manufacture of olanzapine, two unknown impurities were present in pilot batches in the range of 0.

Highly diastereoselective domino synthesis of 6-spirosubstituted pyrido[2,3-d]pyrimidine derivatives in water.

A highly diastereoselective domino reaction of 2,6-diaminopyrimidine-4-one with structurally diverse aryl aldehydes and various barbituric acids in water under microwave irradiation is described. The products are 6-spiro-substituted pyrido[2,3-d]pyrimidines with high diastereoselectivities (up to 99: 1) in which the major diastereomer bears a cis relationship between substituents at the 5- and 7-positions. Furthermore, the mechanism for diastereoselectivity was confirmed by DFT (B3LYP) calculations.

Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a]quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives.

A series of unusual fused heterocyclic compound derivatives, consisting of a pyridine and a imidazole or pyrimidine core, with a bridgehead nitrogen, were successfully synthesized by a microwave-assisted, three-component domino reaction of aldehydes, enaminones, and malononnitrile. In this one-pot reaction, up to five new bonds were formed accompanied by generating the lactam group. This method has the advantages of short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environment impact.

An efficient synthesis of pyrido[2,3-d]pyrimidine derivatives and related compounds under ultrasound irradiation without catalyst.

A series of pyrido[2,3-d]pyrimidine derivatives and related compounds were synthesized via the condensation reaction of an aldehyde, 2,6-diaminopyrimidine-4(3H)-one and either tetronic acid or 1,3-indanedione under ultrasonic irradiation without catalyst. This protocol has the advantages of higher yields, lower cost and convenient procedure.