Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone antibiotic nalidixic acid is known in the published and patent literature. A systematic search for new solid-state forms of the drug yielded two polymorphs (forms II and III) and six cocrystals with resorcinol, catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of these, X-ray crystal structures were determined for polymorph II and cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol, whereas the remaining solid forms were identified by their unique powder X-ray diffraction patterns. Nalidixic acid is intramolecularly O–H···O hydrogen bonded in a six-member ring, and its molecular dimers are assembled via C–H···O synthon. The OH donors on phenolic coformers H bond with the α-keto acid moiety of the drug as connectors and spacers. Intermolecular drug–drug C–H···O interactions in polymorphs are replaced by strong drug–coformer O–H···O hydrogen bonds in cocrystals

Development of an Efficient, Scalable Route for the Preparation of a Novel Insulin-Like Growth Factor‑1 Receptor Modulator

A chromatography-free and efficient synthesis of insulin-like growth factor-1 receptor (IGF-1R) modulator is reported. Herein we describe an improved synthesis for the target compound, which features facile introduction of a novel pyrrolidinyl-pyrimidyl isoxazole <b>8</b>, via in situ sulfone displacement by fluorine. The overall process consists of six chemical steps and five isolations, with introduction of the expensive triheterocyclic unit <b>8</b> towards the end of the synthesis

A Greener Approach for the Large-Scale Synthesis of 1,4,5-Trisubstituted Pyrazole, AZD8329

The development of a convenient, safe and scalable process for <b>AZD8329</b> manufacturing is reported here. Synthesis was achieved in a two-step telescopic process with an excellent overall yield of 75%. In the first step enamine (<b>6</b>) was synthesized with 90% yield through three chemical transformations. In the next step <b>AZD8329</b> was synthesized from the reactions of <b>6</b> and 4-hydrazinobenzoic acid hydrochloride <b>7</b> through two chemical transformations. The process is very efficient and economical, and <b>AZD8329</b> was manufactured in multikilogram scale. A greener approach is demonstrated through usage of a minimum number of solvents and energy and with process mass intensity (PMI) <60 in the manufacturing process

Exploiting the Differential Reactivities of Halogen Atoms: Development of a Scalable Route to IKK2 Inhibitor AZD3264

An efficient and scalable synthesis of AZD3264 is described in which the differential reactivities of various halogen atoms have been employed. The process involves five linear chemical steps with three isolated stages starting from commercially available fragments

Development of a Safe, Scalable Process for the Preparation of an Oxaisoxazolidinone

This report describes the development and scale up of the synthesis of oxaisoxazolidinone <b>1</b>, a significant synthon in the synthesis of the MRSA development compound AZD5847. Studies were carried out to ensure a short-term, risk based preparation of <b>9</b> on a 5 L scale with a solid isolation procedure and a safe, long-term manufacturing process for both <b>1</b> and <b>9</b> through extensive hazards evaluation