A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations over a 12-step sequence. The dioxabicyclo[3.2.1]octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-D-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with L-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.

[reaction: see text] A simple, one-pot procedure is described for the direct conversion of quinoline N-oxides to alpha-amidoquinolines with primary amides. This methodology is complimentary to the Abramovich reaction, which is limited to the introduction of secondary amides via imidoyl chlorides. Although reaction conditions are quite similar, omission of the base is key for successful reaction with primary amides, which were found not to proceed through the intermediacy of an imidoyl chloride but rather through an acyl isocyanate.

Biocatalytic reductive amination catalyzed by engineered imine reductase (RedAms) is a new and powerful tool for the synthesis of substituted chiral amines. Herein, we describe a streamlined synthesis of compound 3, a key intermediate to a CDK 2/4/6 inhibitor 1, relying on the enzymatic reductive amination of a hydroxyketone to introduce the chiral secondary amine with high diastereoselectivity. The improved synthesis of the hydroxyketone precursor by a titanium-catalyzed reductive cyclization and the process development for two SNAr reactions en route to 3 are also presented.

The development of a commercial route toward the JAK1 inhibitor abrocitinib is described. The application of a late-stage Lossen rearrangement provided the desired cis-diaminocyclobutane, which was subsequently sulfonylated using a novel water-tolerable triazole sulfonylating reagent to provide the active pharmaceutical ingredient.

In South Africa, as in many other countries, there appears to have been a demobilization of mass urban movements following the achievement of representative democracy. This apparent demobilization has led to a perception that South Africa's neighbourhood‐based civic organizations are in crisis. This article builds on existing studies by sharpening analysis of the nature of this ‘crisis’. We show that there continue to be high levels of popular engagement with self‐governing civic structures at the local level. The decline in mass direct action in civil society appears to be linked to public confidence in political society, i.e. in the political parties and elected councillors that provide mechanisms for local representation in representative democracy. The crisis facing civic organizations is in large part a crisis of adjustment, as civic activists redefine their roles in the new institutional context and accept that their roles will be more limited than in specific extraordinary periods in the past. What makes this task of redefinition so difficult is that civil and political society cannot be easily separated, but, rather, form a tangled web in the minds of civic activists (and, we suspect, ordinary citizens also). The lesson of this South African case‐study is that changing patterns of popular politics need to be located in a careful analysis of political society as well as civil society, and especially of the real and perceived links between them. En Afrique du Sud, comme dans de nombreux pays, une démobilisation se dessine, semble‐t‐il, dans les mouvements urbains de masse depuis l'accès à une démocratie représentative. Cette sensation laisse à penser que les organisations civiques de quartier sont en crise en Afrique du Sud. S'appuyant sur des études existantes, l'article affine l'analyse de la nature de cette ‘crise’. Il montre qu'il existe toujours des niveaux élevés d'engagement populaire avec, au niveau local, des structures civiques autonomes. Le recul de l'action directe de masse au sein de la société civile semble liéà la confiance générale dans la société politique, c'est‐à‐dire dans les partis et les conseillers élus qui assurent les mécanismes locaux de la représentation démocratique. La crise que connaissent les organisations de citoyens est en grande partie une crise d'ajustement, les activistes devant redéfinir leur rôle dans le nouveau contexte institutionnel et accepter que celui‐ci soit plus limité que durant certaines périodes du passé. Cette opération de redéfinition est particulièrement problématique, car il n'est pas facile de séparer société civile et société politique, celles‐ci étant étroitement m7ecirc;lées dans l'esprit des activistes civiques (et, à notre avis, dans celui des citoyens ordinaires). Cette étude de cas sud‐africaine démontre qu'il faut situer les nouveaux schémas de politique générale par une analyse précise tant de la société politique que de la société civile, notamment en ce qui concerne les liens réels et supposés entre les deux.