Doravirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) currently in phase III clinical trials for the treatment of HIV infection. Herein we describe a robust kilo-scale synthesis for its manufacture. The structure and origin of major impurities were determined and their downstream fate-and-purge studied. This resulted in a redesign of the route to introduce the key nitrile functionality via a copper mediated cyanation which allowed all impurities to be controlled to an acceptable level. The improved synthesis was scaled to prepare ∼100 kg batches of doravirine to supply all preclinical and clinical studies up to phase III. The synthesis affords high-quality material in a longest linear sequence of six steps and 37% overall yield.

Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed, along with operational improvements and extensive safety evaluations of potentially hazardous reactions.

A practical, safe, and scalable synthesis of the stable nitro-oxide radical catalyst ABNO was developed. This process is chromatography-free and avoids the Wolff–Kishner reduction. 1H NMR data for this paramagnetic compound were obtained that allowed an assessment of its chemical purity. Impact sensitivity test data for solid ABNO are also reported.

This chapter describes the procedure for preparation of 9‐azabicyclo[3.3.1]nonane‐N‐oxyl (ABNO). ABNO is an effective catalyst for aerobic oxidation of alcohols to ketones and aldehydes. This type of oxidation is particularly attractive for large scale preparations because of the potential to reduce cost and minimize waste. The chapter presents some of the important points to be considered, the conditions that need to be maintained, characterization data, and the reagents required, as well as the techniques used and the equipment setup that are vital to carrying out the process. It also describes the hazards associated with working with chemicals and the ways to deal with these hazards.

The stability of underground goaf in filling mining is dominated by the interaction mechanism of the backfill-surrounding rock combination. In order to investigate the interaction mechanism and failure characteristics of the backfill-surrounding rock combination, backfill-red sandstone combinations with three different cement–sand ratios were prepared for uniaxial compression tests. The deformation and failure characteristics of the specimens were analyzed. It was found that at the cement–sand ratio of 1:4, the backfill and red sandstone interacted with and restricted each other, and the through cracks appeared in the whole specimens, which indicated that the backfill and red sandstone can jointly resist external loads and play a role in common bearing. However, with the decrease of the cement–sand ratio, the stress mainly acts on the backfill, and the deformation observed in the backfill is large while there is no obvious rupture in the rock. Based on the failure characteristics and the stress–strain curves of the specimens, the damage constitutive relationship that can describe the failure process and deformation characteristics is proposed. Correlated with the experiment results, the damage constitutive equation is established in three stages including compaction pre-synergy stage, quasi-elastic synergy deformation stage and rupture deformation stage. The failure characteristics observed in each stage are analyzed. The research results are of great significance to accurately understanding the interaction between backfill and surrounding rock, which can be used to design and select the mixture ratio of the filling materials.