CI is a separate and unique clinical condition and can occur without a comorbid AI condition, our CI-only group. Past reports of high symptom scores for children with CI are the result of the presence of AI, a common comorbid condition. When AI is factored out, and children with CI only are evaluated, they are not significantly more symptomatic than children with NBV.

5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1H-indole dihydrochloride (1) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatography-free preparation of this compound is described. The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.

Dihalomucononitriles were synthesized and their reactivity evaluated to assess their ability to function as linchpin reagents. Bis(2-chloroacrylonitrile) and bis(2-bromoacrylonitrile) were synthesized from 2,13-benzothiadiazole and shown to undergo conjugate addition reactions with both nitrogen (40-95% yield) and carbon nucleophiles (72-93% yield). Secondary amines were found to undergo monoadditions while carbon nucleophiles added twice. The sequence of addition of the nucleophiles could be controlled giving mixed addition products. The multicomponent coupling products could then be converted to natural product-like motifs using intramolecular cyclization reactions. File list (3) download file view on ChemRxiv Zahara_Hinds_ChemRXIV_2020-FINAL.pdf (743.83 KiB) download file view on ChemRxiv Zahara Hinds SI FINAL_ ChemRXIV.pdf (1.39 MiB) download file view on ChemRxiv Zahara Hinds SI FINAL_ SPECTRA.pdf (8.63 MiB) COMMUNICATION

This report suggests that self‐resolving oligohydramnios is an early sign of malfunctioning kidney in individuals with renal coloboma syndrome (RCS) and demonstrates how a genetic diagnosis can impact patient and fetal management as it outlines two generations of RCS.