Synthesis of 5-Substituted 3-Amino-1H-Pyrazole-4-Carbonitriles as Precursors for Microwave Assisted Regiospecific Syntheses of Pyrazolo[1,5-a]Pyrimidines

A simple route to 3-oxoalkanonitrile 5, aprecursor of the title compounds is described. Reaction of enaminones 2 with hydroxylamine hydrochloride in ethanol yielded aldoximes 3 that were converted readily into 5 in basic medium. This method has been successfully applied with a number of substrates and resulted in excellent yields of the products. Reacting 5 with trichloroacetonitrile afforded 3-amino-2-aroyl-4,4,4-trichloro-2-butenenitriles 6 that condensed with hydrazines to yield 3-amino-1H-pyrazole-4-carbonitrilederivatives 8. Substituted pyrazolo[1,5-a]pyridmidines have been prepared with regioselective condensation reactions of 8 with nonsymmetrical dielectrophiles. The structures of compounds obtained were deduced based on 1H-NMR, 1H-15N HMBC- measurements

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population