Tetramethylchloroformamidinium Hexafluorophosphate– N -Methylimidazole Amidation in Water: Successes, Limitations, and a Regression Model for Prediction

The results of examining the use of TCFH-NMI amidation conditions with water as the primary reaction solvent are described. Greater than 100 examples, consisting of both simple and more complex pharmaceutically relevant active pharmaceutical ingredient structures, were examined, and general trends with respect to scope were discovered. Supervised machine learning XGBoost and Gradient Boosting regression models to predict conversion of TCFH-NMI amidations in water were also developed and are described.