Scale-Up of the Synthesis of a Pyrimidine Derivative Directly on Solid Support

Abstract

The solid-phase synthesis of 4-(2-amino-6-phenylpyrimidin-4yl)benzamide, a compound obtained through combinatorial chemistry and parallel synthesis, can be scaled up directly on solid support in excellent yields and high purity. By applying highly loaded aminomethyl polystyrene as solid support, a good ratio between the product and the starting resin is achieved. For comparison, the synthesis was also performed in solution. The solid-phase synthesis approach has the advantage that the desired compound is easily and quickly accessible in sufficient quantities for early development demands.

Combination of primary amide and dipyrrin for the elaboration of extended architectures built upon both coordination and hydrogen bonding

“…Aldehyde 3 has been prepared as described. 22 Fig. 12 The hydrogen bonding node (a) and its extension into a 2-D (b) in (7) 2 $(Me 2 CO) 3 .…”

Upscaling the Solid-Phase Synthesis of a Tetrahydrocarbazole in Chemical Development

“…This topic was also addressed by Hudson and Zikos who proposed a decreased accessibility of reactive sites on higher loaded resins. However, Meisenbach et al3b reported constant yields independent of the resin loading.…”

“…To address these issues there was need for a higher loaded resin. The synthesis of such highly loaded Rink Amide resin is already known ).…”

“…In general the resins are washed and used directly for the next reaction step. Until now, only a few examples of large-scale solid-phase syntheses of non-peptide molecules are reported . Due to the limited number of publications in this research area we started a project to deepen knowledge and practical experiences on this field.…”

One-Pot Microwave-Promoted Synthesis of Nitriles from Aldehydes via tert-Butanesulfinyl Imines

“…4-Formylbenzamide was prepared as previously reported 12 and purified by chromatography on basic alumina (MeOH-EtOAc, 5:95→20:80) prior to use. The general procedure was followed with a 0.4 M solution of (R)-1 (164 mg, 1.35 mmol, 1.8 equiv), Ti(Oi-Pr) 4 (0.470 mL, 1.50 mmol, 2.0 equiv) and 4-formylbenzamide (112 mg, 0.752 mmol, 1.0 equiv).…”