4-(4'-Chloro-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile → 4-(4'-Isopropyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile

Participants

Reaction Steps

4-(4′-Chloro-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (35) (125 mg, 0.352 mmol) and ferric acetylacetonate (12.44 mg, 0.035 mmol) were dissolved in THF (1791 μl) and NMP (134 μl), then isopropylmagnesium bromide (528 μl, 0.528 mmol) was added dropwise. According to LC/MS, approximately 40% conversion was observed. Additional isopropylmagnesium bromide (528 μl, 0.528 mmol) was added, and the reaction was stirred at rt for an additional 1 hour. The reaction was quenched with 1N HCl, then was extract with EtOAc. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was dry-loaded onto silica gel, then was purified by Biotage™ silica gel chromatgraphy [25 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to obtain the desired product (51.1 mg, 40%). MS (ES+): m/z=363.3 [M+1] (100). HPLC: tR=1.70 minutes over 3 minutes.

Provenance & Evidence