Hydrochloric Acid → 4-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrile

Participants

Reaction Conditions

Reaction Steps

5-Acetyl-2-(methylthio)pyrimidin-4(3H)-one (33) (1.094 g, 5.94 mmol) was dissolved in 1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (12.26 mL, 59.4 mmol), then the reaction mixture was heated at 120° C. for 6 hours. The reaction mixture was concentrated in vacuo, and dried over high vacuum for 1 hour. The crude intermediate was taken up in DMF (31.6 mL), then 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (4.10 g, 29.7 mmol) were added. The reaction mixture was heated at 120° C. for 48 hours. Additional 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (3.69 g, 26.7 mmol) were added, and the reaction mixture was stirred at 120° C. for additional 18 hours. The reaction mixture was cooled to rt, then was slowly poured into an ice-cooled 1N HCl solution while stifling vigorously. The reaction mixture was neutralized with additional 1N HCl, then the reaction mixture was allowed to stir for an additional 30 minutes. The resulting precipitate was filtered, washed multiple times with DI water, 2-propanol, then diethyl ether. The resulting crude product was dried over high vacuum for 18 hours to obtain the desired product as a red/brown solid (940 mg, 47% yield). MS (ES+): m/z=337.2 (100) [MH+]. HPLC: tR=1.35 minutes over 3 minutes. Purity: 72% [HPLC (LC/MS) at 220 nm].

Provenance & Evidence