3-Methylthio-1,2,4-triazine has a phenyl ring and has been shown to be pde5 inhibitory. 3-Methylthio-1,2,4-triazine was treated with potassium amide in liquid ammonia to give 3-amino-1,2,4-triazine, 3,3′-bis(methylthio)-5,5′-bis-1,2,4-triazine and 3-amino-3′-(methylthio)-5,5′-bis-1,2,4-triazine. triazine, 3,3′-bis(methylthio)-5,5′-bis-1,2,4-triazine and 3-amino-3′-(methylthio)-5,5′-bis-1,2,4-triazine. It is also used in the preparation of pharmaceutical products.
The general procedure for the synthesis of 3-(methylthio)-α-triazine from 3-methylthioalkyl-1,2,4-triazine methylhydrazinylideneamino thiosulfate hydrogen iodide (Intermediate 16, 8.5 g, 32.18 mmol) and 40% oxalyl aldehyde (14.70 mL, 128.71 mmol) was as follows: an ice/water (400 mL) solution of Intermediate 16 was added to a 40% oxaldehyde solution with stirring. Subsequently, an ice/water (400 mL) solution of sodium bicarbonate (6.76 g, 80.45 mmol) cooled to 0°C was stirred at 0°C for 5 hours. After completion of the reaction, the reaction mixture was extracted with dichloromethane (DCM, 2 x 150 mL). The organic phases were combined, washed with 1 M citric acid (50 mL), dried over anhydrous magnesium sulfate (MgSO4), and concentrated under reduced pressure to afford 3-methylthioalkyl-1,2,4-triazine (3.60 g, 88% yield) as a yellow solid. The product was characterized by 1H NMR (400 MHz, CDCl3, 27 °C): δ 2.68 (3H, s), 8.38 (1H, d), 8.94 (1H, d).
[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 20, p. 6024 - 6029
[2] Tetrahedron Letters, 1986, vol. 27, # 4, p. 431 - 432
[3] Patent: US2017/152255, 2017, A1. Location in patent: Paragraph 0294; 0295
[4] Tetrahedron Letters, 1987, vol. 28, # 4, p. 379 - 382
