6-Chloro-2-(methylthio)pyrimidin-4-amine

off-white to beige or yellow crystalline powder

[00230] Reagents[00231] Experimental procedure:.bul. ; Take ammonia in THF into a 2 L autoclave and add 4, 6-dichloro-2-(Methylthio) pyrimidine slowly..bul. Heat the reaction mixture to 50-60 ° C and maintain the reaction at 50-60 °C for 3-4 hours (Inbuilt pressure 7- 8 Kg/cm )..bul. Check the progress of the reaction by TLC. Upon completion, the reaction was brought to 25-35 ° C..bul. Concentrate the reaction mixture under vacuum..bul. Charge Hexane and stir for 30-45 minutes at 25-35 ° C..bul. Filter the solid and wash the solid with Hexane..bul. Wash the solid with water (2X400 mL)..bul. Dry the solid at 25-35 °C till M.C reaches to less than 2percent.Yield 352.0 gpercent of Yield: 97.77percent.Purity by HPLC: 99.07percent.Other suitable conditions such as ammonia in MeOH or dioxane could be used accordingly when different analogs are used. Example 1- 2. Preparation of 4-Amino-6-chloro-2- meth lthio)pyrimidine, 6.14, 6-Dichloro-2-(methylthio)pyrimidine (10 g, 51 mmol) was dissolved in a mixtureButanol/NHGeneral procedure: 2-Alkylthio-4-amino-6-hydroxylpyrimidine (2a, b) (27 mmol), POClTo a cold stirring solution of 10 g (52.2 mmol) 6-chloro-2- (methylsulfinyl)pyrimidine-4-amine in 450 ml of DCM, 10 g (56.2 mmol) of N- bromosuccinimide were added, and stirring was continued for 1 hour at room temperature to provide 5-bromo-6-chloro-2-(methylthio)pyrimidine-4-amine, which was used without further purification in the next step (see intermediate 3). The end of the reaction is followed by thin layer chromatography.To a cooled solution of 6-chloro-2-(methylthio)pyrimidin-4-amine (15.0 g, 85 mmol) in DM F (150 ml) was added N-bromosuccinimide (16.7 g, 94 mmol) portionwise with stirring at 0 °C. After 10 min the reaction was quenched by the addition of water at 0 °C. The reaction mixture was diluted with brine and extracted 3 times with EtOAc. The combined organic phases were washed twice with saturated aqueous NaHC03solution, then brine, separated, and filtered through a phase separator with Na2S04to dry. The filtrate was concentrated in vacuo to give the title compound (18.8 g, 74 mmol, 80 percent yield, 92percent purity) as colorless solid which was used in the next step without further purification. M/z = 254/256/258 [M+H]+, Rt = 0.95 min (UPLC 2 min), 1 H NMR (600 MHz, DMSO-d6) delta 8.03 (br s, 1 H), 7.25 (br s, 1 H), 2.42 (s, 3H).

Molecular Weight:175.64
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:174.9970961
Monoisotopic Mass:174.9970961
Topological Polar Surface Area:77.1
Heavy Atom Count:10
Complexity:113
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes