Preparation and application background and overview of 2-methylthiopyrimidine-5-boronic acid pinamate
2-Methylthiopyrimidine-5-boronic acid pinacolate is a pharmaceutical intermediate, which can be prepared from 5-bromo-2-(methylthio)pyrimidine and diboronic acid pinacol ester through a one-step reaction. There are reports in the literature that 2-methylthiopyrimidine-5-boronic acid pinamate can be used to prepare a powerful regulator of TNFα.
Preparation and application of 2-methylthiopyrimidine-5-boronic acid pinamate
To a stirred solution of 5-bromo-2-(methylthio)pyrimidine (950 mg, 4.63 mmol) in DMF (5 mL) was added 4,4,4′,4 at room temperature under argon. ‘,5,5,5′,5′-octamethyl-2,2’-bis(1,3,2-dioxaborolane) (1.77g, 6.95mmol), potassium acetate (1.36 g, methylpyridine 13.90mmol) and palladium diacetate (104mg, 0.463mol). The resulting suspension was degassed with argon for 15 minutes and then heated at 85°C overnight. The reaction mixture was allowed to cool to room temperature. EtOAc (10 mL) was added to the reaction mixture and the reaction mixture was washed with brine (15 mLx3). The organic phase was dried (MgSO4), filtered and concentrated.
Preparation and application of 2-methylthiopyrimidine-5-boronic acid pinamate
CN201380047390.1 reported that 2-methylthiopyrimidine-5-boronic acid pinamate can be used to prepare the following intermediates, which can be used to prepare substituted imidazo[1,2-a]pyridine derivatives . Such compounds are modulators of TNFα and are thus useful as pharmaceutical agents, particularly in the treatment of deleterious inflammatory and autoimmune disorders, neurological and neurodegenerative disorders, pain and nociceptive disorders, cardiovascular disorders, and metabolic disorders. , eye diseases and tumor conditions are beneficial. The compounds according to the sodium carbonate invention serve as potent modulators of human TNFα activity and are therefore useful in the treatment and/or prevention of various human diseases. These include autoimmune and inflammatory conditions; neurological and neurodegenerative conditions; pain and nociceptive conditions; cardiovascular conditions; metabolic conditions; ocular conditions and oncological conditions.
References
[1] [Invented in China] CN200980136208.3 Pyridinone and pyridazinone analogues as GPR119 modulators
[2] [China invention, China invention authorization] CN201380047390.1 Imidazopyridine derivatives as TNF activity modulators
