4-METHYL-2-METHYLSULFANYL-PYRIMIDINE-5-CARBOXYLIC ACID ETHYL ESTER synthesis

Yield: 81%

Reaction Conditions:

with triethylamine in ethanol for 48 h;Reflux;

Steps:

1.a
Example 1; Synthesis of {1 -[2-(2-chloro-benzylamino)-pyrido[4,3-d]pyrimidin-5-yl]-piperidin-4-yl}-(4- ethyl-piperazin-1-yl)-methanone 11 (Compound 72)a. Preparation of 4-Methyl-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester 3Equimolar quantities of ethyl 2-acetyl-3-ethoxy-2-propenoate 1 (20.0 g, 107 mmol), ((amino(imino)methyl)-sulfanyl)methane 2 (9.68 g, 107 mmol) and triethylamine (10.8 g, 107 mmol) in EtOH (100 ml.) were stirred at reflux for 48 hours. Then reaction mixture was concentrated and diluted with water. The biphasic mixture was transferred into a separatory funnel and extracted with DCM. Organic extract was washed with water, dried, filtered, and concentrated. The product was purified by crystallization from etha- nol/water to yield in a colorless solid (18.4 g, 86.7 mmol, 81 %).

References:

MERCK PATENT GMBH;SCHIEMANN, Kai;SCHULTZ, Melanie;STAEHLE, Wolfgang;KOBER, Ingo;WIENKE, Dirk;KRIER, Mireille WO2010/63352, 2010, A1 Location in patent:Page/Page column 88-89