ETHYL 4-(METHYLAMINO)-2-(METHYLSULFANYL)-5-PYRIMIDINECARBOXYLATE

White Solid

Methylamine in EtOH (33percent, 17.5 mL, 140 mmol) was slowly added to a solution of Intermediate 3 (10.0 g, 43.1 mmol) in 120 mL of dichloromethane at 0 °C. The solution was stirred for 30 mm. Water (150 ml) was added, and the resultant mixture was separated, the organic layer was dried over MgSO4, filtered, and concentrated to afford the title compound (9.77 g, 100percent) as white solid.To a solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (10 g, 43 mmol) inanhydrous THF (100 mL) was added triethylamine (6.0 mL, 43 mmol) and monomethylamine (2M in THF, 22 mL, 43 mmol) The reaction mixture was heated to 50 °C overnight, then diluted with water (100 mL) and extracted into ethyl acetate (3 x 100 mL) . The combined organic phases were dried over Na2SQ4, filtered and concentrated to drynessunder reduced pressure to give the title compound (10 g, quantitative yield) as an off—white solid. ‘H NMR (500 MHz, CDC13) : 6 8.60 (s, 1H) , 8.16 (br s, 1H) , 4.31 (q, 2H), 3.07 (d, 3H), 2.54 (s, 3H), 1.36 (t, 3H). LCMS (Method A): RT = 1.14 mi m/z = 228 [M+H].To a 0° C. solution of 20 g (86 mmol) of ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate (Aldrich Chemical Co., Milwaukee, Wis., USA) in 250 mL of dichloromethane was slowly added 35 mL (281 mmol) of a 33percent solution of methylamine in ethanol. After stirring for 30 minutes, 150 mL of water was added and the phases were separated. The organic phase was dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give 19 g (97percent) of ethyl 4-methylamino-2-methylthiopyrimidine-5-carboxylate as a white solid.Step 1: Synthesis of ethyl 4-(methylamino)-2-(methylthio)pyrimidine-5-carboxylateNpercentrCO2Et MeNH2 in MeOH Nt.CO2EtMeSNCI THF, RT MeSNNA mixture of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (5.0 g, 21.5 mmol)and 29percent methylamine (5.75 g, 53.72 mmol, methanol (MeOH) solution) in tetrahydrofuran(THF) (100 mL) was stirred at room temperature for 2 hours. The reaction mixture was then concentrated, followed by the addition of sodium bicarbonate (NaHCO3) (aq., 20 mL), and the resulting solution was extracted with ethyl acetate (EtOAc) (3 x 50 mL). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated toafford ethyl 4-(methylamino)-2-(methylthio)pyrimidine-5-carboxylate (4.68 g, 96percent) as a yellowish solid. MS (ES+) C9H13N302S requires: 227, found: 228 [M + H].Step 1: A mixture of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (5.0 g, 21.5 mmol) and 29percent methylamine (5.75 g, 53.72 mmol, methanol (MeOH) solution) in tetrahydrofuran (THF) (100 mL) was stirred at room temperature for 2 hours. The reaction mixture was then concentrated, followed by the addition of sodium bicarbonate (NaHCOEthyl 4- (methylamino) -2- (methylthio) pyrimidine-5-carboxylate. To a stirred solution of compound 1 (40 g, 172 mmol) in 500 mL of DCM 70 mL of a 23solution of methylamine in ethanol at 0was slowly added. The resulting mixture was stirred at 0for 45 min. After compound 1 was completely consumed as monitored by TLC, 300mL of water was added to the mixture. The organic layer was separated and washed with brine (2 × 200 mL) , dried over anhydrous MgSO.

An intermediate in the preparation of antitumor agents, antiinflammatory agents and tyrosine kinase inhibitors

Molecular Weight:227.29
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:227.07284784
Monoisotopic Mass:227.07284784
Topological Polar Surface Area:89.4
Heavy Atom Count:15
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes