Ethyl 4-(cyclopropylamino)-2-(methylthio)-pyrimidine-5-carboxylate synthesis

Yield:651734-65-5 90%

Reaction Conditions:

with triethylamine in tetrahydrofuran at 20;

Steps:

2.A

Into an Argonaut Technologies' Quest 205 100 mL reactor was added 8.0 g (34.4 mmol) of 4-chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester in 70 mL of dry THF. To the reaction mixture was added 1.1 equivalents of triethylamine followed by a solution of 1.1 equivalents of amine (R^NH2) i? 10 mL of dry THF. The reaction mixture was agitated overnight under a nitrogen atmosphere at room temperature. The THF solution was drained from the reaction vessel, and the residue was washed with THF. The THF solutions were combined, evaporated, and redissolved in 35 mL of ethyl acetate. The ethyl acetate solution was added back into the reaction vessel containing the residue, followed by 40 mL of 0.5 M NaOH. The reaction was agitated and the aqueous layer removed. The ethyl acetate solution was washed twice with 0.5 M NaOH EPO and once with a saturated solution of sodium chloride. The ethyl acetate layer was dried with magnesium sulfate and concentrated in vacuo. The residue was stirred with pentane and evaporated to give the desired product.4-Cyclopropylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester Using procedure A, 4-chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester and 2.16 g (37.8 mmol) of cyclopropylamine were reacted to give 7.80 g (90%) of the title compound as a solid: mp 41°C-42°C. MS (APCI) (m+1)/z 254.0. Analysis calculated for C_{1 1}H₁₅N₃SO₂: C, 52.16; H, 5.97; N, 16.59. Found: C, 52.26; H,5.82; N, 16.53.

References:

WO2006/38112,2006,A1 Location in patent:Page/Page column 30; 31