4-CHLORO-6-(4-METHYLPHENYL)-2-(METHYLTHIO)PYRIMIDINE-5-CARBONITRILE synthesis

Yield:128640-74-4 92%

Reaction Conditions:

with trichlorophosphate at 105; for 3 h;

Steps:

3.1 1.3.6 Synthesis of 5-cyano-6-chloro-2-(methylthio)-4-(p-methylphenyl)pyrimidine (11g)

To the solid pyrimidin-6(1H)-one 10g (0.50 g, 1.94mmol, 1 equiv), POCl₃ (5 ml, 53.80mmol, 27.7equiv) was added. The reaction mixture was heated at 105 °C for 3 h and the excess POCl₃was removed under reduced pressure. Theresidue was purified by column chromatography (60-120 mesh silica) using ethylacetate/hexane (1:9 v/v)as eluent to obtain cream solid product in 92 % yieldat Rf: 0.66[ethyl acetate:hexane/1:4 (v/v)].m.p. 98 °C (dichloromethane/hexane). IR (KBr): ν_max 1483, 2187 cm^-1.¹H NMR(500 MHz, CDCl_3, 25C): δ 2.43 (s, 3H, SCH₃),2.59 (s, 3H, CH₃), 7.31 (d, 2H, J8.1 Hz, ArH), 8.03 (d, 2H, J 8.1 Hz,ArH).¹³C NMR (125 MHz, CDCl₃, 25C): δ 14.3, 26.6, 82.9, 117.0, 128.6, 129.3, 133.1,141.8, 161.9, 166.6, and 175.2. Anal. Calcd. for C₁₃H₁₀ClN₃S:C, 56.72; H, 3.63; N, 15.27, S, 11.63. Found: C, 56.57; H, 3.72; N, 15.22; S,11-.54. EIMS: m/z 275 (M⁺).UV/vis (CH₂Cl₂): λ_max (ε/L mol^-1cm^-1) 270 nm (5440), 324 nm (1370).

References:

Kaur, Hardeep;Balzarini, Jan;De Kock, Carmen;Smith, Peter J.;Chibale, Kelly;Singh, Kamaljit [European Journal of Medicinal Chemistry,2015,vol. 101,art. no. 7951,p. 52 - 62] Location in patent:supporting information