A-Bestmann reagent (0.238 g, 1.24 mmol) dissolved in MeOH (two mL), and powdered K2CO3 (0.240 g, 1.74 mmol) had been stirred at 0 . Following the Thymidylate Synthase Inhibitor Biological Activity common workup and flash chromatography (SiO2, 5g, two EtOAc/hexanes), alkyne 43 was obtained as a white solid (0.102 g, 34 yield more than 3 methods): TLC Rf = 0.3 (5 EtOAc/hexanes); mp 90.3-92 ; 1H NMR (500 MHz,dx.doi.org/10.1021/jm401916j | J. Med. Chem. 2014, 57, 2643-Journal of Medicinal ChemistryCDCl3) 8.67 (d, J = 2.three Hz, 1H), 7.97-7.95 (m, 2H), 7.79 (dd, J = 8.2, two.3 Hz, 1H), 7.68 (d, J = eight.two Hz, 1H), 7.49-7.42 (m, 2H), 7.42- 7.36 (m, 1H), three.83 (qd, J = 7.two, 2.5 Hz, 1H), two.30 (d, J = two.five Hz, 1H), 1.55 (d, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) 156.three, 148.6, 139.three, 136.6, 135.three, 129.0, 128.9, 127.0, 120.five, 85.9, 71.1, 29.2, 24.two; IR (neat cm-1) 3292, 2976, 2930, 2870, 2325, 2107, 1594, 1473, 1293, 1018, 841, 740, 693, 644; HRMS (DART, M+ + H) m/z 208.1144 (calculated for C15H14N, 208.1126). 5-(1-Methyl-prop-2-ynyl)-2-p-tolyl-pyridine (44). In accordance with the common procedure for homologation, methoxymethyl triphenylphosphonium chloride (4.47 g, 3.61 mmol) in dry THF (10 mL), NaOtBu (0.434 g, 4.5 mmol), and Farnesyl Transferase Compound ketone 41 (0.381 g, 1.81 mmol) in THF (five mL) were stirred at 0 . Following the basic workup, the mixture of enol ethers (0.418 g, 1.75 mmol) in THF/H2O (9:1, 6 mL) was hydrolyzed making use of Hg(OAc)2 (1.670 g, 5.26 mmol) at area temperature. Following the basic extraction process, aldehyde (0.197 g, 0.87 mmol) in MeOH (4 mL), the Ohira-Bestmann reagent (0.252 g, 1.31 mmol) dissolved in MeOH (2 mL), and powdered K2CO3 (0.254 g, 1.84 mmol) had been stirred at 0 . Following the common workup and flash chromatography (SiO2, 7 g, 2 EtOAc/hexanes), alkyne 44 was obtained as a pale yellow strong (0.140 g, 33 yield more than 3 actions): TLC Rf = 0.3 (five EtOAc/hexanes); mp 84.1-84.2 ; 1H NMR (500 MHz, CDCl3) eight.65 (d, J = 2.3 Hz, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.77 (dd, J = 8.2, two.3 Hz, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H), three.82 (qd, J = 7.1, two.5 Hz, 1H), 2.39 (s, 3H), two.29 (d, J = 2.five Hz, 1H), 1.54 (d, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) 156.3, 148.six, 139.1, 136.six, 136.three, 135.3, 129.7, 126.9, 120.2, 86.1, 71.0, 29.3, 24.two, 21.5; IR (neat cm-1) 3214, 2973, 2928, 2867, 2109, 1679, 1474, 1386, 1293, 1087, 1014, 818, 764, 697, 534; HRMS (DART, M+ + H) m/z 222.1303 (calculated for C16H16N, 222.1283). 5-(1-Methyl-prop-2-ynyl)-2-phenyl-pyrimidine (45). In accordance with the basic procedure for homologation, methoxymethyl triphenylphosphonium chloride (2.three g, 6.62 mmol) in dry THF (18 mL), NaOtBu (0.797 g, eight.three mmol), and ketone 42 (0.655 g, three.31 mmol) in THF (six mL) had been stirred at 0 . Following the general workup, the mixture of enol ethers (0.398 g, 1.76 mmol) in THF/H2O (9:1, 6 mL) was hydrolyzed using Hg(OAc)2 (1.680 g, 5.28 mmol) at space temperature. Soon after the basic extraction process, aldehyde (0.300 g, 1.41 mmol) in MeOH (4 mL), the Ohira-Bestmann reagent (0.407 g, 2.12 mmol) dissolved in MeOH (2 mL), and powdered K2CO3 (0.410 g, two.96 mmol) had been stirred at 0 . Following the common workup and flash chromatography (SiO2, five g, five EtOAc/hexanes), alkyne 45 was obtained as a white strong (0.066 g, ten yield over 3 measures): TLC Rf = 0.3 (5 EtOAc/hexanes); mp 75.4-76.7 ; 1H NMR (500 MHz, CDCl3) eight.82 (s, 2H), 8.60-8.21 (m, 2H), 7.48- 7.46 (m, 3H), 3.82 (qd, J = 7.1, two.5 Hz, 1H), two.34 (d, J = 2.5 Hz, 1H), 1.57 (d, J = 7.two Hz, 3H); 13C NMR (125 MHz, CDCl3) 163.7, 156.1, 137.6, 133.three, 130.