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 PARP4 web general workup and flash chromatography (SiO2, 5g, two EtOAc/hexanes), alkyne 43 was obtained as a white solid (0.102 g, 34 yield over three 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 = two.3 Hz, 1H), 7.97-7.95 (m, 2H), 7.79 (dd, J = eight.2, 2.3 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.49-7.42 (m, 2H), 7.42- 7.36 (m, 1H), 3.83 (qd, J = 7.two, 2.5 Hz, 1H), 2.30 (d, J = two.five Hz, 1H), 1.55 (d, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) 156.3, 148.six, 139.3, 136.six, 135.3, 129.0, 128.9, 127.0, 120.5, 85.9, 71.1, 29.two, 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). As outlined by the general procedure for homologation, methoxymethyl eIF4 web triphenylphosphonium chloride (4.47 g, three.61 mmol) in dry THF (10 mL), NaOtBu (0.434 g, 4.five mmol), and ketone 41 (0.381 g, 1.81 mmol) in THF (5 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, six mL) was hydrolyzed working with Hg(OAc)two (1.670 g, five.26 mmol) at area temperature. Right after the general extraction procedure, 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) were stirred at 0 . Following the common workup and flash chromatography (SiO2, 7 g, two 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.two ; 1H NMR (500 MHz, CDCl3) eight.65 (d, J = two.three Hz, 1H), 7.86 (d, J = eight.two Hz, 2H), 7.77 (dd, J = 8.2, two.3 Hz, 1H), 7.66 (d, J = 8.two Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H), 3.82 (qd, J = 7.1, 2.five Hz, 1H), 2.39 (s, 3H), two.29 (d, J = 2.5 Hz, 1H), 1.54 (d, J = 7.two Hz, 3H); 13C NMR (125 MHz, CDCl3) 156.3, 148.six, 139.1, 136.six, 136.three, 135.three, 129.7, 126.9, 120.2, 86.1, 71.0, 29.three, 24.2, 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). As outlined by the general process for homologation, methoxymethyl triphenylphosphonium chloride (two.3 g, six.62 mmol) in dry THF (18 mL), NaOtBu (0.797 g, 8.three mmol), and ketone 42 (0.655 g, three.31 mmol) in THF (6 mL) were stirred at 0 . Following the basic workup, the mixture of enol ethers (0.398 g, 1.76 mmol) in THF/H2O (9:1, 6 mL) was hydrolyzed utilizing Hg(OAc)2 (1.680 g, 5.28 mmol) at area temperature. Just after the general extraction process, aldehyde (0.300 g, 1.41 mmol) in MeOH (4 mL), the Ohira-Bestmann reagent (0.407 g, two.12 mmol) dissolved in MeOH (two 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, 10 yield more than 3 measures): TLC Rf = 0.three (5 EtOAc/hexanes); mp 75.4-76.7 ; 1H NMR (500 MHz, CDCl3) eight.82 (s, 2H), eight.60-8.21 (m, 2H), 7.48- 7.46 (m, 3H), 3.82 (qd, J = 7.1, two.five Hz, 1H), 2.34 (d, J = 2.five Hz, 1H), 1.57 (d, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) 163.7, 156.1, 137.six, 133.three, 130.