A-Bestmann reagent (0.238 g, 1.24 mmol) dissolved in MeOH (2 mL), and powdered K2CO3 (0.240 g, 1.74 mmol) had been stirred at 0 . Following the D1 Receptor Synonyms common workup and flash chromatography (SiO2, 5g, two EtOAc/hexanes), alkyne 43 was obtained as a white strong (0.102 g, 34 yield over three steps): TLC Rf = 0.three (five 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.two, 2.3 Hz, 1H), 7.68 (d, J = 8.two Hz, 1H), 7.49-7.42 (m, 2H), 7.42- 7.36 (m, 1H), three.83 (qd, J = 7.two, two.5 Hz, 1H), 2.30 (d, J = 2.five Hz, 1H), 1.55 (d, J = 7.two Hz, 3H); 13C NMR (125 MHz, CDCl3) 156.three, 148.six, 139.three, 136.6, 135.3, 129.0, 128.9, 127.0, 120.five, 85.9, 71.1, 29.2, 24.2; 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 basic process for PI3K Compound homologation, methoxymethyl triphenylphosphonium chloride (four.47 g, three.61 mmol) in dry THF (10 mL), NaOtBu (0.434 g, 4.5 mmol), and ketone 41 (0.381 g, 1.81 mmol) in THF (5 mL) have been 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 employing Hg(OAc)two (1.670 g, 5.26 mmol) at area temperature. Soon after the basic 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 (two mL), and powdered K2CO3 (0.254 g, 1.84 mmol) were stirred at 0 . Following the general workup and flash chromatography (SiO2, 7 g, two EtOAc/hexanes), alkyne 44 was obtained as a pale yellow solid (0.140 g, 33 yield more than 3 measures): TLC Rf = 0.3 (five EtOAc/hexanes); mp 84.1-84.two ; 1H NMR (500 MHz, CDCl3) eight.65 (d, J = 2.three Hz, 1H), 7.86 (d, J = 8.two Hz, 2H), 7.77 (dd, J = 8.2, 2.3 Hz, 1H), 7.66 (d, J = eight.two Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H), 3.82 (qd, J = 7.1, 2.5 Hz, 1H), two.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, 148.6, 139.1, 136.six, 136.3, 135.three, 129.7, 126.9, 120.two, 86.1, 71.0, 29.three, 24.two, 21.five; 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 line with the basic process for homologation, methoxymethyl triphenylphosphonium chloride (2.three 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 (six 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 making use of Hg(OAc)two (1.680 g, five.28 mmol) at room temperature. Just after the basic extraction procedure, 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) have been stirred at 0 . Following the general workup and flash chromatography (SiO2, 5 g, five EtOAc/hexanes), alkyne 45 was obtained as a white solid (0.066 g, ten yield over three methods): TLC Rf = 0.3 (five 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, 2.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.