CDCl3) 1.41 (s, 3H), 1.57 (s, 3H), 1.63.73 (m, 4H), 1.75.85 (m, 1H), 2.05.17 (m, 2H), 2.66 (d, J = 16.4 Hz, 1H), 2.79 (d, J = 16.4 Hz, 1H), 5.02.10 (m, 1H), 6.89.01 (m, 2H), 7.46 (ddd, J = 8.6, 7.2, 1.8 Hz, 1H), 7.84 (dd, J = 7.8, 1.8 Hz, 1H); 13 C NMR (100 MHz, CDCl3) 17.8, 22.5, 24.2, 25.9, 39.5, 47.7, 81.3, 118.5, 120.6, 120.8, 123.5, 126.6, 132.5, 136.3, 160.0, 192.9; HRMS (APCI) calcd for [M+H]+ C16H21O2 245.1536, found 245.1541. Synthesis of 5,7-dimethoxy-2-phenylchroman-4-one (43)–After the reaction between cinnamic acid and the unsymmetrical dimethoxy-substituted benzyne precursor 19, the uncyclized o-hydroxyaryl ketone was isolated in a 68 yield as a yellow solid: mp 7174 : 1H NMR (400 MHz, CDCl3) 3.84 (s, 3H), 3.GMP EGF, Human 92 (s, 3H), 5.96 (s, 1H), 6.11 (s, 1H), 7.33.47 (m, 4H), 7.58.65 (m, 3H), 7.78 (d, J = 15.6 Hz, 1H), 7.91 (d, J = 15.6 Hz, 1H); HRMS (APCI) calcd for [M+H]+ C17H17O4 285.1121, found 285.1129. The latter was dissolved in 5 mL of THF, then 10 mL of water and 10 L of piperidine were added, and the mixture was stirred for 2 h at 40 . After allowing the reaction mixture to cool to room temperature, the mixture was extracted with EtOAc (20 mL 2), the organic fractions were combined, and the solvent was evaporated under reduced pressure. Flash chromatography on silica gel using hexanes/EtOAc as the eluent afforded 42 of the unreacted starting material and 48 of the desired 4-chromanone 43 as a white solid: mp 14446 (lit.Caplacizumab 53 mp 145146 ); 1H NMR (400 MHz, CDCl3) 2.PMID:25955218 80 (dd, J = 16.4, 2.7 Hz, 1H), 2.97.07 (m, 1H), 3.82 (s, 3H), 3.90 (s, 3H), 5.41 (d, J = 14.8 Hz, 1H), 6.10 (s, 1H), 6.16 (s, 1H), 7.31.49 (m, 5H); 13C NMR (150 MHz, CDCl3) 45.6, 55.6, 56.2, 79.3, 93.2, 93.6, 106.0, 126.1, 128.7, 128.8, 138.8, 162.3, 165.0, 166.0, 189.2; HRMS (APCI) calcd for [M+H]+ C17H17O4 285.1121, found 285.1124. The 1H and 13C NMR spectral data are in good agreement with the literature data.53 Methyl 2-(2-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate (45)–This compound was obtained as a yellow solid in a 79 yield starting from the monomethyl ester of itaconic acid: mp 12730 ; 1H NMR (400 MHz, CDCl3) 1.46 (s, 3H), 2.93 (d, J = 16.4 Hz, 1H), 3.02 (d, J = 16.4 Hz, 1H), 3.53 (s, 3H), 7.08 (t, J = 8.1 Hz, 2H), 7.59 (t, J = 7.8 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) 22.6, 41.5, 52.1, 86.5, 113.5, 120.6, 122.2, 124.8, 138.0, 169.3, 171.1, 202.8; HRMS (APCI) calcd for [M+H]+ C12H13O4 221.0808, found 221.0809. 4.4. Procedure for the reaction of 2-alkynoic acids with arynes The aryne precursor (1.5 equiv) was added to a mixture of the 2-alkynoic acid (0.25 mmol) and TBAT (2.0 equiv) in 5 mL of anhydrous toluene, and the reaction mixture was then stirred in a closed vial at 60 for 24 h. After the reaction mixture was allowed to cool to room temperature, the reaction mixture was then poured into brine (15 mL) and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (2 15 mL) and the organic layers were combined and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using hexanes/EtOAc as the eluent to afford the desired chromone derivatives. Chromone (50)–This compound was obtained as a yellow semisolid in a 71 yield running the reaction in 15 mL of THF at 65 , instead of toluene at 60 . The same compound was also obtained in an 18 yield starting from 2-bromoacrylic acid (51) usingNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author M.