H ethyl acetate (2x). The combined organic layer was washed with brine, dried more than Na2SO4 and concentrated to afford product as Toxoplasma Gene ID off-white solid (549 ). Compounds 19496, 23031, 280 were prepared by this system. 1-(5-Fluoroisoquinolin-8-yl)but-2-yn-1-one (194).–194 was ready from 5fluoroisoquinoline-8-carboxylic acid (54 ). ESIMS m/z (M+1): 214.two. Solution was made use of without having P2Y14 Receptor Storage & Stability additional characterization. 1-(2-Bromo-6-(trifluoromethyl)pyridin-3-yl) but-2-yn-1-ol (195).–195 was ready from 2-bromo-6-(trifluoromethyl)-3-pyridine carboxylic acid (68 ). 1H NMR (400 MHz, CDCl3) (ppm): 8.29 (d, 1H, J=7.eight Hz), 8.09 (d, 1H, J=7.eight Hz), three.48 (s, 3H); ESIMS m/z): (M, M+2): 291.two, 293.two. 1-(3,4-Difluorophenyl)but-2-yn-1-one (196).–196 was ready from 3,4difluorobenzoic acid (1.6 g, 89 ). ESIMS m/z (M+1): 181.0. Solution was applied with out additional characterization. 1-(3-Fluoro-4-(trifluoromethyl)phenyl)but-2-yn-1-one (230).–230 was ready from 3-fluoro-4-(trifluoromethyl)benzoic acid as yellow liquid (62 ). 1H NMR (400 MHz, DMSO-d6) (ppm): 8.01.10 (m, 3H), two.26 (s, 3H); ESIMS m/z (M+1): 230.9. 1-(3-(Trifluoromethyl)phenyl)but-2-yn-1-one (231).–231 was ready from 3trifluoromethyl)benzoic acid (83 ). Item was employed without the need of characterization.J Med Chem. Author manuscript; available in PMC 2022 Could 13.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptPalmer et al.Page1-(2-Bromo-6-(trifluoromethyl)pyridin-3-yl)but-2-yn-1-one (280).–280 was ready from 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylic acid (68 ). ESIMS m/z (M, M+2): 292.2, 294.two. Item was applied with out additional characterization. Basic Process K: N-Tosylation of Pyrrole Carboxylate. Sodium hydride (1.5 equiv) was added to a stirred option of pyrrole carboxylate intermediate (1 equiv) in DMF at 0 for 30 min. Tosyl chloride (1.5 equiv) was added at 0 plus the reaction mixture was stirred at RT for 4 h. Water was added and also the reaction mixture then extracted with ethyl acetate (2x). The resulting combined organic layer was washed with brine, dried over Na2SO4 and concentrated. The concentrated item was purified by flash chromatography (silica gel, eluting with hexane: EtOAc mixtures from one hundred to 60:40 ) to afford product as off-white solid (551 ). Compounds 23639 were prepared by this process, compound 240 was ready by a modified procedure. Ethyl 3-methyl-1-(4-methylbenzenesulfonyl)-4-(6-(trifluoromethyl)pyridine-3carbonyl)-1H-pyrrole-2-carboxylate (236).–236 was prepared from 173 (55 ). 1H NMR (300 MHz, DMSO-d6) (ppm): 9.12 (s, 1H), eight.45 (d, 1H, J= 8.1 Hz), 8.23 (s, 1H), eight.13 (d, 1H, J=8.1 Hz), 7.98 (d, 2H, J= 8.4 Hz), 7.50 (d, 2H, J= eight.four Hz), four.25 (q, 2H, J= 7.2 Hz), two,43 (s, 3H), two.40 (s, 3H), 1.22 (t, 3H, J= 7.two Hz); ESIMS m/z (M+1): 480.9. Ethyl 4-(2-fluoro-4-(trifluoromethyl)benzoyl)-3-methyl-1-(4methylbenzenesulfonyl)-1H-pyrrole-2-carboxylate (237).–237 was prepared from 198 (81 ). Solution was applied without characterization. Ethyl 4-(3-fluoro-4-(trifluoromethyl)benzoyl)-3-methyl-1-(4-methylbenzene-1sulfonyl)-1H-pyrrole-2-carboxylate (238).–238 was ready from 233 (78 ). 1H NMR (400 MHz, DMSO-d6) (ppm): eight.16 (s, 1H), 7.92.09 (m, 3H), 7.79.90 (m, 2H), 7.49.51 (m, 2H), four.24 (q, 2H, J= 9.2 Hz), two.43 (s, 3 H), 2.38 (s, 3H), 1.22 (t, 3H, J=9.2 Hz); ESIMS m/z (M-1): 496.two. Ethyl 3-methyl-1-(4-methylbenzene-1-sulfonyl)-4-(3(trifluoromethyl)benzoyl)-1H-pyrrole-2-carboxylate (239).–Title compound was prepared from 234 (81 ). Solution was used.
