Enylfuran-3-yl)methyl 2-bromo-2,2-difluoroacetate (1q)–General Procedure A was followed employing (2-phenylfuran-3-yl)methanol17 (0.52 g, three.0 mmol). Workup offered the title compound as a yellow oil (0.93 g, 93 ). 1H NMR (400 MHz, CDCl3) 7.66 7.59 (m, 2 H), 7.51 7.45 (m, three H), 7.43 7.37 (m, 1 H), 6.61 (d, J = 1.9 Hz, 1 H), 5.40 (s, two H). 13C1H NMR (101 MHz, CDCl3) 159.7 (t, J = 31.six Hz), 153.4, 142.1, 129.9, 129.1, 128.7, 126.six, 113.56, 113.54, 108.8 (t, J = 314.six Hz), 62.six. 19F NMR (376 MHz, CDCl3) -60.75 (s, two F). HRMS (EI): m/z [M]+ calcd for C13H9BrF2O3: 329.9703; discovered: 329.9701 (0.six ppm). IR (film): 3057, 2970, 1774, 1514, 1489, 1375, 1292, 11689, 1122, 1067, 943, 887, 842, 771, 736, 692, 660 cm-1. Dibenzo[b,d]thiophen-4-ylmethyl 2-bromo-2,2-difluoroacetate (1r)–General Procedure A was followed working with dibenzo[b,d]thiophen-4-ylmethanol (1.two g, five.six mmol). Workup and chromatographic purification (hexanes) supplied the title compound as a colorless solid (1.9 g, 89 ). mp 901 . 1H NMR (400 MHz, CDCl3) 8.22 8.15 (m, two H), 7.94 7.86 (m, 1 H), 7.57 7.47 (m, 4 H), five.63 (s, two H). 13C1H NMR (101 MHz, CDCl3) 159.six (t, J = 31.7 Hz), 139.24, 139.15, 136.six, 135.4, 127.7, 127.37, 127.33, 124.90, 124.86, 123.0, 122.six, 122.0, 108.7 (t, J = 314.five Hz), 68.7. 19F NMR (376 MHz, CDCl3) -60.52 (s, 2 F). HRMS (APCI exane/PhMe): m/z [M]+ calcd for C15H9BrF2O2S: 369.9475; located: 369.9471 (1.1 ppm). IR (film): 3064, 2931, 1778, 1585, 1443, 1408, 1298, 1180, 1136, 1047, 982, 941, 883, 827, 789, 746, 710, 669 cm-1. (1-(Methylsulfonyl)-1H-indol-2-yl)methyl 2-bromo-2,2-difluoroacetate (1s)– Common Procedure A was followed utilizing [1-(methylsulfonyl)-1H-indol-2-yl]methanol18 (1.IGF-I/IGF-1 Protein Formulation 1 g, five.0 mmol). Workup and chromatographic purification (hexanes/EtOAc 1:09:1) offered the title compound as a grey strong (1.1 g, 70 ). mp 878 . 1H NMR (400 MHz, CDCl3) eight.05 (dt, J = 8.three, 1.0 Hz, 1 H), 7.66 7.61 (m, 1 H), 7.47 7.40 (m, 1 H), 7.38 7.31 (m, 1 H), six.91 (s, 1 H), five.69 (s, two H), 3.19 (s, 3H). 13C1H NMR (101 MHz, CDCl3) 158.8 (t, J = 31.7 Hz), 137.2, 131.7, 128.3, 126.five, 124.3, 122.0, 114.8, 114.1, 108.7 (t, J = 314.3 Hz), 62.7, 41.1. 19F NMR (376 MHz, CDCl3) -60.63 (s, two F). HRMS (APCIhexane/PhMe): m/z [M]+ calcd for C12H10BrF2NO4S: 380.9482; found: 380.HGFA/HGF Activator Protein Synonyms 9479 (0.8 ppm). IR (film): 3028, 1778, 1452, 1369, 1292, 1175, 1121, 964, 916, 823, 771, 748, 719, 685 cm-1. (5-(Furan-2-yl)-1-methyl-1H-pyrazol-3-yl)methyl 2-bromo-2,2-difluoroacetate (3a)–HO2CCF2Br (0.27 g, 1.five mmol) was added to a round-bottom flask, which was sealed using a rubber septum and attached to an oil bubbler. DCM (six.0 mL) and DMF (0.30 mL) had been injected, along with the answer was cooled to -10 . Oxalyl chloride (0.13 mL, 1.5 mmol) was injected (caution: evolution of noxious gas), and following 5 min, the mixture was permitted to warm to rt.PMID:23291014 After two h, the mixture was cooled to 0 , in addition to a resolution of [5(furan-2-yl)-1-methyl-1H-pyrazol-3-yl]methanol13 (0.19 g, 1.0 mmol) and NEt3 (0.38 mL, two.7 mmol) in DCM (1.5 mL) was added. Right after two.five h, the reaction was quenched with water,Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ Org Chem. Author manuscript; offered in PMC 2016 August 21.Ambler et al.Pageand the aqueous layer was extracted with EtOAc (4 ten mL). The combined organic layers have been washed with brine, dried over Na2SO4, and filtered. Chromatographic purification (hexanes/EtOAc 1:03:two) offered the title compound as a yellow strong (0.29 g, 82 ). m.p. 390 . 1H NMR (400 MHz, CDCl3) 7.