6-BROMO-1,2,4-TRIAZOLO[4,3-1]PYRIDINE

To a mixture of 5-bromo-2-hydrazinylpyridine (7.87 g, 42 mmol) in 200 mL of diethoxymethoxyethane was added p-toluenesulfonic acid (0.30 g, 1.7 mmol), and the mixture was heated to 110° C. and stirred further for 20 hours, then cooled to rt, and concentrated in vacuo. The residue was diluted with HTo a solution of Template 2 (250 mg, 0.534 mmol), Fragment 1 (159 mg, 0.801 mmol), and [l, l'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (39.1 mg, 0.053 mmol) in dioxane (3.6 mL) was added 2M K3PO4 in water (0.80 mL, 1.60 mmol). The biphasic mixture was degassed with nitrogen for 10 min. The vial was sealed and stirred at 90 C for 2.5 hours. Upon completion, the reaction mixture was cooled to 25 C. The reaction mixture was diluted with water and precipitated solids were collected by vacuum filtration. The solid was triturated with isopropanol and ether to afford tert-butyl 4-(2-([l, 2, 4]triazolo[4, 3-a]pyridin-6-yl)-3-isopropyl-lH-indol-5-yl)piperidine-l- carboxylate (237 mg, 0.516 mmol, 97% yield) as an off- white powder. LCMS retention time 0.95 min [TSl]. MS (ES+) m/z: 460.08 (M+H). NMR (400MHz, DMSO-de): 11.11 (s, IH), 9.35 (s, IH), 8.66 (s, IH), 7.90 (d, J=9.2 Hz, IH), 7.55 (s, IH), 7.50 (d, J=10.1Hz, IH), 7.30 (d, J=8.1Hz, IH), 7.02 (d, J=7.5 Hz, IH), 4.10 (d, J=10.8 Hz, 2H), 3.25 (s, IH), 2.94-2.69 (m, 3H), 1.80 (d, J=13.4 Hz, 2H), 1.65-1.48 (m, 2H), 1.47-1.38 (m, 15H).tert-butyl 2, 8-diazaspiro[4.5]decane-8-carboxylate (0.200 g, 0.832 mmol), 6- bromo-[l, 2, 4]triazolo[4, 3-a]pyridine (0.181 g, 0.915 mmol), cesium carbonate (0.407 mg, 1.25 mmol), Pd2(dba)3 (0.019 mg, 0.021 mmol), Xantphos (0.036 mg, 0.062 mmol), and 1, 4-dioxane (3.0 mL) were charged to a microwave tube. The solution was degassed and filled with nitrogen (3X), then heated to 95C for 1 hour. The reaction was cooled to rt and concentrated in vacuo. The resulting residue was purified by prep TLC (5% MeOH/DCM) to provide tert-butyl 2- ([l, 2, 4]triazolo[4, 3-a]pyridin-6-yl)-2, 8-diazaspiro[4.5]decane-8-carboxylate. LC-MS (IE, m/z): 358 [M+l]+.To a mixture of 5-bromo-2-hydrazinylpyridine (7.87 g, 42 mmol) in 200 mL of diethoxymethoxyethane was added p-toluenesulfonic acid (0.30 g, 1.7 mmol), and the mixture was heated to 110 C. and stirred further for 20 hours, then cooled to rt, and concentrated in vacuo. The residue was diluted with H2O (150 mL). The resulted mixture was washed with aqueous NaHCO3 solution (saturated, 40 mL), and extracted with DCM (300 mL*3). The combined organic phases were dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a flash silica gel chromatography (PE/EtOAc (v/v)=2/1) to give the title compound as a yellow solid (6.60 g, 79.77%). MS (ESI, pos. ion) m/z: 197.9 [M+H]+; 1H NMR (600 MHz, CDCl3): delta 8.82 (s, 1H), 8.34 (s, 1H), 7.75 (d, J=9.7 Hz, 1H), 7.36 (d, J=9.7 Hz, 1H).To a mixture of

Molecular Weight:198.02
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Exact Mass:196.95886
Monoisotopic Mass:196.95886
Topological Polar Surface Area:30.2
Heavy Atom Count:10
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes