1-BOC-6-BROMO-INDAZOLE

a) 1, 1 -dimethylethyl 6-bromo- lH-indazole- 1 -carboxylateA suspension of 6-bromo-lH-indazole (82.74 mmol), DMAP (16.55 mmol), and Et1 , 1 -Dimethylethyl 6-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)-1 H-indazole-1 - carboxylate(a) 1 , 1 -Dimethylethyl 6-bromo-1 H-indazole-1 -carboxylateA suspension of 6-bromo-1 /-/-indazole (82.74 mmol), 4-(dimethylamino)pyridine (16.55 mmol), and triethylamine (19.56 ml.) in acetonitrile at 0 °C was treated with bis(1 , 1 - dimethylethyl) dicarbonate (82.74 mmol) in acetonitrile over 15 min such that the internal temperature remained at 5 °C. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction was concentrated in vacuo and the residue purified by flash chromatography (7percent ethyl acetate/petroleum ether) to afford the title product as a solid (23.2 g, 94percent).To a 0 °C solution of 6-bromo-lH-indazole (20 mmol), triethylamine (4 mL), and 4-(dimethylamino)pyridine (4 mmol) in acetonitrile (100 mL) was dropwise added bis( 1 , 1 -dimethylethyl) dicarbonate (20 mmol) in acetonitrile. The reaction mixture was then stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was purified by flash chromatography (10percent ethyl acetate/petroleum ether) to give the title product (63percent).General procedure: tert-Butyl 3-bromo 1H-indazole-1-carboxylate (0.5 mmol), Na2CO3(0.5 mmol), boronic acid (1.0 mmol), Pd(PPh3)2Cl2 (1 molpercent), and 1, 4-dioxane: ethanol = 4:1 (5 mL) were added to10 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After thereaction vial was irradiated at 140 C for 30 min, themicrowave reactor was cooled with air. Product was separatedwith ethyl acetate and saturated aqueous NH4Cl solution.The organic layer was dried with anhydrous sodiumsulfate, filtered, and concentrated. Products were purifiedby silica gel column chromatography using a hexane: ethylacetate = 4:1.General procedure: tert-Butyl 3-bromo 1H-indazole-1-carboxylate (0.5 mmol), Na2CO3(0.5 mmol), boronic acid (1.0 mmol), Pd(PPh3)2Cl2 (1 molpercent), and 1, 4-dioxane: ethanol = 4:1 (5 mL) were added to10 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After thereaction vial was irradiated at 140 C for 30 min, themicrowave reactor was cooled with air. Product was separatedwith ethyl acetate and saturated aqueous NH4Cl solution.The organic layer was dried with anhydrous sodiumsulfate, filtered, and concentrated. Products were purifiedby silica gel column chromatography using a hexane: ethylacetate = 4:1.General procedure: tert-Butyl 3-bromo 1H-indazole-1-carboxylate (0.5 mmol), Na2CO3(0.5 mmol), boronic acid (1.0 mmol), Pd(PPh3)2Cl2 (1 molpercent), and 1, 4-dioxane: ethanol = 4:1 (5 mL) were added to10 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After thereaction vial was irradiated at 140 C for 30 min, themicrowave reactor was cooled with air. Product was separatedwith ethyl acetate and saturated aqueous NH4Cl solution.The organic layer was dried with anhydrous sodiumsulfate, filtered, and concentrated. Products were purifiedby silica gel column chromatography using a hexane: ethylacetate = 4:1.General procedure: To a flame-dried thick-walled vial was added theheteroaryl halide or aryl halide (1.0 equiv), Pd2(dba)3 (0.05 equiv), tri-tert-butylphosphonium tetrafluoroborate (0.12 equiv), cesiumcarbonate (2.0 equiv) and the boronic acid or ester (1.3 equiv).The vial was sealed with a septum and then the vessel was purgedwith argon for several minutes. Next, dioxane (0.2 M, degassed bybubbling either nitrogen or argon) was added. Under a blanket ofargon, the septum was replaced with a Teflon-coated screw cap.The reaction was stirred at rt for 1 h and then the reaction waswarmed to 90 C for 12'24 h as determined by HPLC analysis ofthe reaction mixture. The crude product was either used withoutfurther purification or it was purified by either column chromatographyon silica gel or by reverse phase chromatographyA mixture of tert-butyl 6-bromo-lH-indazole-l-carboxylate (400 mg, 1.34 mmol), 1- methyl-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)-lH-pyrazole (420 mg, 2.02 mmol), bis(tri-t-butylphosphine)palladium(0) (220 mg, 0.27 mmol) and K2C03 (372 mg, 2.69 mmol) in 1, 4-dioxane (6 mL) and H20 (200 mu) was micro waved at 110 °C for lh and at 130 °C for lh. The filtration removed the solid and washed with DCM. The combined filtrate was concentrated in vacuo. The residue was treated with TFA (5 ml), stirred at rt for 30 min), concentrated in vacuo, basified by addition of 7N NH3 in MeOH (10 ml) and purified by ISCO flash chromatography (eluted with 0-100percent EtOAc / hexane) to provide 6-(l -methyl- lH-pyrazol-4-yl)- lH-indazole as the yellow solid.

Molecular Weight:297.15
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:296.01604
Monoisotopic Mass:296.01604
Topological Polar Surface Area:44.1
Heavy Atom Count:17
Complexity:303
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes