Structure of 915411-01-7
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CAS No. : | 915411-01-7 |
Formula : | C7H7BN2O2 |
M.W : | 161.95 |
SMILES Code : | OB(O)C1=CC=CC2=C1NN=C2 |
MDL No. : | MFCD09997801 |
InChI Key : | QAHHYPPRKWNXHT-UHFFFAOYSA-N |
Pubchem ID : | 46839983 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 20℃; for 48.16h;Heating / reflux; | [0228] (b) [3-benzyloxy-5-(lH-indazol-4-yl)-phenyl]-pyridin-3-yl-amine.Suzuki coupling: A round bottom flask was charged with the boronic acid of <n="68"/>7-bromoindazole (144 mg, 0.89 mmol) and teixakistriphenylphosphine palladium (35 mg, 0.03 mmol). 1,2-Dimethoxyethane (4 mL) was added under argon and the mixture was stirred for 10 min at room temperature. A solution of 3-benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine (213 mg, 0.60 mmol) in DME (4.5 mL) and 2M aq Na2CO3 (0.60 mL, 1.24 mmol) were added and the mixture was heated at reflux for 24 h. More tetrakistriphenylphosphine palladium (70 mg, 0.06 mmol) was added and the mixture was refluxed for another 24 h. After completion of the reaction, the mixture was cooled to room temperature, filtered over Hyflo and the filter cake was washed with ethyl acetate (2x20 mL). The filtrate was concentrated under reduced pressure and the oily residue was taken up in brine/ AcOEt 1:1 (80 mL). The layers were separated and the aqueous layer was extracted with AcOEt (40 mL). The combined organics were dried (Na2SO4) and concentrated under reduced pressure to give the crude material (450 mg). Flash chromatography on silica gel (15 g, AcOEt/heptane 3:1) provided pure [3-benzyloxy-5~(lH-indazol-4- yl)-phenyl]-ρyridin-3-yl-amine (230 mg, 98%) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With hydrogenchloride; In water; at 80℃; for 20h; | Indazole 7-pinacol boronate (247 mg, 1.01 mmol) was dissolved in 2 M aqueous HCl (5 mL) and the mixture was heated to 80 C. for 20 h. The reaction mixture was cooled to room temperature, neutralized with 1M NaOH solution (12 mL) to pH 6 and extracted with ethyl acetate (3×20 mL). The combined organics were washed with water (5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the crude boronic acid (148 mg). The crude material was purified by flash chromatography (CH2Cl2/MeOH 95:5) to give 120 mg (74%) of the boronic acid of 7-bromoindazole. |
74% | (iv) Boronic acid of 7-bromoindazole. Indazole 7-pinacol boronate (247 mg, 1.01 mmol) was dissolved in 2 M aqueous HCl (5 mL) and the mixture was heated to 80 C. for 20 h. The reaction mixture was cooled to room temperature, neutralized with 1M NaOH solution (12 mL) to pH 6 and extracted with ethyl acetate (3×20 mL). The combined organics were washed with water (5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the crude boronic acid (148 mg). The crude material was purified by flash chromatography (CH2Cl2/MeOH 95:5) to give 120 mg (74%) of the boronic acid of 7-bromoindazole. | |
74% | [0227] (iv) Boronic acid of 7-bromoindazole. Indazole 7-pinacol boronate(247 mg, 1.01 mmol) was dissolved in 2 M aqueous HCl (5 mL) and the mixture was heated to 80C for 20 h. The reaction mixture was cooled to room temperature, neutralized with IM NaOH solution (12 mL) to pH 6 and extracted with ethyl acetate (3 x 20 mL). The combined organics were washed with water (5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the crude boronic acid (148 mg). The crude material was purified by flash chromatography (CH2Cl2ZMeOH 95:5) to give 120 mg (74%) of the boronic acid of 7-bromoindazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 48h;Heating / reflux; | Suzuki coupling: A round bottom flask was charged with the boronic acid of 7-bromoindazole (144 mg, 0.89 mmol) and tetrakistriphenylphosphine palladium (35 mg, 0.03 mmol). 1,2-Dimethoxyethane (4 mL) was added under argon and the mixture was stirred for 10 min at room temperature. A solution of 3-benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine (213 mg, 0.60 mmol) in DME (4.5 mL) and 2M aq Na2CO3 (0.60 mL, 1.24 mmol) were added and the mixture was heated at reflux for 24 h. More tetrakistriphenylphosphine palladium (70 mg, 0.06 mmol) was added and the mixture was refluxed for another 24 h. After completion of the reaction, the mixture was cooled to room temperature, filtered over Hyflo and the filter cake was washed with ethyl acetate (2×20 mL). The filtrate was concentrated under reduced pressure and the oily residue was taken up in brine/AcOEt 1:1 (80 mL). The layers were separated and the aqueous layer was extracted with AcOEt (40 mL). The combined organics were dried (Na2SO4) and concentrated under reduced pressure to give the crude material (450 mg). Flash chromatography on silica gel (15 g, AcOEt/heptane 3:1) provided pure [3-benzyloxy-5-(1H-indazol-4-yl)-phenyl]-pyridin-3-yl-amine (230 mg, 98%) as a yellow oil. |
98% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 48h;Heating / reflux; | (b) [3-benzyloxy-5-(1H-indazol-4-yl)-phenyl]-pyridin-3-yl-amine. Suzuki coupling: A round bottom flask was charged with the boronic acid of 7-bromoindazole (144 mg, 0.89 mmol) and tetrakistriphenylphosphine palladium (35 mg, 0.03 mmol). 1,2-Dimethoxyethane (4 mL) was added under argon and the mixture was stirred for 10 min at room temperature. A solution of 3-benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine (213 mg, 0.60 mmol) in DME (4.5 mL) and 2M aq Na2CO3 (0.60 mL, 1.24 mmol) were added and the mixture was heated at reflux for 24 h. More tetrakistriphenylphosphine palladium (70 mg, 0.06 mmol) was added and the mixture was refluxed for another 24 h. After completion of the reaction, the mixture was cooled to room temperature, filtered over Hyflo and the filter cake was washed with ethyl acetate (2×20 mL). The filtrate was concentrated under reduced pressure and the oily residue was taken up in brine/AcOEt 1:1 (80 mL). The layers were separated and the aqueous layer was extracted with AcOEt (40 mL). The combined organics were dried (Na2SO4) and concentrated under reduced pressure to give the crude material (450 mg). Flash chromatography on silica gel (15 g, AcOEt/heptane 3:1) provided pure [3-benzyloxy-5-(1H-indazol-4-yl)-phenyl]-pyridin-3-yl-amine (230 mg, 98%) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 80℃; for 22h;Inert atmosphere; Sealed tube; | Example 1 7A(6aS,7S, 1 OaS)-2,7-dimethyl-4-( 1-methyl- 1H-imidazol-5-yl)- 1 Oa-phenyl-5 ,6a,7,9, 10,1 Oahexahydrobenzo[h]quinazolin-8(61 ])-oneIn a pressure tube, the product from Example 13D (2.4 g, 7.0 mmol), 1-methyl-5- (4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-imidazole (2.20 g, 10.6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.41 g, 0.35 mmol) and 2 M sodium carbonate (10.6 mL, 21.1 mmol) in dioxane (60 mL) were combined, and the mixture was sparged with nitrogen for 15 minutes. The tube was sealed and heated to 80 C for 6 hours. The reactionwas cooled to room temperature, and additional 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-imidazole (0.60 g, 2.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.17 mmol) were added. The mixture was sparged with nitrogen for 15 minutes, the tube was sealed, and the mixture was heated to 80C for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with water. The water was back extracted with ethyl acetate. The combined ethyl acetate layers were washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 5% methanol in chloroform to give 1.3 g (46%). Example 92A(6aS,7S, 1 OaS)- 1 Oa-(4-fluorophenyl)-4-( 1H-indazol-7-yl)-2,7-dimethyl-5 ,6a,7,9, 10,1 Oahexahydrobenzo[h]quinazolin-8(61 ])-oneThe titled compound was prepared using the conditions described in Example 1 7A, substituting <strong>[915411-01-7](1H-indazol-7-yl)boronic acid</strong> for 1-methyl-S -(4,4,5,5 -tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-imidazole and Example 68D for Example 13D. Purification wasachieved by flash chromatography on silica gel eluting with 20-33% acetone in heptane togive the titled compound in 100% yield. ‘H NMR (400 MHz, CDC13) ppm 1.17 (d, J=6.5 1Hz, 3 H) 1.97 -2.15 (m, 3 H) 2.36 -2.43 (m, 2 H) 2.48 - 2.55 (m, 1 H) 2.68 - 2.83 (m, 2 H)2.81 (s, 3 H) 3.15 - 3.29 (m, 2 H) 7.02 (t, J=8.62 Hz, 2 H) 7.21 (t, J=7.70 Hz, 1 H) 7.46 - 7.55(m, 3 H) 7.85 (d, J=8.02 Hz, 1 H) 8.14 (s, 1 H) 11.30 (s, 1 H); MS (ESI) m/z 441.3 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 20 - 80℃; for 3h;Inert atmosphere; | To a solution of tert-butyl (2-(2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-iodo-3 - (2-(4-methoxybenzyl)-2H-tetrazol-5 -yl)phenylsulfonamido)ethyl)carbamate (200 mg, 0.214 mmol) inDioxane (4 ml) and water (1 ml)was added Na2CO3(91 mg, 0.857 mmol) (1H-indazol- 7-yl)boronic acid (69.4 mg, 0.428 mmol) and Pd(dppf)C12(49.5 mg, 0.043 mmol)with stirring at room temperature. The reaction mixture was degassed with nitrogen for 3 times. The resulting mixture was warmed to 80C and stirred for 3 hr. The reaction mixture was cooled down to ambient temperature, diluted with water (5mL) and extracted with ethyl acetate (2x lOmL). The combined organiclayers were washed with brine (5 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum to afford yellowoil. The residue was purified by silica gel column chromatographyl2 g, eluted with EtOAc/pctroieum ether (2/1) to afford the title compound as a mixture of PMB tetrazole regioisomers: LCMS (ESI) calc’d for C45H49N90952 [M + H]: 924, found 924. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.575 g | To a stirred solution of lH-indazole-7-boronic acid (0.50 g, 3.09 mmol) and tert-butyl (5- bromothiazol-2-yl)(4-methoxybenzyl)carbamate (0.74 g, 1.85 mmol) in toluene:water (9: 1, 20 ml) was added Na2C03(0.654 g, 6.17 mmol) at rt. The reaction mixture was degassed for 30 min at rt and then treated with Pd(dppf)Cl2(0.22 g, 0.308 mmol). The reaction mixture was heated at 110C for 2 h. The resulting reaction mixture was allowed to cool to rt, poured into water (30 ml) and extracted with EtOAc (2 x 30 ml). The combined organic phase was separated, dried over Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (22% EtOAc in hexane) yielding tert-butyl (5-(lH-indazol-7-yl)thiazol-2-yl)(4- methoxybenzyl)carbamate (0.575 g, 1.32 mmol). LCMS: Method C, 2.67 min, MS: ES+ 437.5; NMR (400 MHz, DMSO-d6) δ ppm: 13.26 (s, 1 H), 8.21 - 8.23 (m, 1 H), 8.03 (s, 1 H), 7.76 (d, J= 8.0 Hz, 1 H), 7.46 (d, J=7.2 Hz, 1 H), 7.29 (d, J=8.4 Hz, 2 H), 7.18 (t, J=7.6 Hz, 1 H), 6.92 (d, J=8.8 Hz, 2 H), 5.24 (s, 2 H), 3.73 (s, 3 H), 1.50 (s, 9 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.21 g | To a stirred suspension of 5-bromopyrazin-2-amine (CAS Number 59489-71 - 3; 0.100 g, 0.575 mmol) and 1 H-indazol-7-ylboronic acid (CAS Number 91541 1 -01 - 7; 0.102 g , 0.630 mmol) in DMF (2.4 ml) and water (0.6 ml) was added K2C03 (0.238 g, 1 .7 mmol) at rt. The reaction mixture was degassed for 30 minutes before addition of PdCI2(dppf) (0.021 g , 0.028 mmol) and heated at 90C for 16 h. The reaction mixture was cooled to rt and quickly poured into saturated aqueous NaHC03 solution (50 ml) and extracted into EtOAc (3 x 20 ml). The combined organic extracts were dried over sodium sulphate and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (100% EtOAc) to yield 5-(1 H-indazol-7-yl)pyrazin-2-amine (0.210 g, 0.995 mmol ). LCMS: Method C, 1 .437 min, MS: ES+ 212.18 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.16 g | To a mixture of 6-bromopyridazin-3-amine (CAS Number 88497-27-2; 0.200 g, 1 .15 mmol) and (1 H-indazol-7-yl)boronic acid (CAS Number 91541 1 -01 -7; 0.277 g, 0.1.72 mmol) in 1 ,4-dioxane:water (1 :0.5; 5 ml) was added K2C03 (0.476 g, 3.45 mmol) at rt. The resulting mixture was degassed with nitrogen for 20 min before addition of PdCl2(dppf) (0.084 g, 0.12 mmol) and the resulting reaction mixture was heated at 100C for 6 h. The resulting reaction mixture was cooled to rt, diluted with water (50 ml) and was extracted with EtOAc (2 x 50 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (compound eluted in 6% MeOH in DCM) to yield 6-(1 H-indazol-7-yl)pyridazin-3- amine (0.16 g, 0.76 mmol). LCMS: Method C, 1 .261 min, MS: ES+ 212.17, 1 H NMR (400 MHz, CDCIs) δ ppm 12.49 (brs, 1 H), 8.21 -8.22 (d, J=1 .6 Hz, 1 H), 8.02-8.04 (d, J=9.2 Hz, 1 H), 7.90-7.92 (d, J=8.0 Hz, 1 H), 7.82-7.83 (d, J=7.2 Hz, 1 H), 6.99-7.01 (d, J=9.6 Hz, 1 H), 4.96 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | To a solution of 2-[(8-bromo-3-oxo-1H-benzo[e]isoindol-2-yl)methyl]prop-2-enamide (30 mg, 87 μmol) in dioxane (2 mL) and water (0.4 mL) were added 1H-indazol-7-ylboronic acid (21.1 mg, 131 μmol), Cs2CO3 (84.7 mg, 260 μmol) and PdCl2dppf (15 mg, 18.4 μmol). The reaction was heated to 100 C for 30 min in a microwave. The reaction mixture was passed through a celite pad, and 1 mL of 2M EDTA was added. The resulting solution was stirred at r.t. for 1 h and washed with brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by reverse phase HPLC using a gradient of water 0.1 % FA/acetonitrile 0.1% FA to afford the title compound (5.4 mg, Yield 16%). LC-MS: [M+H]+383. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 29 1-((1-acryloyl-3-fluoroazetidin-3-yl)methyl)-7-chloro-6-(1H-indazol-7-yl)-4-(2-isopropyl-4-methylpyridin-3-yl)-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione The above title compound was synthesized according to the procedures described in Example 17, except by using <strong>[915411-01-7](1H-indazol-7-yl)boronic acid</strong> instead of 2-fluoro-6-hydroxyphenylboronic acid Step E. LC/MS m/z calculated for C30H27ClFN7O3: 588.18 (M+H)+; found: 588.2 (M+H)+. |
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