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Chemical Structure| 863753-35-9

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Product Details of [ 863753-35-9 ]

CAS No. :863753-35-9
Formula : C10H15BN2O4
M.W : 238.05
SMILES Code : O=C(NC1=NC=CC=C1B(O)O)OC(C)(C)C
MDL No. :MFCD10696635
InChI Key :QOAIOWWKQBFCQE-UHFFFAOYSA-N
Pubchem ID :22135186

Safety of [ 863753-35-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of [ 863753-35-9 ]

* 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.

  • Downstream synthetic route of [ 863753-35-9 ]

[ 863753-35-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 38427-94-0 ]
  • [ 863753-35-9 ]
YieldReaction ConditionsOperation in experiment
Under a nitrogen atmosphere, a solution of tert-butyl iV-(2-ρyridyl)carbamate (15.71 g, 80.9 mmol) and iV.ΛζN'.N'-tetramethylethylenediamine (TMEDA) (25.3 g, 218 mmol) in THF (400 mL) was cooled to -78 0C. M-Butyllithium (81 mL of a 2.5 M solution in hexanes) was added dropwise over a period of 20 minutes. The solution was stirred for ten minutes, and then the addition funnel was rinsed with additional THF (20 mL). The solution was warmed to -6 0C, stirred for two hours, and cooled again to -78 0C. Triisopropyl borate (57.7 g, 307 mmol) was added over a period often minutes. The resulting solution was warmed to 00C and then poured into saturated aqueous ammonium chloride (500 mL). A yellow solid formed and was stirred with diethyl ether (300 mL), isolated by filtration, washed with diethyl ether and water, and air-dried overnight to provide 2-ført-butoxycarbonylamino-3-pyridylboronic acid as a yellow solid.
Manufacturing Example 1-7-22-N-butoxycarbonyl-3-pyridineboronic acid; A tetrahydrofuran solution (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylenediamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added dropwise over a period of 1 hour, which was stirred for 10 minutes. This mixture was warmed to a temperature between -10 C. and -6 C., which was stirred for 2 hours at that temperature. The solution was again cooled to -70 C., and triisobutyl borate (58 g) was added dropwise over a period of 1 hour. This mixture was warmed to 0 C., and then a saturated ammonium chloride aqueous solution was added thereto. Ether was added to the yellow solid thus produced, which was stirred, and the solid was then collected by filtration and washed with ether and water. This solid was dried under a reduced pressure, so as to obtain the title compound (14 g).1H-NMR spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-8.13 (2H, m).
A solution of pyridin-2-yl-carbamic acid tert-butyl ester described in Preparation Example 4-1-1 (16 g) and N,N,N',N'-tetramethyl ethylenediamine (25 g) in tetrahydrofuran (400 mL) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added thereto dropwise over one hour, and stirred for 10 minutes. This mixture was heated to between -10 C. and -6 C., and stirred at this temperature for two hours. Again, this solution was cooled to 70 C., and triisobutyl borate (58 g) was added thereto dropwise over one hour. This mixture was heated to 0 C., then, a saturated aqueous ammonium chloride was added thereto. To the produced yellow solid was added ether, and stirred, and then, a solid was recovered by filtration and washed with ether and water. This solid was in vacuo to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
  • 2
  • [ 863753-35-9 ]
  • [ 1075734-36-9 ]
  • [ 936339-60-5 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 2h;Product distribution / selectivity; Alternative Method 3 for Reference Example 2 3-(3-(4-(Pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine ; Under a nitrogen atmosphere, a mixture of 2-(4(5-iodo-isoxazol-3-ylmethyl)-benzyloxy)-pyridine (200 mg) described in Manufacturing Example 2-8-2, 2-N-t-butoxycarbonyl-3-pyridineboronic acid (134 mg) described in Manufacturing Example 2-7-2, sodium carbonate (82 mg), tetrakis(triphenylphosphine) palladium (59 mg), 1,2-dimethoxyethane (6 mL) and water (1 mL) was stirred at 80 C. for 2 hours. The mixture was cooled to room temperature, and ethyl acetate and water were added thereto. The organic layer was isolated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was adsorbed on silica gel, and purified by silica gel column chromatography (heptane:ethyl acetate=4:1 then 1:1 then ethyl acetate) to obtain the title compound (116 mg).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 2h;Inert atmosphere; Other Method 3 of Reference Example 13-(3-(4-(Pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine; A mixture of 2-(4-(5-iodo-isoxazol-3-ylmethyl)-benzyloxy)-pyridine (200 mg) described in Manufacturing Example 1-8-2,2-N-butoxycarbonyl-3-pyridineboronic acid (134 mg) described in Manufacturing Example 1-7-2, sodium carbonate (82 mg), tetrakis(triphenylphosphine) palladium (59 mg), 1,2-dimethoxyethane (6 mL), and water (1 mL) was stirred under a nitrogen atmosphere for 2 hours at 80 C. This mixture was cooled to room temperature, and ethyl acetate and water were added. The organic layer was separated, washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then filtered. After the filtrate was adsorbed to silica gel, it was purified by silica gel column chromatography (heptane:ethyl acetate=4:1 to 1:1 to ethyl acetate) to obtain the title compound (116 mg).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 2h;Product distribution / selectivity; Under a nitrogen atmosphere, a mixture of 2-(4-(5-iodo-isoxazol-3-yl methyl)-benzyloxy)-pyridine described in Preparation Example 4-2-2 (200 mg), <strong>[863753-35-9]2-N-t-butoxycarbonyl-3-pyridine boric acid</strong> described in Preparation Example 4-1-2 (134 mg), sodium carbonate (82 mg), tetrakis(triphenyl phosphine) palladium (0) (59 mg), 1,2-dimethoxyethane (6 mL) and water (1 mL) was stirred at 80 C. for two hours. This mixture was cooled to room temperature, and ethyl acetate and water were added thereto. The organic layer thereof was separated, washed with water and saturated sodium chloride water, dried over anhydrous magnesium sulfate and then filtered. The filtrate thereof was adsorbed onto silica gel, then, purified by silica gel column chromatography (heptane:ethyl acetate=4:1 to 1:1 to ethyl acetate) to obtain the title compound (116 mg). The starting material, <strong>[863753-35-9]2-N-t-butoxycarbonyl-3-pyridine boric acid</strong>, was synthesised according to the following methods.
With water; sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 2h;Inert atmosphere; [Alternative Method 3 for Reference Example 1] 3-(3-(4-(Pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine Under a nitrogen atmosphere, a mixture of 2-(4-(5-iodo-isoxazol-3-ylmethyl)-benzyloxy)-pyridine (200 mg) described in Manufacturing Example 1-8-2,<strong>[863753-35-9]2-tert-butoxycarbonylamino-3-pyridineboronic acid</strong> (134 mg) described in Manufacturing Example 1-7-2, sodium carbonate (82 mg), tetrakis(triphenylphosphine) palladium (59 mg), 1,2-dimethoxyethane (6 mL) and water (1 mL) was stirred at 80 C. for 2 hours. The mixture was cooled to room temperature, and ethyl acetate and water were added thereto. The organic layer was isolated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was adsorbed on silica gel, and purified by silica gel column chromatography (heptane:ethyl acetate=4:1 then 1:1 then ethyl acetate) to obtain the title compound (116 mg). The starting material <strong>[863753-35-9]2-tert-butoxycarbonylamino-3-pyridineboronic acid</strong> was synthesised as follows.

  • 3
  • [ 13195-76-1 ]
  • [ 38427-94-0 ]
  • [ 863753-35-9 ]
YieldReaction ConditionsOperation in experiment
Manufacturing Example 2-7-2 2-N-t-butoxycarbonyl-3-pyridineboronic acid; A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 2-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered out and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g).1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
Manufacturing Example 1-7-2 2-tert-butoxycarbonylamino-3-pyridineboronic acid A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
  • 4
  • [ 863753-35-9 ]
  • C10H12BrNO2S [ No CAS ]
  • C20H23N3O3S [ No CAS ]
  • 5
  • [ 863753-35-9 ]
  • C10H12BrNO2S [ No CAS ]
  • C20H25N3O4S [ No CAS ]
  • 6
  • [ 863753-35-9 ]
  • 2-(cyclopropanecarbonylamino)-N-(cyclopropylmethyl)-5-[(4-methoxyphenyl)sulfonylhydrazono]-6,7-dihydro-4H-benzothiophene-3-carboxamide [ No CAS ]
  • 5-(2-amino-3-pyridyl)-2-(cyclopropanecarbonylamino)-N-(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
2% With caesium carbonate; In 1,4-dioxane; at 110℃; for 16h;Sealed tube; Inert atmosphere; A sealed tube was charged with intermediate 64 (146 mg, 0.26 mmol), {2-[(tert- butoxycarbonyl)amino]pyridin-3-yl}boronic acid [863753-35-9] (94 mg, 0.39 mmol) and cesium carbonate (130 mg, 0.40 mmol) and was placed under vacuum for 10 minutes. The tube was back filled with nitrogen and the solids suspended in 1,4-dioxane (1.05 mL). The mixture was degassed with nitrogen for 5 minutes before sealing and heating at 110 C for 16 h. The reaction mixture was cooled to r.t. and partitioned between EtOAc (20 mL) and saturated aqueous sodium hydrogen carbonate solution (10 mL). The organic phase was separated and the aqueous phase extracted with EtOAc (2 x 20 mL). The combined organic phases were washed with brine (20 mL), dried (MgSC ), filtered and concentrated in vacuo to afford the crude product (127 mg) as a dark orange semi-solid. The crude product was purified by flash column chromatography on silica (gradient elution with 0 to 100% EtOAc in heptane) to afford the product (14 mg) as a red gum which was further purified by preparative HPLC (low pH) to afford the title compound (2.2 mg, 2%) as a white powder. 6H (500 MHz, DMSO -d6) 11.20 (s, 1H), 7.81 (dd, J 4.9, 1.7 Hz, 1H), 7.63 (dd, J 7.4, 1.4 Hz, 1H), 7.33 (dd, J 7.4, 1.4 Hz, 1H), 6.55 (dd, J 7.4, 4.9 Hz, 1H), 5.75 (s, 2H), 3.19 - 3.13 (m, 1H), 3.12 - 3.06 (m, 1H), 2.98 - 2.86 (m, 2H), 2.86 - 2.78 (m, 1H), 2.76 - 2.64 (m, 2H), 2.03 - 1.94 (m, 1H), 1.94 - 1.86 (m, 1H), 1.87 - 1.77 (m, 1H), 1.04 - 0.95 (m, 1H), 0.92 - 0.77 (m, 4H), 0.40 - 0.34 (m, 2H), 0.22 - 0.16 (m, 2H). LCMS ES+ [M+H]+ 411.2, RT 2.00 minutes, purity 100% (Method 10).
 

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