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CAS No. : | 1034924-06-5 | MDL No. : | MFCD07375144 |
Formula : | C5H7BN2O2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | BTJLWJOEZRVRNL-UHFFFAOYSA-N |
M.W : | 137.93 | Pubchem ID : | 45787274 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* 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 |
---|---|---|
With 2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl; palladium diacetate; sodium carbonate; In 1,4-dioxane; at 125℃; for 3h;Microwave irradiation; Sealed tube; Inert atmosphere; | Compound 1-41 was prepared from compound 1-2 according to the following coupling procedures:[00773] Compound 1-2 (230 umol), boronic acid (690 umol, 3 eq.), sodium carbonate (1.15 mmol, 5 eq.),RuPhos (70 muetaiotaomicron?, 0.30 eq.), and palladium diacetate (35 umol, 0.15 eq.) were combined in a 2 mL microwave- reaction tube with a stir bar which was sealed with a septum. The atmosphere was purged three times with vacuum, backfilling with dry argon, then 1,4-dioxane (1.6 mL) and water (0.4 mL) were added. The reaction was subjected to microwave heating at 125 °C for 3h. The reaction mixture was diluted with DCM (ca. 30 mL), treated with silica gel (ca. 1 g) and concentrated; flash chromatography of this residue (on 15 g silica gel, eluting with a MeOH/DCM or EtOAc/hexanes gradient as required, approx. 750 mL total eluent) gave the product 1-41 as a light-yellow to off- white powder. ESI-MS m/z: 485.8 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,1'-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride-chloroform adduct; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 3h; | The compound (2.34 g, 6.59 mmol) obtained in Example 16-2), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (1.00 g, 7.25 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (0.54 g, 0.66 mmol), and potassium carbonate (2.73 g, 19.76 mmol) were dissolved in a mixed solvent of 1,4-dioxane (20 mL) and water (10 mL), and the mixture was stirred at 90°C for 3 h. The reaction mixture was cooled to room temperature and then diluted with ethyl acetate (150 mL). The organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane = 50:50 to 100:0). The obtained partially purified product was dissolved in methanol (5 mL). 4 N hydrochloric acid-dioxane (2.39 mL) was added to the solution, and the mixture was stirred at room temperature for 2 h. The solvent was distilled off, and the residue was separated into organic and aqueous layers with methylene chloride (150 mL) and saturated aqueous sodium hydrogencarbonate (50 mL). The organic layer was washed with saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (591 mg, yield: 82percent) as a white solid. 1H-NMR (CDCl3) delta: 1.13 (2H, dd, J = 7.4, 3.5 Hz), 1.67 (2H, dd, J = 7.8, 3.5 Hz), 2.80 (3H, s), 7.48-7.61 (4H, m), 8.84 (2H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere; | Into a 5-L 4-neck round-bottom flask purged and maintained with an inert atmosphere ofnitrogen was placed a solution of 6-chloro-9-ethyl-8-iodo-9H-purine (242 g, 784 mmol), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (108 g, 783 mmol), potassium carbonate (162 g, 1.17 mol) and Pd(dppf)C12-DCM (32 g, 39 mmol) in dioxane (2.4 L) and water (480 mL). The resulting solution was stirred overnight at 90°C. The reaction mixture was cooled to room temperature, then extracted with 2 x 1.5 L of ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/dichloromethane/ethyl acetate (5:1:1) providing 6-chloro-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine (Intermediate IV). ?H NMR (300 MHz, CDC13) 9.12 (s, 2 H), 8.80 (s, 1 H), 4.46 (q, J= 7.2 Hz, 2 H), 2.89 (s, 3 H), 1.57-1.51 (t, J 7.2 Hz, 3 H). MS (El) Calc?d for C,2H12N6C1 [M+H], 275; found, 275. | |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere; | Into a 5-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 6-chloro-9-ethyl-8-iodo-9H-purine (242 g, 784 mmol) , <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (108 g, 783 mmol), potassium carbonate (162 g, 1.17 mol) and Pd(dppf)Cl2-DCM (32 g, 39 mmol) in dioxane (2.4 L) and water (480 mL). The resulting solution was stirred overnight at 90 . The reaction mixture was cooled to room temperature, then extracted with 2 x 1.5 L of EtOAc. The organic extracts were combined, dried (MgSO4) and concentrated under vacuum. The residue was purified by chromatography on SiO2(5: 1: 1 petroleum ether/DCM/EtOAc) providing 6-chloro-9-ethyl-8- (2-methylpyrimidin-5-yl) -9H-purine (Intermediate I) .1H NMR (300 MHz, CDCl3) delta 9.12 (s, 2 H) , 8.80 (s, 1 H) , 4.46 (q, J 7.2 Hz, 2 H) , 2.89 (s, 3 H) , 1.57-1.51 (t, J 7.2 Hz, 3 H) . MS (EI) calc?d for C12H12N6Cl [M+H]+, 275 found, 275. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; toluene; at -78℃; for 1h;Inert atmosphere; | Into a 1 0-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 5-bromo-2-iodopyrimidine (590 g, 2.07 mol) in THE (3 L). This was followed by dropwise addition of 1 M solution of dimethyl zinc (3.11 L, 3.11 mol) with stirring at 0°C. To this was added Pd(PPh3)4 (120 g, 104 mmol). The resulting solution was stirred for 3 h at 0°C, then quenched by the addition of 600 mL of aqueous NH4C1. The resultingsolution was extracted with 2 x 1.5 L of ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was applied onto a silica gel colunm and eluted with ethyl acetate/petroleum ether (1:50) to provide 5-bromo-2-methylpyrimidine. Into a 1 0-L 4-neck round-bottom flask purged and maintained with an inert atmosphereof nitrogen was placed a solution of 5-bromo-2-methylpyrimidine (184 g, 1.06 mol) and B(iPrO) 3 (240 g, 1.28 mol) in THE/toluene (3/3 L). This was followed by the dropwise addition of a 2.5 M solution of n-BuLi (510 mL, 1.28 mol) with stirring at -78°C. The resulting solution was stirred for 1 hat -78°C, then quenched by the addition of 200 nit of aqueous NH4CI. The organic phase was dried and concentrated under vacuum. The aqueous phase was adjusted to pH4 with AcOH. The solid was collected by filtration and dried in an oven under reduced pressure providing (2-methylpyrimidin-5 -yl)boronic acid. | |
With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; toluene; at -78℃; for 1h;Inert atmosphere; | Into a 10-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 5-bromo-2-methylpyrimidine (184 g, 1.06 mol) and B (i-PrO)3(240 g, 1.28 mol) in THF/toluene (3/3 L) . This was followed by the dropwise addition of a 2.5 M solution of n-BuLi (510 mL, 1.28 mol) with stirring at -78 . The resulting solution was stirred for 1 h at -78 , then quenched by the addition of 200 mL of aqueous NH4Cl. The organic phase was dried and concentrated under vacuum. The aqueous phase was adjusted to pH 4 with AcOH. The solid was collected by filtration and dried in an oven under reduced pressure providing (2-methylpyrimidin-5-yl) boronic acid. |
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