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Structure of 61676-62-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 61676-62-8 |
Formula : | C9H19BO3 |
M.W : | 186.06 |
SMILES Code : | CC1(C)C(C)(C)OB(OC(C)C)O1 |
MDL No. : | MFCD00192241 |
InChI Key : | MRWWWZLJWNIEEJ-UHFFFAOYSA-N |
Pubchem ID : | 5017741 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 53.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
27.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.12 |
Solubility | 1.41 mg/ml ; 0.00756 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.21 |
Solubility | 1.15 mg/ml ; 0.00619 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.04 |
Solubility | 1.68 mg/ml ; 0.00904 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.01 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.45 |
* 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 |
---|---|---|
78% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2 h; Stage #2: at -78 - 20℃; Stage #3: With methanol In tetrahydrofuran; hexane |
General procedure: n-BuLi in hexane (1.6 M, 65 mL, 0.10 mol) was slowly added toa solution of 2-bromothiophene (11 g, 0.068 mol) in THF (200 mL) at 78 C. After stirring for 2 h at this temperature, the mixturewas added to a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13 g, 0.068 mol) in 150 mL of THF. The mixture was warmed to room temperature and stirred overnight. The reactionwas terminated by adding a small amount of methanol and the resultant solution was washed with water three times. The solution was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: hexane) to give 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)thiophene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h; Stage #2: at -78 - 20℃; for 2.5 h; |
Compound 11 (2-(4-bromophenoxy)tetrahydro-2H-pyran,10.7 g, 41.6 mmol) dissolved in THF (220.0 mL, 20 mL/g)After cooling to -78 ° C, slowly dropping n-butyl lithium(21.6 mL, 54.1 mmol, 2.5 M hexane solution),It was stirred at -78 ° C for 30 minutes.Slowly drip 2-isopropoxy-4,4,5,5-tetramethyl- in the mixed solution1,3,2-dioxaborolane 12 (2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 11.0 mL, 54.1 mmol).Then, the obtained reactant is heated from -78 ° C to room temperature.And further stirred for 2.5 hours.The reaction was quenched by the addition of a saturated ammonium chloride solution.The organic layer is separated by an organic solvent,The organic layer was dried over anhydrous sodium sulfate and filtered and evaporated.The residue was concentrated to silica gel column chromatography (hexane:EtOAc = 10:1)Purification was carried out to give a white solid compound 13 (9.4 g, yield: 74percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h; |
To a solution of 2-(4'-bromophenyl)pyridine (0.468 g, 2 mmol). in anhydrous THF (10 ml) was added dropwse n-BuL (3 ml, 3.6 mmol) at -78"C The reaction was stirred 1 h, then 2-isopropoxy-4,4,5>5-tetramethyl-l,3,2-dioxaborolane (0.52 ml, 2.5 mmol) was added. The mixture was stirred overnight. Then Hie reaction was quenched with water and extracted with dchloromethane (30 ml) 3 times. The organic layer was -washed with brine and dried over MgSO4 and concentrated in vacuo. After column chromatography (silica gel, ethyl acetate: hexane = 1: 20) to give product 0.22 g (39percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: at -78 - 20℃; for 5 h; |
Synthesis of Intermediate 1-1 (0337) 1.93 g (10 mmol) of 5-bromo-2-chloropyrimidine was dissolved in 200 mL of THF, and then, at a temperature of −78° C., 4 mL (2.5M in hexane) of normal butyllithium was added thereto. At the same temperature about one hour thereafter, 2.0 mL (10 mmol) of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was added thereto. At room temperature, the result was stirred for about 5 hours, and then, water was added thereto and a washing process was performed three times thereon using diethylether (100 mL). A washed diethylether layer was dried by using MgSO4, and then, dried under reduced pressure, thereby obtaining a product. The product was separation-purified by silica gel column chromatography, thus preparing 1.56 g (Yield 65percent) of Intermediate 1-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.16667 h; Inert atmosphere Stage #2: at -78 - 20℃; for 24 h; Inert atmosphere |
To a 100-mL flame-dried two necked flask was added M1 (3.0g, 11.6mmol) and freshly distilled THF (80mL). The resulting solution was cooled at−78°C and 8.7mL n-butyllithium (13.9mmol, 1.6M in hexane) was added over 10min under a nitrogen atmosphere. The mixture was stirred at−78°C for 1h. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.6g, 13.9mmol) was added rapidly to the solution, and the resulting mixture was slowly warmed to room temperature for 24h. The mixture was poured into 50mL water and extracted with CHCl3 (300mL). The combined organic layers were washed with brine and dried over anhydrous MgSO4. The solvent was removed by rotary evaporation, and the residue purified by column chromatography on silica gel (ethylacetate:dichloromethane as eluent) to obtain the product as a light-yellow oil (1.6g, yield: 45.0percent). 1H NMR (400MHz; CDCl3; Me4Si): δ=7.77 (d, 2H, J=8.8Hz), 6.90 (d, 2H, J=8.8Hz), 3.94 (t, 2H, J=6.4Hz), 2.46 (t, 2H, J=6.8Hz), 2.26 (s, 6H), 1.88 (m, 2H, J=6.8Hz) 1.25 (s, 12H). 13C NMR (100MHz; CDCl3; Me4Si): 161.57; 136.73; 113.41; 83.13; 74.40; 66.02; 54.09; 45.42; 27.43; 25.00. Anal. Calcd for: C17H28BNO3: C, 66.90; H, 9.25; N, 4.59. Found: C, 66.73; H, 9.23; N, 4.63. IR (KBr, cm−1): 2981, 2936, 2816, 2716, 1566, 1463, 1281, 1245. |
45% | Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 2 h; Inert atmosphere Stage #2: at -78 - 20℃; for 26 h; Inert atmosphere |
Dissolved in dry 30 Compound A 3g in a nitrogen atmosphere, THF, -78° C after the temperature was reduced to 2.2equivalent of n-butyllithium(nBuLi,Aldrich Co.) was slowly added. The reaction mixture was stirred at -78° C for 2 hours andthen, 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,Aldrich) was added, and the mixture was stirred while the temperature gradually to room temperature after stirring at -78° Cfor 2 hours, the height for 24 hours. After the reaction was completed to extract the organic material with chloroform, to giveafter washing the column with water to obtain the compound B, 1.6 g (yield 45.0percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.25% | Stage #1: With n-butyllithium In tetrahydrofuran; hexanes at -78℃; for 1.16667 h; Inert atmosphere; Cooling with ice Stage #3: With ammonium chloride In tetrahydrofuran; hexanes; water |
To a solution of thieno[3,2-b]thiophene (1 .5 g, 10.70 mmol) in THF (25.5 mL) at -78 °C under N 2 is added dropwise a solution of BuLi in hexanes (8.988 mL of 2.5 M, 22.47 mmol), stirred for 20 min, cooling bath is replaced with ice bath and stirred for 50 min. The resultant thick suspension is quenched with 2- isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (4.181 g, 4.584 mL, 22.47 mmol). The reaction mixture is kept for overnight and then quenched with saturated aq. NH4Cl solution. After extraction with CH2Cl2 (2 x 100 mL), the combined extracts are washed with brine and dried (Na2S04). Organic solution is diluted with -20 mL of ethyl acetate, concentrated slowly on rotary evaporator until CH2Cl2 is removed. The resultant white fine crystals are collected by filtration. The solid is washed with heptanes and dried under high vacuum to afford 4,4,5,5-tetramethyl-2-[5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)thieno[3,2-b]thiophen-2-yl]-1 ,3,2-dioxaborolane (2.57 g, 6.554 mmol, 61.25percent) as half-white solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 2H), 1.343 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: With TurboGrignard In tetrahydrofuran at 0 - 20℃; for 2 h; Stage #2: for 1.16667 h; |
Example 47 Preparation of 2-(difluoromethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 5-Bromo-2-(difluoromethoxy)pyridine (1.0 g, 4.5 mmol) was dissolved in dry THF (10 mL), cooled to 0° C., and treated in portions with isopropylmagnesium lithium chloride complex (1.3 M; 3.3 mL, 4.3 mmol). The mixture was allowed to warm to 20° C., stirred for 2 h, treated with 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (910 μl, 4.3 mmol) and stirred for 70 min more. The mixture was quenched with saturated ammonium chloride (NH4Cl; 5 mL) and partitioned between ethyl acetate and water. The organic phase was washed with saturated NaCl, dried (Na2SO4), and evaporated to provide the title compound as a brown oil that was used without further purification (1.1 g, 86percent): 1H NMR (400 MHz, CDCl3) 8.54 (dd, J=1.9, 0.6 Hz, 1H), 8.07 (dd, J=8.2, 1.9 Hz, 1H), 7.54 (t, J=73.0 Hz, 2H), 6.87 (dd, J=8.2, 0.8 Hz, 1H), 1.34 (s, 13H); 19F NMR (376 MHz, CDCl3) δ -89.22. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 21 Preparation of a Poly(carbazole-co-phenylene) Block-Copolymer Part A Synthesis of 9-Phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole A 2L flask was charged with 600 mL dry THF and 3,6-dibromo-9-phenylcarbazole (60 g, 0.15 mole). This was cooled to -78° C. with an acetone-dry ice bath. n-Butyllithium (138 mL of a 2.5M solution in hexanes, 0.34 mole) was added drop-wise via syringe. The reaction was stirred for 20 minutes and then warmed to -50° C. The temperature was reduced to -78° C. and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (64 g, 0.34 mole) added via syringe at such a rate as to maintain the temperature below -60° C. The temperature was maintained at -78° C. for two hours and then poured into an aqueous solution of ammonium acetate (90 g in 2100 mL water). The layers were phase separated and the aqueous phase extracted with methy tert-butyl ketone (2*200 mL). The combined organic phase and extracts were washed with brine (2*200 mL) and dried over magnesium sulfate. Concentration and re-crystallization of the resulting solid from acetone gave pure 9-phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (PBTDC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; In tetrahydrofuran; water; acetone; | Part B: Synthesis of 9-Phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole A 2 L flask was charged with 600 mL dry THF and 3,6-dibromo-9-phenylcarbazole (60 g, 0.15 mole). This was cooled to -78° C. with an acetone-dry ice bath. n-Butyllithium (138 mL of a 2.5M solution in hexanes, 0.34 mole) was added drop-wise via syringe. The reaction was stirred for 20 minutes and then warmed to -50° C. The temperature was reduced to -78° C. and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (64 g, 0.34 mole) added via syringe at such a rate as to maintain the temperature below -60° C. The temperature was maintained at -78° C. for two hours and then poured into an aqueous solution of ammonium acetate (90 g in 2100 mL water). The layers were phase separated and the aqueous phase extracted with methyl-t-butyl ether (2*200 mL). The combined organic phase and extracts were washed with brine (2*200 mL) and dried over magnesium sulfate. Concentration and re-crystallization of the solid obtained from acetone gave pure 9-phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole. This compound can be used to modify the hole transport properties of for example the compound of Example 17. To do this 9-Phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole is used in place of 2-[9,9-dioctyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluoren-2-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in Example 17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | In tetrahydrofuran; ethyl acetate; pentane; | EXAMPLE 467A 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole A solution of <strong>[1075-34-9]5-bromo-2-methyl-1H-indole</strong> (5.04 g, 24 mmol) in THF (25 mL) was added dropwise to a suspension of potassium hydride (3.2 g, 24 mmol) in THF at 0° C. After fifteen minutes at 0° C., the solution was cooled to -78° C. and a t-butyl lithium solution (1.7 M in pentane, 28.2 mL, 48 mmol) was added dropwise via syringe while maintaining the temperature below -55° C. After an additional 15 minutes, the solution was cooled to -78° C. and treated with a 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (9.8 mL, 48 mmol) dropwise via syringe. The solution was stirred at -78° C. for 1.5 hours, allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride. The solution was diluted with ethyl acetate and filtered to remove inorganic material. The filtrate was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO4) and concentrated. The concentrate was purified by flash chromatography on silica gel using 10percent ethyl acetate/hexanes to give 3.9 g (63percent yield) of the desired product. MS (ESI(+)) m/e 258 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | (1) Synthesis of Intermediate 1-1 (0232) 20.0 g (20 mmol) of 2-bromonaphthalene was dissolved in 50 mL of tetrahydrofuran (THF), and then 8.8 mL (22.0 mmol) of n-BuLi (2.5 M in hexane) was slowly dropwise added thereto at about -78 C. After the reaction solution was stirred at the same temperature for about 1 hour, 4.65 mL (25.0 mmol) of 2-isoproxy-4,4,5,5,-tetramethyl-1,3,2-dioxaborolane was slowly dropwise added to the reaction solution, stirred at about -78 C. for about 1 hour, and then further stirred at ambient temperature for about 24 hours. After termination of the reaction, 30 mL of a 10% HCl aqueous solution and 30 mL of H2O were added thereto, followed by extraction three times with 50 ml of diethyl ether. An organic phase was collected and dried using magnesium sulfate, followed by evaporating the solvent. The resulting residue was purified by silica gel column chromatography to obtain 3.7 g of Intermediate 1-1 (Yield: 73%). This compound was identified by liquid chromatography-mass spectrometry (LC-MS). C16H19BO2: M+ 255.1 | |
41% | To a 500 mL 3 -necked round bottomed flask, charged were THF (300 mL) and 2-bromonaphthalene (10 g, 48.3 mmol) , and the mixture was chilled to -78C by using liquefied nitrogen. Then, n-BuLi (14.73 g, 53.1 mmol) was slowly added dropwise thereto. After stirring at ambient temperature for 1 hour, 2- isopropoxy-4, 4, 5, 5-tetramethyl- [1, 3, 2] -dioxaborolane (9.87 g) was slowly added dropwise at -78C to the mixture. After 12 hours, water is poured thereto, to quench the reaction. The reaction mixture was extracted with ether, dried over MgSO4 and evaporated by using a rotary evaporator to remove the solvent. The product was isolated via column chromatography (eluent: hexane/EA = 5/1) .Yield: 4.05 g (41%) m.p. : 93 C1H NMR (300 MHz, CDCl3, ppm): 7.81 (d, 4H), 7.29 (t, 3H), 1. 26 (m , 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a suspension of NaH (60% in mineral oil, 3.5 g, 146 mmol, washed with 200 mL of hexane) in THF (200 mL) was added 4-methyl-1 H-pyrazole (10 g, 122 mmol) at 0 0C dropwise. After stirring at RT for 1 h, to above suspension was added MeI (7.3 mL, 117 mmol) dropwise at 0 0C. The reaction mixture was stirred overnight. The NaI by-product was removed by filtration and the filtrate solution was used directly in the next step.At 00C, to above THF solution of 1 ,4-dimethyl pyrazole was added n-BuLi (2.5M in hexane, 58.5 mL, 146 mmole). The reaction solution was stirred for 2 hour at RT and then cooled to -78C [J. Heterocyclic Chem. 41 , 931 (2004)]. To the reaction solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (27.2 g, 146 mmole). After 15 min at -78C, the reaction was allowed to warm to 00C and stir for 3h. The reaction was diluted with saturated NH4CI solution and extracted with DCM. The organics were dried over Na2SO4 and concentrated under vacuum to afford the title compound as a brown solid (21 g, 78%) which was used directly without further purification: LC-MS: 141 (M-C6H12)"1", 223 (M+H)+. 1H NMR (CDCI3): delta 7.28 (s, 1 H), 4.03 (s, 3H), 2.22 (s, 3H), and 1.32 (s, 12H). | ||
142 mg | 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole A solution of 1,4-dimethyl-1H-pyrazole (480.0 mg, 4.993 mol) in tetrahydrofuran (20 mL, 300 mmol) at 0 C. was added 1.6 M n-butyllithium in hexane (4.7 mL, 7.5 mmol). The solution was stirred at room temperature for 1 h and then cooled to -78 C. To the solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.63 mL, 7.99 mmol). The reaction mixture was stirred at -78 C. for 0.5 h, then warmed up to 0 C. (taking 0.5 h). The reaction was quenched with brine and extracted with EtOAc (3*). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by combi-flash chromatography and eluted with EtOAc/hexane (0-60%). The purification gave 142 mg of product as white solid. | |
Step 1. 1, 4-Dimethyl-5-( 4, 4, 5, 5-tetrame orolan-2-yl)-lH-pyrazole l,4-Dimethyl-7H-pyrazole (50 mg, 0.5 mmol) was stirred in THF (2 mL) and cooled to 0 C. A solution of 1.6 M w-butyllithium in hexanes (390 mL) was added dropwise by syringe and the mixture was allowed to warm to room temperature for 2 h. The mixture was cooled to -78 C and 2-isopropoxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane(110 mL, 0.52 mmol) was added dropwise by syringe. The mixture was stirred at -78 C for 15 min. and at 0 C for 3 h. The mixture was diluted with EtOAc and washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography on silica gel using EtOAc in hexanes gave the sub-title compound. LCMS calc. for CnH2oB 202 (M+H)+: m/z = 223.2; found: 223.0. |
With n-butyllithium; | Step 1 To a solution of 1,4-dimethyl-1H-pyrazole (2.5 g, 26.0 mmol, 1 equiv) in tetrahydrofuran (50 mL) was added n-butyllithium in hexane solution (2.5 M in hexane, 78.0 mmol, 31 mL, 3 equiv) dropwise at 0 C. under nitrogen atmosphere. The resulting solution was stirred at room temperature for 1 h and then cooled to -78 C. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.52 g, 78.017 mmol, 3 equiv) was added and the reaction mixture was stirred at -78 C. for 0.5 hour, then slowly warmed up to 0 C. The reaction was quenched with brine and extracted with EtOAc (250 mL*3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was applied onto a silica gel column eluting with ethyl acetate/petroleum ether (1:5). This resulted in 2.6 g (45%) of 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
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72.3% | <strong>[172921-33-4]1-Bromo-4-chloro-2,5-difluorobenzene</strong> (1.11 g, 4.9 mmol) was dissolved in tetrahydrofuran (THF; 15 mL) and cooled to -10° C. A 2.0M solution of isopropyl-magnesium chloride (2.7 mL, 5.4 mmol) in THF was added dropwise via syringe. The reaction mixture was stirred at -10° C. for 1 h, allowed to warm toward 0° C. for 1 h, then cooled again to -10° C. A solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.0 g, 5.4 mmol) in THF (1.0 mL) was then added dropwise and the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was then added to diethyl ether and extracted with 1N sodium hydroxide twice. The aqueous phases were combined, acidified to pH 3 with concentrated HCl, and extracted with dichloromethane twice. The organic phases were combined, dried, filtered and concentrated to give the title compound (0.97 g, 72.3percent yield) that was used without further purification: 1H NMR (CDCl3) delta 7.45 (dd, 1H), 7.09 dd, 1H), 1.36 (s, 12H). | |
62% | To a solution of l-bromo-4-chloro-2,5-difluorobenzene (200 mg, 0.879 mmol) in THF (10 mL) cooled to -10 0 C was added isopropylmagnesium bromide (1M in THF, 1.055 mL, 1.055 mmol) dropwise and the reaction mixture was stirred at this temperature for 1 h. The reaction mixture was then warmed to 0 °C and stirred for another 1 h. The resultant mixture was again cooled to -10 °C and treated dropwise with a solution of 2-isopropoxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (196 mg, 1.055 mmol). The reaction mixture was allowed to warm up to room temperature and treated with a saturated solution of ammonium chloride (3 mL). The layers were separated and aqueous layer was extracted with dichloromethane (2 x 2 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford crude compound which was purified by column chromatography on a silica (7:3 - Ethyl acetate :hexane) to afford 2-(4- chloro-2,5-difluorophenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (150 mg, 0.546 mmol, 62percent yield) as an oil. 1H NMR (400 MHz, DMSO-d6) delta ppm 7.46 - 7.49 (m, 1H), 7.09 - 7.13 (m, 1 H), 1.35 (s, 12H). | |
62% | To a solution of <strong>[172921-33-4]1-bromo-4-chloro-2,5-difluorobenzene</strong> (200 mg, 0.879 mmol) in THF (10 mL) cooled to -10°C was added isopropylmagnesium bromide (1M in THF, 1.055 mL, 1.055 mmol) dropwise and the reaction mixture was stirred at this temperature for 1 h. The reaction mixture was then warmed to 0 °C and stirred for another 1 h. The resultant mixture was again cooled to -10 °C and treated dropwise with a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (196 mg, 1.055 mmol). The reaction mixture was allowed to warm up to room temperature and treated with a saturated solution of ammonium chloride (3 mL). The layers were separated and aqueous layer was extracted with dichloromethane (2x2 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford crude compound which was purified by column chromatography on a silica (7:3 - Ethyl acetate:hexane) to afford 2-(4-chloro-2,5-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (150 mg, 0.546 mmol, 62percent yield) as an oil. |
3. Preparation of 2-(4-Chloro-2,5-difluorophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane <strong>[172921-33-4]1-Bromo-4-chloro-2,5-difluorobenzene</strong> (1.11 g, 4.9 mmol) was dissolved in tetrahydrofuran (THF; 15 mL) and cooled to -10° C. A 2.0M solution of isopropyl-magnesium chloride (2.7 mL, 5.4 mmol) in THF was added dropwise via a syringe. The reaction mixture was stirred at -10° C. for 1 hour, allowed to warm toward 0° C. for 1 hour, then cooled to -10° C. again. A solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.0 g, 5.4 mmol) in THF (1.0 mL) was then added dropwise and the reaction was allowed to warm to ambient temperature. The reaction mixture was then added to diethyl ether and extracted with 1N sodium hydroxide twice. The aqueous phases were combined, acidified to pH 3 with concentrated HCl, and extracted with dichloromethane twice. The organic phases were combined, dried, filtered and concentrated to give the title compound (0.97 g, 72.3percent yield) that was used without further purification: 1H NMR (CDCl3): delta 7.45 (dd, 1H), 7.09 dd, 1H), 1.36 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
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85% | {2-(2-Bromo-9,9-spirobifluoren-7-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan}3.5 g of 2,7-dibromo-9,9-spirobifluorene (7.38 mmol) was dissolved in 80 ml of tetrahydrofuran in a flask filled with nitrogen gas, and the temperature of the flask was reduced to -78°C. 5.1 ml of normal-butyllithium (1.6M hexane solution) was added dropwise to the resultant mixture via a syringe.The resultant mixture was stirred at -78°C for 30 minutes, and 1.7 ml of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaboralne (8.33 mmol) was slowly added to the resultant mixture.The reaction temperature was raised to room temperature, and the resultant mixture was then stirred for 8 hours.Water was added to the resulting mixture to complete the reaction.The reaction mixture was extracted with dichloromethane, and the remaining moisture existing in the layer was removed with MgSO4.Then, column chromatography (stationary phase: silica gel, mobile phase:ethylacetate:hexane= 1:10 volume ratio) was performed on the resultant layer to obtain 3.26 g of a desired Compound 3 at a yield of 85percent.Mp: 305 °C1HNMR (300 MHz, CDCl3): delta 7.85 (d, 4H J=7.2Hz),7.73(d,1HJ=7.2Hz),7.48(d,1HJ=7.2Hz),7.38(dd,2HJ=7.2Hz),7.16(s,1H),7.11 (dd,2 HJ=7.2Hz),6.79(s,1H),6.71(d,2HJ=7.2Hz), 1.25(s,12H).13CNMR(300MHz,CDCl3):delta 151.8, 147.8, 147.61, 143.8, 142, 140.4, 135.08, 134.93, 131.01, 130.41, 128.08, 128.04, 127.34, 124.29, 122.11, 121.84, 120.29, 119.51, 83.9, 65.9, 48.2, 24.9. |
Yield | Reaction Conditions | Operation in experiment |
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70% | Compound f-5 (5.0 g, 9.0 mmol) into a round bottom flask in a vacuum caught after 4 Holding time Vacuum THF (150mL) into the dissolve. at -78 °C n-butyllithium (2.0M in Hexanes, 11.26mL) was slowly added after the mixture was stirred for two hours. 2 hours later, 2-isopropoxy -4,4,5,5- tetramethyl 1-1,3,2- Sabo dioxane was added to lane (5.52mL) slowly and stirred for 4 hours and allowed to react for 40 hours at room temperature. After completion of the reaction it was cooled with methanol and methylene chloride to remove the remaining moisture in the salt water over anhydrous magnesium sulfate (MgSO4), extract the organic layer and then rotary evaporated to end with ethyl acetate-hexane 1: 9 to 9 column with a solid-state to yield (heptadecane-9-yl)-2,7-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl) -9Hcarbazole (compound F) (yield: 70percent ). |
Yield | Reaction Conditions | Operation in experiment |
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83% | Step 2In a flask 1-cyclopropyl-4-iodo-1H-pyrazole (405 mg, 1.73 mmol) was dissolved in THF (8.0 mL) and the solution cooled to 0° C.Isopropylmagnesium chloride (2.0 M in THF, 1.04 mL, 2.08 mmol) was added dropwise and the mixture stirred at 0° C. for 45 min, after which 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.53 mL, 2.60 mmol) was added and the mixture allowed to warm to room temperature over 1 h.The mixture was quenched with 50percent sat aqueous NH4Cl and extracted with EtOAc.The organic extract was washed with sat.NaCl, dried over MgSO4 and the solution was concentrated.The residue was purified by SiO2 chromatography (20-50percent EtOAc/heptane) to afford 405 mg (83percent) of 1-cyclopropyl-1H-pyrazole-4-boronic acid pinacol ester as a colorless viscous oil. |
Yield | Reaction Conditions | Operation in experiment |
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64% | General procedure: Preparation of N-[4-chloro-2-(4,4,6-trimethyl-[1,3,2]dioxaborinan-2-yl)-phenyl]-2,2-dimethyl-propionamide (33): To a solution of N-(4-chloro-phenyl)-2,2-dimethyl-propionamide (29) (2.11 g, 10 mmol) in dry THF, n-butyl lithium solution was added dropwise (13 ml, 2.1 equiv, 1.6 M in hexanes) under an argon atmosphere at -40 C. The reaction mixture was stirred for 2 h at 0 C during which time a white precipitate formed. The suspension was cooled to -20 C and neat 2-isopropoxy-4,4,6-trimethyl[1,3,2]dioxaborinane (10) (2.8 g, 15 mmol, 1.5 equiv) was added dropwise. After stirring for 1 h at this temperature, the reaction mixture was allowed to warm up to 0 C and subsequently quenched with a saturated aqueous solution of ammonium chloride (30 ml). The layers were then separated and the water layer was further extracted with dichloromethane (3 × 30 ml). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude residue was purified using flash chromatography on silica gel (15% ethyl acetate: hexanes) to obtain the title compound in 74% yield. |
Yield | Reaction Conditions | Operation in experiment |
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49% | Methyl-6-(tetramethyl-l ,3,2-dioxaborolan-2-yl)-7H-indoleTo a solution of 6-bromo-2-methyl-7H-indole (2.0 g, 9.52 mmol) in dry tetrahydrofuran (100 mL) was added sodium hydride (381 mg, 9.53 mmol ) with ice-cooling. After stirring for about 30 min , a solution of n-BuLi (15 mL, 2.5 M solution in hexane) was added dropwise with stirring at -78°C under nitrogen. It was warmed slowly to -40°C during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -78°C followed by dropwise addition of 4,4,5, 5-tetramethyl-2-(propan-2-yloxy)- 1 ,3,2- dioxaborolane (3.54 g, 19.03 mmol). After warming to room temperature, the mixture was quenched with NH4CI (aq) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the residue, which was purified by silica gel columnchromatography (2percent ethyl acetate in petroleum ether) to afford 2-methyl-6-(tetramethyl- l,3,2-dioxaborolan-2-yl)-7H-indole (1.2 g, 49percent).'H-NMR (300 MHz, CDCI3): delta 8.06 (s, 1Eta), 7.91(s, 1Eta), 7.58 - 7.60 (t, 7 = 7.5 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 6.24 (s, 1H), 2.46 (s, 3H), 1.39 (s, 12H) | |
38% | Step 2. 2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole To a solution of <strong>[1075-34-9]5-bromo-2-methyl-1H-indole</strong> (3.0 g, 14.35 mmol) in dry tetrahydrofuran (20 ml) was added sodium hydride (900 mg, 22.5 mmol) with ice-cooling. After stifling for about 30 min, a solution of t-BuLi (27.5 ml, 1.3 M solution in hexane) was added dropwise with stifling at -78° C. under an inert atmosphere of nitrogen. The reaction mixture was warmed slowly to -40° C. over 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -78° C., followed by the addition of 4,4,5,5-tetramethyl-2-(propan-2-yloxy)-1,3,2-dioxaborolane (5.3 g, 28.49 mmol) dropwise. After warming to room temperature, the mixture was quenched with NH4Cl solution (100 ml) and extracted with ethyl acetate (3.x.100 ml). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the residue, which was purified by a silica gel column (2percent ethyl acetate in petroleum ether) to afford 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1.4 g, 38percent). 1H NMR (300 MHz, CDCl3): delta 8.06 (s, 1H), 7.91 (s, 1H), 7.58-7.60 (t, J=7.5 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 6.24 (s, 1H), 2.46 (s, 3H), 1.39 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
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64% | 4-FIuoromethyl-2-phenyI-5-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]- 4,5-dihydro-oxazole (8): To a solution of 7 (760 mg, 2.0 mmol) in THF (5 ml) was added n- BuLi (2 ml, 1.6 M in Hexane, 3.2 mmol) at -78 °C. After stirring for 30 min, isopropyl pinacol boronate (595 mg, 3.2 mmol) was added. Slowly warmed to room temperature and stirred overnight. The reaction mixture was diluted with EtOAc (40 ml) and washed with water (30 ml), dried over Na2S04 and concentrated. The crude product was purified by PTLC (Hexane/ EtOAc, 2: 1) to afford 8 as white solid (490 mg, 64percent). JNMR (300 MHz, CDC13): delta 8.04 ( d, J = 7.0 Hz, 2H), 7.83 ( d, J = 7.0 Hz, 2H), 7.51 (m, 1H), 7.45 (m, 2H), 7.36 (d, J = 7.8 Hz, 2H), 5.87 (d, J = 6.9 Hz, 1H), 4.76 (m, 1H), 4.61 ( m, 1H), 4.35 (m, 1H), 1.34 (s, 12H); C22H25BFN03, LCMS (EI) m/z: 381 (M+). |
Yield | Reaction Conditions | Operation in experiment |
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78% | General procedure: n-BuLi in hexane (1.6 M, 65 mL, 0.10 mol) was slowly added toa solution of 2-bromothiophene (11 g, 0.068 mol) in THF (200 mL) at 78 C. After stirring for 2 h at this temperature, the mixturewas added to a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13 g, 0.068 mol) in 150 mL of THF. The mixture was warmed to room temperature and stirred overnight. The reactionwas terminated by adding a small amount of methanol and the resultant solution was washed with water three times. The solution was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: hexane) to give 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)thiophene |
Yield | Reaction Conditions | Operation in experiment |
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86% | 1-bromo-3-(trifluoromethyl)benzene (5.00 g, 22 mmol) was placed in a 250 ml reaction flask, followed by injecting and evacuating nitrogen gas three times. Next, dehydrated tetrahydrofuran (THF, 100 ml) was added into the reaction flask, followed by slowly adding 9.8 ml n-butyllithium in hexane solution (2.5M, 24 mmol) at -78 C. and stirring at the same temperature for 30 minutes. Thereafter, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.0 ml, 24 mmol) was added into the reaction flask to obtain a mixture, and the temperature of the mixture was raised to room temperature, followed by stirring at room temperature for 12 hours. Next, water was added to terminate the reaction followed by removing THF using a rotary evaporator. Then, dichloromethane and water were added into the mixture for extraction. The dichloromethane layer was collected and added with magnesium sulfate to remove water therein. After water was removed, the dichloromethane layer was filtrated and the filtrate was collected. Next, the dichloromethane layer was concentrated by means of reduced pressure distillation to obtain a colorless oily liquid (5.21 g, 19 mmol, 86% yield). The spectrum analysis for the colorless oily liquid is: 1H NMR (400 MHz, CDCl3, 298K), delta(ppm): 8.04 (s, 1H), 7.95 (d, JHH=7.6 Hz, 1H), 7.68 (d, JHH=7.6 Hz, 1H), 7.46 (t, JHH=7.6 Hz, 1H), 1.34 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
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51% | With n-butyllithium; In tetrahydrofuran; hexane; at -70 - 20℃; for 3h; | To a stirred solution of tert-butyl 4-(4-bromo-lH-pyrazol-1-yl)piperidine-1-carboxylate (25.0g, 0.076 mole) in THF ( 500 ml) at- 70°C was added BuLi 1.6 Min Hexane solution (10 56.75 ml, 0.091 mole) dropwise followed by addition of 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (18.52 ml , 0.091 mole) at same temperature. Reaction mixture wasstirred at -70°C for lh then warmed to room temperature and continued stirring for 2h atroom temperature. Reaction mixture was quenched with ammonium chloride solution (25 ml)water (500 ml), and ethyl acetate (750 ml) was added to reaction mixture, followed by15 extraction with ethylacetate (100 ml x 2). The combined organic layer was washed withbrine, concentrated under vacuum to get crude product which was crystallized from nHeptaneto give pure title compound.Yield: 51 percent (14.7g)HPLC Purity: 96.7percent20 MS (m/z): 378 (M + 1) 1HNMR (400 MHz, CDCh) 8: 7.81 (s, lH), 7.75 (s, lH), 4.27 (m, 3H), 2.9 (m, 2H), 2.14 (m,2H), 1.91 (m, 2H), 1.49 (s, 9H), 1.33 (s, 12 H). |
Yield | Reaction Conditions | Operation in experiment |
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Step 1 : l-Cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyridaziiie To a 100 n L flask is added 4-bromo-l-cyclopropylpyrazol (6.57 g, 35.1 mmol) and anhydrous THF (30 niL). The solution is cooled to -78 °C under nitrogen; then n-butyl lithium (15.5 n L, 2.5 M in hexanes, 38.6 mmol) is added dropwise. The reaction mixture is stirred at the temperature for 1 hr, followed by addition of isopropyl boronate (9.17 g, 94.1 mmol) and stirred below -70 °C for 3 hours. The reaction is quenched with water (20 n L) and the resulted mixture is adjusted to pH 8-9 with aqueous hydrochloride solution (1 N). The combined organic phases are concentrated and used in next step without further purification (6.64 g, 81percent yield). (MS: [M+l] 235) |
Yield | Reaction Conditions | Operation in experiment |
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67% | As follows: the formula (6) Compound 9 (1.0g, 4.44mmol) was added to a single neck flask, pumping Vacuum / nitrogen filling repeated five times, followed by the addition of anhydrous THF30mL, isopropanol / liquid nitrogen after freezing to 78 C In30min slowly added dropwise 2.5M nbutyllithium(1.86mL, 4.66mmol), 1h, add isopropanol Pinacol borate (1.13mL,5.55mmol). Reaction 2h, slowly raising the temperature to room temperature, the reaction 8h, After the reaction was added towater, the product was extracted with methylene chloride, the organic phase was dried over anhydrous magnesium sulfate,separated to The solvent, separated and purified by silica gel column chromatography to give a white solid (6) compound 10co 0.8g, yield 67%. | |
65% | A solution of n-BuLi in n-hexane (2.5M, 1.86mL, 4.67mmol) was added dropwise to a solution of <strong>[324-41-4]2-bromo-6-fluoronaphthalene</strong> (1.00g, 4.44mmol) in anhydrous THF (20mL) under nitrogen at-78C. After the reaction was kept at-78C for 1h, isopropoxyboronic acid pinacol ester (1.12mL, 5.56mmol) was added. The mixture was left to warm up to room temperature overnight. Then it was evaporated under vacuum. The residue was treated with water and extracted with CH2Cl2. The organic phase was further washed with water and brine, and dried over MgSO4. Upon concentration under vacuum, the crude product was purified by column chromatography on silica gel using CH2Cl2 as the eluent to obtain a white solid (0.785g, 65%). 1H NMR (300MHz, DMSO): delta 8.25 (s, 1H), 8.09-8.14 (m, 1H), 7.88 (d, J=8.28Hz, 1H), 7.68-7.75 (m, 2H), 7.40-7.46 (m, 1H), 1.31 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
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65.5% | Preparation 64 2-(2,2-Difluorobenzo[d][1,3]dioxol-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2,2-Difluorobenzo[d][1,3]dioxole (6 g, 38.0 mmol) was dissolved in tetrahydrofuran (100 mL) and cooled to -75 C. sec-Butyllithium (1.4 M in cyclohexane; 29.8 mL, 41.7 mmol) was added dropwise, keeping the temperature below -65 C. The reaction mixture was then stirred at -75 C. for 1 h to ensure complete deprotonation. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.06 g, 38.0 mmol) was then added to the reaction mixture dropwise keeping the temperature below -65 C. The reaction mixture was then allowed to warm to room temperature and sit at room temperature for 2 h and was then partitioned between diethyl ether and water. The aqueous phase was acidified to pH 3 with 12 N HCl. The product was extracted with diethyl ether and the organic phase was dried and concentrated under vacuum to provide the title compound as an off-white solid (7.06 g, 65.5%): 1H NMR (300 MHz, CDCl3) delta 7.43 (dd, J=7.5, 1.5 Hz, 1H), 7.13 (dd, J=7.9, 1.5 Hz, 1H), 7.05 (t, J=7.7 Hz, 1H), 1.37 (s, 12H); EIMS m/z 284. |
Yield | Reaction Conditions | Operation in experiment |
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47% | Flask in 50mL flask 5,8-Dibromoquinoxaline utilizing our after infusion (compound j-1) 2.00 g, it makes the vacuum. After injecting THFanhydous 30mL and slowly inject 5.8 mL tert-butyllithium at -78 C, was stirred at the same temperature for 15 minutes, then it reacted at room temperature for 2 hours. Under the conditions of -78 C then slowly inject 2.0 mL lane 2- isopropoxy -4,4,5,5- tetramethyl 1-1,3,2- Sabo dioxane, and the mixture was stirred for 12 hours. After 12 hours, after the completion of the reaction through the water, after extraction via the ethylacetate and the aqueous solution of NaCl, one can obtain a product of the organic layer extracted lower sides yellow liquid, and injecting the obtained liquid phase in 250mL round bottom flask, methanol 70mL after the injection, the injection was diluted to 20.2 mL of distilled water 10mL KHF2 a stirring. When stirred for 30 minutes when it is generated the filter through the ether to give a yellow solid product of potassium di [5,8-quinoxaline] 4,7-bis (triple as a borate) (Compound J) (yield: 47%) |
Yield | Reaction Conditions | Operation in experiment |
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60% | 10324] 2.59 g (10 mmol) of <strong>[40000-20-2]<strong>[40000-20-2]5-bromo-1,10-phenanthrolin</strong>e</strong> was dissolved in 40 mE of tetrahydrofuran (THF), and 4 mE (2.5 M in hexane) of normal butyllithium was added thereto at a temperature of ?78° C. After one hour, 2.0 mE (10 mmol) of 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxa- borolane was added thereto at the same temperature. The resultant mixture was stirred for 10 hours at room temperature. Then, water was added thereto and the resultant mixture was washed three times by using 30 mE of diethyl ether. The washed diethyl ether layer was dried by using Mg504 and dried under reduced pressure. The product obtained therefrom was separation-purified by silica gel colunm chromatography to obtain 1.84 g (yield of 60percent) of Intermediate I-i. The obtained compound was identified by EC-MS. C18H19BN202: M+1 307.2. |
Yield | Reaction Conditions | Operation in experiment |
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72% | With n-butyllithium; In tetrahydrofuran; at -78 - -40℃; for 18h;Inert atmosphere; | 4-bromodiphenyl ether(6.2g, 25.0mmol) Isopropanol pinacol borate (10.3 mL, 50 mmol)Soluble in dry tetrahydrofuran,Cooled to -78C under nitrogen protection.n-Butyllithium (2.5M, 18 mL, 45 mmol) was added dropwise,After completion of the addition, the mixture was stirred for 6 hours and slowly warmed to -40C for 12 hours.The reaction was added to saturated ammonium chloride solution and extracted three times with ethyl acetate.The organic phases were combined and dried over anhydrous sodium sulfate.It was evaporated to dryness by rotary evaporation and purified by column to give 5.4 g of the target compound in a yield of 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4 g | Was dissolved in 1-methyl-2-phenyl-1 H-benzo [d] imidazole (4.16 g) and tetrahydrofuran (30 ml) to make it -78 ° C. Thereto was added n-butyllithium (1.6 M, n-hexane solution, 15 ml, Kanto Kagaku) and the mixture was stirred for 30 minutes.The temperature was brought to 0 degree, and the mixture was further stirred for 1 hour.2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.85 ml, Tokyo Chemical Industry) was added dropwise thereto,The reaction was allowed to proceed overnight at room temperature.After the reaction,Quench with water,Extracted with chloroform (Wako Pure Chemical Industries, Ltd.)Twice washed with water,The organic layer was collected,The organic layer was dried with anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.) and concentrated.The residue was purified by silica gel column chromatography,4 g of 1-methyl-2- (2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl) -1H-benzo [d] imidazole was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of i-PrMgCl (2 M in THF, 10 mL, 20 mmol) at 0 °C was added slowly a solution of S9 (2.51 g, 10 mmol) in THF (100mL). The resulting solution was stirred at this temperature under Ar for 1 h. 2-isopropoxy-4,4,5,5-tetramethyl[1,3,2]dioxaborolane(2.8 g, 15 mmol) was then added slowly to maintain the temperature below 0 °C. After the addition, the reaction was stirred at room temperature for 1.5 h and then quenched slowly by the addition of aqueous ammonium chloride solution (80 mL). To the mixture was added H2O (80 mL), and extraction was done twice with EtOAc(100 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was concentrated to provide S10 as a pale yellow oil. MS (ESI) m/z: 253.2 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Lithium 2,2,6,6-tetramethylpiperidin-1-ide (2.84 g, 19.27 mmol) was placed in an oven-dried 250-mL round-bottomed flask in a glovebox and removed. Diethyl ether (75 mL) was added and the solution was cooled to -78 C (reaction mixture is not homogeneous). 2-Bromo-1-chloro-3-(trifluoromethyl)benzene (5.00 g, 19.3 mmol, 1.0 equiv) was added as solution in ether (25 mL) dropwise over 10 minutes and the mixture was allowed to stir at -78 C for 1 hour. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.9 mL, 19.27 mmol, 1.0 equiv) was then added to the non-homogeneous reaction mixture over 10 minutes and the reaction was allowed to warm slowly to room temperature overnight. The reaction was quenched with saturated NH4C1 at 0 C and warmed to room temperature, layers separated. The aqueous was further extracted with diethyl ether (2) and the combined organics dried over sodium sulfate, filtered and concentrated. Purification over silica gel using a 0 to 5% ethyl acetate/hexane gradient afforded the title compound (3.87 g, 52% yield) as a viscous yellow oil. |
Tags: 61676-62-8 synthesis path| 61676-62-8 SDS| 61676-62-8 COA| 61676-62-8 purity| 61676-62-8 application| 61676-62-8 NMR| 61676-62-8 COA| 61676-62-8 structure
A104818 [1195-66-0]
2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 1.00
A789000 [94242-85-0]
2,4,4,5,5-Pentamethyl-1,3,2-dioxaborolane
Similarity: 0.75
A247960 [73183-34-3]
4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi(1,3,2-dioxaborolane)
Similarity: 0.69
A362511 [70557-99-2]
2-(Iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 0.68
A562389 [166330-03-6]
2-(Bromomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 0.65
A463112 [126726-62-3]
4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane
Similarity: 0.56
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