Structure of 618442-57-2
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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. : | 618442-57-2 |
Formula : | C30H35B2NO4 |
M.W : | 495.23 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CC3=C(N(C4=CC=CC=C4)C5=C3C=C(B6OC(C)(C)C(C)(C)O6)C=C5)C=C2)O1 |
MDL No. : | MFCD28015750 |
InChI Key : | BMKVLWGCSCKZTD-UHFFFAOYSA-N |
Pubchem ID : | 12177223 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 37 |
Num. arom. heavy atoms | 19 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 153.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.85 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 |
6.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.94 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-7.48 |
Solubility | 0.0000163 mg/ml ; 0.0000000328 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-7.66 |
Solubility | 0.0000108 mg/ml ; 0.0000000217 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-9.68 |
Solubility | 0.000000105 mg/ml ; 0.0000000002 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.37 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.06 |
* 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 |
---|---|---|
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 |
---|---|---|
77% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 95℃; for 24h; | General procedure: Intermediate 1-4 (3.0 g, 0.008 mol) in bis (pinacolato) dibron (2.5 g, 0.010 mol), PdCl2 (dppf) (0.3 g, 0.0004 mol), potassium-acetate (2.2 g, 0.016 mol) in 1, 4-dioxane 80 mL was put into the reaction stirred for 24 hours at 95 . After the reaction cooled to H20: After layer separation the MC column purification (n-Hexane: MC) to afford intermediate 1-4 '2.5 g (yield 71percent). (M / z = 436) |
70% | With phosphoric acid; for 5h; | General procedure: Intermediate A-1 (3.1 g, 0.010 mol) dissolved in 50 mL of concentrated H3PO4 it was stirred for 5 hours. 100 mL of water and this ethyl acetate and extracted with 100 mL , and dried under reduced pressure and the organic layer . This was recrystallized in 100 mL EtOH Intermediate A - 2 ( 2.1g, to give a 72percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 95℃; for 4h; | General procedure: Intermediate 1-4 '(3.0 g, 0.007 mol) in 1,4-dibromobenzene (1.3 g, 0.006 mol) Pd (dba) 2 (0.5 g, 0.00006 mol), sodium-tert-butoxide (2.2 g, 0.022 mol) Tol put in 80 mL was reacted with stirring for 4 hours at 95 . After the reaction cooled to H2O: After layer separation the MC column purification (n-Hexane: MC) to afford 2.1 g of Intermediate 1-5 (yield 77percent) (m / z = 465). Intermediate 1-4 (6.0 g, 0.016 mol), intermediate 8-2 (5.0 g, 0.010 mol) into the Example 1-Preparation Example 6 in the same manner as used in the synthesis 4.8 g (yield: to give a 70percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | A 500 mL three-neck round-bottom flask was filled with nitrogen, and then Compound C (61.8 mmol, 25.0 g), Compound G (28.1 mmol, 13.9 g), 250 mL of tetrahydrofuran (THF), and 125 mL of ethanol (EtOH) were added thereto, and the resulting mixture was stirred for 30 minutes. Further, potassium carbonate (K2CO3) (224.8 mmol, 31.1 g) was dissolved in 125 mL of water (H2O), and then the resulting solution was added to the 500 mL three-neck round-bottom flask. Subsequently, tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (2.2 mmol, 2.6 g) was added to the 500 mL three-neck round-bottom flask, and then the resulting mixture was refluxed for 6 hours while the light is blocked.[0131] The reaction mixture was cooled, and then extracted by using ethyl acetate (EA) and distilled water and concentrated, the concentrate was dissolved in 125 mL of tetrahydrofuran (THF), and the resulting solution was put into 1,250 mL of methanol and stirred for 20 minutes, and then filtered, thereby obtaining 21.3 g of a pale brown solid Compound 5 (yield 85percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 5h;Inert atmosphere; Reflux; | According to the preparation of compound 180-1 of step (1) in Example 10,the difference is,Using compound 203-1 instead of N-phenylcarbazole-3-boronic acid,Using compound 1-5 instead of 3-bromocarbazole,To give compound 203 (yield 35percent) 3-Bromocarbazole (0.1219 mol) was dissolved in 300 ml of toluene,And N-phenylcarbazole-3-boronic acid (0.1209 mol) was added under nitrogen,30 ml of ethanol,Potassium carbonate (0.2418 mol),30ml water,Tetrakis (triphenylphosphine) palladium (0.00122 mol)And then heated to reflux reaction 5h,HPLC reaction is completed, the reaction solution spin and add dichloromethane and water extraction, take the organic phase of silica gel funnel,The organic phase was dried under reduced pressure to give compound 180-1 (yield 78percent) by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tetrakis(triphenylphosphine) palladium(0); potassium acetate; In 1,4-dioxane; for 5h;Reflux; | 3,6-dibromo-N-phenylcarbazole (0.075 mol) was dissolved in 300 ml of dioxane,Under the addition of bis (pinacolato) diboron (0.164 mol)Potassium acetate (0.375 mol),Tetrakis (triphenylphosphine) palladium (0.00075 mol)And heated to reflux reaction 5h,The reaction was complete and the reaction was quenched and the reaction was quenched with dichloromethane and water. The organic phase was passed through a silica gel funnel and the organic phase was dried under reduced pressure. The resulting solid was subjected to column chromatography to give compound 203-1 (yield 45percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Inert atmosphere; Reflux; | 9-phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -9H-carbazole 10.0 g (20.19 mmol) of8.75 g (44.42 mmol) of 3-bromobenzofurane, 12.28 g (88.85 mmol) of K2CO3, Pd (PPh3) 4 0.47 g (0.40 mmmol)100 ml of toluene,Suspended in distilled water (50 ml), and stirred under reflux for 12 hours under a stream of nitrogen.After completion of the reaction, the reaction solution was extracted with dichloromethane, filtered through silica gel, and distilled under reduced pressure. Then, hexane: dichloromethane = 7: 3 (v / v) To obtain 6.7 g (Yield: 70percent) of Compound 17 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 12h;Reflux; Inert atmosphere; | 9-phenyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -9H-carbazole 10.0 g (20.19 mmol)9.47 g (44.42 mmol) of 3-bromobenzothiophene,12.28 g (88.85 mmol) of K2CO3, Pd (PPh3) 4 0.47 g (0.40 mmmol) 100 ml of toluene,Suspended in distilled water (50 ml), and stirred under reflux for 12 hours under a stream of nitrogen. After completion of the reaction, the reaction solution was extracted with dichloromethane, filtered through silica gel, and distilled under reduced pressure. Then, hexane: dichloromethane = 7: 3 (v / v)To obtain Compound 217.3 g (Yield: 71percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.3% | Under a nitrogen stream3,6-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -9-phenylcarbazole 10.0 gmmol),4- (3,5-Dibromo-phenyl) -2,6-diphenyl-pyrimidine 9.41 g (20.19 mmol) K2CO3 16.7 g,800 ml of toluene,Then, 200 ml of a mixed solution was put into a 2-liter 2-neck round bottom flask, stirred for 30 minutes at room temperature,Pd (PPh3) 4 (70 mg, 0.61 mmol) was added thereto and refluxed for 18 hours.After the reaction was completed, the reaction mixture was extracted with methylene chloride, added with MgSO 4 and filtered.After removal of the solvent of the obtained organic layer, the residue was purified by column chromatography to obtain the target compound Macrocycle-II (4.93 g, yield 22.3percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.6 g | Under a nitrogen stream3,6-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -9-phenylcarbazole 10.0 gmmol),4- (3,5-Dibromo-phenyl) -2,6-diphenyl-pyrimidine 9.41 g (20.19 mmol) K2CO3 16.7 g,800 ml of toluene,Then, 200 ml of a mixed solution was put into a 2-liter 2-neck round bottom flask, stirred for 30 minutes at room temperature,Pd (PPh3) 4 (70 mg, 0.61 mmol) was added thereto and refluxed for 18 hours.After the reaction was completed, the reaction mixture was extracted with methylene chloride, added with MgSO 4 and filtered.After removal of the solvent of the obtained organic layer, the residue was purified by column chromatography to obtain the target compound Macrocycle-II (4.93 g, yield 22.3percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -9-phenylcarbazole,One equivalent (20 g, 40.49 mmol),3-Bromo-9-phenylcarbazole, 2Equivalent (26 g, 81 mmol), 33.5 g of K2CO3, 800 ml of toluene,And 200 ml of water was added to a 2-L 2-neck round bottom flask. The mixture was stirred at room temperature for 30 minutes,Pd (PPh3) 4 (1.4 g, 1.21 mmol) was added and refluxed for 24 hours.After the reaction was completed, the reaction mixture was extracted with methylene chloride, added with MgSO 4 and filtered.After removing the solvent of the obtained organic layer, it was purified by column chromatography to obtain intermediate compound 1 (24.80 g, yield 82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | The compound 2 (15.0 g, 16.98 mmol) obtained above and 3,6-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-phenylcarbazole (8.15 g, 16.98 mmol),14.0 g of anhydrous K2CO3,800 ml of toluene,The mixture was stirred for 30 minutes at room temperature, and then Pd (PPh3) 4 (0.60 g, 0.52 mmol) was added thereto.And the mixture was refluxed for 24 hours.After the reaction was completed, the reaction mixture was extracted with methylene chloride, added with MgSO 4 and filtered.After removing the solvent of the obtained organic layer, the residue was purified by column chromatography to obtain the target compound Macrocycle-I(4.42 g, yield 27percent). |