Structure of 1698-16-4
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CAS No. : | 1698-16-4 |
Formula : | C16H10BrN |
M.W : | 296.16 |
SMILES Code : | BrC1=CC2=C(NC3=C2C4=CC=CC=C4C=C3)C=C1 |
MDL No. : | MFCD22054961 |
InChI Key : | YHAHNQXQOZYZLP-UHFFFAOYSA-N |
Pubchem ID : | 68016353 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 17 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 81.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.53 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.73 |
Solubility | 0.000548 mg/ml ; 0.00000185 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.41 |
Solubility | 0.00114 mg/ml ; 0.00000386 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.48 |
Solubility | 0.00000987 mg/ml ; 0.0000000333 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) |
Yes |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.32 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
2.0 |
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 |
0.0 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) |
1.62 |
* 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 |
---|---|---|
73% | With triphenylphosphine; In 1,2-dichloro-benzene; at 200℃; | General procedure: Wherein the Sub 1-I-1 (66.39 g, 238.7mmol) after a round bottom flask was dissolved in o-dichlorobenzene (1194ml),it was added triphenylphosphine (156.54 g, 596.8 mmol) and stirred at 200 . After completion ofreaction was removed by distillation and the o-dichlorobenzene and water,extracted CH2Cl2. The resulting compound and the organic layer was dried overMgSO4 and concentrated to silicagel column and the product was recrystallizedfrom 35.25 g (yield: 60%) was obtained. |
With triphenylphosphine; In 1,2-dichloro-benzene; for 24h;Reflux; | General procedure: To a round bottom flask was dissolved Sub 2-2-3 (1 eq.) and triphenylphosphine (3 equivalents) in o-dichlorobenzene, was refluxed for 24 hours. Of methanol surface reaction being terminated after removing the solvent using, a concentrated product column derivative by HPLC using column charged with a desired to separate Sub 2-2 a obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.4% | With sodium hydrogensulfite; In water; at 120℃; | 2-naphthol (20.0 g, 138.8 mmol), NaHSO3 (28.8 g, 277.4 mmol), distilled water (160 mL) and 4-bromophenylhydrazine (31.2 mL, 166.4 mmol) were heated to TheAfter 12 hours distilled water was added and the resulting solid was filtered off under reduced pressure.The solid thus obtained was added to aqueous HCl and heated to 100°After 1 hour, following extraction with dichloromethane, the product was washed with distilled water and aqueous NaOH solution. Column separation gave compound A (9.2 g, 31.0 mmol, 22.4%). |
With sodium hydrogensulfite; In water; at 120℃; for 12h; | 20.0 g (138.8 mmol) of 2-naphthol, 28.8 g (277.4 mmol) of NaHSO3, 160 mL of distilled water, and 31.2 mL (166.4 mmol) of 4-bromophenylhydrazine were heated to 120. After 12 hours, the reaction mixture was added with distilled water, and the produced solid was vacuum filtered. The solid thus obtained was added to an aqueous hydrochloric acid solution and heated to 100. After 1 hour, the resultant product was extracted with dichloromethane, washed with distilled water and aqueous NaOH, and purified by column separation, thus obtaining 9.2 g (31.0 mmol) of Compound 2-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 18-crown-6 ether; copper; potassium carbonate; at 180℃; for 12h; | 9.2 g (31.0 mmol) of Compound 2-1, 2.0 g (31.0 mmol) of Cu, 0.4 g (1.6 mmol) of 18-crown-6, 12.8 g (93.2 mmol) of K2CO3, and 100 mL of 1,2-dichlorobenzen were mixed and stirred under reflux to 180 for 12 hours. The reaction mixture was cooled to room temperature, vacuum distilled, extracted with dichloromethane and then washed with distilled water, followed by performing drying with MgSO4, vacuum distillation, and column separation, thus obtaining 7.6 g (20.4 mmol) of Compound 2-2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 24h; | Preparation of compound 3-3 [148] After dissolving compound 3-2 (20 g, 92 mmol) in dimethylformamide (DMF) at 0C, N-bromosuccinimide (NBS) (16.3 g, 92 mmol) was slowly added to the reaction mixture and the reaction mixture was stirred for 24 hours. After completing the reaction, the organic layer was extracted EA and was dried with MgSO4 to remove the remaining moisture. The obtained organic layer was separated through column to obtain compound 3-3 (23.5 g, 87 %). |
86% | With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 20℃; for 12h; | The 20.4g (0.1mol) 7H- benzo [c] carbazole was dissolved in tetrahydrofuran (THF, 500mL), and then the resulting solution was stirred at 0 10 minutes. Thereto was added N- bromosuccinimide (NBS, 18.68g, 0.105mol), the resulting mixture was stirred at normal temperature for 12 hours, then extracted with ethyl acetate and distilled water. The organic layer was dried over anhydrous magnesium sulfate (MgSO4) was dried, then the solvent was removed, and subjected to silica gel column chromatography to give 25.4g (86%) Compound B-1. |
80% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 24h; | After dissolving compound 1-9 (8.7 g, 40.1 mmol) in dimethylformamide (DMF) (50 mL), and adding N-bromosuccinimide (NBS) (4.7 g, 40.1 mmol), the reaction mixture was stirred for a day at room temperature. After terminating the reaction, the reaction mixture was extracted with EA, and the organic layer was concentrated. The resulting product was purified by a silica column to give compound 1-10 (9.5 g, 80 %). |
78% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 24h; | Preparation of Compound 7-1 [193] 7H-benzo[c]carbazole (50g, 0.23mol) was dissolved in DMF 1.4L, and NBS (41g, 0.23mol) was added, after which the mixture was stirred at room temperature for 24 hours. After termination of the reaction, the resultant mixture was extracted with EA and the organic layer was distilled under reduced pressure. Silica column separation was then performed, yielding Compound 7-1 (53.2g, 78%). |
77% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere; Cooling with ice; | Under nitrogen atmosphere, N-bromosuccinimide (12.6 g) was added to a solution of 7H-benzo [c] carbazole (15.7 g) in N, N-dimethylformamide (250 mL) under ice cooling, and the temperature was raised to room temperature And the mixture was stirred for 2 hours. The resulting reaction solution was extracted with toluene, the toluene layer was washed with saturated brine, dried with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the objective 10-bromo-7H-benzo [c] carbazole (16.2 g, yield 77%) |
39% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 12h; | After introducing 7H-benzo[cjcarbazole (50 g, 230 mmol) and DMF (200 mL) into a flask, the mixture was stirred, and N-bromosuccinimide (42 g, 230 mmol) dissolved in DMF (50 mL) was added thereto. The resultant mixture was stirred at room temperature for 12 hours, and extracted with distilled water and MC. The obtained organic layer was dried with magnesium sulfate, and distilled under reduced pressure. The residue was purified by column chromatography to obtain compound A (10-bromo-7H-benzo[cjcarbazole) (1 6g, yield: 23.5%) |
70.8 g | With N-Bromosuccinimide; In dichloromethane; at -5 - 0℃; for 3h; | D: Add 65.1 g of benzo [c] carbazole and 600 ml of dichloromethane to a clean and dry 1000 mL four-neck reaction flask.Stir until dissolved, then cool to -5 , add 54g NBS in batches, after the addition is complete, hold the reaction at -5-0 for 3h,HPLC followed the completion of the benzo [c] carbazole reaction. After the reaction was completed, 300 ml of clear water was added to the reaction material.After stirring for a period of time, the layers were separated, the organic phase was removed, and the solvent was removed under reduced pressure to obtain a dark brown oil.450 ml of toluene and 3 g of activated carbon were added, and the mixture was stirred under reflux for 1 h, then filtered while hot, and the solvent was removed under reduced pressure from the filtrate.A pale yellow oil was obtained, 90 ml of ethanol was added, and after dissolving, crystallized at room temperature, suction filtration was performed,A white solid was obtained, 70.8 g was obtained by drying, HPLC: 99.27%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 12h;Reflux; | 200mL of tetrahydrofuran is introduced into the compound B-1 and diphenyl 14.8g (50mmol) prepared in Synthesis Example 5 and [b, d] furan-4-yl boronic acid (12.7g, 60mmol), followed by Pd (PPh3) 4 (2.89g, 2.5mmol) and 100mL2MK2CO3 aqueous solution, the resulting mixture was stirred for 12 hours while refluxing. The temperature was cooled to normal temperature and distilled water was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate (MgSO4) was dried, then the solvent was removed, and subjected to silica gel column chromatography to give 16.1g (42mmol, 84%) Compound E-1. |
78% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 15h; | Preparation of Compound 8-1 [206] Compound 7-1 (10 g, 33.8 mmol), dibenzo[b,d]furan-4-ylboronic acid (8.6 g, 40.56 mmol), Pd(PPh3)4 (2 g, 1.7mmol), K2CO3 (34 g, 321 mmol), toluene 60mL, EtOH 12mL and purified water 12mL were mixed and then stirred at 120C for 15 hours. After termination of the reaction, the resultant mixture was allowed to stand and the water layer was removed, after which the organic layer was concentrated. Silica column purification was then carried out, yielding Compound 8-1 (10.2 g, 78%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With dipotassium hydrogenphosphate; copper(l) iodide; ethylenediamine; In toluene; at 120℃; for 24h; | Preparation of compound 3-4 [150] After adding compound 3-3 (20 g, 6.5 mmol), iodobenzene (15 mL, 135 mmol), CuI (6.4 g, 33.6 mmol), ethylenediamine (2.3 mL, 33.6 mmol) and K2PO4 (43 g, 202.5 mmol) to a flask and dissolving the reaction mixture by adding toluene (300 mL), the reaction mixture was stirred for 24 hours at 120C. After completing the reaction, the organic layer was extracted EA and was dried with MgSO4 to remove the remaining moisture. The obtained organic layer was separated through column to obtain compound 3-4 (19 g, 76 %). |
70% | With copper(l) iodide; caesium carbonate; ethylenediamine; In toluene; at 120℃; for 5h; | After dissolving 10-bromo-7H-benzo[cjcarbazole (26 g, 87.79 mmol), iodobenzene (12 mL, 105.35mmol), CuT (8.4 g, 43.89 mmol), ethylene diamine(EDA) (3 mL, 43.89 mmol), and Cs2CO3 (85 g, 263.37 mmol) in toluene (500 mL) of a flask, the mixture was under reflux at 120C for 5 hours. After completion of the reaction, the mixture was extracted with ethyl acetate. The remaining moisture was removed from the obtained organic layer with magnesium sulfate. The product was dried, and purified by column chromatography to obtain compound 1-1 (18 g, yield: 70%). |
70% | With copper(l) iodide; ethylenediamine; In toluene; at 120℃; for 5h; | The flask was charged with 10-bromo-7H-benzo [c] carbazole(26 g, 87.79 mmol), iodobenzene (12 mL, 105.35 mmol),CuI (8.4 g, 43.89 mmol), Ethylenediamine (EDA) (3 mL, 43.89 mmol),Cs2CO3 (85 g, 263.37 mmol)And 500 mL of toluene, and the mixture was refluxed at 120 C for 5 hours.After the reaction was completed, the organic layer was extracted with ethyl acetate, and magnesium sulfateTo remove residual water, dried and separated into a column to obtain Compound 1-1 (18 g, yield: 70%). |
53% | With copper(l) iodide; caesium carbonate; ethylenediamine; In toluene; for 24h;Reflux; | Preparation of Compound 7-2 [195] Compound 7-1 (30g, 0.10mol), iodobenzene (22.6mL, 0.20mmol), CuI (9.6g, 0.05mol), Cs2CO3 (99g, 0.030mol), and EDA (13.7mL, 0.20mol) were added to toluene 500mL and stirred under reflux for 24 hours. The mixture was extracted with EA, distilled under reduced pressure and column separated using MC/Hex, yielding Compound 7-2 (20g, 53%). |
37% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; for 5h;Reflux; Inert atmosphere; | Under nitrogen atmosphere, 10-bromo-7H-benzo [c] carbazole (16.0 g), iodobenzene (22.0 g), copper (I) iodide (5.14 g), ethylenediamine (6.4 9 g), phosphorus A mixture of tripotassium acid (22.9 g) and toluene (100 mL) And refluxed for 5 hours. The reaction solution was cooled to room temperature, extracted with toluene, the toluene layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography and recrystallization to obtain the objective 10-bromo-7-phenylbenzo [c] carbazole (7.52 g: yield 37%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 95℃; for 3h; | After dissolving compound 1-7 (6 g, 17.8 mmol), compound 1-10 (4.4 g, 14.9 mmol), K2CO3 (6.2 g, 44.7 mmol) and Pd(PPh3)4(860 mg, 0.75 mmol) in toluene (100 mL)/EtOH(20 mL)/purified water (20 mL), the reaction mixture was stirred for 3 hours at 95?. After terminating the reaction, the reaction mixture was cooled to room temperature, and left standing to remove the water layer. After concentrating, the oil layer was triturated with MC and filtered to obtain compound 1-11 (7 g, 92 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.7% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 12h;Reflux; | After introducing compound A (10-bromo-7H-benzo[cjcarbazole) (16 g, 54 mmol), (9-phenyl-9H-carbazol-3-yl)boronic acid (17 g, 59.4 mmol), Pd(PPh3)4 (3.1 g, 2.7 mmol), K2C03 (25.7 g, 108 mmol), distilled water (50 mL), toluene (250 mL), and ethanol(EtOH)(50 mL) in a flask, the mixture was stirred under reflux for 12 hours. After cooling to room temperature, the mixture was extracted with EA and distilled water, dried with magnesium sulfate, distilled under reduced pressure, and purified by column chromatography to obtain compound B(1 0-(9-phenyl-9H-carbazol-3-yl)-7H-benzo[cj carbazole) (22 g, yield: 88.7%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triphenylphosphine; In 1,2-dichloro-benzene; at 200℃; | Said Sub 2-I-13 obtained in the synthesis (109.26 g, 332.90 mmol) triphenylphosphine to (218.32 g, 832.40 mmol),o-dichlorobenzene (1000 ml) adding an 200 C stirring section. When reaction is completed the via fractional distillation to remove the dichlorobenzene- o CH2Cl2extracted and water. Organic layer MgSO4to dry a silicagel column with a compound formed after the products and recrystallization obtained a 69.02 g (yield: 70%). |
With TPP; In 1,2-dichloro-benzene; at 150℃; for 24h; | General procedure: Sub-7-1 (1 equivalent) to the round flask, After mixing with TPP (3 equivalents) and dichlorobenzene, the mixture was refluxed at 150 C for 24 hours, and then dichlorobenzene was removed under reduced pressure. Then, the mixture was extracted with MC and water. The organic layer was dried with MgSO 4 and concentrated. And recrystallized to obtain the product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 80℃; | Said Sub 2-II-13 obtained in the synthesis (69.02 g, 173.20 mmol) of toluene (600 ml) in round bottom flask to senses a rotation velocity of the disk in, 3-iodobicyclo[4.2.0]octa-1, 3, 5-triene (59.76 g, 259.80 mmol), Pd2(dba)3(4.75 g, 5.19 mmol), 50% P (t-Bu)3(3.50 ml, 8.66 mmol), NaOt-Bu (72.35 g, 752.70 mmol) it agitated. adding an 80 C stirring section. When reaction is completed CH2Cl2extracted and water. Organic layer MgSO4to dry a silicagel column with a compound formed after the products and recrystallization obtained a 49.66 g (yield: 72%) |