Structure of 1205748-61-3
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CAS No. : | 1205748-61-3 |
Formula : | C27H18ClN3 |
M.W : | 419.91 |
SMILES Code : | ClC1=NC(C2=CC(C3=CC=CC=C3)=CC=C2)=NC(C4=CC(C5=CC=CC=C5)=CC=C4)=N1 |
MDL No. : | MFCD30536777 |
InChI Key : | SVNMSEVGOAHNKQ-UHFFFAOYSA-N |
Pubchem ID : | 58299118 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 31 |
Num. arom. heavy atoms | 30 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 126.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.67 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
4.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
7.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
7.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
7.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
6.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-7.63 |
Solubility | 0.00000992 mg/ml ; 0.0000000236 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-8.16 |
Solubility | 0.00000293 mg/ml ; 0.000000007 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-11.87 |
Solubility | 0.0000000006 mg/ml ; 0.0 mol/l |
Class? Solubility class: Log S scale |
Insoluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-3.53 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 |
1.0 |
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 |
0.0 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) |
3.01 |
* 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 |
---|---|---|
59% | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; for 18h;Inert atmosphere; Reflux; | Synthesis Example 2; This example illustrates the preparation of Compound A2, shown below. A 500mL one-neck round-bottom flask equipped with a condenser and nitrogen inlet was charged with 5.55g (26.1 mmol) of potassium phosphate and 10OmL of Dl water. To this solution, 6.74g (17.44 mmol) of 2-(3-(dibenzo[b,d]thiophen-4-yl)phenyl)-4,4,5,5-tetramethyl-1 ,3,2- dioxaborolane, 6.1 g (14.53 mmol) of 2,4-di(biphenyl-3-yl)-6-chloro-1 ,3,5- triazine, and 160ml_ of 1 ,4-dioxane were added. The reaction mixture was sparged with nitrogen for 35 minutes. In the drybox, 0.4g (0.44 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 0.28g (1 .15 mmol) of tricyclohexylphosphine were mixed together in 40ml_ of 1 ,4-dioxane, taken out of the box and added to the reaction mixture. Reaction mixture was sparged nitrogen for five minutes then refluxed for 18 hours. The reaction was cooled to room temperature and 1 ,4-dioxane was removed on the rotary evaporator. The residue was diluted with methylene chloride and water, then brine was added to the mixture, which was let to stand for 30 minutes. Lower level was removed along with gray solids. The aqueous layer was extracted two more times with methylene dichloride. The combined organic layers were stripped until dry. The resulting gray solid was placed on a filter paper at the bottom of a coarse fritted glass funnel and washed with 100 ml_ of water, 800 ml_ of LC grade methanol and 500 ml_ of diethyl ether. Solids were recrystallized from minimal amount of hot toluene. Yield 5.48g (59%) of desired product. Mass spectrometry and 1H NMR (CDCI2CCI2D) data were consistent with the structure of the desired product. |
59% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; for 18h;Reflux; Inert atmosphere; | A 500ml_ one-neck round-bottom flask equipped with a condenser and nitrogen inlet was charged with 5.55g (26.1 mmol) of potassium phosphate and 10OmL of Dl water. To this solution, 6.74g (17.44 mmol) of 2-(3-(dibenzo[b,d]thiophen-4-yl)phenyl)-4,4,5,5-tetramethyl-1 ,3,2- dioxaborolane, 6.1 g (14.53 mmol) of 2,4-di(biphenyl-3-yl)-6-chloro-1 ,3,5- triazine, and 160ml_ of 1 ,4-dioxane were added. The reaction mixture was sparged with nitrogen for 35 minutes. In the drybox, 0.4g (0.44 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 0.28g (1 .15 mmol) of tricyclohexylphosphine were mixed together in 40ml_ of 1 ,4-dioxane, taken out of the box and added to the reaction mixture. Reaction mixture was sparged nitrogen for five minutes then refluxed for 18 hours. The reaction was cooled to room temperature and 1 ,4-dioxane was removed on the rotary evaporator. The residue was diluted with methylene chloride and water, then brine was added to the mixture, which was let to stand for 30 minutes. Lower level was removed along with gray solids. The aqueous layer was extracted two more times with methylene dichloride. The combined organic layers were stripped until dry. The resulting gray solid was placed on a filter paper at the bottom of a coarse fritted glass funnel and washed with 100 mL of water, 800 mL of LC grade methanol and 500 mL of diethyl ether. Solids were recrystallized from minimal amount of hot toluene. Yield 5.48g (59%) of desired product. Mass spectrometry and1H NMR (CDCI2CCI2D) data were consistent with the structure of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | 5.2 g Magnesium (0.215 mol) was introduced in 500 ml 4-necked flask, 50 g of bromobiphenyl (214 mmol) in 200 ml THF was added dropwise. The reaction mixture was heated for 1.5 h and then subsequently cooled to room temperature. Cyanuric chloride (17.2 g, 93 mmol) in 150 ml THF was introduced to the second flask,and cooled to 0C. Grignard reagent was added, and the mixture was stirred at room temperature for 12 h. After this, 150 ml of HCl was added to the reaction mixture, aqueous phase was extracted 3 times with dichloromethane. The combined organic phases washed with water, dried using Na2SO4 and evaporated. Then the residue was recrystallized from EtOH. The yield is 32.8 g (78 mmol, 84%). | |
65% | In THF (20ml), was prepared 3-bromo-1,1'-biphenyl (10.73l, 64.3mmol) and Mg (4.69g, 193mmol) and then refluxed for 2 hours [1,1' biphenyl]-3-solution in THF (80ml) of the Il magnesium bromide was added dropwise at 0 to a solution of 2,4,6-trichloro-1,3,5-triazine (3.96g, 21.45mmol). The reaction mixture was slowly warmed to room temperature, and stirred for 16 hours and quenched with 10% aqueous HCl. Extracted with DCM, washed with water, and dried with sodium sulfate (Na2SO4). Evaporation of the solvent by silica gel column chromatography using heptane / DCM as eluent (9/1 ~ 7/3, v / v), purified the crude product as a white solid of 2,4-di-([1,1'-biphenyl]-3-yl)-6-chloro-1,3,5-triazine (2.30g, 65%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; at 80℃; for 23h;Inert atmosphere; | Intermediate 26 (39.5 mmol) was dissolved in 0.2 L of tetrahydrofuran (THF) under a nitrogen environment, Intermediate 27 (39.5 mmol) and tetrakis(triphenylphosphine)palladium (0.46 g, 0.4 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (13.6 g, 98.8 mmol) was added thereto, and the obtained mixture was heated and refluxed at 80 C. for 23 hours. When a reaction was complete, water was added to the reaction solution, dichloromethane (DCM) was used for an extraction, anhydrous MgSO4 was used to remove moisture from an extract, and the extract was filtered and concentrated under a reduced pressure. The obtained residue was separated and purified through flash column chromatography to obtain Compound A-2 (a yield of 75%). (0188) calcd. C45H29N3: C, 88.35; H, 4.78; N, 6.87. found: C, 88.35; H, 4.78; N, 6.87. |
74% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In monoethylene glycol diethyl ether; water; toluene; for 16h;Reflux; Inert atmosphere; | DME (100 ml), toluene (100 ml), and in water (10 ml), 4,4,5,5-tetramethyl-2-(triphenylene-2-yl) 1,3,2-dioxaborolane (2.53 g, 7.14 mmol), 2,4-di-([1,1'-biphenyl]-3-yl)-6-chloro-1,3,5-triazine (2.50g, 5.95mmol), Pd(PPh3)4 (0.69g, 0.60mmol), and K2CO3 (1.65g, 11.91mmol) was the solution of the reflux for 16 hours under nitrogen. After cooling to room temperature, the reaction mixture was diluted with water. The solid was collected by filtration, washed with water, ethanol, and washed with toluene, then redissolved in boiling toluene and filtered through a short plug of silica gel. Evaporation of the solvent, toluene, was re-crystallized compound 5 as a white solid (2.70g, 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Magnesium (0.215 mol) of 5.2 g ofInitially, 500 ml 4- nine (four-necked) Introduced into the flask, and 200 ml of THF in 50 gA solution of bromobiphenyl (214 mmol) was slowly added dropwise thereto.Heating for 1.5 hours at the boiling point of the reaction mixture, andThen allowed to cool to room temperature.The cyanogen chloride (cyanogenchloride) (17.2 g, 93 mmol) in 150 ml of THF First it introduced into a second flask and cooled to 0 . Then, the coolingIt was added dropwise a Grignard (Grignard) reagent at this temperature and the mixture was stirred at room temperature for 12 hours.After said time, and extracted three times, the aqueous phase was added to 150 ml of HCl to the reaction mixture with dichloromethane.Washing the organic phase with water, combined, dried over Na2SO4, and evaporated.The residue was recrystallized from EtOH. The yield was 32.8 g (78 mmol, 84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.5 g of intermediate A1A from above was slurried into 125 mL dry THF in a nitrogen filled glove box and 0.32 g sodium hydride was added with stirring. After 4 hrs, 4.725 g 1,3,5-Triazine, 2,4-bis([1,1?-biphenyl]-3-yl)-6-chloro- was added as a solid over a period of 10 mins. The slurry rapidly darkens to a deep red after heating to 40 C. The red slurry was filtered through a fine frit and the filter cake was washed with dry THF until all red color was eluted. Evaporation of the red solution yielded golden yellow crude solid of structure A2B |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.4 g of intermediate A4A from above was slurried into 120 mL dry THF in a nitrogen filled glove box and 0.238 g sodium hydride was added with stirring. After 150 mins, 3.57 g 1,3,5-Triazine, 2,4-bis([1,1?-biphenyl]-3-yl)-6-chloro- was added. The slurry rapidly darkens to a deep red after heating to 50 C. The red slurry was filtered through a fine frit and the filter cake was washed with dry THF until all red color was eluted. Evaporation of the red solution yielded a crude golden yellow solid of structure A4B |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.3 g of intermediate A5A from above was slurried into 150 mL dry THF in a nitrogen filled glove box and 0.284 g sodium hydride was added with stirring. After 30 mins, 4.21 g 1,3,5-Triazine, 2,4-bis([1,1?-biphenyl]-3-yl)-6-chloro was added as a solid over a period of 90 mins. The slurry rapidly darkens to a deep red after heating to 50 C. The red slurry was filtered through a fine frit and the filter cake was washed with dry THF until all red color was eluted. Evaporation of the red solution yielded a crude golden yellow solid of structure A5B |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; | General procedure: 295g (1.6mol, 1.0eq) of 2,4,6-trichloro-1 ,3,5-triazine [108-77-0] 1 are solved in 800ml dried THF in a four-necked flask under an inert atmosphere. The solution is cooled with an ice bath to about 0C and 800ml (1.6mol, 1.0eq) of a 2mol/l phenylmagnesiumchloride solution are added slowly to maintain the temperature below 10C. Then, the mixture is stirred at room temperature overnight and after the reaction had finished, 800ml of toluene and 1.2L of HCI 2% are added. The organic phase is separated, extracted three times with water and dried over sodium sulfate. The solvent is evaporated under reduced pressure until the product precipitates. After washing the solid with ethanol, 242g (1.1mol, 67%) of the desired product 3a are obtained. Other examples are obtained analogously: |
55% | In tetrahydrofuran; at 0℃; | 100.0 g (542.3 mmol) of cyanuric chloride and 700 mL of anhydrous THF were put in a 2 L flask, 361.4 mL of 3-Biphenylmagnesium bromide (3 M) was added thereto, and the mixture was slowly added thereto in a dropwise fashion at 0 C. When a reaction was complete, water was poured into the reaction solution, the mixture was stirred for 30 minutes, and an organic layer therefrom was separated, concentrated after removing moisture by using magnesium sulfate, and purified with methanol and hexane to obtain white solid Intermediate 5-1 (122.9 g, yield of 55%). (0188) calcd. C27H18ClN3: C, 77.23; H, 4.32; Cl, 8.44; N, 10.01; found: C, 77.25; H, 4.31; Cl, 8.44; N, 10.00. |
55% | In tetrahydrofuran; at 0℃; | Cyanuric chloride (100.0 g, 542.3 mmol) and anhydrous THF (700 mE) were put in a 2 E flask, and 3-biphenyl magnesium bromide (3 M, 361.4 mE) was slowly added thereto in a dropwise fashion at 00 C. When the reaction wascomplete, water was poured into the reaction solution, themixture was stirred for 30 minutes, an organic layer thereinwas separated, concentrated after removing moisture withmagnesium sulfate, and punfied with methanol and hexaneto obtain an intermediate 1-9 as a white solid (122.9 g, ayield: 55%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 110℃;Inert atmosphere; | 30g (80mmol, 1.0eq) of 7a, 21g (88mmol, 1.1eq) 9,9-Dimethyl- 9H-fluoren-4-yl-boronic acid [1246022-50-3] and 17g (160mmol, 2.0eq) sodium carbonate are dissolved in 400ml toluene, 250ml water and 170ml ethanol under an inert atmosphere. Then, 0.93g (0.80mmol, 0.01eq) tetrakis(triphenylphosphine)palladium is added and the mixture refluxed over night at 110C. After the reaction is completed, 300ml water were added and the precipitated (36g) solid is filtered. The organic layer is separated, washed with water and dried over sodium sulfate. After evaporation of the solvent, another 5.1g of the crude product are obtained. The combined solids are purified by hot extraction from toluene/heptane, recrystallized twice from toluene/heptane and sublimed to give 20g (38mmol, 47%) of the desired product 9a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water;Reflux; | General procedure: Sub 1-1 (14.8g, 80 mmol), THF 360 mL, Sub 1-2-1 (16.3g, 80 mmol), Pd (PPh 3 )4 (2.8g, 2.4mmol), NaOH (9.6g, 240mmol ), followed by the addition of 180 mL of water, it was refluxed with stirring. When the reaction was complete, the ether was extracted with water and the organic layer is MgSO 4 dried and concentrated and then the produced organic silicagel column and recrystallized to give the product 12.3g (68%). Sub 1-3-1 (12.2g, 54 mmol), Sub 1-4-1 (11.0g, 54 mmol) for the synthesis in the same manner as in the Sub 1-3-1 and recrystallized product was 9.5g (66% ) it was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 60℃; for 12h;Inert atmosphere; | The intermediate 1-9 (3.0 g, 7.1 mmol), the intermediate 1-4 (5.0 g, 8.6 mmol), potassium carbonate (2.5 g, 17.9 mmol), and tetrakis(triphenylphosphine) palladium (0) (0.3 g, 0.2 mmol) were added to 1,4-dioxane (20 mE) and water (10 mE) in a 100 mE flask, and the mixture was heated at 60 C. under a nitrogen flow for 12 hours. The obtained mixture was added to methanol (100 mE), a solid crystallized therein was filtered, dissolved in toluene, filtered through silica gel/Celite, and then, recrystallized with methanol after removing an appropriate amount of an organic solvent to obtain a compound 6 (4.07 g, a yield:68%). calcd. C63H43N3: C, 89.86; H, 5.15; N, 4.99.found: C, 89.86; H, 5.15; N, 4.98. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 60℃; for 12h;Inert atmosphere; | The intermediate 1-9 (3.0 g, 7.1 mmol), the intermediate 1-14 (5.0 g, 8.6 mmol), potassium carbonate (2.5 g, 17.9 mmol), and tetrakis(triphenylphosphine) palladium (0) (0.3 g, 0.2 mmol) were added to 1,4-dioxane (20 mE) and water (10 mE) in a 100 mE flask, and the mixture was heated at 60 C. under a nitrogen atmosphere for 12 hours. The obtained mixture was added to methanol (100 mE), a solid crystallized therein was filtered, dissolved in toluene, filtered through silica gel/Celite, and recrystallized with methanol afier removing an appropriate amount of an organic solvent to obtain a compound 14 (4.19 g, a yield: 70%). calcd. C63H43N3: C, 89.86; H, 5.15; N, 4.99.found: C, 89.84; H, 5.15; N, 4.99. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 3h;Reflux; | General procedure: Sub 1-1 (11.6 g, 33.62 mmol), Sub 2-1 (5.27 g, 33.62 mmol), Pd2 (dba) 3 (1 g, 0.1 mmol)(t-Bu) 3P(0.4 g, 0.002 mmol),After NaOt-Bu (9.61 g, 100 mmol) was dissolved in anhydrous toluene,And refluxed for 3 hours.When the reaction is completed, the temperature of the reaction is cooled to room temperature,Extracted with CH2Cl2 and wiped with water.A small amount of water was removed with anhydrous MgSO4, filtered under reduced pressure, and the organic solvent was concentrated to give the productThe silicagel column and desired by recrystallization11.5 g of P1-1 was obtained. (Yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 100℃; for 3h; | General procedure: Sub 1-1 (13.3 g, 33.62 mmol), Sub 2-1 (5.27 g, 33.62 mmol), Pd2 (dba) 3 (1 g, 0.1 mmol)(t-Bu) 3P (0.4 g, 0.002 mmol),NaOt-Bu (9.61 g, 100 mmol) was added to a solution ofAfter dissolving in anhydrous toluene,And refluxed for 3 hours.When the reaction is completed, the temperature of the reaction is cooled to room temperature,Extracted with CH2Cl2 and wiped with water. A small amount of water was removed with anhydrous MgSO 4, filtered under reduced pressure, and the organic solvent was concentrated. The resulting product was purified by silicagel column and recrystallized to obtain 12.38 g of desired P 1-1 (yield: 78%). |
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