Structure of 1255308-97-4
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CAS No. : | 1255308-97-4 |
Formula : | C18H11NS |
M.W : | 273.35 |
SMILES Code : | C1(NC2=C3C=CC=C2)=C3C4=C(C5=CC=CC=C5S4)C=C1 |
MDL No. : | MFCD22571687 |
InChI Key : | NPHLAWPEXYBGTP-UHFFFAOYSA-N |
Pubchem ID : | 66585208 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 20 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 88.69 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
6.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.89 |
Solubility | 0.000351 mg/ml ; 0.00000129 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.43 |
Solubility | 0.000101 mg/ml ; 0.00000037 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.58 |
Solubility | 0.00000721 mg/ml ; 0.0000000264 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) |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-3.89 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 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.24 |
* 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 |
---|---|---|
90% | for 10 h; Reflux | General procedure: 4-(2-Nitrophenyl)dibenzo[b,d]furan (10.00 g, 34.57 mmol) wasdissolved in triethylphosphite (100 mL) and refluxed for 10 h. Thereaction mixture was cooled to room temperature and extractedwith ethyl acetate and distilled water. The organic layer was treatedwith anhydrous magnesium sulfate, and the solvent was removedby rotary evaporation. Impurities were removed by column chromatographyon silica gel using dichloromethane/n-hexane toobtain a yellowish powder. The results are as follows: |
78.19% | at 150℃; for 7 h; | Compound 2-1 (10g, 32.74mmol) was mixed with triethylphosphite 100mL, and stirred at 150°C for 7 hours. The mixture was cooled to room temperature and distilled under reduced pressure. Subsequently, recrystallization was conducted using EA, yielding Compound 2-2 (7g, 25.60mmol, 78.19percent). |
78.19% | at 150℃; for 7 h; | Compound 12-1 10g (32.74mmol) was mixed with triethylphosphite 100ml, and then the mixture was stirred at 150 for 7 hours. The resultant material was cooled to room temperature, distilled under reduced pressure, and recrystallized with EA, thereby obtaining Compound 12-2 7g (25.60mmol, 78.19percent). |
77.6% | With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Inert atmosphere; Heating | 500mL of the round bottom flask in a nitrogen atmosphere in M-22 (14.0 g, 45.8 mmol), triphenylphosphine (36 g, 137.5 mmol) dissolved in dichlorobenzene and then to 160 ° C at the 24-hour stirring was dongan.After the reaction the reaction was cooled to room temperature, the dichlorobenzene was removed under reduced pressure. The reaction of methylene chloride / hexane (1: 1) and purified over a silica column with a mixed solvent Kell intermediate M-23 9.7 g (Yield: 77.6percent) was obtained. |
76% | at 180℃; for 5 h; Inert atmosphere | Intermediate I-36 (140 g, 458 mmol) was dissolved in 0.7 L of triethylphosphite in a nitrogen atmosphere,And the mixture was refluxed by heating at 180 DEG C for 5 hours. After completion of the reaction, water is added to the reaction solution After precipitation, it was filtered. The residue thus obtained was purified by flash column chromatographyTo obtain Intermediate I-37 (95.1 g, 76percent). |
71.13% | With triethyl phosphite In 1,2-dichloro-benzene at 150℃; for 5 h; | After mixing compound 3-1 (11 g, 36.02 mmol), P(OEt)3 (100 mL) and 1,2-dichlorobenzene (100 mL), the reaction mixture was stirred at 150°C under reflux. After 5 hours, the reaction mixture was cooled to room temperature, was distillated under reduced pressure, and was filtered through column to obtain compound 3-2 (7 g, 25.60 mmol, 71.13 percent). |
70% | at 90℃; for 12 h; | After mixing compound 2-1 (88 g, 0.29 mol), P(OEt)3 (960 mL, 0.4 M) and triethylphosphite (960 mL), the reaction mixture was stirred for 12 hours at 90°C. After terminating the reaction, the reaction mixture was distilled to remove triethylphosphite, and was filtered through column to obtain compound 2-2 (40 g, 70 percent) |
70% | at 150℃; for 6 h; | After adding compound C-2-1 (88 g, 0.29 mol) to P(OEt)3 (960 mL, 0.4 M), the mixture was stirred for 6 hours at 150°C. After completing the reaction, P(OEt)3 was removed by distillation, and then the remaining product was separated with a column to obtain, white solid, compound C-2-2 (40 g, 70 percent). |
61% | With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Reflux | Dissolve the intermediate C and triphenylphosphine obtained in step 3) in o-dichlorobenzene, was refluxed for 24 hours. After the reaction was completed after using a reduced pressure distillation to remove the solvent, and the concentrated product was separated by column chromatography to obtain the desired intermediate D (yield: 61percent). |
61% | With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Reflux | The intermediate B obtained from the previous step, and triphenylphosphine were dissolved in o-DCB(o-dichlorobenzene), followed by reflux for 24 hours. After the completion of the reaction, vacuum distillation was carried out for removal of a solvent. Then, the concentrated product was purified by column chromatography to give a required intermediate C (yield: 61percent). |
60% | With triphenylphosphine In 1,2-dichloro-benzene at 180℃; | Sub 1-3 (1) (30.5g, 100 mmol), PPh3 (65.5g, 250mmol), after loading the 1,2-dichlorobenzene (500ml) and the reaction proceeds at 180 . After completion of reaction, drying after the removal of 1,2-dichlorobenzene and the organic layer was extracted with water and CH2Cl2 over MgSO4, silicagel column and re-crystallization and the resulting organic material and then concentrated to give 16.4g of Sub 1 (1). (Yield: 60percent) |
56% | With triethyl phosphite In 1,2-dichloro-benzene for 13 h; Reflux | Compound H-2-2 (74.8 g, 245.0 mmol), triethylphosphite [P(OEt)3] (500.0 mL) and 1,2-dichlorobenzene (1,2-DCB) (200.0 mL) were reflux stirred in a 1L RBF. After 13 hours, the solvent was distilled, and the solid was dissolved in CHCl3and was separated through column chromatography on silica gel to obtain compound H-2-3 (38.0 g, 56 percent) |
45% | With triphenylphosphine In 1,2-dichloro-benzene at 185℃; for 20 h; | Intermediate D 13.7g (44.9mmol), in addition triphenylphosphine 29.4g the (112mmol) in o-dichlorobenzene 200ml, and the mixture was stirred at 185° C 20 hours. The solvent was distilled off under reduced pressure, a solid precipitated by addition of methanol was collected by filtration, by heating suspension washing by adding toluene to yield intermediate E 5.5g (45percent yield) |
6 g | for 12 h; Reflux | Compound 31-1 (8 g), triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 ml) were placed in a 250 ml three-necked round bottom flask, and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. Column separation using a dichloromethane and hexane mixed solvent was carried out on the substance produced by concentration to obtain 6 g of the title compound. |
6 g | for 12 h; Reflux | A 250 mL three-necked round bottom flask was charged with 8 g of compound 31-1, Triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 mL) were added and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. The material formed by concentration was dissolved in dichloromethane, 6 g of the title compound was obtained by column separation using a hexane mixed solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethyl phosphite; for 10h;Reflux; | General procedure: 4-(2-Nitrophenyl)dibenzo[b,d]furan (10.00 g, 34.57 mmol) wasdissolved in triethylphosphite (100 mL) and refluxed for 10 h. Thereaction mixture was cooled to room temperature and extractedwith ethyl acetate and distilled water. The organic layer was treatedwith anhydrous magnesium sulfate, and the solvent was removedby rotary evaporation. Impurities were removed by column chromatographyon silica gel using dichloromethane/n-hexane toobtain a yellowish powder. The results are as follows: |
78.19% | With triethyl phosphite; at 150℃; for 7h; | Compound 2-1 (10g, 32.74mmol) was mixed with triethylphosphite 100mL, and stirred at 150C for 7 hours. The mixture was cooled to room temperature and distilled under reduced pressure. Subsequently, recrystallization was conducted using EA, yielding Compound 2-2 (7g, 25.60mmol, 78.19%). |
78.19% | With triethyl phosphite; at 150℃; for 7h; | Compound 12-1 10g (32.74mmol) was mixed with triethylphosphite 100ml, and then the mixture was stirred at 150 for 7 hours. The resultant material was cooled to room temperature, distilled under reduced pressure, and recrystallized with EA, thereby obtaining Compound 12-2 7g (25.60mmol, 78.19%). |
77.6% | With triphenylphosphine; In 1,2-dichloro-benzene; for 24h;Inert atmosphere; Heating; | 500mL of the round bottom flask in a nitrogen atmosphere in M-22 (14.0 g, 45.8 mmol), triphenylphosphine (36 g, 137.5 mmol) dissolved in dichlorobenzene and then to 160 C at the 24-hour stirring was dongan.After the reaction the reaction was cooled to room temperature, the dichlorobenzene was removed under reduced pressure. The reaction of methylene chloride / hexane (1: 1) and purified over a silica column with a mixed solvent Kell intermediate M-23 9.7 g (Yield: 77.6%) was obtained. |
76% | With triethyl phosphite; at 180℃; for 5h;Inert atmosphere; | Intermediate I-36 (140 g, 458 mmol) was dissolved in 0.7 L of triethylphosphite in a nitrogen atmosphere,And the mixture was refluxed by heating at 180 DEG C for 5 hours. After completion of the reaction, water is added to the reaction solution After precipitation, it was filtered. The residue thus obtained was purified by flash column chromatographyTo obtain Intermediate I-37 (95.1 g, 76%). |
71.13% | With triethyl phosphite; In 1,2-dichloro-benzene; at 150℃; for 5h; | After mixing compound 3-1 (11 g, 36.02 mmol), P(OEt)3 (100 mL) and 1,2-dichlorobenzene (100 mL), the reaction mixture was stirred at 150C under reflux. After 5 hours, the reaction mixture was cooled to room temperature, was distillated under reduced pressure, and was filtered through column to obtain compound 3-2 (7 g, 25.60 mmol, 71.13 %). |
70% | With triethyl phosphite; at 90℃; for 12h; | After mixing compound 2-1 (88 g, 0.29 mol), P(OEt)3 (960 mL, 0.4 M) and triethylphosphite (960 mL), the reaction mixture was stirred for 12 hours at 90C. After terminating the reaction, the reaction mixture was distilled to remove triethylphosphite, and was filtered through column to obtain compound 2-2 (40 g, 70 %) |
70% | With triethyl phosphite; at 150℃; for 6h; | After adding compound C-2-1 (88 g, 0.29 mol) to P(OEt)3 (960 mL, 0.4 M), the mixture was stirred for 6 hours at 150C. After completing the reaction, P(OEt)3 was removed by distillation, and then the remaining product was separated with a column to obtain, white solid, compound C-2-2 (40 g, 70 %). |
61% | With triphenylphosphine; In 1,2-dichloro-benzene; for 24h;Reflux; | Dissolve the intermediate C and triphenylphosphine obtained in step 3) in o-dichlorobenzene, was refluxed for 24 hours. After the reaction was completed after using a reduced pressure distillation to remove the solvent, and the concentrated product was separated by column chromatography to obtain the desired intermediate D (yield: 61%). |
61% | With triphenylphosphine; In 1,2-dichloro-benzene; for 24h;Reflux; | The intermediate B obtained from the previous step, and triphenylphosphine were dissolved in o-DCB(o-dichlorobenzene), followed by reflux for 24 hours. After the completion of the reaction, vacuum distillation was carried out for removal of a solvent. Then, the concentrated product was purified by column chromatography to give a required intermediate C (yield: 61%). |
60% | With triphenylphosphine; In 1,2-dichloro-benzene; at 180℃; | Sub 1-3 (1) (30.5g, 100 mmol), PPh3 (65.5g, 250mmol), after loading the 1,2-dichlorobenzene (500ml) and the reaction proceeds at 180 . After completion of reaction, drying after the removal of 1,2-dichlorobenzene and the organic layer was extracted with water and CH2Cl2 over MgSO4, silicagel column and re-crystallization and the resulting organic material and then concentrated to give 16.4g of Sub 1 (1). (Yield: 60%) |
58% | With triphenylphosphine; In 1,2-dichloro-benzene; at 180℃; for 12h; | 20 g (65.49 mmol) of the intermediate compound [90-1], 51.5 g (196.49 mmol) of triphenyl phosphine, and 200 mL of 1,2-dichlorobenzene were stirred in a 500 mL reaction flask at 180 C. for 12 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and then 1,2-dichlorobenzene was distilled under reduced pressure. The organics produced by distillation under reduced pressure were separated through column chromatography, and then recrystallized with dichloromethane and metalol to obtain 10.3 g (58%) of an intermediate compound [90-2]. |
56% | With triethyl phosphite; In 1,2-dichloro-benzene; for 13h;Reflux; | Compound H-2-2 (74.8 g, 245.0 mmol), triethylphosphite [P(OEt)3] (500.0 mL) and 1,2-dichlorobenzene (1,2-DCB) (200.0 mL) were reflux stirred in a 1L RBF. After 13 hours, the solvent was distilled, and the solid was dissolved in CHCl3and was separated through column chromatography on silica gel to obtain compound H-2-3 (38.0 g, 56 %) |
45% | With triphenylphosphine; In 1,2-dichloro-benzene; at 185℃; for 20h; | Intermediate D 13.7g (44.9mmol), in addition triphenylphosphine 29.4g the (112mmol) in o-dichlorobenzene 200ml, and the mixture was stirred at 185 C 20 hours. The solvent was distilled off under reduced pressure, a solid precipitated by addition of methanol was collected by filtration, by heating suspension washing by adding toluene to yield intermediate E 5.5g (45% yield) |
6 g | With triphenylphosphine; for 12h;Reflux; | Compound 31-1 (8 g), triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 ml) were placed in a 250 ml three-necked round bottom flask, and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. Column separation using a dichloromethane and hexane mixed solvent was carried out on the substance produced by concentration to obtain 6 g of the title compound. |
6 g | With triphenylphosphine; for 12h;Reflux; | A 250 mL three-necked round bottom flask was charged with 8 g of compound 31-1, Triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 mL) were added and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. The material formed by concentration was dissolved in dichloromethane, 6 g of the title compound was obtained by column separation using a hexane mixed solvent. |
6 g | With triphenylphosphine; In 1,2-dichloro-benzene; for 12h;Reflux; | Compound 31-1 (8 g), triphenylphosphine (20.6 g), 1,3-dichlorobenzene (56 mL) were added to a 250 mL three-necked round bottom flask, and the mixture was stirred under reflux for 12 hours. The solvent was removed by concentration under reduced pressure. The resulting material was concentrated to give 6 g of the title compound through column separation using a mixed solvent of dichloromethane and hexane. |
With triphenylphosphine; In 1,2-dichloro-benzene; for 12h;Inert atmosphere; Reflux; | Protect with N2, add 35g (100mmol) M1, add 17.7g triphenylphosphine (100mmol), 1000ml o-dichlorobenzene, heat and reflux for 12h, complete the reaction, evaporate the solvent, and silica gel column chromatography to obtain M2 intermediate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.19% | With triethyl phosphite; In 1,2-dichloro-benzene; at 150℃; for 12h; | General procedure: After mixing compound 1-1(47 g, 0.16 mol), triethylphosphite 600mL, and1,2-dichlorobenzene 300 mL, the reactant mixture was heated to 150C and stirred for12 hours. After the reaction is completed, unreacted triethylphosphite and1 ,2-dichlorobenzene were removed using a distillation apparatus. The remainingmixture was washed with distilled water, and extracted with EA. The extracted organiclayer was dried with anhydrous MgSO4, and the solvent was removed with a rotaryevaporator. The residue was purified by column chromatography to obtain compound1-2 (39 g, 81%). |
78.19% | With triethyl phosphite; In 1,2-dichloro-benzene; at 150℃; for 12h; | General procedure: Preparation of compound 1-2[94]After mixing compound 1-1 (47.0 g, 0.16 mol), triethyl phosphite (600.0 mL), and 1,2-dichlorobenzene (300.0 mL), the mixture was stirred for 12 hrs while heating to 150C. Upon completing the reaction, unreacted triethyl phosphite and 1,2-dichlorobenzene were removed by using a distillation equipment. The residue was rinsed with distilled water and extracted with EA, and the organic layer was dried with anhydrous MgSO4. After removing the solvent by using a rotary evaporator, the obtained product was purified through column chromatography to obtain compound 1-2 (39.0 g, 81 %). |
65% | With triphenylphosphine; In N,N-dimethyl acetamide; for 20h;Inert atmosphere; Reflux; | General procedure: In an argon atmosphere, 166 ml of dimethylacetamide was added to a mixture of 24.0 g (83.0 mmol) of intermediate 2-4 and 54.4 g (207.4 mmol) of triphenylphosphine. The resultant mixture was stirred for 20 h while refluxing under heating. [0173] After the reaction, the mixture was cooled to room temperature. The reaction product was added with 400 ml of water and extracted with dichloromethane in a separatory funnel. The organic layer was dried over MgSO4, filtered and concentrated. The concentrate was purified by silica gel column chromatography, to obtain 14.5 g of white solid, which was identified as the following intermediate 2-5 by FD-MS analysis (yield: 68%). |
With triphenylphosphine; In 1,2-dichloro-benzene; at 180℃; for 12h; | General procedure: Weigh 0.01mol of intermediate a1 in 100mL of o-dichlorobenzene, add 1 × 10-4mol of triphenylphosphine, and react at 180 C for 12h. After the reaction is completed, cool to room temperature, filter, and spin-filter the filtrate. The residue was passed through a silica gel column to obtain intermediate II-1; HPLC purity of intermediate II-1 was 99.82%, yield 76.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 12h; | After dissolving compound 2-2 (5 g, 18.29 mmol) and compound 3-3 (7.8 g, 21.94 mmol) in DMF (150 mL), NaH (1.09 g, 27.43 mmol, 60 % in mineral oil) was slowly added to the mixture, and was stirred for 12 hours at room temperature. And then, MeOH was added to the reaction mixture. The obtained solid was filtered under reduced pressure, and was recrystallized with EA and DMF to obtain compound C-105 (6.5 g, 60 %).[120]MS/FAB found 593; calculated 592.71 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | After dissolving NaH 60 % (0.9 g, 0.02 mol) in DMF (50 mL), the solution was stirred. After dissolving compound 2-2 (4.69 g, 0.017 mol) in DMF (20 mL), the solution was added to the NaH solution, and was stirred for 1 hour. After dissolving compound 1-3 (6.1 g, 0.017 mol) in DMF (100 mL), the solution was stirred. And then, the mixed solution of compound 2-2 was added to the mixed solution of compound 1-3, and was stirred for 12 hours. After terminating the reaction, the obtained yellow solid was filtered, and was recrystallized to obtain compound C-94 (3 g, 30 %).[109]MS/FAB found 593; calculated 592.71 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.74% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 12h; | After dissolving compound 3-2 (3.5 g, 12.83 mmol) and compound 2-1 (4 g, 11.66 mmol) in DMF (150 mL), 60% NaH in mineral oil (0.7 g, 17.50 mmol) was slowly added to the mixture, and was stirred for 12 hours at room temperature. After terminating the reaction, distilled water was added to the reaction mixture. The obtained solid was filtered under reduced pressure, and the obtained solid was washed with EA, DMF and THF sequentially, to obtain compound C-88 (3.7 g, 49.74 %).[139]MS/FAB found 580; calculated 579.71 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydride; In tetrahydrofuran; for 4h; | After dissolving 2,4,6-trichloro-1,3,5-triazine (43.5 g, 236 mmol) in THF (230 mL), the reaction mixture was stirred at -78C (reaction mixture A). After dissolving compound 3-2 (22 g, 79 mmol) in THF (150 mL), the reaction mixture was putted into NaH (4.7 g, 118 mmol) (reaction mixture B). After putting reaction mixture B into reaction mixture A slowly, the reaction mixture was stirred for 4 hours. After stirring, distilled water (500 mL) was added slowly, and was stirred for 30 minutes. The obtained solid was filtered through column chromatography and recrystallized to obtain compound 3-3 (31 g, 92 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.74% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; for 15h;Reflux; | After mixing compound 3-2 (30 g, 109.7 mmol), 4-bromoiodobenzene (62 g, 219.4 mmol), CuI (20.9 g, 109.7 mmol), ethylenediamine (14.7 mL, 219.4 mmol), K3PO4 (58 g, 274.3 mmol) and toluene (600 mL), the reaction mixture was stirred under reflux. After 15 hours, the reaction mixture was cooled to room temperature, CuI and K3PO4 was removed by filtering under reduced pressure. The remaining solution was washed with distilled water, was extracted with MC. The obtained organic layer was dried with MgSO4, was filtered, was distillated under reduced pressure to remove the solvent, and was filtered through column to obtain compound 10-1 (37 g, 78.74 %). |
49% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; at 120℃; | After mixing <strong>[1255308-97-4]5H-[1]benzothieno[3,2-c]carbazole</strong> (10 g, 36.6 mmol), iodo-4-bromobenzene (20 g, 73.2 mmol), CuI (3.5 g, 18.3 mmol), EDA (4.5 mL, 73.2 mmol), K3PO4 (19.4 g, 91.5 mmol), and toluene 200 mL, the mixture was stirred at 120C overnight. After completing the reaction, the mixture was washed with distilled water, and then extracted with EA. The organic layer was dried with MgSO4, and solvent was removed with a rotary evaporator. Then, the remaining product was purified by column chromatography using MC and hexane as developing solvents to obtain compound 6-1 (7.7 g, 49 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.25% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 12h; | After dissolving compound 1-5 (10.5 g, 27.44 mmol) and compound 3-2 (5 g, 18.29 mmol) in DMF (100 mL), 60% NaH in mineral oil (1.08 g, 27.44 mmol) was slowly added to the mixture, and was stirred for 12 hours at room temperature. After terminating the reaction, distilled water was added to the reaction mixture. The obtained solid was filtered under reduced pressure, and the obtained solid was dissolved in CHCl3, and was filtered through column to obtain compound C-87 (7.5 g, 67.25 %).[134]MS/FAB found 620; calculated 619.78 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | After mixing <strong>[1255308-97-4]5H-[1]benzothieno[3,2-c]carbazole</strong> (8.8 g, 40.5 mmol) and DMF 180 mL, NaH (1.9 g, 60% dispersion in mineral oil, 49 mmol) was added to the mixture while stirring, and then the mixture was stirred for 30 minutes. Then, a solution in which compound 5-1 (11 g, 16.5 mmol) dissolved in DMF 20 mL, was slowly added dropwise to the reaction mixure. Then, the mixture was stirred for 4 hours at room temperature. After completing the reaction, the mixture was washed with distilled water, and then extracted with EA. The organic layer was dried with MgSO4, and solvent was removed with a rotary evaporator. Then, the remaining product was purified by column chromatography using MC and hexane as developing solvents to obtain, yellow solid, compound 5-2 (19 g, 100 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.7% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; for 12h; | After dissolving compound C-2-2 (5 g, 18.29 mmol), and compound C-2-5 (7.5 g, 20.12 mmol) in DMF (200 mL), NaH (60 %, 1.09 g, 27.43 mmol) was added to the mixture. Then, the mixture was stirred for 12 hours, and then methanol was added to the mixture. Then, solid was filtered, and then the remaining product was separated with a column to obtain compound C-60 (7 g, 62.7 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; at 120℃; for 22h; | After mixing compound 1-4 (2-bromo-7,7-dimethyl-5-phenyl-indeno[2,1-b]carbazole) (7.5 g, 17 mmol), compound 3 (<strong>[1255308-97-4]5H-benzothiopheno[3,2-c]carbazole</strong>) (4.3 g, 15.5 mmol), CuI (1.5 g, 7.9 mmol), ethylenediamine (2 mL, 31 mmol), K3PO4 (10 g, 47 mmol) and toluene 90 mL in a 250 mL RBF, the mixture was stirred at 120C for 22 hours. The reaction mixture was worked up by EA/H2O, then the moisture was removed with MgSO4, and then distilled under reduced pressure. The crude product was purified by column chromatography with MC:hexane (Hx), and then recrystallized in toluene to obtain 5.7 g of white solid compound C-17 (58 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | NaH (60% in mineral oil) 3.3 g (83.90 mmol) was diluted in DMF 10 mL. Compound 12-2 18.3 g(67.12 mmol) was dissolved in DMF 60 mL, and this solution was added into the above reaction solution, followed by stirring for 1 hour. 2,4-Dichloropyrimidine 10g(67.12mmol) was dissolved in DMF 60 mL, and this solution was added into the above reaction solution. The resultant material was stirred at room temperature for 4 hours, and then distilled water 40 mL was added thereinto. Then, extraction with EA, wash with distilled water and aqueous NaCl solution, drying over MgSO4, distillation under reduced pressure, and purification using column chromatography were sequentially performed, thereby obtaining Compound 12-3 5.4 g (14.0mmol, 21 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 100℃; | To a round bottom flask Sub 1 (1) (5.4g, 20mmol), Sub 2 (1a) (7.1g, 24mmol), Pd2 (dba) 3 (0.3g, 0.6mmol), P (t-Bu) 3 (0.2 g, 2mmol), t-BuONa (5.8g, 60mmol), and the reaction allowed to proceed at 100 after the into toluene (300mL). Then when the reaction is complete the organic layer was dried and extracted with water and CH2Cl2 over MgSO4, concentrated and the resulting organic silicagel column and recrystallized to obtain 8.3g of 2-1. (Yield: 78%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With copper(l) chloride; potassium hydroxide; In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 48h;Inert atmosphere; | 250mL round bottom flask in a nitrogen atmosphere under the M-23 (9.7g, 35.4 mmol), bromobenzene (11.1 g, 70.9 mmol), copper chloride (1.6g, 17.4 mmol), potassium hydroxide (20g, 356.4 mmol) the stirring for 48 hours at 150 C and then dissolved in xylene and then 100 down the reaction to room temperature and remove the xylene under reduced pressure. And then the remaining solid was dissolved in methylene chloride and washed with water several times and remove the water over anhydrous magnesium sulfate, and filtrated to remove the solvent. Removing the solvent and then the nucleic acid / methylene chloride (1: 2) over silica gel column with a solvent to obtain the title compound M-24 11 g (89%). |
With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; In toluene; at 100℃; for 3.5h; | In the reaction flask, 21.8 g (100 mmol) of M2 was added,2-bromonaphthalene 16.5g (110mmol), Pd2 (dba) 3 0.9g (0.785mmol, 0.5%),1500 ml of toluene and 43.3 g (314 mmol) of potassium carbonate were reacted at 100 C for 3.5 h.When the reaction is complete, stop the reaction. After cooling to room temperature and filtering, the obtained solid was purified by recrystallization from toluene to obtain yellow powder M3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium phosphate; copper(l) iodide; (S,S)-1,2-diaminocyclohexane; In 1,4-dioxane; for 48h;Inert atmosphere; Reflux; | Under an argon atmosphere, intermediate F 5.9g (10mmol), Intermediate E 3.0g (11mmol), copper iodide 1.9g (10mmol), trans-1,2-cyclohexanediamine 1.1 g (10 mmol), tricalcium phosphate potassium 4.2g of (20 mmol) was added to the dehydrated 1,4-dioxane 30 ml, and stirred heated to reflux for 48 hours. Reaction solution to the residue obtained was concentrated under reduced pressure, the addition of toluene 300ml was heated to 120 , and insoluble matters were filtered off. By purifying the residue obtained by concentrating the filtrate under reduced pressure by silica gel column chromatography (hexane / toluene = 3/1) to yield intermediate G 3.9g (65% yield) as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 6h; | The intermediate C obtained from the previous step, 4-bromobiphenyl, Pd2(dba)3, P(tBu)3, and NaOtBu were dissolved in a toluene solvent, followed by reflux for 6 hours at 110 C. After the completion of the reaction, the reaction product was subjected to vacuum filtration through celite and silica gel by using a hot toluene solvent. The temperature was cooled to room temperature, and the deposited product was recrystallized again by toluene and acetone so as to give a required compound 1-3 (yield: 70%). |
65% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 6h; | Intermediate D and bromobiphenyl, Pd2 (dba) 3, P (tBu) 3, and was dissolved NaOtBu in toluene solvent synthesized, and stirred for 6 hours at 110C . After the reaction was terminated by extraction with sikhim the temperature of the reaction to room temperature and CH2Cl2 was wiped with water. Removed a small amount of water over anhydrous MgSO4, and then filtered under reduced pressure, the organic solvent was concentrated and the resulting product was greater column Using the Roman chromatography to give the desired compound 4 (yield: 65%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 6h; | Step 4) Intermediate D and 4,4'-dibromobiphenyl, Pd2(dba)3, P(tBu)3 was dissolved and NaOtBu in toluene solvent in the synthesis, was stirred for 6 hours at 110 C . After the reaction was terminated by extraction with cooling, the temperature of the reaction to room temperature and CH2Cl2 was wiped with water. Removed a small amount of water over anhydrous MgSO4, and then filtered under reduced pressure, the product was concentrated to produce an organic solvent, purified by column chromatography to obtain the desired compound 56 (yield: 52%). |
Tags: 1255308-97-4 synthesis path| 1255308-97-4 SDS| 1255308-97-4 COA| 1255308-97-4 purity| 1255308-97-4 application| 1255308-97-4 NMR| 1255308-97-4 COA| 1255308-97-4 structure
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