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CAS No. : | 6267-02-3 | MDL No. : | MFCD00030130 |
Formula : | C15H15N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JSEQNGYLWKBMJI-UHFFFAOYSA-N |
M.W : | 209.29 | Pubchem ID : | 22647 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.2 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 71.43 |
TPSA : | 12.03 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -4.5 cm/s |
Log Po/w (iLOGP) : | 2.45 |
Log Po/w (XLOGP3) : | 4.34 |
Log Po/w (WLOGP) : | 3.69 |
Log Po/w (MLOGP) : | 3.74 |
Log Po/w (SILICOS-IT) : | 3.81 |
Consensus Log Po/w : | 3.61 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -4.43 |
Solubility : | 0.00783 mg/ml ; 0.0000374 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -4.31 |
Solubility : | 0.0103 mg/ml ; 0.0000493 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -6.01 |
Solubility : | 0.000206 mg/ml ; 0.000000984 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 2.49 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
98% | With phosphoric acid In water at 35℃; for 2 h; | A mixture of 2-(2-(phenylamino)phenyl)propan-2-ol (3, 1.0 g, 4.5 moles) in 85.0percent> phosphoric acid (15 ml) was stirred at 35 °C for 2h until judged complete by TLC. The reaction mixture was then poured onto crushed ice and the precipitate was filtered, washed with water, and dried to afford the title compound (0.90 g, 98percent> yield) as a white powder. 1H NMR (300 MHz, CDC13) δ 7.39 (d, 2H, J = 8.1 Hz), 7.11 (t, 2H, J = 7.2 Hz), 6.92 (t, 2H, J = 7.2 Hz), 6.71 (d, 2H, J = 7.8 Hz), 6.15 (br s, 1H), 1.61 (s, 6H); LCMS (ESI) m/z 210 (MH+). |
98% | at 35℃; for 2 h; | To a 50 ml one-necked flask was added lg (4.5 mmol) of compound B2, 15 ml (85percent) of phosphoric acid, and stirred at 35 ° C for two hours. The mixture was then poured into 50 ml of ice water to precipitate a solid.After suction filtration, washing with water repeatedly gave 0.98 g of product 83, yield 98percent. |
90% | at 20℃; for 16 h; | 160 mL of an excess amount of phosphoric acid as a solvent was added to Compound 1C(3.26 g, 14.37 mmol), and the mixture was stirred at room temperature. After stirring for 16 hours or longer, 200 to 250 mL of distilled water was slowly added. Thereafter, the mixture was stirred for 0.5 to 1 hour, and a precipitated solid was filtered. An organic layer was extracted from the filtered solid using an aqueous sodium hydroxide solution and a dichloromethane solvent. The extracted organic layer was dehydrated using magnesium sulfate and the remaining organic solvent was removed to obtain a white solid 1D(2.7 g, yield 90percent). |
87% | Stage #1: at 20℃; for 12 h; |
Preparation of Compound 1-3 [99] After Compound 1-2 (80 g, 0.35 mol) was added to H3PO4 (1.7 L), the mixture was stirred for 12 hours at room temperature. Upon completion of the reaction, the reaction mixture was neutralized with distilled water and the produced solid was filtered while being washed with water. The solid was dissolved with dichloromethane, extracted and neutralized with NaOH. After drying an organic layer with MgSO4 and removing a solvent by the rotary type evaporator, Compound 1-3 (64 g, 87percent) was obtained via recrystallization with hexane. |
87% | Stage #1: at 20℃; for 12 h; Stage #3: With sodium hydroxide In dichloromethane |
Compound 3-2 (80g, 0.35mol) was added to H3PO4 1.7L and the mixture was stirred at room temperature for 12 hours. After termination of the reaction, the mixture was neutralized with distilled water, and the produced solid was washed with water and filtered. The solid was dissolved in dichloromethane, extracted, and neutralized with NaOH. The organic layer was dried with anhydrous MgSO4, and the solvent was removed using a rotary evaporator. Subsequently recrystallization was conducted using hexane, yielding Compound 3-3 (64g, 87percent). |
87% | at 20℃; for 12 h; | 80 g (0.35 mole) of the compound obtained in the previous step was added to 1.7L of phosphoric acid and the mixture was stirred for 12 hours at room temperature. Upon completion of the reaction, the reaction mixture was neutralized with distilled water and the produced solid was filtered while being washed with water. The solid was dissolved in dichloromethane, extracted and neutralized with sodium hydroxide. After drying the organic layer with magnesium sulfate and removing the solvent by a rotary type evaporator, 64 g 9,9-dimethyl-9,10-dihydroacridine (87percent) was obtained via recrystallization in hexane. |
87% | at 35℃; for 2 h; | To a flask charged with 2-(2-(phenylamino)phenyl)propan-2-ol (5.00 g, 22.0 mmol) was added phosphoric acid (85percent, 76 mL). The reaction was stirred and heated to 35 °C. After 2 h, the crude reaction mixture was cooled to room temperature and slowly poured onto ice. The mixture was extracted with dichloromethane. The combined organic layers were washed with water and brine. The 10 washed organic layer was dried over Na2S04, filtered and concentrated. The resulting solid product, afforded in 87percent yield, was used without further purification. |
69% | at 20℃; Inert atmosphere | In N2in the gas purification system, the use of a compound "c" (33.1mmol) is added to the excess phosphoric acid solvent (160 ml) in, and the stirring solution at room temperature. The solution and then stirring 16 hours or more, and distilled water is slowly added (200 to 250 ml). Stirring the solution 0.5 to 1 hours, and the precipitated solid filter. The filtering of the solid using aqueous sodium hydroxide solution and dichloromethane solvent extraction. From the extraction of using magnesium sulphate remove the moisture in the organic layer, and removing the organic solvent, so as to obtain a white solid compound "d". (Yield: 69percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | at 0℃; | 20.0 g (88.00 mmol) of the intermediate (A) synthesized in the above step 1 was suspended in terrahydrofuran (293 ml), and then 102.7 ml of methylmagnesium bromide (3M) was slowly added dropwise at 0 ° C. After completion of the reaction, the reaction solution was extracted with dichloromethane and distilled under reduced pressure. 100 ml of sulfuric acid diluted to 10percent in distilled water was added to the distillation product, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was extracted with dichloromethane and distilled water, and the organic layer was subjected to silica gel filtration. The organic solution was removed and recrystallized from dichloromethane and hexane to obtain 15.0 g (yield: 81percent) of the intermediate product (B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 20℃; for 5 h; | 15 g of 2-isopropyl-N-phenylaniline obtained in Preparation Example 3 was placed in a round bottom three-necked flask,Concentrated sulfuric acid was added dropwise at room temperature and the mixture was stirred.After completion of the dropwise addition,The mixture was further stirred at room temperature for 5 hours. then,The organic layer was washed with ethyl acetate and water, extracted, concentrated and separated by column,9,9-dimethyl-9,10-dihydroacridine (13.4 g, 90percent yield) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bromine In chloroform for 8 h; Inert atmosphere | Under a nitrogen atmosphere (N2 purging), Compound 1D(2.7 g, 12.93 mmol) was added to chloroform(200ml), followed by stirring. After stirring, 3 equivalents of bromine were slowly added dropwise. After 8 hours, the reaction was quenched by addition of an aqueous sodium thiosulfate solution. Then, extraction was performed. Thereafter, purification was performed using a column using a developing solvent of methylenechloride(MC):hexane (1:5) to obtain a white solid 1E(4.24 g, yield 90percent). |
69% | With phenyltrimethylammonium tribromide In tetrahydrofuran at 20℃; | To a stirred solution of 9,9-dimethyl- 10H- acridine (4, 0.50 g, 2.4 mmol) in dry THF (10 mL), was added trimethylphenylammonium tribromide (PTT) (1.8 g, 4.8 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After the reaction was judged complete (TLC), the reaction mixture was poured in water (30 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were dried over anhydrous MgS04, filtered and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with gradient elution (0 to 30percent EtOAc-hexane) to afford the title compound as a light brown oil (0.6 g, 69percent yield). 1H NMR (300 MHz, DMSO- 6) δ 1.47 (s, 6 H) 6.74 (d, J=8.48 Hz, 2 H) 7.22 (dd, J=8.48, 2.26 Hz, 2 H) 7.46 (d, J=2.07 Hz, 2 H) 9.18 (s, 1 H). LCMS (ESI) m/z 368 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium carbonate at 180℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With phosphoric acid; In water; at 35℃; for 2h; | A mixture of 2-(2-(phenylamino)phenyl)propan-2-ol (3, 1.0 g, 4.5 moles) in 85.0%> phosphoric acid (15 ml) was stirred at 35 C for 2h until judged complete by TLC. The reaction mixture was then poured onto crushed ice and the precipitate was filtered, washed with water, and dried to afford the title compound (0.90 g, 98%> yield) as a white powder. 1H NMR (300 MHz, CDC13) delta 7.39 (d, 2H, J = 8.1 Hz), 7.11 (t, 2H, J = 7.2 Hz), 6.92 (t, 2H, J = 7.2 Hz), 6.71 (d, 2H, J = 7.8 Hz), 6.15 (br s, 1H), 1.61 (s, 6H); LCMS (ESI) m/z 210 (MH+). |
98% | With phosphoric acid; at 35℃; for 2h; | To a 50 ml one-necked flask was added lg (4.5 mmol) of compound B2, 15 ml (85%) of phosphoric acid, and stirred at 35 C for two hours. The mixture was then poured into 50 ml of ice water to precipitate a solid.After suction filtration, washing with water repeatedly gave 0.98 g of product 83, yield 98%. |
98.7% | In tetrahydrofuran; at 25℃; for 3h;Molecular sieve; | Step 1) in the method for preparing 9,9-dimethylacridine in this example is the same as step 1) in Example 2. Step 2) is: 28g Hbeta molecular sieve is sequentially added to the reactor, and 2- ( 2- (phenylamino) phenyl) propane-2-ol (1.10kg, 4.59mol),5.37L THF, stirred at 25 C for 3h to fully mix the reaction, TLC determined the end of the reaction, filtered after the reaction, then recovered THF under reduced pressure, distilled off the residue and recrystallized with ethanol, then dried to obtain 9,9-dimethylformate The acridine was 0.97 kg, the purity was 92%, and the yield was 98.7%. |
90% | With phosphoric acid; at 20℃; for 16h; | 160 mL of an excess amount of phosphoric acid as a solvent was added to Compound 1C(3.26 g, 14.37 mmol), and the mixture was stirred at room temperature. After stirring for 16 hours or longer, 200 to 250 mL of distilled water was slowly added. Thereafter, the mixture was stirred for 0.5 to 1 hour, and a precipitated solid was filtered. An organic layer was extracted from the filtered solid using an aqueous sodium hydroxide solution and a dichloromethane solvent. The extracted organic layer was dehydrated using magnesium sulfate and the remaining organic solvent was removed to obtain a white solid 1D(2.7 g, yield 90%). |
87% | Preparation of Compound 1-3 [99] After Compound 1-2 (80 g, 0.35 mol) was added to H3PO4 (1.7 L), the mixture was stirred for 12 hours at room temperature. Upon completion of the reaction, the reaction mixture was neutralized with distilled water and the produced solid was filtered while being washed with water. The solid was dissolved with dichloromethane, extracted and neutralized with NaOH. After drying an organic layer with MgSO4 and removing a solvent by the rotary type evaporator, Compound 1-3 (64 g, 87%) was obtained via recrystallization with hexane. | |
87% | Compound 3-2 (80g, 0.35mol) was added to H3PO4 1.7L and the mixture was stirred at room temperature for 12 hours. After termination of the reaction, the mixture was neutralized with distilled water, and the produced solid was washed with water and filtered. The solid was dissolved in dichloromethane, extracted, and neutralized with NaOH. The organic layer was dried with anhydrous MgSO4, and the solvent was removed using a rotary evaporator. Subsequently recrystallization was conducted using hexane, yielding Compound 3-3 (64g, 87%). | |
87% | With phosphoric acid; at 20℃; for 12h; | 80 g (0.35 mole) of the compound obtained in the previous step was added to 1.7L of phosphoric acid and the mixture was stirred for 12 hours at room temperature. Upon completion of the reaction, the reaction mixture was neutralized with distilled water and the produced solid was filtered while being washed with water. The solid was dissolved in dichloromethane, extracted and neutralized with sodium hydroxide. After drying the organic layer with magnesium sulfate and removing the solvent by a rotary type evaporator, 64 g 9,9-dimethyl-9,10-dihydroacridine (87%) was obtained via recrystallization in hexane. |
87% | With phosphoric acid; at 35℃; for 2h; | To a flask charged with 2-(2-(phenylamino)phenyl)propan-2-ol (5.00 g, 22.0 mmol) was added phosphoric acid (85%, 76 mL). The reaction was stirred and heated to 35 C. After 2 h, the crude reaction mixture was cooled to room temperature and slowly poured onto ice. The mixture was extracted with dichloromethane. The combined organic layers were washed with water and brine. The 10 washed organic layer was dried over Na2S04, filtered and concentrated. The resulting solid product, afforded in 87% yield, was used without further purification. |
76% | With phosphoric acid; at 50℃; for 2.5h; | The compound 12? (95.0 g, 418 mmol) was dissolved in tetrahydroffiran (THF) (1,500 mE), and methylmagnesium bromide (3 M ether solution, 488 mE, 1.46 mol) was added dropwise thereto at room temperature. Afier the resultant was reacted for an hour at 500 C., water (500 mE) and 1 M hydrochloric acid (1,000 mE) were added thereto, and extraction was performed on the resultant by using ethylacetate. An oil layer was washed with water and saturated saline, and then the resultant was dried over sodium sulfate,filtered, and concentrated, thereby obtaining a compound 13?. The obtained compound 13? was dissolved in phosphoric acid (950 mE), and the resultant was reacted for 2.5 hours at50 C. Afier the resultant was returned to room temperature,water (1,000 mE) was added thereto, and the resultant was recrystallized from ethanol/hexane, thereby obtaining acompound 14? (66.4 g, yield: 76%). |
69% | With phosphoric acid; at 20℃;Inert atmosphere; | In N2in the gas purification system, the use of a compound "c" (33.1mmol) is added to the excess phosphoric acid solvent (160 ml) in, and the stirring solution at room temperature. The solution and then stirring 16 hours or more, and distilled water is slowly added (200 to 250 ml). Stirring the solution 0.5 to 1 hours, and the precipitated solid filter. The filtering of the solid using aqueous sodium hydroxide solution and dichloromethane solvent extraction. From the extraction of using magnesium sulphate remove the moisture in the organic layer, and removing the organic solvent, so as to obtain a white solid compound "d". (Yield: 69%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Under the protection of argon,Dissolve 12g of N-phenylanthranilic acid in 50mL of methanol solvent,And stir evenly at 450r/min,Get mixed solution;Heat the reaction system to 60C,To the above mixed solution at a rate of 20 drops/min,Add 7mL of thionyl chloride solution dropwise,After the dropwise addition, the system was kept at 60C and stirred for 12h.After the reaction, the solvent was removed by rotary evaporation,Add 60mL toluene and sodium bicarbonate aqueous solution for extraction,Combine the organic phases and dry with anhydrous magnesium sulfate,After spinning, column chromatography was performed with ethyl acetate/n-hexane as the eluent to obtain a yellow oil.Put 2g of the obtained yellow oil in 20mL of tetrahydrofuran,The system was cooled to -78C and 5mL of 3.0M methyl lithium was slowly added.The system was warmed to room temperature and stirred for 1 hour.After the reaction, quench with ice water,And extracted with ethyl acetate,The organic phase is dried over anhydrous sodium sulfate,After rotary evaporation, column chromatography with ethyl acetate/n-hexane as eluent gave a yellow oil.Then this oil was acidified with 85% phosphoric acid solution at a temperature of 50C,Quench with ice water,The precipitate was collected by filtration to obtain 9,9-dimethylacridine A as a white target product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene;Inert atmosphere; Reflux; | In a three ways flask 6.5 g of bromo-benzene (0.042 mol), 8.0 g of dimethyl acridine (0.038 mol) and 1 1.0 g of sodium tert.-butanoate (0.1 1 mol) were introduced. Everything was kept under inert atmosphere and the solids were dissolved in 190 ml of toluene. The catalyst was prepared in a 50 ml flask, by mixing 870 mg of Pd(dba)2 (1.5 mmol) and 3.0 ml of P(tBu)3 (3 mmol) in 30 ml of toluene. This catalyst solution was added to the reaction medium and the medium was warmed for one night at reflux. After complete conversion, the reaction medium was filtrated on a celite pad (diatomaceous earth), and the solvent was removed under vacuum. Purification using flash chromatography (Ch C /hexane) afforded 10.6 g of target compound (N-Phenyl-dimethylacridine) in 96 % yield. |
96% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene;Inert atmosphere; Reflux; | In a three ways flask 6.5 g of bromo-benzene (0.042 mol), 8.0 g of dimethyl acridine (0.038 mol) and 11.0 g of sodium ter-butanoate (0.11 mol) were introduced. Everything was kept under inert atmosphere and the solids were dissolved in 190 ml of toluene. The catalyst was prepared in a 50 ml flask, by mixing 870 mg of Pd(dba)2 (1.5 mmol) and 3.0 ml of P(tBu)3 (3 mmol) in 30 ml of toluene. This catalyst solution was added to the reaction medium and the medium was warmed for one night at reflux. After complete conversion, the reaction medium was filtrated on a celite pad (diatomaceous earth), and the solvent was removed under vacuum. Purification using flash chromatography (CH2CI2/hexane) afforded 10.6 g of target compound (N-Phenyl-dimethylacridine) in 96 % yield. |
81% | With tri-tert-butyl phosphine; sodium t-butanolate;palladium diacetate; In toluene; at 120℃; for 12h; | Preparation of Compound 1-4 [101] Compound 1-3 (64 g, 0.30 mol), bromobenzene (52.8 g, 0.33 mol), Pd(OAc)2 (1.37 g, 6.11 mmol), P(t-Bu)3 (50%, 7.3 mL, 15.28 mmol) and NaOt-Bu (58 g, 0.61 mol) were dissolved in toluen (1.2 L), and the mixture was stirred for 12 hours at 120 . Upon completion of the reaction, the reaction mixture was neutralized with distilled water and extracted with ethylacetate. After drying an organic layer with MgSO4 and removing a solvent by the rotary type evaporator, Compound 1-4 (71 g, 81%) was obtained through purification by column chromatography using ethylacetate as a developing solvent. |
81% | With sodium t-butanolate;tri-tert-butyl phosphine; palladium diacetate; In toluene; at 120℃; for 12h; | Compound 3-3 (64g, 0.30mol), bromobenzene (52.8g, 0.33mol), Pd(OAc)2 (1.37g, 6.11mmol), P(t-Bu)3 50% (7.3mL, 15.28mmol) and NaOt-Bu (58g, 0.61mol) were dissolved in toluene 1.2L and stirred at 120C for 12 hours. After termination of the reaction, the mixture was neutralized with distilled water and extracted with EA. The organic layer was dried with anhydrous MgSO4, and the solvent was removed using a rotary evaporator. Subsequently, column chromatography purification was conducted using EA as a developer, yielding Compound 3-4 (71g, 81%). |
80% | With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In toluene;Inert atmosphere; Reflux; | Bromobenzene (Br-Ph, 1.88 g, 12 mmol), <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong>(2.1 g, 10 mmol), cesium carbonate (6.6 g, 20 mmol), tri-tert-butylphosphane(300 mg, 1.5 mmol) and palladium (II) acetate (112 mg,0.5 mmol) are dissolved in 200 mL of toluene under N2. Then, themixture is stirred to reflux overnight. After completion of the reaction,dichloromethane (DCM) and water are added to the cooled mixture.The organic layer is separated and dried over MgSO4, then concentratedin vacuo. The residue solid is purified by column chromatography togive the product as white solid (2.29 g, 80%): 1H NMR (600 MHz,CDCl3) delta 7.62 (t, J=7.8 Hz, 2H), 7.54-7.47 (m, 1H), 7.45 (dd, J=7.6,1.7 Hz, 2H), 7.36-7.30 (m, 2H), 6.96 (ddd, J=8.4, 7.1, 1.6 Hz, 2H),6.91 (td, J=7.4, 1.4 Hz, 2H), 6.25 (dd, J=8.1, 1.3 Hz, 2H), 1.69 (s,6H). MS (EI) m/z: [M]+ calcd for C21H19N 285.15, found 285.28. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; water; ethyl acetate; | a) 2,7-Dibromo-9,9-dimethyl-9,10-dihydroacridine N-Bromosuccinimide (94.5 g, 531 mmol) is added in portions to a solution of 9,9-dimethyl-9,10-dihydroacridine (CAS 6267-02-3, 45 g, 252 mmol) in chloroform (1000 ml) at 0 C. with exclusion of light, and the mixture is stirred at this temperature for 2 h. 500 ml of water are subsequently added to the mixture. After phase separation, the organic phase is washed with water, and the aqueous phase is extracted with chloroform. The combined organic phases are dried over sodium sulfate and evaporated in vacuo. The residue is dissolved in ethyl acetate and filtered through silica gel. The crude product is subsequently recrystallized from heptane. Yield: 64.7 g (176 mmol), 70% of theory, colourless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 90℃; for 3h;Inert atmosphere; | Catalyst Pd(dba)2 (5 % mol, 490 mg) and the phosphine P(tBu)3 (4% mol, 0.675 ml_ of 1 M P(tBu)3 in toluene) were introduced at room temperature in toluene (10 ml_, anhydrous and well degassed) in a two way flask. After 15 min under nitrogen, the other reagents 3 CI-SBF (1 eq, 5.98 g, 16.9 mmol), <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> (1eq, 3.53 g, 16.9 mmol) and tBuONa (3 eq, 5.0 g, 60.6 mmol) were introduced and the reaction medium was warmed at 90 C for 3 hours. At the end of the reaction, the medium was filtrated on diatomaceous earth (celite) and solvent was evaporated under vacuunn. The solid was absorbed on silica gel and a dry flash chromatography was realized (methylene chloride / hexane). After solvent evaporation, the solid was recrystallized in hexane (m = 7.66 g, yield = 87%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 10.0h;Cooling with ice; | 9,10-Dihydro-9,9-dimethylacridine (50.0 g, 0.24 mol) was dissolved in 250 mlCool down in the DMF with an ice water bath. Subsequently, NBS (85.2 g, 0.48 mol) was dissolved in 150 ml of DMF, and slowly added dropwise thereto.10h. After completion of the reaction, the reaction solution was poured into a large amount of water and filtered to give a white solid. After vacuum drying the white solid,Petroleum ether: dichloromethane (10:1) was purified by column chromatography to give the product 87.8 g, yield 93%. |
90% | With bromine; In chloroform; for 8.0h;Inert atmosphere; | Under a nitrogen atmosphere (N2 purging), Compound 1D(2.7 g, 12.93 mmol) was added to chloroform(200ml), followed by stirring. After stirring, 3 equivalents of bromine were slowly added dropwise. After 8 hours, the reaction was quenched by addition of an aqueous sodium thiosulfate solution. Then, extraction was performed. Thereafter, purification was performed using a column using a developing solvent of methylenechloride(MC):hexane (1:5) to obtain a white solid 1E(4.24 g, yield 90%). |
86% | With N-Bromosuccinimide; at 140℃; for 48.0h; | In the first step, 9,9'-dimethylacridine (2.09 g, 10 mmol), N-bromosuccinamide (NBS, 4.25 g, 24 mmol) were added to a 250 mL reactor.Under an argon atmosphere, 100 mL of N.N'-dimethyldiphenylamine (DMF) which had been previously dewatered and deoxygenated was injected, and reacted at 140 C for 48 hours.After cooling to room temperature, the reaction solution was poured into 200 mL of ice water, and extracted three times with dichloromethane.Column chromatography (dichloromethane: n-hexane, v: v, 1: 3) was separated and purified to obtain 3.1 g of a white powder.That is, the first intermediate has a yield of 86%. |
69% | With phenyltrimethylammonium tribromide; In tetrahydrofuran; at 20℃; | To a stirred solution of 9,9-dimethyl- 10H- acridine (4, 0.50 g, 2.4 mmol) in dry THF (10 mL), was added trimethylphenylammonium tribromide (PTT) (1.8 g, 4.8 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After the reaction was judged complete (TLC), the reaction mixture was poured in water (30 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were dried over anhydrous MgS04, filtered and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with gradient elution (0 to 30% EtOAc-hexane) to afford the title compound as a light brown oil (0.6 g, 69% yield). 1H NMR (300 MHz, DMSO- 6) delta 1.47 (s, 6 H) 6.74 (d, J=8.48 Hz, 2 H) 7.22 (dd, J=8.48, 2.26 Hz, 2 H) 7.46 (d, J=2.07 Hz, 2 H) 9.18 (s, 1 H). LCMS (ESI) m/z 368 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In tetrahydrofuran; at 0℃; | 20.0 g (88.00 mmol) of the intermediate (A) synthesized in the above step 1 was suspended in terrahydrofuran (293 ml), and then 102.7 ml of methylmagnesium bromide (3M) was slowly added dropwise at 0 C. After completion of the reaction, the reaction solution was extracted with dichloromethane and distilled under reduced pressure. 100 ml of sulfuric acid diluted to 10% in distilled water was added to the distillation product, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was extracted with dichloromethane and distilled water, and the organic layer was subjected to silica gel filtration. The organic solution was removed and recrystallized from dichloromethane and hexane to obtain 15.0 g (yield: 81%) of the intermediate product (B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With copper(l) iodide; rac-diaminocyclohexane; sodium t-butanolate; In 1,4-dioxane; for 6h;Inert atmosphere; Reflux; | 100 mL of 1,4-dioxane was placed in a flask having been substituted with nitrogen, to which 9,9-dimethyl-9,10-dihydroacridan (10 g, 47.8 mmol), 1-bromo-4-iodobenzene (14.9 g, 52.58 mmol), copper iodide (0.18 g, 0.96 mmol), sodium tert-butoxide (9.2 g, 95.6 mmol), and 1,2-diaminocyclohexane (0.55 g, 4.78 mmol) were then added. The reaction solution was heated and refluxed for 6 hours. Thereafter, the temperature was lowered, and impurities were removed with Celite. The resulting filtrate was purified by column chromatography to provide an intermediate (1) as a white solid matter (15.5 g, 89%). 1H NMR (500 MHz, CDCl3): 7.75 (d, J=8.5 Hz, 2H), 7.45 (dd, J=9.5 Hz, 2 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 6.95 (m, 4H), 6.24 (dd, J=9.5 Hz, 1.5 Hz, 2H), 1.54 (s, 6H) |
80% | <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> (760 mg, 3.6 mmol) was added to a 50 mL two-neck eggplant flask and purged with nitrogen. Thereafter, dry toluene (11 mL) was added to the reaction vessel and cooled to 0 C. with ice. To this solution was added 1.55 M n-BuLi n-hexane solution (2.5 mL, 1.1 eqiv, 3.9 mmol) dropwise and stirred at 0 C. for 1 h.Thereafter, Pd2 (dba)3 .CHCl3 (190 mg, 5.0 mol%, 1.8 × 10 mmol), 2- (di-tert-butylphosphino) biphenyl [John Phos] (140 mg, 12 5 mol, 4.5 x 10 mmol), 1-bromo-4-iodobenzene (3.6 g, 3.5 equiv, 13 mmol) and dry toluene (3 mL) and the mixture was stirred at 50 C. for 18 hours. After the reaction, filtration with Celite, methylene chloride was added to the reaction solution, and the organic layer was extracted by washing with purified water and saline. Then it was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography to obtain the objective compound 1 (1.1 g, yield 80%) as a white solid. | |
75% | 9,9-Dimethyl-9,10-dihydroacridine (2.09 g, 10 mmol), p-bromoiodobenzene (3.1 g, 11 mmol), iodideCopper (0.38 g, 0.2 mmol) and sodium tert-butoxide (1.92 g, 20 mmol) were added to the reaction flask, and nitrogen was exchanged three times (10 min/time).The solvent (1,4-dioxane) was injected under the protection of nitrogen, and 2 ml of 1,2-diaminocyclohexane was injected after the raw material was partially dissolved.(Reagent), after the injection is completed, the reaction is refluxed at 110 C for 6 h, extracted, concentrated, powdered, separated and purified by column chromatography to obtain white.Color solid product 2, yield 75%. |
74.7% | With copper(l) iodide; In 1-methyl-pyrrolidin-2-one; at 120℃; for 12h; | 5g (23 · 9mmol) of 9,9-dimethylacridine and 7.4g (26.3mmol) of 4-bromoiodobenzene were mixed.457 mg (2.4 mmol) of cuprous iodide was added,Then add 50ml of NMP,Stir and heat at 120C for 12 hours.After cooling to room temperature, the mixture was filtered, and the filtrate was poured into 500 ml of water and filtered. The filter cake was washed with water to give a white solid, which was recrystallized from ethanol to give 6.5 g of a white solid. The yield was 74.7%. |
74% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 3h;Inert atmosphere; Reflux; | S7 (2.5 mmol), S8 (2.6 mmol), (dibenzylideneacetone) dipalladium (0) (0.12 mmol),Sodium tert-butoxide (4 mmol) and tri-tert-butylphosphine tetrafluoroborate (0.25 mmol) were put into a 100 mL three-necked flask,While stirring, degassing and nitrogen replacement were repeated 3 times quickly, and 40 mL of toluene was added via a syringe.The mixture was heated under reflux under a stream of nitrogen for 3 hours.After the reaction, water was added to the reaction solution cooled to room temperature, extraction was performed with dichloromethane, and the solution was washed with saturated brine.After the organic layer was dried with anhydrous sodium sulfate, the solvent was distilled off and purified by column chromatography.Intermediate S9 (1.85 mmol, 74%) was obtained. |
70% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 70 - 105℃; for 12h;Inert atmosphere; Reflux; | Under the protection of nitrogen, add 9,9-dimethylacridine 50mmol, p-bromoiodobenzene 50mmol, toluene 105mL and 100mmol sodium tert-butoxide to the reaction flask, stir and heat to 70-80 , then quickly add three 5 mmol of tert-butylphosphine in toluene solution and 10 mmol of Pd2 (dba) 3. After the addition, the temperature was continuously raised to 100-105 C and the reaction was refluxed for 12 hours. After the reaction was completed, the temperature was lowered, and the organic phase was extracted with water, washed, dried, and filtered. concentrate. After passing through the column with a mixed solvent of dichloromethane and n-heptane, it was recrystallized to LC> 99.5%, and dried to obtain compound 10- (4-bromophenyl) -<strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong>. , Ie intermediate 1 (yield 70%). |
65.8% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 80℃; for 20h;Inert atmosphere; | 4.0 g (11.12 mmol) of <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> was weighed2.44 ml (5.40 g, 11.12 mmol) of bromoiodobenzene,3.98 g (38.24 mmol) of anhydrous sodium tert-butoxide,1.46 ml (0.58 mmol) of tri-tert-butylphosphine,0.086 g (0.38 mmol) of palladium acetate in a 250 mL three-necked flask,Then, 100 mL of anhydrous toluene was added as a reaction solvent.Under nitrogen protection,And the mixture was heated to 80C for 20 hours.After completion of the reaction,After the solvent was removed under reduced pressure, dichloromethane (100 mL × 3) was added to extract the reaction solution,The extracts were combined and dried over anhydrous magnesium sulfate,Spin dry solvent.The crude product was purified by column chromatography using petroleum ether and methylene chloride (PE: DCM = 15: 1)4.56 g of a white crystalline powder was obtained,The yield was 65.8%. |
65.7% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In tetrahydrofuran; at 80℃; for 20h;Inert atmosphere; | Weigh 2.0 g (9.56 mmol) of <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong>, 2.70 g (9.56 mmol) of bromoiodobenzene, 18.4 g (191.2 mmol) of anhydrous sodium tert-butoxide, 0.73 ml (0.29 mmol) of tri-tert-butylphosphine, 0.043 g (0.19 mmol) of palladium acetate in a 250 mL three-necked flask, Then 100 mL of dry tetrahydrofuran was added as the reaction solvent. Under nitrogen, heated to 80 C for 20 hours. After the reaction, The reaction solution was extracted with dichloromethane (50 mL x 3) after solvent extraction, The extracts were combined and dried over anhydrous magnesium sulfate, dried to dry the solvent and dried. The crude product was treated with petroleum ether and dichloromethane (PE:DCM=15:1) And the residue was purified by column chromatography to obtain 2.28 g of white crystalline powder, Yield 65.7%. |
63% | With tri-tert-butylphosphonium tetrafluoroborate; palladium diacetate; caesium carbonate; In toluene; at 130℃; for 12h;Inert atmosphere; | A three-necked flask was charged with 9,9-dimethylacridine (1 g, 4.78 mmol), p-bromoiodobenzene (1.48 g, 5.26 mmol), palladium acetate (0.14 g, 0.15 mmol), and cesium carbonate (3.89 g, 11.93 mmol), tri-tert-butylphosphine tetrafluoroborate (0.044 g,0.15 mmol), added to 30 mL of dry toluene, and heated to 130 C for 12 h under the protection of nitrogen. After the reaction, the reaction solution was poured into saturated brine, and then subjected to liquid separation extraction with dichloromethane and ethyl acetate, and the solvent was distilled off under reduced pressure. The crude product was subjected to column chromatography to obtain intermediate M3 with a yield of 63%. . |
60% | With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Inert atmosphere; Reflux; | Under nitrogen protection(14 gg, 0.05 mol) and 9,9 '-dimethylacridine (l (K45g, 0.05piomicron1) were dissolved in 100 mL of DMF under nitrogen atmosphere, And then put the catalyst copper (3.2 g, 27 mmol) and acid addition of potassium carbonate (13.8 g, 0.1 mol),. The system was heated to reflux for 24 hours. After cooling to room temperature, 500 mL of water was added to quench the reaction. The product was filtered to give crude product. The crude product was purified by silica gel column chromatography and the eluent was purified by purification with V ethyl acetate: V n-hexane = 1: 6 to give an off-white powder in a yield of 60%. |
53% | With 1,10-Phenanthroline; copper(l) chloride; potassium hydroxide; In toluene; at 120℃; for 24h;Inert atmosphere; | 9,9-Dimethyl acridine (5.0 g, 24.7 mmol), 2-bromo-5-iodobenzene (9.06 g, 32·1 mmol), cuprous chloride (489) were sequentially added to a 250 mL single-mouth bottle. Mg, 4.94 mmol), potassium hydroxide (6·92 g, 124 mmol), 1,10-phenanthroline (891 mg, 4.94 mmol) and 130 mL of toluene, and the mixture was stirred at 120 C for 24 h under nitrogen. The reaction solution was cooled to room temperature, extracted with dichloromethane (3×30 mL). The organic layer was washed with brine (3×30 mL), dried, filtered, and evaporated to remove solvent. A white solid was obtained in 4.78 g, yield 53%. |
50% | In a 50 mL three-necked flask, 2.09 g (10.00 mmol) of 9,9-dimethylacridine, 3.11 g (11.00 mmol) of 1-bromo-4-iodobenzene, 1.92 g (20.00 mmol) of NaOtBu, 4-Dioxane (20 mL) was added and the mixture was nitrogen-flowed for 1 hour. Thereafter, 40 mg (0.20 mmol) of CuI and 110 mg (1.00 mmol) of L-proline were added and heated to reflux. After 18 hours, the formation of the target product was confirmed by TLC and MS measurement, and the reaction was stopped. Thereafter, the reaction solution was added to 200 mL of water, extracted three times with 100 mL of toluene, dehydrated with sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain 1.82 g (yield 50%) of a white solid. | |
21% | With potassium carbonate; rac-diaminocyclohexane; copper(l) chloride; In dimethyl sulfoxide; at 110℃; for 16h;Inert atmosphere; | 9,10-Dihydro-9,9-dimethylacridine (25.0 g, 119.6 mmol), 1-bromo-4-iodobenzene (38.0 g, 134.3 mmol), cuprous chloride (I) (2.37 g, 23.9 mmol), dimethyl sulfoxide (250 ml), potassium carbonate (33.1 g, 239.2 mmol) and 1,2-diaminocyclohexane (6.8 g, 59.8 mmol). A 500 ml double neck round bottom reaction flask was added, and the reaction system was filled with nitrogen. The system was heated to 110 C in an oil bath. After 16 hours of reaction, the system was cooled and the reaction was poured into 300 ml of water and stirred, followed by acetic acid. After extracting the ethyl ester, the extract is quenched with saturated brine, and then the water is removed with magnesium sulfate and filtered. The filtrate is removed by a rotary evaporator, and then purified by silica gel column chromatography with hexane as eluent. The light brown solid was compound 2-6-b (9.15 g, 21%). |
With copper(l) iodide; sodium butanolate; In 1,4-dioxane; at 80℃; for 6h; | Compound 125 can be synthesized by a person of ordinary skill following Scheme 5 illustrated in FIG. 6. In the first step, compound S5-1 (available for purchase from Acros Organics, CAS No. 589-87-7) is combined with compound S5-2 (available for purchase from ArkPharm, Inc., CAS No. 6267-02-3), nBuONa and Cul in dioxane at 80 C for 6 hours to form compound S5-3. In the second step, compound S5-3 is is added to hexanes and cooled to 0 C before dropwise addition of nBuLi, followed by addition of B(OMe)3. The reaction can be allowed to stir before being quenched with aqueous HC1 to form compound S5-4. In the third step, compound S5-4 can be combined with compound S5-5 (available for purchase from Acros Organics, CAS No 626-39-1), Pd(OAc)2 and K3P04 in THF at 45 C for 24 hours to form compound S5-6. In the fourth step, compound S5-6 can be combined with compound 55- 7 (available for purchase from Acros Organics, CAS No 1692-15-5), Pd(OAc)2 and K3P04 in THF at 45 C for 24 hours to form compound 125. It is understood that steps 1, 2, 3, and 4 can be performed and optimized by a person having ordinary skill in the art without undue experimentation. | |
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 160℃; for 24h;Inert atmosphere; | Under a nitrogen atmosphere, <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> (1 g, 4.78 mmol),4-bromo-1-iodobenzene (1.75g, 6.21mmol),K2CO3 (1.32g, 9.56mmol) and Cu (1.21g, 19.1mmol) were dissolved in 12mLN, N-dimethylformamide (DMF) solution,Stir at 160 C for 24 hours. After returning to room temperature, the reaction mixture was poured into water,It was extracted with dichloromethane, and the organic layer was completely washed with brine, and then dried over anhydrous magnesium sulfate.Purification by silica gel column chromatography gave a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; at 110℃; for 24h;Inert atmosphere; Darkness; | 9,9-Dimethyl-9,10-dihydroacridine(2.8 mmol), 2-(4-bromophenyl)-4,6-diphenylwas added to a 250 mL three-necked flask under a nitrogen atmosphere.-1,3,5-triazine 1.1 g (2.8 mmol), 0.90 g of sodium t-butoxide,59.8 mg of palladium acetate, tri-tert-butylphosphine, heated to 110 C, and stirred for 24 hours in the dark.After completion of the reaction, the solvent in thereactionsystem was suspended, extracted three times with dichloromethane and water to give an organic phase.Dichloromethane was distilled off under reduced pressure, and purified by silica gel columnto yield 1.30 g of product of formula P20. |
90% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 110℃; for 24h;Inert atmosphere; | Under a nitrogen atmosphere,Add <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> to a 250 ml three-necked flask(2.8mmol),2-(4-bromophenyl)-4,6-diphenyl-1,3,5-triazine 1.1 g (2.8 mmol), 0.90 g of sodium t-butylate,Add 59.8 mg of palladium acetate,Tri-tert-butylphosphine,Heated to 110 C,The reaction was stirred for 24 hours in the dark.After the reaction,The solvent in the reaction system is suspended,Extract three times with dichloromethane and water.Take the organic phase.Distilling off the dichloromethane under reduced pressure,Purified on silica gel column,The product of the formula P20 was obtained in 1.30 g, yield 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Example 17 10-(2-Bromobenzyl)-<strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> 9.7 g (0.243 mol) of NaH, 60% in mineral oil, are dissolved in 500 ml of dimethylformamide under protective atmosphere. 22.1 g (0.106 mol) of <strong>[6267-02-3]9,9-dimethyl-9,10-dihydroacridine</strong> are dissolved in 500 ml of DMF and added dropwise to the reaction mixture. After 1 h at room temperature, a solution of 60.6 (242 mmol) of 2-bromobenzyl bromide in 500 ml of DMF is added dropwise. The reaction mixture is stirred at room temperature for 1 h, then poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene and recrystallised from toluene/n-heptane. The yield is 37 g (94%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tri-tert-butyl phosphine; palladium diacetate; potassium carbonate In 5,5-dimethyl-1,3-cyclohexadiene for 16h; Inert atmosphere; Reflux; | Synthesis of bis[4-(9,10-dihydro-9,9-dimethylacridine)phenyl]diphenylsilane (SiDMAC) Bis(4-bromophenyl)diphenylsilane (2.47 g, 5.00 mmol), 9,10-dihydro-9,9-dimethylacridine (2.09 g, 10.0 mmol),potassium carbonate (4.15 g, 30.0 mmol) were added to a round bottom flask. After nitrogen flow for one hour, xylene (60ml), palladium(II) acetate (44.9 mg, 0.20 mmol), tri-tert-buthlphosphoine (0.02 ml, 0.80 mmol) were added and nitrogenbubbled through the mixture for 1 hour. The resultant mixture was vigorously stirred for 16 hours at reflux temperatureunder N2 flow and cooled to room temperature. The precipitate was filtered, and washed with water several times,subsequently the residue was purified by chromatography on silica gel (eluent: hexane: ethyl acetate = 20: 1) to afford SiDMAC (1.87 g, 50%) as white powder: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With aluminum (III) chloride; In 1,2-dichloro-ethane; at 60℃; for 1h;Cooling with ice; | (Synthesis of Exemplary Compound (A-21)) (0496) Compound (A-21) in which D1 in Formula (I) is a compound represented by Formula (III) may be prepared by the following reaction scheme. Compound 47 was synthesized by the method described in Chemishe Berichte 1980, 113, 358-384. Compound 47 was dissolved in 1,2-dichloroethane, cooled in an ice bath, and then, aluminum chloride and t-butyl chloride were added. This reaction solution was heated to 60 C., and followed by stirring for 1 hour to obtain Compound 48 in 80% yield. Compound 48 and methyl ortho-iodobenzoate were dissolved in diphenyl ether, and copper powder, copper iodide and calcium carbonate were added, overheated to 180 C. under a nitrogen atmosphere, and followed by stirring for 4.5 hours to obtain Compound 49 in 86% yield. Compound 49 was dissolved in dehydrated tetrahydrofuran, and a 3 M methyl Grignard reagent (ethyl ether solution) was added dripwise thereto. After that, the reaction solution was heated to a reflux temperature, and followed by stirring for 1 hour to obtain Compound 50 in 95% yield. Compound 50 was added to phosphoric acid, and followed by stirring at 90 C. for 2 hours to obtain Compound 51 in 40% yield. Compound 51 was dissolved in dehydrated N,N-dimethylformamide, and trifluoromethanesulfonic anhydride was added dropwise thereto. The reaction solution was heated to 90 C. under a nitrogen atmosphere, and followed by stirring for 1 hour to obtain Compound 52 in 80% yield. Compound 52 and benzindandione were added to a 2-propanol solvent under a nitrogen atmosphere, and refluxed for 3 hours. After allowing to cool, suction filtration was performed, and recrystallization was performed with tetrahydrofuran. Suction filtration was performed to obtain Compound (A-21) in 45% yield. The compound was identified by 1H-NMR. (0499) 1H-NMR (400 M Hz, in CDCl3): delta (ppm)=1.25 (s, 3H), 1.30 (s, 3H), 1.40 (s, 18H), 1.97 (s, 3H), 2.14 (s, 3H), 7.25-7.30 (m, 2H), 7.42 (d, J=16.0 Hz, 2H), 7.49 (d, J=15.0 Hz, 1H), 7.57 (m, 1H), 7.64-7.72 (m, 3H), 8.00 (s, 1H), 8.07-8.13 (m, 2H), 8.37 (d, J=15.0 Hz, 1H), 8.50 (d, J=15.0 Hz, 2H), 9.15 (s, 1H). |
64% | With aluminum (III) chloride; In 1,2-dichloro-ethane; at 80℃; for 2h; | To a dichloroethane solution (60 mL) of <strong>[6267-02-3]9,9-dimethyl-9,10-dihydro-acridine</strong> (1) (4.00 g, 19.1 mmol) Under which aluminum chloride(AlCl3, 3.83 g, 28.7 mmol) and t-butyl chloride (21 mL, 191 mmol) were added under ice-cooling (0 C., the same applies hereinafter). Subsequently, the reaction mixture was stirred at 80 C. for 2 hours, and then poured into ice water. The mixture was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off from the filtrate at room temperature (25 C., the same applies hereinafter) using a rotary evaporator to obtain a crude product. The crude product was recrystallized from hexane to obtain 3.94 g (yield: 64%) of 2,7-di-tert-butyl-9,9-dimethyl-9,10-dihydro- acridine (2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 90℃; for 8h;Inert atmosphere; | Under an Ar atmosphere, 2.50 g of N-[1,1?-biphenyl]-4-yl-N-(3?-bromo[1,1?-biphenyl]-4-yl)-[1,1?-biphenyl]-4-amine, 1.04 g of <strong>[6267-02-3]9,10-dihydro-9,9-dimethylacridine</strong>, 0.328 g of Pd2(dba)3.CHCl3, 1.31 g of t-BuONa, 65 mL of dehydrated toluene and 0.49 mL of a 2 M (t-Bu)3P/dehydrated toluene solution were added to a 200 mL three necked flask, followed by heating and stirring the resultant at about 90 C. for about 8 hours. After air cooling the obtained mixture, water was added, an organic layer was separated, and solvents were distilled. The crude product thus obtained was separated by silica gel column chromatography (using a mixture solvent of dichloromethane and hexane) and recrystallized using a mixture solvent of toluene/hexane to produce 2.71 g of Example Compound 3 as a white solid (Yield 88%). The identification of the product was conducted by detecting molecular ion peaks using FAB-MS, and a value of 680.32 (C51H40N2) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 120℃; for 12h;Inert atmosphere; | In N2in the gas purification system, the use of a compound "d" (0.3mol), 4-bromobenzyl sulfone (0.15mol), Pd (OAc)2(6.11mmol), P(t-Bu)3(50 wt %, 15 . 28mmol) sodium and tertiary butyl alcohol (0.61mol) is added to the toluene solvent and stirring. In the solution 120 C and the temperature of the refluxing under stirring 12 hours. After the completion of reaction, the solution is cooled to the room temperature and water and ethyl acetate extraction. From the extraction of using magnesium sulphate remove the moisture in the organic layer, and removing the solvent. The material through the use of hexane and ethyl acetate to carry out wet refining column chromatography, thereby obtaining compound 20. (Yield: 80%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 90℃; for 5h; Inert atmosphere; | 21-2 [Reaction formula 21-2] In N2in the gas purification system, the catalyst Pd (dba)2(5mol %) and P(t-Bu)3(4mol %) added to the toluene solvent and stirring for about 15 minutes. Add another compound 2 (33.8mmol), compound "d" (16.9mmol) and NaOt-Bu (60.6mmol), and the mixture at 90 °C stirring at a temperature of 5 hours. After the reaction is finished, a diatomite filter mixture to, and removing the solvent. The filtering of the solid by using the hexane and dichloromethane refining by column chromatography, using hexane recrystallization and, so as to obtain compound 21. (Yield: 59%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 120℃; for 12h;Inert atmosphere; | In N2in the gas purification system, the use of a compound "d" (0.3mol), 5,8-di bromo-Oxoquinoxaline (0.15mol), Pd (OAc)2(6.11mmol), P(t-Bu)3(50 wt %, 15 . 28mmol) sodium and tertiary butyl alcohol (0.61mol) is added to the toluene solvent and stirring. In the solution 120 C and the temperature of the refluxing under stirring 12 hours. After the completion of reaction, the solution is cooled to the room temperature and water and ethyl acetate extraction. From the extraction of using magnesium sulphate remove the moisture in the organic layer, and removing the solvent. The material through the use of hexane and ethyl acetate to carry out wet refining column chromatography, so as to obtain compound 22. (Yield: 79%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.6% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 110℃; for 14h; Inert atmosphere; | 10.a A storage tube was loaded with 1.0 g (4.8 mmol, 1 eq.) 9,10-Dihydro-9,9- dimethylacridine, 1.48 g 2-bromonaphthalene (7.1 mmol, 1.5 eq.), 27.5 mg of bis(dibenzylideneacetone)palladium(0) (0.48 pmol, 1 mol%), 134 pL of 1M in toluene tx-tert- butylphosphine (0.134 mmol, 3 mol %), 1.4 g sodium /ert-butoxide (14.4 mmol, 3 eq.), and 50 mL tolueneunder nitrogenatmosphere. The solution was heated to 110°C. After 14 hours, the reddish- purple liquid with a white precipitate was passed directly through a silica plug and rinsed with toluene. All blue fluorescent portions were collected and concentrated via rotary evaporation. The product was recrystallized 3 times with DCM/methanol at -25°C. The product was collected via vacuum filtration, washed with methanol, and dried overnight under vacuum to yield 1.16 g (72.6% yield). NMR (400 MHz, Chloroform-7) d 8.14 (d, 7= 8.6 Hz, 1H), 8.04 - 7.98 (m, 1H),7.91 (dt, J= 4.7, 1.8 Hz, 2H), 7.60 (dqd, J = 8.3, 6.9, 1.5 Hz, 2H), 7.55 - 7.48 (m, 2H), 7.44 (dd, 7= 8.6, 2.0 Hz, 1H), 7.03 - 6.90 (m, 4H), 6.39 - 6.27 (m, 2H), 1.77 (s, 6H).13C NMR (101 MHz, Chloroform-7) d 140.97, 138.49, 134.81, 132.85, 130.95, 130.13, 130.00, 128.93, 128.02, 127.89, 126.73, 126.43, 126.32, 125.22, 120.55, 114.16, 36.02, 31.31.HRMS(ESI) calculated for M+ for C25H21N, 336.17468; Found, 336.1755. |
72.6% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 110℃; for 14h; Inert atmosphere; | |
71% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate In toluene for 33h; Reflux; | 1 Preparation of intermediate compound [2-1] In 500 mL reaction flask, 9,9-dimethyl-9,10-dihydro-acridine 10.0g (47.78mmol), 2- bromonaphthalene 10.88g (52.56mmol), sodium tert-butoxide 6.89g (71.67mmol) , palladium acetate de 0.11g (0.48mmol), put the tri tert-butyl phosphine in 160 mL of toluene 0.19g (0.96mmol) was stirred for 33 hours under reflux. After completion of the reaction by filtration, extracted with dichloromethane and dried over anhydrous magnesium sulfate, the filtrate was concentrated under reduced pressure to give the one behind, the intermediate compound of off-white solid separated and It was purified by a silica gel chromatography [2-1] 11.38g (71%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | 1.46 g of 9,9-dimethylacridine,240 mg of 70% oil dispersion of sodium hydride and.20 ml of tetrahydrofuran was added to 50 ml.Liter single-ended round-bottomed flask,After refluxing under argon for 30 minutes, 0.75 g was added.4,7-dichloro-1,10 phenanthroline,Then refluxed at 60 C for 24 hours,After cooling to room temperature, saturated saline was quenched,Extracted with dichloromethane, and dried over anhydrous sodium sulfate.The organic phase was filtered and dried. The product was 1.57 g in a ratio of methanol: methylene chloride at a volume ratio of 1:30. White solid, Yield.88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.3% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 130℃; for 21h;Inert atmosphere; | 0.627 g (3.00 mmol) of 9,10-dihydro-9,9-dimethylacridine (DMAC) was placed in a 50 ml four-necked flask,1.16 g (3.00 mmol) of 4 '- (4-bromophenyl) -2,2': 6,2 "- terpyridine (Br 2 TP)0.865 g (9.00 mmol) of sodium t-butoxide (t-BuONa) was added and nitrogen flow was carried out for 15 minutes.After nitrogen flow,30 ml of xylene was added and nitrogen bubbling was carried out for 1 hour.After nitrogen bubbling, 0.0337 g (0.150 mmol) of palladium (II) acetate (Pd (OAc) 2) and 0.106 ml (0.450 mmol) of tri (t-butylphosphine) (P (t-Bu) 3) In addition, it was refluxed at 130 C. for 21 hours.Disappearance of the raw material was confirmed by thin layer chromatography (TLC), and the reaction was terminated (red black solution). Cooled to room temperature, suction filtered and extracted with a separating funnel.After extraction, purification was carried out by silica gel column chromatography (silica gel; 500 cc, developing solvent; chloroform: methanol = 10: 1).The fraction considered as the target substance is recovered,A red black viscous matter was obtained,After drying under reduced pressure at 60 C.,1.48 g of a red solid was obtained.Because there was a little garbage mixed,Dispersed and washed with hexane,After drying under reduced pressure at 60 C.,1.26 g (yield 81.8%) of a red solid was obtained. Furthermore, 600 mg of a red solid of Ac-2 TP was purified by sublimation using a sublimation analyzer under conditions of nitrogen gas 100 cc / min, high temperature part 300 C., low temperature part 150 C. to obtain 278 mg of transparent yellow crystals (yield 46 .3%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tri-tert-butyl phosphine; potassium tert-butylate; palladium diacetate; In toluene; at 110℃; for 24h; | 10 g (4718 mmol) of acridine; 18.4 g (57.34 mmol) of 9-(3-bromophenyl)-9H-carbazole, 8 g (71.67 mmol) of potassium tert-butoxide, 0.536 g (2.39 mmol) of palladium acetate, 0.774 ml (1.91 mmol) of tri-tert-butylphosphine (50 percent by weight (wt %) toluene), and 60 ml of toluene were allowed to react at a temperature of 110 C. for 24 hours. After the reaction was completed, the resulting product was filtered to produce crude products. The crude products obtained therefrom were recrystallized twice, each using toluene:methanol; thereby obtaining 14.6 g (68%) of Compound A. This compound was identified using LC-Mass. LC-Mass (calculated: 450.59 g/mol. found: MA-H=451 g/mol). |
68% | With tri-tert-butyl phosphine; potassium tert-butylate; palladium diacetate; In toluene; at 110℃; for 24h; | Acridine (10 g, 47.78 mmol), 9-(3-bromophenyl)-9H-carbazole (18.4 g, 57.34 mmol), potassium-tert-butoxide (8 g, 71.67 mmol), palladium acetate (0.536 g, 2.39 mmol), tri-tert-butylphosphine (50 wt % toluene) (0.774 mL, 1.91 mmol), and 60 mL of toluene were reacted at a temperature of 110 C. for 24 hours. Once the reaction was completed, filtering was performed thereon to obtain a crude product. The obtained crude product was re-crystallized twice by using toluene and methanol to obtain Compound A (14.6 g, 68%). Compound A was identified by LC-Mass.LC-Mass (calc.: 450.59 g/mol, found: M+H=451 g/mol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In o-xylene; at 115℃; for 2h;Inert atmosphere; | n a flask purged with nitrogen,9,9-Dimethyl-9,9-dihydroacridine (17.4 g, 83 mmol), 1-bromo-4- (3-chloropropyl) benzene (19.4 g, 83 mmol), Palladium acetate (187 mg, 0.83 mmol), Sodium t-butoxide (12.0 g, 125 mmol), And o-xylene (348 mL)Was prepared by bubbling a solution with argon gas,Tetrakistri t-butylphosphine (520 mg, 2.57 mmol) was added and the mixture was heated and stirred at 115 C. for 2 hours.The reaction solution was returned to room temperature and filtrated with Celite.Next, the separated organic phase was concentrated and the residue was purified by silica gel column chromatography (stationary phase: neutral silica gel, mobile phase: hexane / toluene) to obtain Intermediate A1-1 as a pale yellow oil (Yield 28.2 g, yield 94% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With aluminum (III) chloride In 1,2-dichloro-ethane at 80℃; for 6h; | Synthesis of 2,7-di-(1-adamantyl)-9,9-dimethyl-9,10-dihydroacridine (7) To a dichloroethane solution (20 mL) of 9,9-dimethyl-9,10-dihydro-acridine (1) (1.11 g, 5.30 mmol) Aluminium chloride (1.41 g, 10.6 mmol) and 1-adamantyl chloride (1-AdCl, 3.62 g, 21.2 mmol) were added under ice-cooling. Subsequently, the reaction mixture was stirred at 80 ° C. for 6 hours, and then poured into ice water. The mixture was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off from the filtrate at room temperature under reduced pressure using a rotary evaporator to obtain a crude product. The obtained crude product was purified by medium pressure liquid chromatography (MPLC, carrier: silica gel, solvent: hexane containing 20-25% by volume of dichloromethane) to obtain 396mg 2,7-di- (1-adamantyl) -9,9-dimethyl -9,10-dihydro-acridine (7) (yield: 16%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Inert atmosphere; Reflux; | In the argon atmosphere, Intermediate A (4.4 g, 21 mmol) synthesized according to the method described in JP-A-2010180204, Intermediate B (4.7 g, 10 mmol) synthesized according to the method described in International Publication No. 2003/080760, (Dibenzylideneacetone) dipalladium (0.37 g, 0.4 mmol) Tri-t-butylphosphonium tetrafluoroborate (0.46 g, 1.6 mmol)Sodium t-butoxide (2.7 g, 28 mmol) Anhydrous toluene (100 mL), And heated to reflux for 8 hours. After the reaction solution was allowed to cool to room temperature, Separating the organic layer, The organic solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography, The title compound GH-4 (3.6 g, yield 50%) was obtained. |
50% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Reflux; Inert atmosphere; | In the argon atmosphere,Intermediate A (4.4 g, 21 mmol) synthesized according to the method described in JP-A-2010-180204,Intermediate B (4.7 g, 10 mmol) according to the method described in International Publication No. 2003/080760,(Dibenzylideneacetone) dipalladium (0.37 g, 0.4 mmol)Tri-butyl-tetrafluoroborate (0.46 g, 1.6 mmol)Sodium butoxide (2.7 g, 28 mmol)Anhydrous toluene (100 mL),And heated to reflux for 8 hours.After the reaction solution was allowed to cool to room temperature,Separating the organic layer,The organic solvent was distilled off under reduced pressure.The resulting residue was purified by silica gel column chromatography,The title compound GH-4 (3.6 g, yield 50%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | 9,9-dimethyl-9,10-dihydroacridine (3.14 g, 15 mmol) Was added sodium hydride (0.72 g, 30 mmol)In dehydrated N, N-dimethylformamide (DMF: 30 mL). The resulting solution was stirred at room temperature for 30 minutes,A solution of bis (p-fluorophenyl) sulfone (1.91 g, 7.5 mmol) in dehydrated DMF (30 mL) was added. Thereafter, the mixture was further stirred at 50 DEG C for 1 hour, cooled, and then injected into 400 mL of water. The resulting yellow solid was filtered and dried,The crude product was further recrystallized from chloroform and ethyl ether to obtain 3.8 g of pale yellow crystals (yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.6% | With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene; for 16h;Reflux; | 1.55 g (4.0 mmol) of 4- (4-bromophenyl) -2,6-diphenylpyrimidine (B 26 DPPM), dimethylacridine (DMAC) 0.84 g (4.0 mmool),1.66 g (12 mmol) of potassium carbonate (K 2 CO 3) and 25 mL of xylene were added and nitrogen bubbling was carried out for 40 minutes. Next, 45 mg (0.20 mmol) of Pd (OAc) 2 and 174 mg (0.60 mmol) of [(tBu) 3 PH) BF 4 were added and heated under reflux for 16 hours.Consumption of raw materials and production of the desired product were confirmed by TLC, the reaction was terminated, and the temperature was returned to room temperature (deep brown clear solution). After returning to room temperature, suction filtration was carried out, and the filtrate was separated (100 mL × 2, brine 100 mL), dried over Na 2 SO 4 and concentrated.Thereafter, in order to remove the catalyst, purification was carried out by silica gel chromatography (silica gel; 400 cc, developing solvent; hexane: dichloromethane = 2: 1 (vol / vol)) to recover and concentrate only the fraction of the objective substance. Thereafter, dispersion washing was carried out with methanol to obtain 1.98 g of a pale yellow solid having high purity, and the yield was 96.6%. Production of Ac-26 DPPM (molecular weight 513) was confirmed by 1 H-NMR and MS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃;Inert atmosphere; | In a 50 mL four-necked flask purged with nitrogen, 1.49 g (6.96 mmol) of ClPhINN, 1.60 g (7.66 mmol) of <strong>[6267-02-3]9,10-dihydro-9,9-dimethylacridine</strong>, 1.92 g (13.9 mmol) of potassium carbonate, 35 mL of toluene was added, Nitrogen bubbling was carried out for 1 hour. after that, 79.0 mg (0.35 mmol) of Pd (OAc) 2 and 308 mg (1.05 mmol) of [(tBu) 3 PH] BF 4 were added, 110 C, And heated to reflux under a nitrogen atmosphere. Consumption of raw materials was confirmed by TLC (developing solvent dichloromethane) The reaction was stopped. After suction filtration, The mixture was separated twice with 50 mL of water and 50 mL of saturated brine, Dehydrated with magnesium sulfate, And concentrated. Silica gel was packed in a Phi 4.2 cm column tube to a height of 15 cm, The desired product was isolated by silica gel column chromatography (developing solvent toluene) (Rf value: 0.2). This was collected, Concentrate, Dried under reduced pressure, 2.09 g (yield: 77%) of a white to pale yellow solid was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate; In dimethyl sulfoxide; at 150℃; for 8h; | 1 mmol of the starting material CN-1-1, 3.0 mmol of potassium carbonate and 2.5 mmol of the starting material F-7-2, Was added to 10 mL of dimethylsulfoxide and heated at 150 C for 8 hours. After cooling to room temperature, 200 mL of water was added to the system to precipitate a solid which was purged and purified by column chromatography to give a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate; In dimethyl sulfoxide; at 150℃; for 8h; | 1 mmol of the starting material F-7-1, 3.0 mmol of potassium carbonate and 2.5 mmol of the starting material F-7-2, Was added to 10 mL of dimethylsulfoxide and heated at 150 C for 8 hours. After cooling to room temperature, 200 mL of water was added to the system to precipitate a solid which was filtered and chromatographed by column chromatography The solid was purified to yield 13%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium t-butanolate In toluene for 8h; Inert atmosphere; Reflux; | 8 Embodiment 8 compound 8 250 ml three-neck bottle, in an atmosphere of nitrogen, adding 0.01 µM (3.38 g) 2, 7 - dibromo -9 - fluorenone, 0.025 µM (5.23 g) compound M8, 0.03mol (2.88 g) tert sodium butylate, 10-4Mol (0.073 g) Pd (dppf) Cl2, 180 ml toluene, heating reflux for 8 hours, sampling board, the reaction is complete; natural cooling, filtering, collecting the filtrate to carry out decompression and steaming and (-0.09 mpa, 85 °C), to column chromatography, to obtain the target product, purity 98%, yield 82%. |
58% | Stage #1: 9,9‐dimethyl‐10H‐acridine; 2,7-dibromofluorene-9-one With palladium diacetate; sodium t-butanolate In toluene for 0.5h; Inert atmosphere; Stage #2: With tri-tert-butyl phosphine In toluene for 72h; Inert atmosphere; Reflux; | Synthesis of 27DACRFT (1) 2,7-Dibromo-9-fluorenone (0.676 g, 2 mmol), 9,9-dimethyl-9,10-dihydroacridine (1.046 g, 5 mmol), sodium tert-butoxide (0.48 g, 5 mmol) and palladium acetate (45 mg, 0.2 mmol) were dissolved in toluene (180 mL) and stirred under an argon (Ar) flow in a 250 mL three-necked flask for 30 minutes. Then, tris(1,1-dimethylethyl)phosphine (1.0 M solution in toluene, 0.4 mL) was dropped into the mixture, followed by heating under reflux for 72 hours. The formed precipitate was extracted with dichloromethane (DCM) and washed with deionized water after cooling to room temperature. The organic layer was separated and further purified by chromatography on silica gel to afford the title compound as orange powder (0.7 g, 58%) after evaporation of the solvent. 1H NMR (500 MHz, CDCl3): δ 7.96 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 7.8, 1.6 Hz, 3H), 7.35 (dd, J = 7.8, 1.7 Hz, 1H), 7.00 (dddd, J = 16.3, 14.9, 7.3, 1.5 Hz, 4H), 6.48 (dd, J = 8.1, 1.3 Hz, 2H), 1.66 (s, 6H). 13C NMR (126 MHz, CDCl3): δ 191.52 (s), 148.06 (s), 146.52 (s), 140.18 (s), 133.31 (s), 131.37 (s), 126.74 (s), 126.49 (s), 125.41 (s), 122.56 (s), 121.49 (s), 114.85 (s), 36.16 (s), 30.94 (s). EI-MS (electron ionization mass spectrometry, m/z): calcd for C43H34N2O 594.76; found 595.7 [M +]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium t-butanolate; In toluene; for 10h;Inert atmosphere; Reflux; | 250 ml three-neck bottle, in an atmosphere of nitrogen, adding 0.01 muM (3.38 g) 3, 6 - dibromo -9 - fluorenone, 0.025 muM (5.23 g) compound M8, 0.03mol (2.88 g) tert sodium butylate, 10-4Mol (0.073 g) Pd (dppf) Cl2, 180 ml toluene, heating reflux for 10 hours, sampling board, the reaction is complete; natural cooling, filtering, collecting the filtrate to carry out decompression and steaming and (-0.09 mpa, 85 C), to column chromatography, to obtain the target product, purity 97%, yield 79%. |
71% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 18h;Inert atmosphere; | Place a mixture of <strong>[216312-73-1]<strong>[216312-73-1]3,6-dibromo-9H-fluoren-9-on</strong>e</strong> (1.02 g, 3 mmol),9,9-dimethyl-9,10-dihydroacridine (1.47 g, 7 mmol), Pd2(dba)3(0.110 g, 0.12 mmol), t-Bu3PHBF4 (0.035 g, 0.12 mmol), t-BuONa(1.681 g, 15 mmol) in a 100-ml two necked flask under an argon atmosphere.Then 50 mL dry toluene was added. After stirring for 18 h at110 C, the reaction mixture was cooled to room temperature, thenfiltered using dichloromethane (DCM) as wash solvent. The filtrate wasreduced by evaporation. The crude product was purified by columnchromatography on silica gel (eluent: PE/DCM=1:1, v/v), 1.27 g orange-red solid powder was obtained. Yield 71%.1H NMR (600 MHz, CDCl3) delta=7.95 (d, J=7.8 Hz, 2H), 7.46 (d,J=4.0, 4H), 7.45 (d, J=1.5 Hz, 2H), 7.34 (d, J=7.8, 1.7 Hz, 2H),7.00 (t, J=7.7, 1.6 Hz, 4H), 6.95 (t, J=7.5, 1.2 Hz, 4H), 6.47 (d,J=8.1, 1.2 Hz, 4H), 1.66 (s, 12H). 13C NMR (150 MHz, CDCl3) delta191.47, 148.04, 146.50, 145.83, 140.16, 133.30, 131.36, 126.71,126.47, 125.39, 122.55, 121.48, 114.83, 36.15, 30.93. MS (MALDITOF) m/z = 595.500 [M+]. Elem. Anal. Calcd for C43H34N2O: C,86.84; H, 5.76; N, 4.71; O, 2.69; found: C, 86.25; H, 5.96; N, 4.69. |
50% | General procedure: 2,7-Dibromo-9-fluorenone (0.676 g, 2 mmol), 9,9-dimethyl-9,10-dihydroacridine (1.046 g, 5 mmol), sodium tert-butoxide (0.48 g, 5 mmol) and palladium acetate (45 mg, 0.2 mmol) were dissolved in toluene (180 mL) and stirred under an argon (Ar) flow in a 250 mL three-necked flask for 30 minutes. Then, tris(1,1-dimethylethyl)phosphine (1.0 M solution in toluene, 0.4 mL) was dropped into the mixture, followed by heating under reflux for 72 hours. The formed precipitate was extracted with dichloromethane (DCM) and washed with deionized water after cooling to room temperature. The organic layer was separated and further purified by chromatography on silica gel to afford the title compound as orange powder (0.7 g, 58%) after evaporation of the solvent. Synthesis of 36DACRFT (2): 36DACRFT (2) was synthesized in a similar way as described for 27DACRFT (1) starting from <strong>[216312-73-1]3,6-dibromo-9-fluorenone</strong> instead of 2,7-dibromo-9-fluorenone (0.676 g, 2 mmol). The precipitate was extracted with dichloromethane (DCM) and washed with deionized water after cooling to room temperature. The organic layer was separated and further purified by chromatography on silica gel to afford the title compound as orange powder (0.6 g, 50%) after evaporation of the solvent. 1H NMR (500 MHz, CDCl3): delta 7.95 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 7.7, 1.6 Hz, 3H), 7.35 (dd, J = 7.8, 1.7 Hz, 1H), 6.99 (dtd, J = 25.2, 7.3, 1.4 Hz, 4H), 6.48 (dd, J = 8.1, 1.3 Hz, 2H), 1.66 (s, 6H). 13C NMR (126 MHz, CDCl3): delta 148.06 (s), 146.52 (s), 140.18 (s), 133.31 (s), 131.37 (s), 126.73 (s), 126.49 (s), 125.41 (s), 122.56 (s), 121.49 (s), 114.85 (s), 36.16 (s), 30.94 (s). EI-MS (electron ionization mass spectrometry, m/z): calcd for C43H34N2O 594.76; found 595.6 [M+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium tert-butylate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere; | (2) Intermediate 2 (0.80 g, 2.19 mmol) and <strong>[6267-02-3]9,10-dihydro-9,9-dimethylacridine</strong> (0.69, 3.29 mmol) were added to the reaction flask and dissolved in 20 mL of ultra-dry DMF solution. In a three-pass purge, t-BuOK (0.49 g, 4.38 mmol) was added under nitrogen protection, heated to 110 C. and reacted at this temperature for 12 hours. After being extracted with dichloromethane and water, the powder was concentrated and then passed through a column to obtain the final product CP-BZ-DAMC with a yield of 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 12h;Reflux; | 50.0 g (238.90 mmol) of the intermediate (B) synthesized in the step 2 of the above Example 1,2-Bromo-7-iodo-9,9-dimethyl-9H-fluorene104.9 g (262.79 mmol),4.4 g (4.78 mmmol) of sodium tert-butoxide (34.4 g, 358.35 mmol) and tris (dibenzylideneacetone) dipalladium (0) were suspended in 796 ml of toluene and then 4.5 ml of tri- mmol) were added, and the mixture was stirred under reflux for 12 hours. Extracted with dichloromethane and distilled water, and the organic layer is subjected to silica gel filtration. The organic solution was removed and recrystallized from dichloromethane and hexane to obtain 102.3 g (yield: 89%) of the intermediate product (L). |
81% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 2h;Inert atmosphere; Reflux; | Add toluene solvent to the reaction bottle,Then add 9,10-dihydro-9,9-dimethylacridine (31.39g, 150mmol), <strong>[319906-45-1]2-bromo-7-iodo-9,9-dimethylfluorene</strong> (65.85g, 165mmol), tertiary Sodium butoxide (43.25g, 450mmol),After evacuated and filled with nitrogen three times,Pd(OAc)2 (0.34g, 1.5mmol) was added,Replaced three times with vacuum and nitrogen,After that, P(t-Bu)3 (12 mL of 1.0 M toluene solution, 12 mmol) was added, and nitrogen substitution was performed three times.The mixture was refluxed under nitrogen atmosphere for 2h,After the reaction stopped, the mixture was cooled to room temperature,Filter through celite to obtain filtrate, concentrate the filtrate,Add 20mL methanol, recrystallize at rest,Filtration yielded intermediate 43-3 (58.37g, 81%). The purity of the solid detected by HPLC was ?99.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 12h;Reflux; | (47.78 mmol) of the compound (B) synthesized in the step 1 of Example 1, 19.2 g (47.48 mmol) of 3,6-dibromo-9-phenyl-9H- carbazole, 6.9 g of sodium tert-butoxide (71.67 mmol),After 0.9 g (0.96 mmmol) of tris (dibenzylideneacetone) dipalladium (0) was suspended in 159 ml of toluene, 0.9 ml (3.82 mmol) of tri-tert-butylphosphine was added and the mixture was refluxed for 12 hours.Extracted with dichloromethane and distilled water, and the organic layer is subjected to silica gel filtration. The organic solution was removed and recrystallized from dichloromethane and hexane to obtain 20.2 g (yield: 80percent) of the intermediate product (S). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 48h;Inert atmosphere; | 1.3 g of 1,3-bis (4-bromophenyl) -3-hydroxyprop-2-en-1-one, 1.5 g of 9,9-dimethylacridine, 68 mgPalladium acetate, 270 mg of tri-t-butylphosphine tetrafluoroborate, 670 mg of sodium tert-butoxide and 50 ml of double distilled toluene were added to 100 mlLiter single-necked round bottom flask, refluxed under argon for 48 hours, cooled to room temperature, quenched with saturated brine, methylene chlorideExtract, dry the organic phase over anhydrous sodium sulfate, filter and spin dry. The product was eluted with n-hexane: dichloromethane 1: 1 by volumeG Yellow solid, 78% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 48h;Inert atmosphere; | 2.1 g of 1- (4-bromophenyl) -3-hydroxy-3-phenylprop-2-en-1-one, 1.5 g of 9,9-dimethylacridine, 68G palladium acetate, 270 mg tri-t-butylphosphine tetrafluoroborate, 670 mg sodium t-butoxide, and 50 ml double distilled toluene were added to 100Ml single-necked round bottom flask, refluxed under argon for 48 hours, cooled to room temperature, saturated brine to quench, dichloromethaneExtract with hexane, dry the organic phase over anhydrous sodium sulphate, filter and spin dry. The product was eluted with n-hexane: dichloromethane 1: 1 by volumeG Yellow-green solid, yield 87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 130℃; for 12h; | Intermediate 2 (1.00g, 2 mmol)), 9, 10-dihydro -9, 9-dimethyl acridine (0.63 g, 3 mmol)), t-BuONa (0.58 g, 6 mmol) and P (t-Bu)) 3 (0.32 g,0.16 mmol) and Pd(OAc) 2 (0.036 g, 0 16 Mmol) into a reaction flask, and dissolving in 60 mL of toluene solution, extracting for three times, heating to 130 DEG c, refluxing, and reacting at the temperature for 12 hours; extracting by dichloromethane and water, concentrating, and passing through acolumn, and the yield of the final product is 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; XPhos; In toluene; for 24h;Inert atmosphere; Reflux; | To a flask charged with <strong>[27012-25-5]5-bromo-2-phenylpyridine</strong> (2.00 g, 9.56 mmol), 9,9-dimethyl-9,10-dihydroacridine (2.69 g, 11.5 mmol), tris(dibenzylideneacetone) dipalladium (175 mg, 0.191 mmol), 210 (dicyclohexylphosphino)-2',4',6'-tri-i-propyl-1,1'-biphenyl (X-PHOS) (273 mg, 0.573 mmol), and potassium f-butoxide (2.15 g, 19.1 mmol) under a N2 atmosphere was added toluene (75 mL) at room temperature. The flask was attached to a reflux condenser and heated to reflux. After 24 h, the crude reaction mixture was cooled to rt, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and brine, and 15 then dried over MgSCv The resulting solution was filtered and concentrated. The resulting residue was purified via silica gel chromatography, eluted with hexane:CH2Cl2 = 1:1, to afford the product as a white solid in 71% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 90℃;Inert atmosphere; | General procedure: Under a nitrogen atmosphere, 100 ml of toluene, 1 g of intermediate 10 (2.99 mmol), 1.40 g of dimethyl acridine (2.5 equ) were added to a three-necked flask, and 0.90 g of sodium t-butylate was added thereto with stirring, followed by addition of 59.8. Mg palladium acetate, tri-tert-butylphosphine, reacted at 90 C overnight. The temperature was lowered, and the organic phase was extracted with dichloromethane, dried and passed through a column. The product was obtained in 1.50 g, yield 68%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M1 (5 mmol, 1.75 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g), tris(dibenzylideneacetone) dipalladium (0.1) Methyl acetate (92 mmol), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium tert-butoxide (10 mmol, 1.12 g) was dissolved in 30 mL of toluene, and the mixture was stirred and refluxed at 110 C for 24 hours under nitrogen atmosphere. After the reaction, it was extracted with dichloromethane. Concentrate the extract by rotary evaporation, Column chromatography (petroleum ether: dichloromethane = 4:1, volume ratio) gave white solid (2.03 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M4 (5 mmol, 2.48 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g), tris(dibenzylideneacetone) dipalladium (0.1mmol, 92mg), tri-tert-butylphosphine tetrafluoroborate (0.2mmol, 58mg), potassium t-butoxide (10mmol, 1.12g) dissolved in 30mL of toluene, stirred under reflux of nitrogen at 110 C for 24 hours . After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation. Column chromatography (petroleum ether: methylene chloride = 4:1, volume ratio) gave pale blue-green solid (2.66 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M7 (5 mmol, 1.82 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g), tris(dibenzylideneacetone) palladium (0·1mmol, 92mg), tri-tert-butylphosphine tetrafluoroborate (0.2mmol, 58mg), potassium t-butoxide (10mmol, 1.12g) dissolved in 30mL of toluene, stirred at 110 C under nitrogen atmosphere 24 hours. After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation. Column chromatography (petroleum ether: methylene chloride = 4:1, vol.) gave a white solid (2.11g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M10 (5 mmol, 2 · 56 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.00 g), tris(dibenzylideneacetone) palladium (0.1 mmol, 92 mg), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium t-butoxide (10 mmol, 1.12 g) dissolved in 30 mL of toluene and stirred at 110 C under nitrogen. 24 hours. After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation. Column chromatography separation (petroleum ether: dichloromethane = 4:1, volume ratio) afforded pale blue green solid (2.72 g, yield: 85%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, (5 mmol, 2 · 32 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.00 g), tris(dibenzylideneacetone) palladium (0.1 mmol, 92 mg), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium t-butoxide (10 mmol, 1.12 g) dissolved in 30 mL of toluene and stirred at 110 C under nitrogen. 24 hours. After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation. Column chromatography (petroleum ether: methylene chloride = 4:1, volume ratio) gave white solid (2.31 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M17 (5 mmol, 3 · 05 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1 · 05 g), tris(dibenzylideneacetone) palladium (0.1mmol, 92 mg), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium t-butoxide (10 mmol, 1.12 g) dissolved in 30 mL of toluene and stirred at 110 C under nitrogen atmosphere. Reflux for 24 hours. After completion of the reaction, the mixture was extracted with methylene chloride, and the extract was concentrated by rotary evaporation and purified by column chromatography ( petroleum ether: methylene chloride = 4:1,The volume ratio) gave a pale blue-green solid (2.94 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M21 (5 mmol, 2 · 58 g),<strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g),Tris(dibenzylideneacetone)dipalladium (0.1 mmol, 92 mg), Tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), Potassium tert-butoxide (10 mmol, 1.12 g) was dissolved in 30 mL of toluene, and stirred at 110 C under reflux for 24 hours under nitrogen. After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation.Column chromatography (petroleum ether: methylene chloride = 4:1, vol.) gave a white solid (2.74 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M23 (5 mmol, 3 · 23 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g), tris(dibenzylideneacetone) dipalladium ( 0.1 mmol, 92 mg), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium t-butoxide (10 mmol, 1.12 g) was dissolved in 30 mL of toluene, and stirred under reflux at 110 C for 24 hours under nitrogen. . After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation.Column chromatography (petroleum ether: dichloromethane = 4:1, volume ratio) gave a pale blue-green solid (3.29 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | In a 100 mL round bottom flask, M24 (5 mmol, 3 · 31 g), <strong>[6267-02-3]9,10-dihydro-9,9-dimethyl acridine</strong> (5 mmol, 1.05 g), tris(dibenzylideneacetone) dipalladium ( 0 · lmmo 1,92 mg), tri-tert-butylphosphine tetrafluoroborate (0.2 mmol, 58 mg), potassium t-butoxide (10 mmol, 1.12 g) dissolved in 30 mL of toluene and stirred at 110 C under nitrogen atmosphere. 24 hours. After the reaction was completed, it was extracted with dichloromethane, and the extract was concentrated by rotary evaporation. Column chromatography (petroleum ether: methylene chloride = 4:1, volume ratio) gave pale blue-green solid (3.36 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; In toluene; at 110℃; for 10h;Inert atmosphere; | In a 100 mL round bottom flask, <strong>[2050-47-7]4,4'-dibromodiphenyl ether</strong> (30 mmol, 9.77 g), 9,10-dihydro-9,9-dimethyl acridine (5 mmol, 1.05 g), three (dibenzylacetone)dipalladium (0.1 mmol, 92 mg), 1,1'-bis(diphenylphosphino)ferrocene (0.2 mmol, 111 mg), potassium t-butoxide (10 mmol, 1.12 g) dissolved in 40 mL The toluene was stirred and refluxed at 110 C for 10 hours under a nitrogen atmosphere. After completion of the reaction, the mixture was extracted with methylene chloride. Extraction, rotary evaporation concentrated extract, column chromatography (petroleum ether: dichloromethane = 50:1, volume ratio) to give a white solid(1.03 g, yield: 45%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 3h;Reflux; Inert atmosphere; | S1 (10 mmol), 9,9-dimethyl-9,10-dihydroacridine S2 (10.5 mmol),(dibenzylideneacetone) dipalladium (0) (0.05 mmol),Sodium tert-butoxide (14 mmol),4,5-bisdiphenylphosphino-9,9-dimethyloxaindole (0.2 mmol) was placed in a 50 mL three-necked flask, and while stirring, the degassing and nitrogen substitution were repeated three times, and 20 mL of toluene was added by a syringe.The mixture was heated to reflux for 3 hours under a stream of nitrogen.After the reaction, it is added to the reaction solution which is left to cool to room temperature.The water was extracted with dichloromethane and washed with saturated brine.After drying the organic layer with anhydrous sodium sulfate, the solvent is distilled off and purified by column chromatography.Intermediate S3 (9 mmol, 90%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With copper; potassium carbonate; In ethylene glycol; at 100℃; for 1h;Inert atmosphere; | 9.9-dimethyl acridine (10 g, 47.8 mmol) under nitrogen<strong>[112671-42-8]4-bromo-1-iodo-2-nitrobenzene</strong> (32.74 g, 99.85 mmol),Potassium carbonate (13.8 g, 99.85 mmol), copper (6.35 g, 99.85 mmol),Ethylene glycol (350 ml) was stirred, and the reaction was stirred at about 100 C for about 1 hour.It was extracted with acetone, and the organic layer was taken, and a hydrochloric acid solution (hydrochloric acid: deionized water = 1:10 vol.%) (500 ml) was added.After washing with deionized water,Recrystallization of acetone and methanol,Intermediate 1-1 (12 g, 59%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 48h; | Intermediate 5 (1.0 g, 1.93 mmol), 9,9'-dimethyl acridine (1.26 g, 5.98 mmol), sodium tert-butoxide(0.93 g, 9.69 mmol), palladium acetate (0.035 g, 0.16 mmol), tri-tert-butylphosphine tetrafluoroborate (0.34 g, 1.17 mmol)Add to a 100 mL round bottom flask with 40 mL of toluene, reflux at 110 C for 48 hours, then dissolve with 10 mL of saturated sodium chloride.The solution was quenched with methylene chloride, dried over anhydrous sodium sulfate and then dichloromethane/ petroleum ether (v/v = 1 :1) Separation by silica gel column chromatography as a eluent. The product was a yellow powder with a yield of 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 48h; | Intermediate 3 (1.3 g, 3.60 mmol), 9,9'-dimethyl acridine (0.98 g, 4.67 mmol), sodium tert-butoxide(0.58 g, 6.04 mmol), palladium acetate (0.023 g, 0.10 mmol), tri-tert-butylphosphine tetrafluoroborate (0.088 g,0.30 mmol) was added to a 100 mL round bottom flask with 40 mL of toluene, refluxed at 110 C for 48 hours, then 10 mL of saturated chlorine.Quenching the aqueous solution of sodium chloride, first extracting with dichloromethane, drying with anhydrous sodium sulfate, and finally using dichloromethane/petroleum ether(v/v = 2: 3) Separation by silica gel column chromatography as a eluent. The product was a yellow powder with a yield of 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With caesium carbonate; In dimethyl sulfoxide; at 20 - 60℃; for 10h; | 9.9-dimethyl acridine (10 g, 47.8 mmol) under nitrogen1-fluoro-2-nitrobenzene (7.4 g, 52.6 mmol), cesium carbonate (13.8 g, 71.7 mmol) was stirred in a solvent dimethyl sulfoxide.After stirring at room temperature for about 2 hours, the temperature was raised to 60 C and stirred for 8 hours.It was extracted three times with dichloromethane and deionized water, and after rotary evaporation, dried over anhydrous MgSO4.The compound was recrystallized from methylene chloride / methanol to afford Intermediate 1-1 (14.1 g, 89%).Mass Spectrum: theoretical value 330, measured 330.14. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.8 g | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In toluene; for 10h;Inert atmosphere; Reflux; | 1-Phenyl-3,5-dibromobenzene (3.1 g, 10 mmol), 9,9-dimethyl acridine (2.3 g, 11 mmol) was added to a reaction flask, sodium t-butoxide (1.2 g, 12 mmol), Pd2(dba)3 (0.1g, 0.1mmol), 50ml of toluene were added to the reaction flask in sequence, nitrogen The reaction was refluxed for 10 hours under reduced pressure, cooled to room temperature, water (100 ml) was added, and the mixture was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined and washed with saturated brine and water. After passing through a silica gel column, 2.8 g of product was obtained, and HPLC purity was 99.3% to give S5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 50 - 150℃;Inert atmosphere; | (1) In a 500mL three-necked bottle,Put 9,9-dimethyl-9,10-dihydroacridine (12.56 g, 60 mmol),<strong>[89598-96-9](3-bromophenyl)boronic acid</strong> (12.05 g, 60 mmol),Sodium tert-butoxide (11.52 g, 120 mmol),Tri-tert-butylphosphine tetrafluoroborate (0.07 g, 0.24 mmol), 200 mL of toluene,Palladium acetate (0.03 g, 0.12 mmol) was added under a nitrogen atmosphere.The temperature is raised to 50-150 ° C for 4 to 48 hours, and the liquid phase monitoring reaction is completed.Cool to room temperature, add 50 ~ 200mL petroleum ether, filter,The solid was beaten with a mixture of hexane and dichloromethane.17.38 g of (3-(9,9-dimethylacridin-10(9H)-yl)phenyl)boronic acid can be obtained.Yield 88percent |
88% | With tri-tert-butylphosphine tetrafluoroborate; palladium diacetate; sodium t-butanolate; In toluene; at 50 - 150℃;Inert atmosphere; | (1) In a 500mL three-necked bottle, 9,9-dimethyl-9,10-dihydroacridine (12.56 g, 60 mmol), <strong>[89598-96-9](3-bromophenyl)boronic acid</strong> (12.05 g, 60 mmol), sodium tert-butoxide (11.52 g, 120 mmol), tri-tert-butylphosphine tetrafluoroborate (0.07 g, 0.24 mmol), 200 mL of toluene, palladium acetate (0.03 g, 0.12 mmol) was added under a nitrogen atmosphere, and the temperature was raised to 50 to 150 ° C for 4 to 48 hours. The liquid phase monitoring reaction was completed, cooled to room temperature, 50-200 mL of petroleum ether was added, filtered, and the solid was beaten with a mixture of hexane and dichloromethane. 17.38 g of (3-(9,9-dimethylacridin-10(9H)-yl)phenyl)boronic acid was obtained in a yield of 88percent; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 24h;Inert atmosphere; | 2-bromo-5-iodo1,3-xylene (10 mmol), 9,9-dimethyl acridine (10 mmol), Cu under a nitrogen atmosphere(20 mmol), K2CO3 (20 mmol) and N,N-dimethylformamide (20 ml) were combined to form a solution.Mixing the above mixed solution with nitrogenThe vacuum was evacuated three times and heated and stirred at 130 C for 24 h. The reaction mixture was filtered through celite and usedWash with dichloromethane (20 ml).The solvent was evaporated under reduced pressure and purified by column chromatography (hexane/dichloromethane: 10:1) to yield white crystals of 9-(4-bromo-3,5-dimethylphenyl)-dimethyl acridine. S2-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.9% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; sodium t-butanolate; In toluene; at 111℃; for 24h;Inert atmosphere; | Under argon protection,Add 316 g (0.5 mol) of B1 to a 1000 mL reactor equipped with a reflux unit.252 g (0.6 mol) of 9,9-dimethyl acridine,4.5 g (20 mmol) of Pd(OAc) 2, 124.9 g (1.3 mol) of tBuONa, 17.4 g (60 mmol) of HPtBu3BF4, and 600 mL of toluene.Heating (heating temperature 111 C) was refluxed for 24 hours.After the reaction system is cooled to room temperature,Adding a large amount of water and dichloromethane to it for extraction,The extracted organic phase is dried over anhydrous sodium sulfate.Filtration followed by distillation of the organic liquid phase gave a crude product.The crude product is purified by column chromatography.Obtained 298 g of red powder,That is, the red heat-activated delayed fluorescent material having circular polarization luminescent properties of the present invention.The red powder was C1 and the yield was 66.9%. |
66.9% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 24h;Reflux; Inert atmosphere; | General procedure: Themixture of (-)-(R,R)/(+)-(S,S)-CAI-Br (1.58 g, 2.50 mmol), 9,9-dimethyl-9,10-dihydro- acridine (DMAC, 1.26 g, 6.00 mmol), Pd(OAc)2(22.5 mg, 0.1 mmol), tBuONa (624.65 mg, 6.50 mmol), and HPtBu3BF4(87.04 mg, 0.3 mmol) in 40 mL toluene was refluxed under argon for24 h. After cooling to room temperature, the reaction mixture was extractedwith dichloromethane, washed with brine and dried over anhydrousMgSO4. After the solvent was removed under reduced pressure,the residue was purified by column chromatography to give the targetchiral materials as orange-red solids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.2% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; sodium t-butanolate; In toluene; at 111℃; for 24h;Inert atmosphere; | Under argon protection,Add 316 g (0.5 mol) of B2 to a 1000 mL reactor equipped with a reflux unit.252 g (0.6 mol) of 9,9-dimethyl acridine,4.5 g (20 mmol) of Pd(OAc) 2, 124.9 g (1.3 mol) of tBuONa, 17.4 g (60 mmol) of HPtBu3BF4, and 600 mL of toluene.Heating (heating temperature 111 C) was refluxed for 24 hours.After the reaction system is cooled to room temperature, a large amount of water and dichloromethane are added thereto for extraction.The extracted organic phase is dried over anhydrous sodium sulfate.Filtration followed by distillation of the organic liquid phase gave a crude product.The crude product is purified by column chromatography.Get 290g of red powder,That is, the red heat-activated delayed fluorescent material having circular polarization luminescent properties of the present invention.The red powder was C2 and the yield was 65.2%. |
65.2% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 24h;Reflux; Inert atmosphere; | General procedure: Themixture of (-)-(R,R)/(+)-(S,S)-CAI-Br (1.58 g, 2.50 mmol), 9,9-dimethyl-9,10-dihydro- acridine (DMAC, 1.26 g, 6.00 mmol), Pd(OAc)2(22.5 mg, 0.1 mmol), tBuONa (624.65 mg, 6.50 mmol), and HPtBu3BF4(87.04 mg, 0.3 mmol) in 40 mL toluene was refluxed under argon for24 h. After cooling to room temperature, the reaction mixture was extractedwith dichloromethane, washed with brine and dried over anhydrousMgSO4. After the solvent was removed under reduced pressure,the residue was purified by column chromatography to give the targetchiral materials as orange-red solids. (-)-(R,R)-CAI-DMAC (1.45 g, 65.2%). 1H NMR (500 MHz, CDCl3):delta 8.85-8.83 (m, 1H), 8.71-8.69 (m, 1H), 8.66-8.64 (m, 1H), 8.52-8.50(m, 1H), 7.97-7.90 (m, 2H), 7.76-7.74 (m, 1H), 7.68 (d, J=7.7 Hz,1H), 7.63-7.44 (m, 6H), 6.98-6.66 (m, 8H), 6.58-6.46 (m, 2H),5.90-5.85 (m, 4H), 2.77 (d, J=23.2 Hz, 2H), 2.08-1.92 (m, 4H),1.84-1.63 (m, 14H). 13C NMR (126 MHz, CDCl3): delta 164.3, 164.2, 164.0,163.9, 143.7, 143.6, 140.0, 132.9, 132.6, 132.2, 131.8, 130.7, 130.53,130.48, 130.3, 129.8, 129.6, 129.5, 127.9, 127.7, 126.7, 125.9, 124.5,123.8, 123.7, 123.0, 122.9, 121.2, 121.1, 114.0, 113.9, 53.6, 53.4,53.2, 36.0, 32.7, 32.6, 32.1, 29.6, 29.4, 29.2, 25.6. HR-MS (APCI): m/zcalcd for C60H49N4O4+ [M + H]+ 889.3748, found 889.3741. Anal.calcd for C60H48O4N4: C, 81.06; H, 5.44; N, 6.30. Found: C, 81.07; H,5.44; N, 6.15. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.4% | Reflux tube,25ml with thermometerIn a four-necked flask, 0.452 g (1.5 mmol) of 2Cl-PRZ, 0.628 g (3 mmol) of 9,10-dihydro-9,9?-dimethylacridine (DMAC), 0.432 g (4.5 mmol) of t-BuONa And nitrogen flow was performed for 15 minutes. After nitrogen flow, 20 ml of xylene was added and nitrogen bubbling was performed for 1 hour. After nitrogen bubbling, 16.8 mg (0.075 mmol) of Pd (OAc) 2 and 65.3 mg (0.45 mmol) of (t-Bu) 3 P were added and refluxed at 137 C. for 12 hours. The disappearance of the raw material was confirmed by TLC, and the reaction was completed (red black solution). The mixture was cooled to room temperature and extracted by suction filtration and liquid separation. After extraction, purification was performed by silica gel column chromatography (silica gel: 170 cc, developing solvent: toluene). The fraction considered to be the target product was collected to obtain a yellow viscous body, and after drying under reduced pressure at 60 C., 0.761 g (yield: 78.4%) of a white yellow solid was obtained. Further, this white yellow solid was purified by sublimation to obtain 2Ac-PRZ. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 20 - 90℃; for 2h;Inert atmosphere; | General procedure: general procedure for Buchwald-Hartwig cross-couplingreaction. Tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.04equiv.) and tri-tert-butylphosphine ((t-Bu)3P, 0.04 equiv.) were dissolvedunder argon in dry toluene and stirred for 10 min at room temperature.Then, Br-BP-TA or Br-DPS-TA (1.0 equiv.), 9,9-dimethyl-10Hacridane(1.2 equiv.), sodium-tert-butoxide (t-BuONa, 6.0 equiv.) anddry toluene were added. The reaction mixture was heated at 90 C for2 h. After cooling, the reaction mixture was diluted with DCM and theorganic phase was washed with water and brine. After being dried overNa2SO4 and filtered, the solvent was removed and the residue waspurified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 20 - 90℃; for 2h;Inert atmosphere; | General procedure: general procedure for Buchwald-Hartwig cross-couplingreaction. Tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.04equiv.) and tri-tert-butylphosphine ((t-Bu)3P, 0.04 equiv.) were dissolvedunder argon in dry toluene and stirred for 10 min at room temperature.Then, Br-BP-TA or Br-DPS-TA (1.0 equiv.), 9,9-dimethyl-10Hacridane(1.2 equiv.), sodium-tert-butoxide (t-BuONa, 6.0 equiv.) anddry toluene were added. The reaction mixture was heated at 90 C for2 h. After cooling, the reaction mixture was diluted with DCM and theorganic phase was washed with water and brine. After being dried overNa2SO4 and filtered, the solvent was removed and the residue waspurified by column chromatography.4-(9,9-Dimethylacridan-10-yl)-4?-(thianthrene-1-yl)benzophenone (ABP-TA) was prepared by method B from Pd2(dba)3 (0.04 g,0.042 mmol), (t-Bu)3P (0.009 g, 0.042 mmol), Br-BP-T (0.50 g,1.0 mmol), 9,9-dimethyl-10H-acridane (0.25 g, 1.2 mmol), t-BuONa(0.58 g, 6.0 mmol) and 20 mL of dry toluene. The crude product waspurified by column chromatography using hexane/DCM (1/1) aseluent. The product was crystallized from the eluent and was obtainedas yellow crystals (fw=603 g/mol, mp=185-186 C) in 82% yield.1H NMR (400 MHz, CDCl3), delta (ppm): 8.16 (d, J=8.4 Hz, 2H, Ar),8.04 (d, J=8.3 Hz, 2H, Ar), 7.60 (d, J=8.1 Hz, 2H, Ar), 7.57-7.48 (m,6H, Ar), 7.41 (dd, J=7.6, 1.5 Hz, 1H, Ar), 7.35-7.19 (m, 4H, Ar),7.05-6.96 (m, 4H, Ar), 6.38 (dd, J=8.0, 1.4 Hz, 2H, Ar), 1.71 (s, 6H,CH3).13C NMR (100 MHz, CDCl3), delta (ppm): 195.47, 145.49, 144.61,141.36, 140.50, 137.01, 136.52, 136.23, 136.09, 135.55, 134.94,132.70, 130.96, 130.69, 130.04, 129.67, 129.12, 128.92, 128.85,128.63, 127.97, 127.71, 127.30, 126.45, 125.37, 121.14, 114.41,36.11, 31.11.IR numax in cm-1: (CH Ar) 3067; (CH Al) 2957; (C=O) 1655, 1603;(C=C Ar) 1472; (CN) 1268; (CH Ar) 925; (CS) 745.MS (APCl+, 20 V), m/z (%) = 604 ([M+H]+, 100).Elemental analysis. Calcd. for C40H29NOS2 (%): C 79.57, H 4.84, N2.32, O 2.65, S 10.62. Found (%): C 79.60, H 4.82, N 2.35, O 2.63. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.1% | 7.32 g (35 mmol) of 9,9-dimethyl acridine was added to a 250 ml three-necked flask, 100 ml of N,N-dimethylformamide was added as a reaction solvent, and the mixture was stirred on a magnetic stirrer in an ice bath. 10min. 0.72 g (30 mmol) of NaH was added portionwise to the reaction flask and stirring was continued for 1 h. 2.07 g (10 mmol) of <strong>[3029-64-9]2,4,6-trichloro-5-cyanopyrimidine</strong> was dissolved in 40 ml of N,N-dimethylformamide solution, and added dropwise to the reaction system. After the addition, at room temperature The reaction was carried out for 24 h. After the reaction was completed, the reaction solution was poured into 200 ml of 10percent diluted hydrochloric acid, and the mixture was filtered under reduced pressure, washed with water and dried, and the crude product was obtained from petroleum ether and dichloromethane (PE: DCM=10: 1) Pass the column for the mobile phase. 4.29 g of a white solid powder was obtained in a yield of 59.1percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | 9,9-Dimethyl-9,10-dihydroacridine (2.09 g, 10 mmol), 2-bromo-5-iodobenzene (1.57 mL, 2.07 g/ml, 11 mmol), cuprous iodide ( 0.38g, 0.2mmol)Sodium tert-butoxide (1.92 g, 20 mmol) was added to the reaction flask, and nitrogen gas was exchanged three times (10 min/time), and the solvent (1,4-dioxane) was injected under a nitrogen atmosphere.After the raw material is partially dissolved, inject 2ml.1,2-diaminocyclohexane (coordinating agent),After the injection, the reaction was refluxed at 110 C for 6 h, extracted, concentrated, and powdered.Purification by column chromatography gave a white solid product 2, yield 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 120℃; for 24h;Inert atmosphere; Glovebox; | The synthetic route of the target compound 1 is as follows: To a 100 mL two-necked flask was added raw material 1 (1.93 g, 5 mmol), <strong>[6267-02-3]9,10-dihydro-9,9-dimethylacridine</strong> (1.25 g, 6 mmol), palladium acetate Pb (OAc) (45 mg, 0.2 mmol). And tri-tert-butylphosphine tetrafluoroborate (t-Bu)3HPBF4 (0.17 g, 0.6 mmol), then sodium tert-butoxide NaOt-Bu (0.58 g, 6 mmol) was added to a glove box Under a argon atmosphere, 40 mL of toluene which was previously deaerated by water and deoxygenated was charged, and reacted at 120 C for 24 hours. The mixture was cooled to room temperature, and the reaction solution was poured into 200 mL of ice water, and extracted with dichloromethane three times. The organic phase was combined, and the mixture was separated into silica gel, and purified by column chromatography (dichloromethane: n-hexane, v: v, 3:2). 2.3 g of compound 1 in white powder, yield 89%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium phosphate; copper(l) iodide; trans-1,2-Diaminocyclohexane at 110℃; for 24h; Inert atmosphere; | 2 Synthesis of Compound P8 Weigh S1 (8.0 mmol), S8 (4.0 mmol),CuI (0.4 mmol), trans 1,2-diaminocyclohexane(0.48 mmol), anhydrous K3PO4 (8.0 mmol), under a nitrogen atmosphere40 mL of toluene was added and reacted at 110 ° C for 24 h.The reaction mixture was cooled to room temperature.The reaction mixture was quenched by the addition of an appropriate amount of aqueous ammonium chloride.The organic phase was extracted 3 times with dichloromethane (80 mL) and the organic phase was collected.And dried with anhydrous Na2SO4. Filter the dried solution,The solvent was removed by a rotary evaporator to give a crude material.The crude product was purified by silica gel column chromatography.Using n-hexane/dichloromethane (3/1) as eluent, Final purification to obtain a solidS9 (2.4 mmol, 60%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Stage #1: 9,9‐dimethyl‐10H‐acridine With sodium t-butanolate In dimethyl sulfoxide at 20℃; for 0.0833333h; Stage #2: 2,3,4,5,6-pentafluorostyrene In dimethyl sulfoxide at 20℃; for 10h; | 2.2. General procedure for the synthesis of monomers General procedure: Sodium tert-butoxide (1.2 eq) was added to the DMSO or DMF solutionof NH-heterocyclic compound (1 eq) and stirred for 5 min atroom temperature for the salt formation. The mixture was addeddropwise to the solution of 2,3,4,5,6-pentafluorostyrene (1.5 eq) inDMSO or DMF. The reaction mixture was stirred for 10 h at ambienttemperature. Then the reaction mixture was poured into water andextracted with ethyl acetate. The organic phase was collected, driedover anhydrous Na2SO4 and concentrated under reduced pressure. Thecrude product was purified by column chromatography on silica gelusing hexane and dichloromethane in a volume ratio of 5:1 as eluentmixture of solvents. The product was recrystallized from eluent mixtureof solvents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 110℃; for 24h; Inert atmosphere; | |
70% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 110℃; for 48h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.7% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 110℃; for 72h;Inert atmosphere; | Specifically: 5-bromobenzo[b]thiophene 1,1-dioxide (2.43 g, 10.0 mmol), carbazole (2.29 g, 11.0 mmol), Pd(OAc) 2 (0.0225 g, 0.1 mmol) , t-BuONa (0.0192g, 0.2mmol) and P(tBu)3 (0.1mL) were added to a round bottom flask containing 100mL of toluene, argon gas for 30min, then argon gas protection, 110 C reaction for 72h, cooling After room temperature, the solvent was evaporated, then extracted with EtOAc (EtOAc) The solvent was removed to give a crude product which was purified by column chromatography to afford product (3.2 g, 85.7%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In (2)H8-toluene; at 110 - 130℃; for 24h; | The intermediate and the first raw material containing the group R1, the catalyst, and sodium tert-butoxide were added to a three-necked flask, and argon was used for pumping.The first raw material is <strong>[6267-02-3]9,10-dihydro-9,9-dimethylacridine</strong>;The molar ratio of the first raw material to the intermediate is 5: 8 to 5: 6;The catalyst includes palladium acetate and tri-tert-butylphosphine tetrafluoroborate;The palladium acetateThe molar ratio to the tri-tert-butylphosphine tetrafluoroborate is 1: 5 to 1: 3. Dehydrated toluene was added to the reaction container, and the reaction was performed at a temperature of 110 C. to 130 C. for 24 hours. After cooling to room temperature, a first mixed solution was obtained.The first mixed solution was introduced into 180 to 220 ml of ice water, and extracted with dichloromethane for multiple times to obtain an extract. The extract is dried over anhydrous sodium sulfate, filtered, and spin-dried, and then subjected to column chromatography with silica gel of 200 to 300 mesh, and rinsed with eluent to obtain the target compound 1, which is a light of the present invention. The output material is coupled with a yield of 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 12h;Inert atmosphere; Reflux; | 9,9-Dimethylacridine (0.70 g, 4.78mmol) and <strong>[18648-66-3]2-(4-bromophenyl)-1,1-diphenylethylene</strong> (1.34 g, 5.74 mmol) were dissolved in anhydroustoluene (10 ml) under Ar. Sodium tert-butoxide (0.64 g, 9.56 mmol), palladium acetate (0.02 g, 0.09mmol), and a solution of tri-tert-butylphosphine in toluene (1.00 M, 0.02 ml, 0.09 mmol) were addedto the solution and the reaction mixture was refluxed for 12 h. When the reaction was finished (TLCcontrol), the mixture was cooled down to the room temperature and extracted with ethyl acetate. Theorganic extract was washed with water and dried (Na2SO4). Then, the solvent was evaporated undervacuum. The product was purified by silica gel column chromatography using hexane as an eluent.White crystals were obtained after recrystallization from hexane with the yield of 72% (1.11 g). Mp =188-191 C. MS (ES+), m/z = 463 [M]+. 1H NMR (400 MHz, CDCl3) delta (ppm): 1.57 (s, 6H), 6.19 (d, J = 8.1Hz, 2H), 6.82 (t, J = 7.3 Hz, 2H), 6.88 (t, J = 7.6 Hz, 2H), 6.98-7.02 (m, 3H), 7.17 (d, J = 8.3 Hz, 2H), 7.19-7.22 (m, 2H), 7.23-7.32 (m, 8H), 7.34 (d, J = 6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) delta (ppm): 31.1, 35.9,114.1, 120.5, 125.1, 126.3, 127.2, 127.6, 127.7, 127.8, 128.3, 128.8, 130.1, 130.3, 130.8, 131.9, 137.4, 139.4,140.1, 140.9, 143.2, 143.7. IR numax (KBr): 3054, 3028 (C-H, Ar); 2958 (C-H); 1587 (C6H5-); 1471, 1446 (-CH3); 1321 (Ph-CH3); 1267 (C-N-, Ar); 923, 751 (C=C-H); 698 (CH=CH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 108℃; for 13h; | In a flask, 2PTO (1.65 g, 5 mmol), DMAc (1.05 g, 5 mmol), palladiumacetate (0.07 g, 0.4 mmol), tri-tert-butylphosphine tetrafluoroborate(0.09 g, 0.4 mmol), t-BuONa (0.98 g, 10 mmol), and toluene (50 mL)were mixed and heated to 108 C about 13 h. After the solution wascooled to 25 C, using dichloromethane to extract and then anhydrousMgSO4 to dry over. Then get rid of dichloromethane under decreasingpressure, a white product (yield 90%) was obtained by column chromatography.1H NMR (400 MHz, CDCl3) [ppm]: 8.41 (d, J 8.4 Hz,1H), 8.23 (d, J 7.6 Hz, 1H), 7.62-7.50 (m, 3H), 7.43-7.29 (m, 6H),7.20 (d, J 8.0 Hz, 1H), 6.99-6.92 (m, 4H), 6.67 (s, 1H), 6.62 (d, J 8.8 Hz, 1H), 6.23 (d, J 7.6 Hz, 2H), 1.61 (s, 6H). 13C NMR (100 MHz,CDCl3) [ppm]: 145.75, 143.06, 140.85, 140.10, 138.44, 132.99, 131.58, 130.81, 130.07, 129.93, 126.50, 125.39, 124.00, 123.45,122.85, 122.54, 121.65, 121.30, 119.03, 117.51, 114.55, 36.01, 31.11.MS (MALDI-TOF): calculated for C33H26N2O2S, 514.17; found 514.32,[M]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.22% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos In toluene Inert atmosphere; Reflux; | Synthesis of Intermediate 5: Add 9,9-dimethyl-9,10-dihydroacridine (1.0g, 4.782mmol) into the two-necked flask,Intermediate 2 (5.839g, 14.346mmol), sodium tert-butoxide (1.149g, 11.955mmol),2-Dicyclohexylphospho-2,4,6-triisopropylbiphenyl (XPhos) (227.97mg, 0.478mmol)And three (dibenzylideneacetone) two palladium (218.95mg, 2.391mmol),Then vacuumize and release nitrogen,Replace three times.Add 30mL of toluene as a solvent to the two-necked bottle,The reaction was heated at reflux and stirred overnight.After the reaction,The reaction solution was extracted with dichloromethane,Dry with absolute ethanol,The organic solvent was spun off by evaporation under reduced pressure.Using petroleum ether as the eluent, 980 mg of white granular solid compound 26 was obtained.The yield was 38.22%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9,9-Dimethylacridine (2.30 g, 11 mmol) was dissolved in 50 mL of N,N-dimethylformamide (DMF) and stirred at 0C under argon atmosphere. Anhydrous potassium tert-butoxide (1.68 g, 15 mmol) was added to the reaction system in batches, and stirring was continued at 0 C. for 5 h. The 4-fluoro-4'-bromobenzophenone (2.79 g, 10 mmol) prepared in Preparation Example 1 was slowly added to the above reaction system, the temperature was naturally raised to room temperature, and the reaction was continued for 12 h. The temperature was raised to 60 C, and the reaction was continued to stir for 12 h, and then lowered to room temperature. The reactant was poured into dilute hydrochloric acid solution, washed with water for three times, and fully extracted with dichloromethane. The dichloromethane organic phase was dried over sufficient anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give the crude product. The crude product was separated by column chromatography (the eluent was a mixed solvent of petroleum ether and dichloromethane with a volume ratio of 5:1) to obtain the first intermediate (4-bromo-4'-(9,9-dichloromethane). methylacridine)-benzophenone). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 9,9‐dimethyl‐10H‐acridine With Cs2CO3 In N,N-dimethyl-formamide at 60℃; for 0.25h; Inert atmosphere; Stage #2: 2,5-dibromo-1,3-difluorobenzene In N,N-dimethyl-formamide at 155℃; for 12h; Inert atmosphere; | 3.1 1) Synthesis of intermediate (3) First, 9,9-dimethylacridine (DMAC) (9.21 g, 44 mmol), Cs2CO3(32.50 g, 100 mmol) were sequentially added to a 250 mL two-necked round-bottomed flask, and then, under the condition of Ar atmosphere , 50 mL of ultra-dry DMF was injected through a syringe to obtain a suspension, which was stirred at 60 °C for 15 min.Finally, 5-bromo-2-chloro-1,3-difluorobenzene (5.44 g, 20 mmol) was added at one time from the side opening of the reaction flask, and the temperature was raised to 155° C. for 12 h.After the reaction was completed, it was lowered to room temperature, the insoluble inorganic salt was filtered off, and then the high-boiling DMF solvent was removed by vacuum concentration, and the residue was purified by a column machine, and the optimized eluent formula was DCM/PE (1:5, v/v) to give intermediate (3) as a white powder. |
Tags: 6267-02-3 synthesis path| 6267-02-3 SDS| 6267-02-3 COA| 6267-02-3 purity| 6267-02-3 application| 6267-02-3 NMR| 6267-02-3 COA| 6267-02-3 structure
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