Structure of 589-87-7
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Rajapaksha, Ishanka N. ; Wang, Jing ; Leszczynski, Jerzy ; Scott, Colleen N. ;
Abstract: NIR dyes have become popular for many applications, including biosensing and imaging. For this reason, the mol. switch mechanism of the xanthene dyes makes them useful for in vivo detection and imaging of bioanalytes. Our group has been designing NIR xanthene-based dyes by the donor-acceptor-donor approach; however, the equilibrium between their opened and closed forms varies depending on the donors and spacer. We synthesized donor-acceptor-donor NIR xanthene-based dyes with an alkyne spacer via the Sonogashira coupling reaction to investigate the effects of the alkyne spacer and the donors on the maximum absorption wavelength and the mol. switching (ring opening) process of the dyes. We evaluated the strength and nature of the donors and the presence and absence of the alkyne spacer on the properties of the dyes. It was shown that the alkyne spacer extended the conjugation of the dyes, leading to absorption wavelengths of longer values compared with the dyes without the alkyne group. In addition, strong charge transfer donors shifted the absorption wavelength towards the NIR region, while donors with strong π-donation resulted in xanthene dyes with a smaller equilibrium constant DFT/TDDFT calculations corroborated the exptl. data in most of the cases. Dye 2 containing the N,N-dimethylaniline group gave contrary results and is being further investigated.
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Keywords: donor-acceptor-donor ; NIR dyes ; xanthene dyes ; amine donors ; alkyne spacers
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Purchased from AmBeed: 589-87-7 ; 768-60-5 ; 201802-67-7 ; 262861-81-4 ; 57102-42-8 ; 17573-94-3 ; 1066-54-2 ; 205877-26-5 ; 28611-39-4 ; 1195931-66-8
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CAS No. : | 589-87-7 |
Formula : | C6H4BrI |
M.W : | 282.90 |
SMILES Code : | C1=CC(=CC=C1Br)I |
MDL No. : | MFCD00001051 |
InChI Key : | UCCUXODGPMAHRL-UHFFFAOYSA-N |
Pubchem ID : | 11522 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.49 |
Solubility | 0.00923 mg/ml ; 0.0000326 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.4 |
Solubility | 0.112 mg/ml ; 0.000397 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.2 |
Solubility | 0.0181 mg/ml ; 0.0000638 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.39 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.22 |
* 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 |
---|---|---|
74.6% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water; toluene for 5 h; Reflux | A mixture of 1-bromo-4-iodobenzene (2.0 g, 7.07 mmol), 4,4,5,5-tetramethyl-2-(thiophen-2-yl)-1,3,2-dioxaborolane (2.97 g, 14.1 mmol), Pd(PPh34 (408 mg, 0.35 mmol), and Na2CO3 (1.49 g, 14.1 mmol) were dissolved in toluene (40 mL), THF (15 mL), and H2O (15 mL) and the reaction mixture was refluxed for 5 h. After completion of the reaction (indicated by TLC), the solvent was removed under vacuum, H2O (30 mL) and CH2Cl2 (40 mL) were added. The organic layer was separated and dried on anhydrous MgSO4. The solvent was removed under reduced pressure. Then the crude product was purified by flash column chromatography on silica gel to give 2-(4-bromophenyl) thiophene (1.26 g, 74.6percent). Spectral data matched well with values reported in the literature.27 1HNMR (400 MHz, CDCl3: 7.48 (d, 3.6 Hz, 4 H), 7.29(d, 4.4 Hz, 2 H), 7.07 (dt, 1.4, 4.4 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere; | The compound 1-bromo-4-iodobenzene (20 g, 104.5 mmol) was dissolved in 0.5 L of tetrahydrofuran (THF) in a nitrogen atmospherePyridin-4-yl-boronic acid (15.4 g, 125.4 mmol) and tetrakis (triphenylphosphine) palladium (1.2G, 1 mmol) were added and stirred. Saturated water-saturated potassuim carbonate (17.3 g, 125.4 mmol) was added and heated to 80 CThe mixture was heated to reflux for a period of time. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM)The water was removed with MgSO4, filtered and concentrated under reduced pressure. The residue thus obtained was purified by flash column chromatographySeparation and purification were conducted to obtain the compound I-6 (15 g, 80%). |
58% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 20 - 110℃; for 24.166h;Inert atmosphere; | Specifically: under argon protection, p-bromoiodobenzene (3.4 g, 12 mmol), 4-pyridineboronic acid (1.3 g, 10 mmol), tetrakis(triphenylphosphine)palladium (0.58 g, 0.5 mol) and sodium carbonate (3.2 g, 30 mmol) was added to a 250 mL three-neck bottle. After adding toluene (100 mL), ethanol (30 mL) and water (10 mL), the mixture was evaporated, and then stirred at room temperature for 10 minutes, then heated to reflux to 110 C and stirred for 24 h. Then, it was filtered, concentrated, extracted with saturated brine, dried, and purified by column chromatography to give the product 4-pyridinebromobenzene (yield 58%). |
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 80℃; | EXAMPLE 3; Synthesis of (2S)-N-(cyanomethyl)-4-methyl-2-[(R)-phenyl(4'-pyridin-4-yl-1,1'-biphenyl-4-yl)methyl]oxy} pentanamide; Step 1 4-(4-bromophenyl)pyridine; Pyridin-4-ylboronic acid (500 mg, 4.07 mmol), 1-bromo-4-iodobenzene (1.27g, 4.47 mmol) and 2M Na2CO3 (6.1 ml, 12.2 mmol) were dissolved in 20 ml DMF and the solution was degassed 3 times. PdCl2(dppf) (149mg, 0.203 mmol) was added and the mixture was stirred overnight at 80C. The solution was cooled, poured into 100 ml NaHCO3 (sat.) and extracted 3 times with 20ml ethyl acetate. The combined organic layers were then washed with 4 x water, then dried with Na2SO4. 4-(4-bromophenyl)pyridine was obtained and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 85℃; for 4h; | A mixture of pyridine-3-boronic acid 1,3-propanediol cyclic ester, 4-bromoiodobenzene (1.1 eq), [1,1'-bis (diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq) and 2M aqueous sodium carbonate (5 eq) in N,N-dimethylformamide (2 ml/mmol) was stirred at 85 C. for 4 hours. After quenching with saturated aqueous ammonium chloride solution, the mixture was partitioned between ethyl acetate and water, and the crude product from the organic phase was chromatographed on silica gel eluting with a 1:9 mixture of ethyl acetate and hexane to afford the 3-(4-Bromophenyl)pyridine compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; ethyl acetate; N,N-dimethyl-formamide; | Step 2 3-(4-Bromophenyl)Pyridine A mixture of pyridine-3-boronic acid 1,3-propanediol cyclic ester, 4-bromoiodobenzene (1.1 eq), [1,1'-bis (diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq) and 2M aqueous sodium carbonate (5 eq) in N,N-dimethylformamide (2 ml/mmol) was stirred at 85° C. for 4 hours. After quenching with saturated aqueous ammonium chloride solution, the mixture was partitioned between ethyl acetate and water, and the crude product from the organic phase was chromatographed on silica gel eluding with a 1:9 mixture of ethyl acetate and hexane to afford the 3-(4-Bromophenyl)pyridine compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; ethyl acetate; N,N-dimethyl-formamide; | Step 1: 3-(4-Bromophenyl)pyridine. A mixture of pyridine-3-boronic acid 1,3-propanediol cyclic ester, 4-bromoiodobenzene (1.1 eq), [1,1'-bis (diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq) and 2M aqueous sodium carbonate (5 eq) in N,N-dimethylformamide (2 mL/mmol) was stirred at 85° C. for 4 hours. After quenching with saturated aqueous ammonium chloride solution the mixture was partitioned between ethyl acetate and water and the crude product from the organic phase was chromatographed on silica gel eluding with a 1:9 mixture of ethyl acetate and hexane to afford the 3-(4-bromophenyl)pyridine compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With caesium carbonate;palladium diacetate; In 1,4-dioxane; | Part A. 1-Benzyl-4-(4-bromo-phenyl)-[1,4]diazepan-5-one: Commercially available <strong>[55186-89-5]1-benzyl-(1,4)-diazepan-5-one</strong> (14.7 mmol), p-bromoiodobenzene (1 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.15 eq), cesium carbonate (1.5 eq), and palladium acetate (0.1 eq) were placed in a round bottom flask and it was evacuated and flushed 3* with nitrogen. To this mixture was then added 200 mL of dioxane and the resulting solution was again evacuated and flushed 3* times with nitrogen gas. The mixture was allowed to stir at 75 C. overnight during which time the mixture turned from brown to bright yellow suspension. The mixture was cooled and diluted with dichloromethane and then was filtered through a pad of celite. The filtrate was removed under reduced pressure and the residue was purified by flash column chromatography eluding with 50% EtOAc/Hex to give compound 1 as an off-white solid (63%). Mass spectrum, ESI (M+H) 359.3, 361.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.0% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; for 1.5h;Inert atmosphere; Reflux; | In a 1000 ml reaction flask, with mechanical stirring, Ar gas protection, adding 10. 01g (molecular weight 282,0 · 0355 mol), pyridine -3-boric acid 4 · 37 g (molecular weight 123, 0.0355 mol), catalyst Pd (PPh3) 4 dosage 2 · 14g (molecular weight 1154, 0.00185mol), sodium carbonate aqueous solution 200ml (2M), toluene 200ml, ethyl 200ml. The mixture was stirred under reflux and the reaction was monitored by TLC. After 1.5 hrs of reaction, the plate was found and the reaction was found to be complete. It was cooled, extracted with ethyl acetate, evaporated to dryness and purified by column chromatography. The eluent was petroleum ether: ethyl acetate = 20:1 (V1/V2), yielding white solid 7.73 g, molecular weight 232, HPLC at 98.1% yield: 92.0% |
56% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 5h;Inert atmosphere; Heating; | In the three-necked flask, Join p-Bromoiodobenzene (28g, 0.1mol),3-pyridyl boronic acid (12.3g, 0.1mol),Potassium carbonate (27.2g, 200mmol),Tetrakistriphenylphosphine palladium (0.8g),Tetrahydrofuran (200ml) and water (50ml),Heated under a nitrogen atmosphere for 5 hours.cool down,filter,The crude product was purified by column chromatography to give the product 13g,Yield 56%. |
38% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 12h; | A synthetic scheme of 3- (4-broniophenyl)pyridine is shown in (C-1). In a 100 mL three-necked flask were placed 2.4 g (20 mmol) of 3-pyridineboronic acid, 5.6 g (19 mmol) of para-bromoiodobenzene, and 4.5 g (42 mmol) of sodium carbonate. The atmosphere in the flask was replaced with nitrogen, and to the flask were added 15 mL of water, 25 mL of DME, and 10 mL of ethanol. The mixture was degassed by being stirred under reduced pressure, to which 0.22 g (0.19 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. The mixture was stirred under nitrogen stream at 80 C for 12 hours. After a predetermined time, water was added to the mixture, and an organic substance was extracted with chloroform from the aqueous layer. The obtained extract was washed with a saturated aqueous sodium chloride solution together with the organic layer and then dried over magnesium sulfate. The mixture was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), and the filtrate was condensed to obtain an oily substance. The obtained substance was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1); thus, 1.8 g of the target yellow oily substance was obtained with a yield of 38 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In Solmix A-11; water; toluene; for 2h;Inert atmosphere; Reflux; | First Step: 4-Bromoiodobenzene (1) (20.0 g), <strong>[212386-71-5]4-ethoxy-2,3-difluorophenylboronic acid</strong> (2)(14.4 g), potassium carbonate (29.3 g), Pd(Ph3P)2Cl2 (1.49 g), toluene (100 ml) , Solmix A-11 (100 ml), and water (100 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated under reflux for 2 hours. The reaction mixture was cooled to 25 C, and then poured into water (500 ml) and toluene (500 ml), and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and an extractive operation to an organic phase was carried out. The organic phase obtained was fractionated, washed with water, and then dried over anhydrous magnesium sulfate. The solution obtained was concentrated under reduced pressure, and the residue obtained was purified with a fractional operation by means of column chromatography using toluene as the eluent and silica gel as the stationary phase powder. The product was further purified by means of recrystallization from Solmix A-11 and dried, giving 20.8 g of 4-ethoxy-4'-bromo-2,3-difluoro-1,1'-biphenyl (3). The yield based on the compound (1) was 94.0%. |
94% | With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In Solmix A-11; water; toluene; for 2h;Reflux; Inert atmosphere; | 4-Ethoxy-2,3-difluorophenylboronic acid (7) (14.4 g), 4-bromoiodobenzene (8) (20.0 g), potassium carbonate (29.3 g), Pd (Ph3P)2Cl2 (1.49g), toluene (100ml), Solmix A-11 (100ml) and water (100 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated under reflux for 2 hours. The reaction mixture was cooled to 25 C, and then poured into water (500 ml) and toluene (500 ml), and mixed. The mixture was then allowed to separate into organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with water and dried over anhydrous magnesium sulfate. Then, the solution was concentrated under reduced pressure, and the residue obtained was purified by means of column chromatography (silica gel; toluene). The product was further purified by means of recrystallization (Solmix A-11), giving 20.8 g of 4-ethoxy-4'-bromo-2,3-difluoro-1,1'-biphenyl (9). The yield based on the compound (8) was 94.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Preparation of Intermediate 1 -(4-bromophenyl)cvclobutanol (10-1); 1-Bromo-4-iodobenzene (1.6293g, 5.75mmol) dissolved in tetrahydrofuran (1OmL). Reaction cooled to -78C and n-butyl lithium (2.5/W solution in hexane, 2.42mL, 6.05mmol) added and continued to stir at -78C for 20 minutes. Cyclopentanone (0.448mL, 6.05mmol) added to cold solution and once addition was complete, reaction was warmed to room temperature and stirred for 16 hours. Reaction was diluted with aqueous saturated ammonium chloride and extracted with a 1 :1 solution of ethyl acetate in tetrahydrofuran. Pooled organics dried over sodium sulfate, filtered and concentrated to give a thick oil. Oil purified on silica gel eluting with a gradient from 0% to 30% ethyl acetate in heptane to give 1-(4-bromophenyl)cyclobutanol (0.8033g, 65%) as a clear oil. | |
47.9% | With isopropylmagnesium chloride; In tetrahydrofuran; at 0℃; for 3h;Inert atmosphere; | To a 250 mL round-bottom flask were added 1-bromo-4-idiobenzene (2.0 g, 7.07 mmol) and anhydrous tetrahydrofuran (10 mL). Then to the mixture were added isopropylmagnesium chloride solution (3.9 mL, 7.78 mmol) and cyclobutanone (643 mg, 9.19 mmol) under nitrogen protection. The resulting mixture was stirred at 0C for 3 h. The reaction mixture was cooled to rt and to the mixture was added saturated brine (30 mL). The resulting mixture was extracted with EtOAc (80 mL*3). The combined organic layers were washed with water (150 mL*2) and saturated brine (100 mL*2), dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated in vacuo, and the residue was purified by silica-gel column chromatography (PE:EtOAc=20:1, V/V) to give a white solid (600 mg, 47.9%). MS(ESI, pos.ion)m/z:228.0 (M+2); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.74% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; for 15h;Reflux; | After mixing compound 3-2 (30 g, 109.7 mmol), 4-bromoiodobenzene (62 g, 219.4 mmol), CuI (20.9 g, 109.7 mmol), ethylenediamine (14.7 mL, 219.4 mmol), K3PO4 (58 g, 274.3 mmol) and toluene (600 mL), the reaction mixture was stirred under reflux. After 15 hours, the reaction mixture was cooled to room temperature, CuI and K3PO4 was removed by filtering under reduced pressure. The remaining solution was washed with distilled water, was extracted with MC. The obtained organic layer was dried with MgSO4, was filtered, was distillated under reduced pressure to remove the solvent, and was filtered through column to obtain compound 10-1 (37 g, 78.74 %). |
49% | With potassium phosphate; copper(l) iodide; ethylenediamine; In toluene; at 120℃; | After mixing <strong>[1255308-97-4]5H-[1]benzothieno[3,2-c]carbazole</strong> (10 g, 36.6 mmol), iodo-4-bromobenzene (20 g, 73.2 mmol), CuI (3.5 g, 18.3 mmol), EDA (4.5 mL, 73.2 mmol), K3PO4 (19.4 g, 91.5 mmol), and toluene 200 mL, the mixture was stirred at 120C overnight. After completing the reaction, the mixture was washed with distilled water, and then extracted with EA. The organic layer was dried with MgSO4, and solvent was removed with a rotary evaporator. Then, the remaining product was purified by column chromatography using MC and hexane as developing solvents to obtain compound 6-1 (7.7 g, 49 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12.0h;Inert atmosphere; | General procedure: General procedure for the palladium-catalyzed reaction A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51 mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2 (3*3 mL). The chemoselectivity (3aa/4aa=92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2=97/3) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
102 g | 4-iodoyridine 149g and THF 689mL flown into a flask, the temperature of the contents kept 1 °C, 2.0M isopropylmagnesium chloride THF soln. 400 ml is dropwise added. after dropwise addition 15 minutes stirred, tetramethylethylenediaminezinc(II) chloride complex 202g is added, with stirring, 25 minutes at room temperature. Next, p-bromoiodobenzene 226g and tetrakis(triphenylphosphine)palladium(0) 0.34g was added and heated to reflux for 3 hours. The reaction liquid cooling to room temperature, sodium salt aqueous acetic acid ethylenediaminediacetic 4 · 4 (730g/1.7L) is added, the organic layer. After intercalating organic layer is dried by a drying agent, distilling the crude product is obtained and the solvent is reduced. This crude product is silica gel column chromatography (developing solvent: toluene-toluene/ethyl acetate = 9/1 (volume ratio)) is purified by, 4-(4-bromophenyl)pyridine 102g is obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h; | 1.46 g (5.09 mmol) of 2,6-dibromonaphthalene, 0.75 g (2.99 mmol) of (6-bromonaphthalene-2-yl) boronic acid, 0.29 g (0.25 mmol) of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), and 0.62 g (4.48 mmol) of K2CO3 were dissolved in 60 ml of a mixed solution of THF/H2O (a volume ratio of 2/1) to prepare a reaction solution, followed by stirring the reaction solution at a temperature of 70 C. for 5 hours. After cooling the reaction solution to room temperature, 40 ml of water was added to the reaction solution and extracted the reaction solution three times with 50 ml of diethyl ether to collect organic layers. The collected organic layers were dried with magnesium sulfate and a solvent was evaporated therefrom to obtain residues. The obtained residues were isolated and purified by using silica gel column chromatography to obtain 0.91 g of Intermediate 39-A (yield 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene;Reflux; | 8.2 g of 4-Bromoiodobenzene (SM A1) in a round bottom flask,10 g of 3,9'-bicarbazole (SM B1), 5.8 g t-BuONa, 0.8 g Pd 2 (dba) 3,1.6 ml of (t-Bu) 3 P was dissolved in 70 ml of toluene and stirred under reflux.The reaction was confirmed by TLC and the reaction was terminated after the addition of water.The organic layer was extracted with MC, filtered under reduced pressure, and then purified by column purification and recrystallization.12.1 g (yield 81%) of 9- (4-Bromophenyl) -9H-3,9'-bicarbazole (Sub C1) was obtained. |
70% | With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 15h;Inert atmosphere; | Under a nitrogen atmosphere (N2 purging), Compound 2A(10 g, 35.48 mmol), 0.6 equivalent of Compound 4A, 0.1 equivalent of CuI, 3.5 equivalents of diaminocyclohexane, and 4.0 equivalents of potassium phosphate were added to 1,4-dioxane(350 ml), and stirred in a 90 C. oil bath. After 15 hours, water was added to the reaction mixture, and extraction was performed. Then, purification was performed using a column using a developing solvent of hexane: MC (3:2) to obtain a white solid 4B(12.07 g, yield 70%). |
With potassium phosphate; copper(l) iodide; In toluene; at 80℃; for 0.166667h; | Compound J78 can be synthesized by a person of ordinary skill following Scheme 1 illustrated in FIG. 2. The starting material Sl-1 is available for purchase from Alfa Aesar (CAS No. 57102-42-8). The starting material SI -2 is available for purchase from Acros Organics (CAS No. 95-51-2). In the first step compound Sl-1 is combined with compound S I -2, potassium tert-butoxide, Pd(OAc)2, and PtBu3 in toluene at 120 C for 24 hours to form compound S I -3. In the second step, compound S I -3 is combined with potassium carbonate, Pd(OAc)2, and PtBu3HBF4, in DMA at 180 C for 24 hours to form compound S I -4. In the third step, compound SI -4 is combined with compound S 1-5 (available for purchase from Acros Organics, CAS No. 589-87-7), K3P04 and copper iodide in toluene at 80 C for 10 minutes to form compound SI -6. In the fourth step, compound SI -6 is cooled to 0 C in a hexanesxyclopentylmethyl ether solution before dropwise addition of nBuLi and subsequent dropwise addition of Bu3SnCl to form compound S l-7. Compound Sl-7 is combined with compound S I -8 (available for purchase from Tokyo Chemical Industry Co., CAS No. 3740- 92-9) with Pd(OAc)2 to form compound J78. It is understood that steps 1, 2, 3, 4, and 5 can be performed and optimized by a person having ordinary skill in the art without undue experimentation. |
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 90℃; for 12h; | In the nitrogen environment (N2 purging), 7A,0.6 equivalent of 2A, 0.1 equivalent of CuI,3.5 equivalents of diaminocyclohexane, 4.0 equivalents of potassium phosphate were added to 1,4-dioxaneAnd stirred in an oil bath at 90 C.Water was added to the reaction mixture after 12 hours, and after extraction, white solid 7B was obtained after column using Hexane: MC (4: 1) developing solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 75℃; for 2h;Inert atmosphere; | A mixture of tert-butyl 3 -(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-5,6- dihydropyridine- 1 (2H)-carboxylate (10 g, 32.3 mmol), 1 -bromo-4-iodobenzene (9.13 g, 32.3 mmol), [1,1 ?-Bis(diphenylphosphino)ferrocene] dichloropalladium(II) (2.35 g, 3.22 mmol) and sodium carbonate (10.2 g, 96.8 mmol) in dioxane (80 mL) and water (20 mL) was purged withN2 and stirred at 75 °C for 2 h. After that, the solution was cooled to RT and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/ito 5/1) to afford the title compound (8 g, 73percent) as a colorless oil. MS (ES+) C16H20BrNO2 requires: 337, 339, found: 282, 284 [M-55]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With potassium phosphate; copper(l) iodide; 2-(N,N-dimethylamino)athanol; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere; | Compound 60 (2 g, 7.07 mmol), Compound 167 (3.14 g, 14.1 mmol), 2-(dimethylamino) ethanol (2.34 mL, 23.3 mmol), Copper (1) iodide (135 mg, 0.707 mmol) and tripotassium phosphate (4.50 g, 21.2 mmol) was dissolved in DMF (18 ml), and the mixture was stirred at 100°C under nitrogen atmosphere. Water was added thereto, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride, then was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain Compound 168 (340 mg, 14percent). Compound 168; Method B LC/MS retention time = 2.80 min. MS (ESI) m/z = 340.15(M+H)+. |
Tags: 589-87-7 synthesis path| 589-87-7 SDS| 589-87-7 COA| 589-87-7 purity| 589-87-7 application| 589-87-7 NMR| 589-87-7 COA| 589-87-7 structure
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