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Chemical Structure| 67-71-0 Chemical Structure| 67-71-0
Chemical Structure| 67-71-0

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Dimethyl sulfone is an endogenous metabolite.

Synonyms: DMSO2; NSC 63345; MSM

4.5 *For Research Use Only !

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Silvia Caggi ; Alexis Johnston ; Dipak T. Walunj ; Aanya R. Moore ; Benjamin H. Peer ; Ravyn W. Everett , et al.

Abstract: We have previously shown that heterotrimeric G-protein subunit alphai2 (Gαi2) is essential for cell migration and invasion in prostate, ovarian and breast cancer cells, and novel small molecule inhibitors targeting Gαi2 block its effects on migratory and invasive behavior. In this study, we have identified potent, metabolically stable, second generation Gαi2 inhibitors which inhibit cell migration in prostate cancer cells. Recent studies have shown that chemotherapy can induce the cancer cells to migrate to distant sites to form metastases. In the present study, we determined the effects of taxanes (docetaxel), anti-androgens (enzalutamide and bicalutamide) and histone deacetylase (HDAC) inhibitors (SAHA and SBI-I-19) on cell migration in prostate cancer cells. All treatments induced cell migration, and simultaneous treatments with new Gαi2 inhibitors blocked their effects on cell migration. We concluded that a combination treatment of Gαi2 inhibitors and chemotherapy could blunt the capability of cancer cells to migrate and form metastases.

Keywords: cell migration ; chemotherapy ; HDACi ; Gαi2 ; cancer ; metastases

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Blount, Grace S ; Seymour, Austin ; Williams, Dylan ; Douglas, Daylon ; Miller, Joshua ; Sejoro, Sarah , et al.

Abstract: 9-Aminoacridine structures hold much potential for accessing small molecule therapeutics. This core is present in a range of pharmaceuticals for the treatment of ailments such as malaria, inflammation, viral and bacterial infections, and cancer. For the latter, there remains a need to develop and/or improve chemotherapeutics to counteract issues of uptake, drug resistance, and selectivity for cancer cells over healthy cells. In the design of molecules to address these issues, identifying structural units that present as promising leads for drug development is key. In this study, four 9-aminoacridine derivatives under consideration as precursors for a drug design project are assessed for their cytotoxicity with representative cell lines PC3 and A549 and for their leadlikeness with SwissADME. Together, the cytotoxicity and in silico investigations coalesce around the same derivative as the most promising lead.

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Alternative Products

Product Details of Dimethyl sulfone

CAS No. :67-71-0
Formula : C2H6O2S
M.W : 94.13
SMILES Code : O=S(C)(C)=O
Synonyms :
DMSO2; NSC 63345; MSM
MDL No. :MFCD00007566
InChI Key :HHVIBTZHLRERCL-UHFFFAOYSA-N
Pubchem ID :6213

Safety of Dimethyl sulfone

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P264-P280-P305+P351+P338-P337+P313

Application In Synthesis of Dimethyl sulfone

* 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.

  • Downstream synthetic route of [ 67-71-0 ]

[ 67-71-0 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 67-71-0 ]
  • [ 3095-48-5 ]
  • [ 56066-81-0 ]
YieldReaction ConditionsOperation in experiment
In water; dimethyl sulfoxide; A suspension of 33 g. of dimethylsulfone and 11 g. of sodium hydride (50percent dispersion in oil) in 160 ml. of absolute dimethylsulfoxide was stirred at 50° C. under an atmosphere of nitrogen and the exclusion of moisture for 3 hours. Then, 18 g. of <strong>[3095-48-5]4-amino-3,5-dimethyl-benzoic acid methyl ester</strong> were added. The mixture was stirred at 80° C. for 30 minutes and at room temperature for 1 hour and then dissolved in 400 ml. of water. The solution was neutralized with glacial acetic acid. The precipitate which formed was removed by filtration with suction, washed with water, dried and recrystallized from ethyl acetate, whereby there was obtained 4'-amino-3',5'-dimethyl-2-(methylsulfonyl)-acetophenone having a melting point of 179°-180° C.
  • 2
  • [ 67-71-0 ]
  • [ 3095-48-5 ]
  • [ 77-78-1 ]
  • [ 56066-87-6 ]
  • 3
  • [ 67-71-0 ]
  • [ 56441-97-5 ]
  • [ 51908-43-1 ]
  • 4
  • [ 67-71-0 ]
  • [ 1131-52-8 ]
  • 1-(3-Ethoxy-4-methoxyphenyl)-2-methylsutfonylethylamine [ No CAS ]
  • [ 253168-94-4 ]
YieldReaction ConditionsOperation in experiment
39% With hydrogenchloride; n-butyllithium; trifluoroborane diethyl ether; In tetrahydrofuran; hexane; lithium hexamethyldisilazane; EXAMPLE 1 1-(3-Ethoxy-4-methoxyphenyl)-2-methylsutfonylethylamine To a stirred solution of dimethyl sulfone (3.70 g, 39.4 mmol) in tetrahydrofuran (350 mL), was added n-butyllithium (17.5 mL, 2.5 M, 43.8 mmol) under nitrogen at -78 C. and the mixture was stirred at 78 C. for 25 min. To a stirred solution of 3-ethoxy-4-methoxybenzaldehyde (7.10 g, 39.4 mmol) in tetrahydrofuran (40 mL) under nitrogen in a separate flask at 0 C. was added lithium hexamethyldisilazide (43.0 mL, 1.0 M, 43.0 mmol) in hexane. After 15 min, boron trifluoride etherate (10.0 mL, 78.9 mmol) was added to the resulting mixture at 0 C. After 5 min, this solution was added to the -78 C. sulfone solution via syringe. The solution was allowed to warm to room temperature over one hour. The resulting mixture was then quenched with potassium carbonate (32 g) and water (200 mL). The mixture was stirred for 30 min and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3*200 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), and then dried over magnesium sulfate. The solvent was removed in vacuo and the resulting solid stirred with ether (100 mL) and 4 N hydrochloric acid (100 mL) for 15 min. The aqueous layer was separated and the organic layer extracted with 4 N hydrochloric acid (30 mL). The combined aqueous layers were washed with ether (50 mL), stirred, and cooled in an ice bath and the pH adjusted to 14 with sodium hydroxide (5 N). This solution was extracted with ethyl acetate (3*100 mL) and the combined organic layers were washed with brine (50 mL) and dried over sodium carbonate and sodium sulfate. Removal of solvent in vacuo gave an oil which was stirred with ether (20 mL) for 20 min to give a suspension. The suspension was filtered and the solid was washed with ether (20 mL) and then dried in a vacuum oven to yield 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine as an off-white solid (4.17 g, 39%): mp, 116.5-117.0 C.; 1 H NMR (CDCl3) delta 1.47 (t, J=7 Hz, 3H, CH3), 1.92 (br s 2H, NH2), 2.91 (s, 3H, SO2 CH3), 3.19 (dd, J=3.5, 14 Hz, 1H, CHH), 3.36 (dd, J=9.3, 14 Hz 1H, CHH), 3.87 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 4.60 (dd, J=3.5, 9 Hz, 1H, CH), 6.83-6.93 (m, 3H, Ar); 13 C NMR (CDCl3) delta 14.75, 42.42, 50.94, 55.99, 63.18, 64.44, 110.71, 111.67, 118.21, 135.55, 148.72, 149.09; Anal Calcd for C12 H19 NO4 S: C, 52.73; H, 7.01; N, 5.12. Found: C, 52.82; H, 6.69; N, 4.99.
  • 5
  • [ 67-71-0 ]
  • [ 52079-23-9 ]
  • [ 1177369-50-4 ]
YieldReaction ConditionsOperation in experiment
99% To a suspension of NaH (60% in mineral oil, 552 mg, 12.0 mmol) in THF (5 mL) was added a solution of (S)-3-hydroxydihydrofuran-2(3H)-one (46a, 1.02 g, 10.0 mmol) in TetaF (5 mL) slowly drop wise at 0 0C under N2 atmosphere. The reaction mixture was stirred for 30 minutes and dimethylsulphate (1.4 mL, 15.0 mmol) was added. The reaction mixture was stirred at r.t. overnight and the TLC shows completion of the reaction. Cold water (25 mL) was added to the reaction mixture and extracted with ethyl acetate. Organic layer washed with brine, dried over anhydrous Na2SO4 and filtered. Concentrated to provide (S)-3-hydroxydihydrofuran-2(3H)- one (46a) as yellow oil, which was dissolved in MeOH. Catalytic amount of K2CO3 (50 mg) was added at 0 0C and the reaction mixture stirred for Ih. TLC shows completion of the reaction. Cold water (25 mL) was added to the reaction mixture and extracted with ethyl acetate. Organic layer washed with brine, dried over anhydrous Na2SO4 and filtered. Concentrated to provide (S)- methyl 4-hydroxy-2-methoxybutanoate (46b, 1.5g, 99%) as yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 2.07 - 2.28 (m, 1 H) 2.36 - 2.58 (m, 1 H) 3.36 (s, 3 H) 3.49 (s, 3 H) 3.85 - 4.07 (m, 1 H) 4.29 - 4.42 (m, 2 H).
  • 6
  • [ 67-71-0 ]
  • [ 1131-52-8 ]
  • [ 253168-94-4 ]
YieldReaction ConditionsOperation in experiment
91.5% 1) Add Me2SO2 352 g (3.74 mol) to a 5 L dry three-necked bottle. THF (1665 mL), stirring, Replace with nitrogen three times and protect; cool down to - 20 C, Add 1 L (2.5 mol) of n-hexane solution of n-butyllithium, Control within -20 ~ 0 C. After the addition is completed, Continue to control the temperature -20 ~ 0 C reaction for 1 h, prepare the lithium salt R1 of dimethyl sulfone; 2) At the same time as the above operation, Add another 3-ethoxy-4-methoxybenzaldehyde 150 g (0.83 mol) to another 2 L dry three-necked flask. THF (666 mL), Start stirring, replace with nitrogen three times and protect; cool down to - 10 C, Adding lithium hexamethyldisilazide Tetrahydrofuran solution 1 L (1.0 mol) controlled internal temperature -10 ~ 0 C, After the addition is completed, Continue to control the temperature -10 ~ 0 C reaction for 1 h to prepare the lithium imide salt R2; 3) R1 is cooled to -30 ~ -40 C, R2 is dropped into R1, and the internal temperature is controlled at -30 ~ -40 C. After the addition is completed, it is stirred at the same temperature for 1 h; 4) Cool down to -30 ~ -20 C, add 589 g (4.15 mol) of boron trifluoride etherate to the reaction solution, and control the internal temperature -60 ~ -50 C. After the addition is completed, the temperature is naturally raised to 0 C; 5) The reaction solution was quenched by adding 183 g (1.33 mol) of potassium carbonate to a 1.11 L aqueous solution, and the temperature was not more than 15 C. After the addition was completed, the filtrate was separated, and the filtrate was separated. The filter cake was washed twice with DCM 1 L and extracted with water. Combine the organic phases and concentrate to dryness under pressure; 6) Add DCM 600 mL, 4 N HCl 660 mL, Stir at 30 C for 0.5 h, Liquid separation, The organic layer was extracted once with 300 mL of 4 N HCl. Combine the water phase, DCM 600 mL extraction. Add 4 N NaOH to the water layer to adjust the pH to 12 ~ 14, Extract DCM 800mL twice, After concentration, 234.4 g of crude product was obtained, and the yield was 103.3%. The purity is 91.5%; 7) Add the above crude product 234.4 g to a 1 L three-necked flask. Toluene 900 mL, Heat to reflux to dissolve, Cooling to room temperature to precipitate a solid, Crystallization in ice bath for 2 h, Filtration to give 207.7 g of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine. The total yield was 91.5%; The purity is 98.8%.
  • 7
  • [ 67-71-0 ]
  • [ 60758-86-3 ]
  • [ 253168-94-4 ]
YieldReaction ConditionsOperation in experiment
76.1% Dimethylsulfone (191. Ig, 2.03 moles, from Aldrich Chemicals, Milwaukee, WI) and tetrahydrofuran (1.65 L, from Aldrich Chemicals, Milwaukee, WI) were charged to a 12 L three-necked flask at room temperature. The mixture was cooled to 0-5C. n-BuLi (750 ml of 2.5M solution in hexanes, from Aldrich Chemicals, Milwaukee, WI) was added to the flask at a rate such that the reaction mixture was maintained at 0-5C. A line rinse with 150 ml tetrahydrofuran followed. The mixture was stirred at 0-5C for 60-70 minutes. 3-ethoxy-4- methoxybenzonitrile (300.0 g, 1.69 moles, in 750 ml tetrahydrofuran) was then charged to the flask at a rate such that the reaction mixture was maintained at 0-5 C . A line rinse with 300 ml tetrahydrofuran followed. The mixture was stirred at 0-5C for another 10-15 minutes. After warming to room temperature, the reaction mixture was stirred at room temperature for 1.5-2 hours, while purged with nitrogen. NaBH4 (83.1 g, 2.20 moles, from Aldrich Chemicals, Milwaukee, WI) and 150 ml of tetrahydrofuran were then charged to the reaction mixture. The reaction mixture was stirred at 0-50C for 15-30 minutes. HOAc (450 ml, 7.83 moles, from Fisher Scientific, Pittsburgh, PA) was charged to the flask at a rate such that the reaction mixture was maintained at 0-50C. The mixture was stirred at 0-50C for an additional 2-3 hours. The mixture was then charged with 2.25 L of NaOH (2.5N, pH 12 to 13, from Fisher Scientific, Pittsburgh, PA), and stirred at 0-50C for another 15-30 minutes. After warming to room temperature, the reaction mixture was heated to reflux at about 600C. After reflux for 12-14 hours, the mixture was cooled to 35-40C, and 3.0 L of water was added. The mixture was further cooled to 0-5C over a period of 1.5-2 hours. The mixture was filtered under vacuum, and the filtered solid was washed with 2 L of deionized water. The solid was dried in a tray at 50-550C under vacuum. The yield of 2-(3-ethoxy-4-methoxyphenyl)-l-(methanesulfonyl)-eth- 2-ylamine was found to be 352 g (76.1%) based on a 300 g input of 3-ethoxy-4- methoxybenzonitrile (HPLC indicated 99.74% purity by peak area).
65% In a flask, 5 litres of tetrahydrofuran was charged followed by 1.06 kg of dimethylsulfone. This reaction mass was cooled for 25 to 30 minutes at 0C. Aftercooling, 1M potassium-hexamethyldisilazane was added followed by 10 litres of tetrahydrofuran. The reaction mass was stirred for an hour at 0 to 10 C. After stirring, 1 kg of 3-ethoxy-4-methoxybenzonitrile was dissolved in 2 litres tetrahydrofuran and was added to the above reaction mass. The reaction mass was stirred for 30 minutes and cooled. After cooling, 0.433 kg of sodium borohydride was added followed bytetrahydrofuran and 5 litres of acetic acid and the total reaction mass was stirred for 3- 4 hours at 0 to 10 C. After completion of reaction, sodium hydroxide solution was added to it and stirred for 45 minutes. The reaction mass was warmed and further heated for 3 to 4 hours at 60 to 65C. After completion of reaction, the reaction solution was allowed to cool to room temperature for half an hour. The layers were separated. The combinedorganic layer was treated with aq. HC1 and water was added to the concentrated mass. The aqueous layer was treated with ethyl acetate. Finally sodium hydroxide solution was added to the aqueous layer and solid was precipitated. The solid was filtered, washed with water and dried at 50C and further 1.0 kg (65%) of material was unloaded.
50% Dimethyl sulfone (0.639 g, 0.067 mmoles) was added to dimethylsulfoxide (10 ml) and stirred at room temperature for 5-10 minutes. Potassium tertiary butoxide (1.89 g, 0.169 mmoles) was added slowly to the reaction mixture at 30C and stirred for three hours. 3-ethoxy-4-methoxy benzonitrile (1.0 g, 0.056 mmoles) in tetrahydrofuran (2 ml) was added to the reaction mixture over a period of 30 minutes and was stirred for three hours at room temperature. Sodium borohydride (0.213 g,0.056 mmoles) was added to the reaction mixture at 30 C and maintained for one hour. Ammonium chloride (10 ml) was added to the reaction mixture and extracted with ethyl acetate (20 ml). The ethyl acetate layer was washed with water (10 ml). The ethyl acetate layer was distilled at 30 C to provide crude compound. The crude compound was washed with methyl tertiary butyl ether to provide the title compound as pale yellow colored solid.Yield: 750 mg (50%)
 

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