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Chemical Structure| 1309647-27-5

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Product Details of [ 1309647-27-5 ]

CAS No. :1309647-27-5
Formula : C10H7NO4S
M.W : 237.23
SMILES Code : O=S(C(C=CC=C1C(C=C2)=O)=C1C2=O)(N)=O

Safety of [ 1309647-27-5 ]

Application In Synthesis of [ 1309647-27-5 ]

* 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 [ 1309647-27-5 ]

[ 1309647-27-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 606-25-7 ]
  • [ 1309647-27-5 ]
YieldReaction ConditionsOperation in experiment
58.43% With cerium(IV) sulphate; sulfuric acid; acetic acid; In water; at 65℃; for 0.45h; Dissolve anhydrous cerium sulfate (160g, 677.45mmol) with 750ml 2mol/L dilute sulfuric acid,The temperature is controlled at 65C. Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, and stir at this temperature.Slowly add dropwise to the cerium sulfate aqueous system, start timing from the dropwise addition,Monitoring by thin layer chromatography, the reaction was stopped after 27 minutes, and after the reaction solution was cooled, Filter, extract the filtrate with 1200ml of dichloromethane, dry and remove water, and then rotate under low pressure.A light yellow solid was obtained, which was dried under vacuum,5,8-dioxo-dihydronaphthalene (6.72 g, yield 58.43%) was obtained. It is directly used in the next reaction without purification.
58.43% With cerium(III) sulfate; sulfuric acid; acetic acid; at 65℃; for 0.45h; The anhydrous cerium sulfate (160g, 677.45mmol) was dissolved in 750ml of 2mol/L dilute sulfuric acid, and the temperature was controlled at 65C.Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, stir at this temperature, and slowly add dropwise to the cerium sulfate aqueous system. Start timing, TLC monitoring, and stop the reaction after 27 minutes. After the reaction solution is cooled, filter, and extract the filtrate with 1200ml of dichloromethane, dry and remove water, and then rotate at low pressure to obtain a pale yellow solid, which is dried in vacuum to obtain 5, 8 -Dioxo-dihydronaphthalene (6.72 g, yield 58.43%). It is directly used in the next reaction without purification. The experimental data are as follows:
58.43% With cerium(IV) sulphate; sulfuric acid; acetic acid; In water; at 65℃; for 0.45h; The anhydrous cerium sulfate (160g, 677.45mmol) was dissolved in 750ml of 2mol/L dilute sulfuric acid, and the temperature was controlled at 65C. . Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, and stir at this temperature. Slowly add dropwise to the cerium sulfate aqueous system, start timing from the dropwise addition, Monitoring by thin layer chromatography, the reaction was stopped after 27 minutes, and after the reaction solution was cooled, Filter, extract the filtrate with 1200ml dichloromethane, After drying and removing water, low-pressure rotary evaporation is obtained to obtain a light yellow solid, which is dried in vacuum. 5,8-dioxo-dihydronaphthalene (6.72g, yield 58.43%) was obtained.
19% With chromium(VI) oxide; In water; acetic acid; at 90℃; for 0.3h;Reflux; Naphthalenesulfonamide (500 mg, 2.41 mmol) was dissolved in slowly warming glacial acetic acid (5.0 mL). The mixture was heated to 90 C and chromium trioxide (1.08 g, 10.85 mmol), which was dissolved in a mixture of water and glacial acetic acid (3 mL, v/v: 1/1), and added to the mixture solution. The above solution was stirred under reflux for 18 min and quenched with iced water (50 mL). The solution was cooled to 0 C and stirred 1 h at room temperature. The precipitated yellow powder was filtered and the remaining solution was extracted with ether (3×100 mL). The organic layer was collected, dried, and removed at reduced pressure. The yellow powder was combined and purified with silica column chromatography ethyl acetate/hexane (v/v: 2/3) to yield 1 (110 mg, 19%); mp (186-188 C).
19.3% b. PREPARATION OF 5,8-DIOXO-5,6,7,8-TETRAHYDRONAPHTHALENE-1- SULFONAMIDE (COMPOUND 1) [00460] The structure of 5,8-dioxo-5,6,7,8-tetrahydronaphthalene-l-sulfonamide (Compound 1) is shown below: [00461] The numbering scheme for Compound 1 is shown below: [00462] 5,8-dioxo-5,6,7,8-tetrahydronaphthalene-l-sulfonamide was synthesized as previously described (Lin, L., et al. Int. J. cancer. 2012, 130, 1459-69) with some modifications; procedures are shown in Scheme 1. Naphthalenesulfonylchloride reacted with ammonium hydroxide at room temperature, precipitated white crystal <strong>[606-25-7]naphthalenesulfonamide</strong> with high purity ready for next step synthesis and 90.2% yield. Naphthalenesulfonamide was oxidized by chromium trioxide in an acidic environment. This reaction is highly time sensitive, since the longer reaction times result in more byproducts. To achieve the optimal reaction time, the solvent can be preheated to reflux, and then add chromium trioxide into the reaction system. 5H-naphth[l,8-c<i]isothiazol-5-one, 1, 1-dioxide was not very stable during the column separation, so flash column was used for purification. SCHEME 1 [00463] Naphthalenesulfonamide (500 mg, 2.41 mmol) was dissolved in slowly warming glacial acetic acid (5.0 mL). The mixture was heated to 90 C and chromium trioxide (1.08 g, 10.85 mmol), which was dissolved in a mixture of water and glacial acetic acid (1 : 1 v/v, 3 mL), was added to the mixture solution. The above solution was stirred under reflux for 18 minutes. The solution was cooled to 0 C and water (50 mL) was added and stirred overnight at room temperature. The precipitated yellow powder was filtered and the remaining solution was extracted with ether (3x 100 mL). The organic layer was collected, dried, and removed at reduced pressure. The yellow powder was combined and purified with silica column chromatography ethyl acetate-hexane (2:3 v/v) to yield the desired sulfonamide (1 10 mg, 19.3%); mp (186-188 C).
17.48% With chromium(VI) oxide; acetic acid; In water; at 85℃; <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (0.5 g, 2.4 mmol) was added to a 25 ml round bottom flask containing 5 ml of glacial acetic acid, controlled at 85C, Chromium trioxide (1.09 g, 10.9 mmol) was dissolved in 1 ml of water and 1ml of glacial acetic acid, Slowly drip into the system, from the start of the drip, 16 minutes after the reaction, the reaction solution into 80ml ice water containing 100ml beaker quenching, standing overnight, precipitation of light yellow solid, filtration, vacuum drying, 5,8-dioxo-<strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (100 mg, yield 17.48%). Directly used for the next reaction without purification
15.4% With chromium(VI) oxide; acetic acid; In water; for 0.25h;Reflux; [0092] Synthesis of Compound 3:; Compound 2 (500 mg, 2.41 mmol) was dissolved in glacial acetic acid (5.0 ml). Chromium trioxide ( 1.08 g, 10.85 mmol) was dissolved in a mixture of water/glacial acetic acid ( 1 : 1 , 2 ml) and added to the solution of compound 2 in glacial acetic acid and was stirred under reflux for 15 mins. The solution was cooled to 0C and water (25 ml) was added and the resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with water (500 ml) and extracted with ether (3 x 100 ml). The organic layer was collected and dried under reduced pressure and purified with silica column chromatography ethyl acetate/hexane (2:3) to yield compound 3 (88 mg, 15.4%); m.p ( 187-188C); 1 H NMR (300 MHz, DMSO) δ 7.23 (2H, d, J = 9 Hz), 7.43 (2H, S), 8.1 1 ( 1 H, t, J = 9 Hz), 8.34 ( 1 H, d, J= 9 Hz), 8.515 ( 1 H, d, J=9 Hz). ([M+Na]+ 260.7).
With chromium(VI) oxide; acetic acid; In water; at 20 - 45℃; The compound 2 (24 g) was suspended in acetic acid (300 mL) and was heated to dissolved completely, then cooled to 40 ~ 45 C (water bath), and CrC (52 g) solution in H2O (50 mL) and acetic acid (50 mL) was added over 1 ~ 1.5 h and the water bath temperature was maintained around 42 C. After the addition, the reaction mixture was stirred for additional 2 h at room temperature. Then 1 L of water was added and filtered. The obtained yellow solid was washed with large amount of water and dried by air. H NMR spectrum of the crude product indicated that it contained about 50 % of starting material 2 besides the desired 5,8- dioxo-5,8-dihydro<strong>[606-25-7]naphthalene-1-sulfonamide</strong> (3). (0264) [0240] The crude product (36 gm from 6 batch reactions) was dissolved in minimum acetone at room temperature and hexane was added till precipitate was just observed, then place it in refrigerator (about -20 C) overnight. Filtration afforded 13.6 g of compound 3 with purity of 93 %, the final yield was about 8.3 %.
With chromium(VI) oxide; acetic acid; In water; at 40 - 45℃; Firstly, 1-naphthalenesulfonyl chloride (1, 50 g; what does it mean? 50 g?) was stirred with 28% ammonium hydroxide (300 mL) in acetone (1 L) at rt for about 3 h, concentrated, cooled to rt (room temperature, filtered, washed and dried by air, 42 g of white powder <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (2) was obtained. Secondly, the compound 2 (48 g) was dissolved completely suspended in acetic acid (480 mL) and then cooled to 40 ~ 45C, and CrO3 (104 g) solution in H2O (100 mL) and acetic acid (100 mL) was added in 1 ~ 1.5 h, which was then stirred, filtered,washed and dried by air to obtainthe crude product (24 g). 48g crude product was dissolved in minimum acetone at rt and hexane was added slowly till precipitate was just observed, then place it in refrigerator (about -20C) overnight. Filtration afforded 26.9 g of compound 3. Thirdly, the compound 3 (15.45 g) was dissolved in CH2Cl2 (1.2 L) and methanol (162 mL) at rt, then cooled to -20 ~ -15C and Et3N (1.54 mL) was added. After stirringfor about 15 min, 3-hydroxy-1-pyrone (8.74 g) in 300 mL of CH2Cl2 was added and stirred for about 30 min, then 2 ~ 3 h at rt. The formed yellow precipitate was collected by filter to getthe first crop of LLL12 (3.24 g). Filtrate was concentrated at 33C by rotary evaporation underhose vacuum to 150 ml. Add 250 ml CH2Cl2 to precipitate, filter and wash with small quantityCH2Cl2 to get 2nd crop of LLL12(5.27g). Further purification by silica gel flash column chromatographyeluted with mixed solvents of acetone and hexanes (1:1, V/V) afforded 3.95 g ofLLL12. Finally, LLL12 (2.01 mg) was suspended in pyridine (15 g) at rt, then dimethycarbamylchloride (1.02 g) was added and stirred at rt overnight. Then the reaction mixtures were filteredand washed with CH2Cl2 and then large quantity of acetone (about 1 L) to afford the compound of LLL12B.

  • 2
  • [ 1309647-27-5 ]
  • [ 170017-74-0 ]
  • tert-butyl 4-(2-((1,4-dioxo-5-sulfamyl-1,4-dihydronaphthalen-2-yl)amino)phenyl)piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With copper(II) acetate monohydrate; acetic acid; at 118℃; for 3h; A mixture of 5,8-dioxo-1-naphthalenesulfonamide(0.5 g, 2.1 mmol), tert-butyl 4-(2-aminophenyl)piperazineacetate-(0.787 g, 2.53 mmol) and copper acetate monohydrate (42 mg, 0.21 mmol) were added to a 25 ml round bottom flask containing 12 ml of glacial acetic acid and heated at reflux at 118 C. The reaction was stirred at this temperature for 3 hours. Solvent, Liquid chromatography to isolate the compound tert-butyl 4-(2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)-1-carboxylate (0.568 g, yield 51%)
  • 3
  • [ 1309647-27-5 ]
  • [ 170017-74-0 ]
  • 4-(2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalene-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With acetic acid; at 25℃; for 26h; Add 5,8-dioxo-dihydronaphthalene (56.5g, 238.17mmol), Tert-butyl 4-(2-aminophenyl)piperazine-1-carboxylate (60g, 217.90mmol) and copper acetate monohydrate (5.6g, 28.05mmol) were added to a 2L round bottom flask containing 1200ml of glacial acetic acid in, React at 25C, stir and react at this temperature for 26 hours; The solvent was distilled off under reduced pressure to obtain a crude product. Add 1500ml of absolute ethanol to the crude product, boil at 110C, and monitor the liquid phase of the reaction product after all conversions, stop heating, cool naturally and stir for 6h, filter to obtain a filter cake, remove general impurities after column chromatography, and add 10 times equivalent After the dichloromethane is completely dissolved, slowly add 25 times equivalent of isopropanol dropwise, and remove the same amount of dichloromethane after low-pressure rotary evaporation at 33C. After all the crystals are precipitated, filter to obtain purple-red crystals, which are dried under low pressure to obtain 4- (2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester, purity 97 %. (67.53g, yield 83%).
51% With monohydrate copper acetate; acetic acid; at 118℃; for 3h; Put 5,8-dioxo-dihydronaphthalene (0.5g, 2.11mmol),Tert-butyl 4-(2-aminophenyl)piperazine-1-carboxylate (0.787g, 2.53mmol) and copper acetate monohydrate (42mg, 0.21mmol) were added to a 25ml round bottom flask containing 12ml of glacial acetic acid Heated at 118C under reflux, stirred and reacted at this temperature for 3 hours; the solvent was distilled off under reduced pressure, and the compound (4-(2-((1,4-dioxo-5-sulfamoyl-1) was separated by liquid chromatography. ,4-Dihydronaphthalene-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester) (0.568 g, yield 51%). The experimental data are as follows:
51% With acetic acid; at 118℃; for 3h; Put 5,8-dioxo-dihydronaphthalene (0.5g, 2.11mmol), Tert-Butyl 4-(2-aminophenyl)piperazine-1-carboxylate (0.787g, 2.53mmol) and copper acetate monohydrate (42mg, 0.21mmol) were added to a 25ml round bottom flask containing 12ml of glacial acetic acid, Heat to reflux at 118C, stir and react at this temperature for 3 hours; The solvent was distilled off under reduced pressure, and the compound (4-(2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)amino)phenyl was isolated by liquid chromatography ) Piperazine-1-carboxylic acid tert-butyl ester) (0.568 g, yield 51%).
  • 4
  • [ 1309647-27-5 ]
  • [ 170017-74-0 ]
  • 4-(2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With monohydrate copper acetate; acetic acid; at 26℃; for 26h; Add 5,8-dioxo-dihydronaphthalene (56.5g, 238.17mmol),Tert-butyl 4-(2-aminophenyl)piperazine-1-carboxylate (60g, 217.90mmol) and copper acetate monohydrate (5.6g, 28.05mmol) were added to a 2L round bottom flask containing 1200ml of glacial acetic acid The reaction was carried out at 25C, and the reaction was stirred at this temperature for 26 hours; the solvent was distilled off under reduced pressure to obtain a crude product.Add 1500ml of absolute ethanol to the crude product and boil at 110C. After the liquid phase monitors the complete conversion of the reaction products, stop the heating, cool and stir for 6 hours, filter to obtain a filter cake, remove general impurities after column chromatography, and add 10 times the equivalent After the methylene chloride is completely dissolved, slowly add 25 times equivalent of isopropanol dropwise, and remove the same amount of methylene chloride after low-pressure rotary evaporation at 33C. After all the crystals are precipitated, filter to obtain purple-red crystals, which are dried under low pressure to obtain 4- (2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester, purity 97 %. (67.53g, yield 83%).
  • 5
  • [ 1309647-27-5 ]
  • [ 170017-74-0 ]
  • C25H26N4O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With acetic acid; at 25℃; for 26h; Add 5,8-dioxo-dihydronaphthalene (56.5g, 238.17mmol), Tert-butyl 4-(2-aminophenyl)piperazine-1-carboxylate (60g, 217.90mmol) and copper acetate monohydrate (5.6g, 28.05mmol) were added to a 2L round bottom flask containing 1200ml of glacial acetic acid Medium, 25 reaction, Stir and react for 26 hours at this temperature; Remove the solvent by distillation under reduced pressure, Got crude. Add 1500ml of absolute ethanol to the crude product, boil at 110C, and monitor the liquid phase to monitor the conversion of all the reaction products, stop heating, cool naturally and stir for 6h, filter to obtain a filter cake, remove general impurities after column chromatography, and add 10 times equivalent After the dichloromethane is completely dissolved, slowly add 25 times equivalent of isopropanol dropwise, and remove the same amount of dichloromethane after low-pressure rotary evaporation at 33C. After all the crystals are precipitated, filter to obtain purple-red crystals, which are dried under low pressure to obtain 4- (2-((1,4-dioxo-5-sulfamoyl-1,4-dihydronaphthalen-2-yl)amino)phenyl)piperazine-1-carboxylic acid tert-butyl ester, purity 97 %. (67.53g, yield 83%).
 

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