Home Cart 0 Sign in  

[ CAS No. 747-36-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 747-36-4
Chemical Structure| 747-36-4
Structure of 747-36-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 747-36-4 ]

Related Doc. of [ 747-36-4 ]

Alternatived Products of [ 747-36-4 ]

Product Details of [ 747-36-4 ]

CAS No. :747-36-4 MDL No. :
Formula : C18H28ClN3O5S Boiling Point : -
Linear Structure Formula :- InChI Key :JCBIVZZPXRZKTI-UHFFFAOYSA-N
M.W : 433.95 Pubchem ID :12947
Synonyms :
HCQ sulfate;Hydroxychloroquine (sulfate) (CRM);HCQ;NSC 4375

Safety of [ 747-36-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P305+P351+P338 UN#:N/A
Hazard Statements:H302-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 747-36-4 ]

* 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 [ 747-36-4 ]

[ 747-36-4 ] Synthesis Path-Downstream   1~30

YieldReaction ConditionsOperation in experiment
In water-d2 Irradiation; phosphate buffer pD 7, singlet oxygen formation; rate constant for quenching of singlet oxygen;
With dihydrogen peroxide In water at 10℃; for 0.0833333h; High pressure; 2.5. Photodegradation tests A batch system was used to perform photodegradation experiments.The light used in the experiment was solar light and UV-A light. The batch photocatalytic system in this study was exposed to direct sunlightwith an intensity of 76-72 kW and UV-A light with a light density of 6 W.The parameters studied in this experiment include pH different [3,5,7],concentration of TiO2/β-Bi2O3 nanocomposite as a catalyst (0.05, 0.1,0.3, 0.4 g/L), hydroxychloroquine concentration (1, 10, 20, 40 mg/L),H2O2 concentration (1,2, 3, 4 mg.L 1), temperature (10, 20, 40, and60 C) and irradiation time (5,10,15,20,30,45,60,90,120 min). (0.1 M)HCl and (0.1 M) NaOH were used to adjust the pH, and a magnetic stirrerat 70 rpm was used to blend the system. Photodegradation experiment indark conditions and photolysis was also performed. It should be notedthat before exposing the sample to sunlight, and UV-A light irritation,the solution was first stirred for 30 min in the dark to ensure anadsorption-adsorption balance between the TiO2/β-Bi2O3 photocatalystand the hydroxychloroquine drug. Over a period, 5 ml of the solutionwas extracted. After centrifugation at 2000 rpm for 15 min, theadsorption rate of hydroxychloroquine was measured by a spectrophotometer(UV-770 Brite) at 343 nm. Equation [1] was used to calculatethe HCQ removal percentage [23]:
  • 2
  • [ 556-52-5 ]
  • [ 747-36-4 ]
  • [ 877128-78-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; water at 20℃; for 48h; I-A The purpose is to prepare an activated chloroquine substance comprising an aldehyde derivative of a chloroquine substance. (N42) To 4.33 grams (10 millimoles) of hydroxychloroquine (HQ) sulfate (Acros, 98%), dissolved in 25 mL of water was added about 3 mL of 0.1 N NaOH to adjust the pH to about 7.3. To this solution was added about 3.1 mL of glycidol (Sigma-Aldrich, 96%), for about a 4× molar excess of glycidol. The solution was mixed and put in the dark at room temperature (rt) for 48 hours or more to allow coupling of the glycidol to the hydroxyl groups. The hydroxychloroquine-glycidol product was isolated by splitting the solution into 4 aliquots and diluting with about 6 volumes of isopropanol. The mixtures were placed in a -20° C. for several hours to allow precipitation, then centrifuged 30 minutes at about 2500 rpm. The pellets were dissolved in about 5 mL of water, pooled and precipitated as before, then dissolved in a final volume of 9.5 mL water.
  • 3
  • [ 5455-98-1 ]
  • Plaquenil [ No CAS ]
  • [ 877128-80-8 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-oxiranylmethylisoindole-1,3-dione; Plaquenil With sodium hydroxide In water; N,N-dimethyl-formamide at 20℃; for 48h; Stage #2: With sodium hydroxide; hydrazine In water; N,N-dimethyl-formamide at 20℃; for 48h; II To 2.16 grams (5 millimoles) of hydroxychloroquine (HQ) sulfate (Acros, 98%), dissolved in 8 mL of water (pH 5), was added about 0.2 mL of 1 N NaOH to adjust the pH to about 6.5. To this solution was added about 25 mL of N-(2,3-epoxypropyl)phthalimide (EPP, Sigma-Aldrich, 98%), in 80% DMF/water, for about a 2× molar excess. The solution was mixed and put in the dark at room temperature (rt) for 48 hours or more to allow coupling of the EPP to the hydroxyl groups. To remove the phthalate by hydrolysis, the pH was adjusted to about 9 with about 3 mL of 1 N NaOH. Then about 0.8 mL (2× molar excess) of hydrazine hydrate (64%, fw 50.06) was added, mixed and put in the dark at rt for 48 hours or more. The reaction mixture was then concentrated by evaporation. The hydroxychloroquine amine product was purified by Sephadex G15 size exclusion gel chromatography in 50% MetOH/water and concentrated by evaporation under N2. HQ concentration was determined by fluorescence and amine concentration was determined using TNBS as described previously.
  • 5
  • hydroxychloroquine sulphate [ No CAS ]
  • [ 118-42-3 ]
YieldReaction ConditionsOperation in experiment
97.6% With sodium hydroxide In lithium hydroxide monohydrate at 20℃; Cooling with ice; 1 The aliquot of hydroxychloroquine sulfate (21.7 g, 50 mmol) was weighed into a 500 mL three-150 mL of water was added under ice-cooling.150 mL of a 12% aqueous sodium hydroxide solution (50 mL) A white oil was formed during the addition, at which time 50 mL of ethyl acetate was added.After slowly warming to room temperature, 100 mL of ethyl acetate was added and the organic phase was separated;The aqueous phase was extracted twice more with ethyl acetate and the organic phases were combined.The organic phase was washed with saturated sodium chloride solution, water, dried over anhydrous sodium sulfate,Filtered, concentrated and dried to obtain hydroxychloroquine 6.5 g of 48.8 mmol of a colorless transparent oil in a yield of 97.6%.
91% With sodium hydroxide In lithium hydroxide monohydrate; ethyl acetate at 0℃; for 1h; 3 At 0°C, 10.9 g of hydroxychloroquine sulfate was dissolved in 75 ml of water, and then 25 ml of 12% NaOH aqueous solution was added. After stirring for half an hour, 25 ml of ethyl acetate was added, and stirring was continued for half an hour. The reaction solution was naturally warmed to room temperature and extracted three times with 100 ml of ethyl acetate. The organic phases were combined, washed with 150 ml of saturated brine and water in turn, dried with anhydrous sodium sulfate, and filtered to remove sodium sulfate. The organic solvent was removed with a rotary evaporator to obtain 7.7 g of free hydroxychloroquine in the shape of a light yellow viscous liquid with a yield of 91%.
91% With sodium hydroxide In lithium hydroxide monohydrate at 0℃; for 0.5h; 4 At 0° C., 10.9 g of hydroxychloroquine sulfate was dissolved in 75 mL of water, and then 25 mL of 12% NaOH aqueous solution was added. After stirring for half an hour, 25 mL of ethyl acetate was added, and stirring was continued for half an hour. The reaction solution was naturally warmed to room temperature, and extracted three times with 100 mL of ethyl acetate. The organic phases were combined, washed with 150 mL of saturated brine and water in turn, dried with anhydrous sodium sulfate, and filtered to remove sodium sulfate. The organic solvent was removed with a rotary evaporator to obtain 7.7 g of free hydroxychloroquine in the shape of a light yellow viscous liquid with a yield of 91%.
90% With ammonia In chloroform at 20℃; for 1h;
With ammonium hydroxide In lithium hydroxide monohydrate
With amberlyst A26 (OH) In lithium hydroxide monohydrate

  • 6
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ammonia / chloroform / 1 h / 20 °C / pH 9 2.1: 1,1'-carbonyldiimidazole / chloroform / 2 - 5 h / 20 °C 2.2: 10 - 12 h / 70 °C / Reflux
  • 7
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ammonia / chloroform / 1 h / 20 °C / pH 9 2.1: 1,1'-carbonyldiimidazole / chloroform / 2 - 5 h / 20 °C 2.2: 10 - 12 h / 70 °C / Reflux
  • 8
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ammonia / chloroform / 1 h / 20 °C / pH 9 2.1: 1,1'-carbonyldiimidazole / chloroform / 2 - 5 h / 20 °C 2.2: 10 - 12 h / 70 °C / Reflux
  • 9
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ammonia / chloroform / 1 h / 20 °C / pH 9 2.1: 1,1'-carbonyldiimidazole / chloroform / 2 - 5 h / 20 °C 2.2: 10 - 12 h / 70 °C / Reflux
  • 10
  • [ 118-42-3 ]
  • Plaquenil [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With sulfuric acid In water at 15 - 55℃; for 5h;
98.6% With sulfuric acid In ethanol at 5 - 10℃; for 12h; Large scale; 1 Example 1 Preparation of hydroxychloroquine sulfate crystal form B Add 1100g of hydroxychloroquine and 8800ml of ethanol to the reaction flask, stir until it dissolves, and control the temperature to 5-10°C.Drop 330g of 70% sulfuric acid aqueous solution with mass fraction, and control the temperature not to exceed 10°C. After the dripping is completed, keep stirring at 510 for 12h,After filtering, vacuum drying at 50°C to constant weight,Obtained 1401.2 g of hydroxychloroquine sulfate of crystal form B with a yield of 98.6% and a purity of 99.93% by HPLC
96.1% With sulfuric acid In ethanol at 0 - 30℃; for 5h; 1.1.2; 2.2.2; 3.3.2; 4.4.2; 5.5.2; 6 5.2 Preparation of hydroxychloroquine sulfate General procedure: In a three-necked round bottom flask, 10.0 g of hydroxychloroquine obtained in Example 5.1 and 40.0 g of 95% ethanol were added. After the dissolution was completed, the temperature was lowered to 0 ° C to 10 ° C.The concentrated sulfuric acid was slowly added dropwise to adjust the pH to 4.5 to 5.5, and the control temperature was within 10 °C.Then, the reaction is kept at 20 ° C to 30 ° C for 3 hours, and after the reaction is completed, the temperature is lowered to 0 ° C to 10 ° C for 2 hours, and then filtered.Drying under reduced pressure to obtain 12.4 g of hydroxychloroquine sulfate, the melting point is 239.5 ° C ~ 240.5 ° C, HPLC purity 99.8%,The largest single impurity is <0.1%, and the yield is 96.1%.
95.1% With sulfuric acid In water Heating; 1.2; 6 Add the hydroxychloroquine solid (250.0g, 0.74mol) and purified water (400mL) obtained in the previous step into the reaction flask, add sulfuric acid (80.2g, 0.82mol) dropwise to the reaction kettle, heat and stir until the solution is clear, add activated carbon ( 7.5g), stir and decolorize for 0.5h, filter by suction, add ethanol (2L) dropwise to the filtrate, and slowly lower the temperature to 0-10°C. After suction filtration, the filter cake is transferred to a drying box and dried under reduced pressure at 45-55°C for 12 hours. 307.1 g of hydroxychloroquine sulfate solid was obtained, the yield was 95.1%, the purity was 99.9%, and the maximum single impurities was 0.04%.
94.5% With sulfuric acid In ethanol at 45℃; for 10h; 1.b-4.b b. hydroxychloroquine sulfate preparation 100g of hydroxychloroquine was dissolved in 500g of absolute ethanol, and concentrated sulfuric acid was added dropwise at 20 °C until the solution was cloudy (pΗ3.5~5), heated at 45 ° C for 10 hours, Cooled to 20 ° C and insulated for 1 h, and then suction filtration to obtain hydroxychloroquine sulfate, purity 99.93%, maximum single impurity is 0.05%, and the yield is 94.5%.
93.2% With sulfuric acid In ethanol; water at 20℃; for 3h; Large scale; 4-6 Example 6 Preparation of Hydroxychloroquine Sulfate Add 300 kg of hydroxychloroquine prepared in accordance with Example 3, 1500 kg of absolute ethanol, 120 kg of 90% sulfuric acid, and react at room temperature for 3 hours after the addition is completed. The temperature is lowered to 10-15°C, stirred for 5 hours, filtered, and dried. Hydroxychloroquine sulfate was obtained with a yield of 93.2% and a purity of 99.81%.
92.88% With sulfuric acid In ethanol; ethyl acetate for 2h; 1.2; 2.2; 3.2; 4.2; 5.2; 6.2; 2.2; 3.2 Synthesis of hydroxychloroquine sulfate: Take 50.0g of hydroxychloroquine refined product and add it to a 1000mL four-necked flask, add 150mL ethyl acetate, 350mL ethanol, warm up and stir to dissolve, until completely dissolved, drop 14.7g of concentrated sulfuric acid, after the addition, stir for 2 hours, cool down to crystallize, filter with suction, rinse the filter cake twice with 50mL ethyl acetate, and dry in vacuum. 60.0 g of hydroxychloroquine sulfate was obtained, the yield was 92.88%, the HPLC purity was 98.44%, and the maximum single impurity content was 0.07%.
91.9% With sulfuric acid In ethanol at 0 - 30℃; for 0.5h; 1.2; 2.2; 3.2; 4.2; 5.2; 6.2 Preparation of crude hydroxychloroquine sulfate: Put 84.88g (0.25mol) of refined hydroxychloroquine and 915mL of 95% ethanol into the reactor and stir to dissolve.The reaction mass was cooled to 0-10°C and 24.07g concentrated sulfuric acid was added dropwise,Continue to stir for 0.5 hours after the addition is complete,Then heat to 2030 and stir,Filter, rinse the filter cake with 95% ethanol 100mL x 3,The wet product was vacuum dried at 80°C for 22 hours to obtain 101.63 g (0.23 mol) of crude hydroxychloroquine sulfate.The HPLC purity is 99.87%, and the yield is 92.7%.
90.2% With sulfuric acid In ethanol at 25 - 50℃; for 9h; 3 b. Preparation of hydroxychloroquine sulfate 100 g of hydroxychloroquine obtained in the previous step is dissolved in 500 g of absolute ethanol, and concentrated sulfuric acid is added dropwise to the solution at 25 ° C.Turbid, heating at 50 ° C for 9 hours, cooling to 20 ° C for 1 h, suction filtration to obtain hydroxychloroquine sulfate, purity 99.74%, the largest single miscellaneous0.17%, the yield was 90.2%.
38 g With sulfuric acid In ethanol at 20 - 30℃; Green chemistry; 5 Example 5: Preparation of hydroxychloroquinoline sulfate 9.52g concentrated sulfuric acid was slowly added to 34g of absolute ethanol solution, then slowly drip 34g of hydroxychloroquinoline crude and 51g of ethanol solution, control temperature is 20 ~ 30 ° C, the addition is completed, stirred for 2 ~ 3h, a large amount of solid precipitation, Drying gave 38 g of hydroxychloroquinoline sulfate, HPLC ≥ 99.2, a single impurity ≦ 0.1%.
1.25 kg With sulfuric acid In methanol at 0 - 20℃; for 11h; Large scale; 7-9 Example 8: Preparation of hydroxychloroquine sulfate Dissolve 1 kg of hydroxychloroquine free base in 5 L of 75% methanol, cool to 0-5 degrees, add 0.32 kg of concentrated sulfuric acid, and add dropwise.After that, stirring was continued for 1 hour, and the mixture was stirred at room temperature for 10 hours. The crystals were slowly precipitated, suction filtered, and the filter cake was washed once with 75% ice methanol.Dry to obtain 1.25 kg of white crystals.
12.2 g With sulfuric acid In ethanol; water at 20 - 40℃; for 18h; 6-10 Example 6 Synthesis of Hydroxychloroquine Sulfate 10.0 g of hydroxychloroquine product was added to a 250 mL four-necked flask.Add 100mL of ethanol and stir to dissolve at room temperature.Equivalent dilute sulfuric acid (2.97g concentrated sulfuric acid + 7mL water) was added dropwise.Control the drop rate, the internal temperature of the reaction liquid is not higher than 40 ° C, plus,Stir at room temperature for 18 hours, filter, rinse with 10 mL × 2 ethanol, and dry at 50 ° C for 2 hours.12.2 g of a white crystalline powder was obtained with an HPLC purity of >99.6% and a maximum single impurity <0.1%.
40.1 g With sulfuric acid In ethanol; isopropyl alcohol at 60 - 65℃; 4-6 Example Six Synthesis of Hydroxychloroquine Sulfate 10.0g concentrated sulfuric acid was slowly added to 60ml isopropanol solution, and then slowly dripped into a solution of 34g hydroxychloroquine and 100ml ethanol. Control the temperature at 6065. After the addition, stir for 23h. A large amount of solids were precipitated, and 40.1 g of hydroxychloroquinoline sulfate was obtained by drying, with HPLC≥99.5% and single impurity≤0.1%.

Reference: [1]Current Patent Assignee: SHANGHAI PHARMACEUTICALS HOLDING COMPANY LIMITED - CN108727263, 2018, A Location in patent: Paragraph 0046; 0047; 0052
[2]Current Patent Assignee: NANJING YINUO PHARMACEUTICAL TECH; NANJING HEALTHNICE PHARMACEUTICAL; NANJING HEALTHNICE PHARMACEUTICAL TECH - CN112480000, 2021, A Location in patent: Paragraph 0035-0036
[3]Current Patent Assignee: TSINGHUA TONGFANG CO., LTD - CN104230803, 2017, B Location in patent: Paragraph 0036; 0037; 0043-0046; 0050; 0051; 0057-0065
[4]Current Patent Assignee: REYOUNG PHARMACEUTICAL HOLDINGS LTD - CN111423373, 2020, A Location in patent: Paragraph 0043; 0048-0049; 0062; 0066
[5]Current Patent Assignee: SHANGHAI ZHONGXI SUNVE PHARAMACEUTICAL - CN108658858, 2018, A Location in patent: Page/Page column 8-10
[6]Current Patent Assignee: ZHUHAI RUNDU PHARMACEUTICAL CO LTD - CN111606851, 2020, A Location in patent: Paragraph 0016-0018
[7]Current Patent Assignee: JIANGXI GUOYAO PHARMACEUTICAL; WUXI JIYU SHANHE PHARMACEUTICAL - CN113185459, 2021, A Location in patent: Paragraph 0039; 0042-0044; 0047-0049; 0052-0054; ...
[8]Current Patent Assignee: CINKATE MEDICINE CHEMICAL INTERMEDIATE SHANGHAI - CN113072491, 2021, A Location in patent: Paragraph 0099; 0151; 0159-0164; 0165; 0173-0178; 0179; ...
[9]Current Patent Assignee: SHANGHAI PHARMACEUTICALS HOLDING COMPANY LIMITED - CN108689929, 2018, A Location in patent: Paragraph 0103; 0106-0107; 0108; 0111-0112
[10]Current Patent Assignee: WUHAN WUYAO PHARMACEUTICAL - CN103724261, 2016, B Location in patent: Paragraph 0017; 0041-0046
[11]Current Patent Assignee: NANJING TIANJI LIANMENG PHARMACEUTICAL TECH - CN109456266, 2019, A Location in patent: Paragraph 0003
[12]Current Patent Assignee: SHANGHAI INSTITUE OF TECHNOLOGY - CN109280029, 2019, A Location in patent: Paragraph 0043-0052
[13]Current Patent Assignee: NANJING GRITPHARMA - CN112745263, 2021, A Location in patent: Paragraph 0022; 0040-0045
  • 11
  • [ 1510-21-0 ]
  • [ 747-36-4 ]
  • [ 2244484-72-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Plaquenil With sodium hydroxide Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.5h; Stage #3: cholesteryl hemisuccinate With dmap In dichloromethane at 20℃; for 48h; 1 After the hydroxychloroquine sulfate is desalted and dried with a NaOH solution,Hydroxychloroquine, cholesterol succinic acid monoester, DMAP, EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) are dosed according to a molar ratio of 1..1.2..1.2..1.2 . Hydroxychloroquine and 0.6 times EDCI were first dissolved in a small amount of dichloromethane and stirred for 30 minutes. The remaining EDCI and DMAP and cholesterol succinic acid monoester were placed in a reaction flask, and an appropriate amount of dichloromethane was added thereto, followed by stirring at room temperature for 48 hours. The reaction was subjected to spot plate monitoring with a mobile phase (volume ratio: methylene chloride: methanol = 7..1). At the end of the reaction, the reaction solution was concentrated, and then separated by column chromatography. The mobile phase was dichloromethane.. methanol = 100.. 1 (volume ratio) to obtain a pale yellow semi-solid compound 1
  • 12
  • [ 2143950-81-4 ]
  • [ 747-36-4 ]
YieldReaction ConditionsOperation in experiment
93.8% With sulfuric acid In ethanol at 50 - 60℃; for 1h; 7.C (C) salt formation reaction 70 g of the hydroxyquinoline obtained in the step (B), 200 g of 95% ethanol is added to the reaction flask, and the temperature is raised.Dissolve and add 18.8g of 80% sulfuric acid to 50-60 ° C. After the addition is completed, the reaction is kept for 1 hour, and the temperature is lowered to 0.Crystallization at ~10 ° C for 2.0 hours, filtration, drying at 50-60 ° C to obtain 58.1 g of hydroxychloroquine sulfate, molar yield 93.8%, purity ≧99.8%, total chowder 0.2%, maximum single choke 0.1%, unknown impurity ≦ 0.1%, burning residue ≦ 0.2%, moisture ≦0.3%, heavy metal ≦ 10ppm.
  • 13
  • [ 86-98-6 ]
  • [ 747-36-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 19 h / 110 - 130 °C 2: sodium t-butanolate / isopropyl alcohol 3: sulfuric acid / ethanol; water / 18 h / 20 - 40 °C
Multi-step reaction with 3 steps 1: cetyltrimethylammonim bromide; potassium fluoride / acetonitrile / 2 h / 80 °C / Inert atmosphere 2: acetonitrile / 3 h 3: sulfuric acid / water / Heating
  • 14
  • [ 69559-11-1 ]
  • Plaquenil [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 19 h / 110 - 130 °C 2: sodium t-butanolate / isopropyl alcohol 3: sulfuric acid / ethanol; water / 18 h / 20 - 40 °C
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.5 h / 0 - 5 °C / Inert atmosphere 1.2: 1 h / 0 - 5 °C / Inert atmosphere 2.1: tetrahydrofuran / 2 h / 60 - 65 °C 3.1: sulfuric acid / isopropyl alcohol; ethanol / 60 - 65 °C
  • 15
  • [ 86-98-6 ]
  • [ 69559-11-1 ]
  • hydroxychloroquine sulphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With sulfuric acid; triethylamine In butan-1-ol at 25℃; for 0.0216667h; 1-10 Weigh 1.98g (10mmol, 1.0equiv) of 4,7 dichloroquinoline, 7mL triethylamine (50mmol, 5.0equiv) and fully dissolve in 10mL n-butanol, prepare a solution as material I; Measure 3.48g 5- [(N-ethyl-N-(2-hydroxyethyl)amino]-2-pentylamine (20mmol, 2.0equiv), dissolved in 17mL n-butanol, as material II; Measure 3.2mL H2SO4 (60mmol, 6equiv) ), as material III. After the material I and material II are pumped into the first mixer by pump I and pump II, respectively, and fully mixed, enter the microchannel reactor A to react, and after the reaction is completed, the reaction solution enters the second mixer. At the same time, the material III is pumped into the second mixer through the pump III, fully mixed with the previous reaction solution, and then enters the microchannel reactor B for reaction, wherein the feed flow rate of the material I is 5.0mL/min, and the material II is fed The material flow rate is 5.0mL/min, and the material III feed flow rate is 1mL/min. Wherein, the inner diameter of the pipe of the microchannel reactor is 1.0mm, the length is 20m, the volume is 15.7mL, the residence time is 1.3min, and the temperature of the reactor is 25 ° C. Collect The outflowing reaction solution, after post-processing hydroxychloroquine sulfate 4.08g, yield 94%,
45.76% Stage #1: 4,7‐dichloroquinoline; 5-(N-ethyl-N-2-hydroxyethylamine)-2-pentylamine With potassium iodide In phenol at 120 - 130℃; for 18h; Stage #2: With sulfuric acid at 5℃; for 6h; 1 Preparation of crude hydroxychloroquine sulfate Put 0.91Kg 4,7-dichloroquinoline, 0.9kg phenol and 10g potassium iodide into a 20L reactor, stir and heat to 120°C, slowly add 5-(N-ethyl-N-2-hydroxyethylamino)-2 dropwise -Amylamine 1.32Kg, after dripping, continue stirring at 125-130°C for 18 hours.Cool to room temperature, add 20% sodium hydroxide lye to adjust to pH 12 with stirring, extract three times with toluene, concentrate under reduced pressure to remove toluene, and dissolve the residue in 1.5L absolute alcohol, cool to room temperature, slowly add concentrated sulfuric acid, adjust pH to 6-7.5, stir and slowly crystallize.Place it at 5°C for more than 6 hours.The crude hydroxychloroquine sulfate wet product is obtained by filtration.Vacuum drying at 80°C for 4 hours.0.89 kg of crude hydroxychloroquine sulfate was obtained, with a purity of 95%, mp 235-240°C, and a yield of 45.76%.
Multi-step reaction with 2 steps 1.1: N-hexadecyl-N,N,N-trimethylammonium bromide; potassium fluoride / acetonitrile / 2 h / 80 °C / Inert atmosphere 1.2: 3 h / Heating 2.1: sulfuric acid / water monomer / Heating
  • 16
  • [ 747-36-4 ]
  • [ 137433-24-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / water; ethyl acetate / 1 h / 0 °C 2: diethylamine / hexane; isopropyl alcohol / 35 °C
  • 17
  • [ 747-36-4 ]
  • [ 137433-23-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / water; ethyl acetate / 1 h / 0 °C 2: diethylamine / hexane; isopropyl alcohol / 35 °C
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 0.5 h / 0 °C 2: diethylamine / isopropyl alcohol; hexane / 35 °C / Resolution of racemate
  • 18
  • [ 747-36-4 ]
  • [ 155204-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydroxide / water; ethyl acetate / 1 h / 0 °C 2: diethylamine / hexane; isopropyl alcohol / 35 °C 3: sulfuric acid / ethanol / 1 h / 60 °C
Multi-step reaction with 3 steps 1: sodium hydroxide / water / 0.5 h / 0 °C 2: diethylamine / isopropyl alcohol; hexane / 35 °C / Resolution of racemate 3: sulfuric acid / ethanol / 1 h / 60 °C
Multi-step reaction with 3 steps 1: sodium hydroxide / water / 0.5 h / 0 °C 2: diethylamine / isopropyl alcohol; hexane / 35 °C / Resolution of racemate 3: sulfuric acid / ethanol / 1 h / 60 °C
  • 19
  • [ 747-36-4 ]
  • [ 2488706-20-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydroxide / water; ethyl acetate / 1 h / 0 °C 2: diethylamine / hexane; isopropyl alcohol / 35 °C 3: sulfuric acid / ethanol / 1 h / 60 °C
YieldReaction ConditionsOperation in experiment
However, the invention is not limited to these medicines and therapeutic uses but comprises all medicines within the spirit and scope of the inventive idea, and the claims that follow.1.An intranasal COVID-19 medicine, comprising the combination of: aprotinin;hydroxychloroquine phosphate or hydroxychloroquine sulfate; andivermectin.
  • 21
  • [ 141-75-3 ]
  • [ 747-36-4 ]
  • [ 2243715-61-7 ]
YieldReaction ConditionsOperation in experiment
9% With pyridine In dichloromethane at 20℃; for 3.08333h; 25; 46 General Procedure: Synthesis of n-Butyryl-Hydroxychloroquine, Compound E-89 Hydroxychloroquine sulfate (1099 mg, 2.53 mmol) was charged into a round bottom flask. H2O (10 mL) and dichloromethane (10 mL) were added. Pyridine (412 µL, 5.1 mmol) was added and the reaction stirred vigorously for 5 min. Butyric anhydride (420 µL, 2.65 mmol) was added and the reaction stirred at room temperature for 3h. The phases were separated and the dichloromethane layer was washed successively with a saturated aqueous NH4Cl solution (2 x 15 mL), H2O (2 x 10 mL), dried over Na2SO4 and evaporated in vacuo. Co-evaporation with toluene is necessary to remove residual pyridine from the system. This was followed by re-dissolving the residue in DCM and solvent evaporation twice to produce a yellow oil (93 mg, 9% yield).
  • 22
  • [ 16649-49-3 ]
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane for 0.5h; Schlenk technique; Sonication;
  • 23
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 24
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 25
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 26
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 27
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 28
  • [ 747-36-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: amberlyst A26 (OH) / lithium hydroxide monohydrate 2: 1 h / 20 °C
  • 29
  • [ 747-36-4 ]
  • [ 1057094-59-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ammonium hydroxide / lithium hydroxide monohydrate / 0.5 h / 20 °C 2: pyridine; N,N-dimethyl-4-aminopyridine / lithium hydroxide monohydrate; acetonitrile / 20 °C / Inert atmosphere
  • 30
  • [ 747-36-4 ]
  • [ 2454241-26-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: ammonium hydroxide / lithium hydroxide monohydrate / 0.5 h / 20 °C 2.1: pyridine; N,N-dimethyl-4-aminopyridine / lithium hydroxide monohydrate; acetonitrile / 20 °C / Inert atmosphere 3.1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0 °C / Inert atmosphere 3.2: 0 °C
Same Skeleton Products
Historical Records