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[ CAS No. 100986-85-4 ] {[proInfo.proName]}

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Chemical Structure| 100986-85-4
Chemical Structure| 100986-85-4
Structure of 100986-85-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 100986-85-4 ]

CAS No. :100986-85-4 MDL No. :
Formula : C18H20FN3O4 Boiling Point : -
Linear Structure Formula :- InChI Key :GSDSWSVVBLHKDQ-JTQLQIEISA-N
M.W : 361.37 Pubchem ID :149096
Synonyms :
(-)-Ofloxacin;MP-376;Levofloxacin, Levaquin, Tavanic, Iquix, Quixin;Fluoroquinolone

Calculated chemistry of [ 100986-85-4 ]

Physicochemical Properties

Num. heavy atoms : 26
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.44
Num. rotatable bonds : 2
Num. H-bond acceptors : 6.0
Num. H-bond donors : 1.0
Molar Refractivity : 101.83
TPSA : 75.01 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.78 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.25
Log Po/w (XLOGP3) : -0.39
Log Po/w (WLOGP) : 1.2
Log Po/w (MLOGP) : 0.98
Log Po/w (SILICOS-IT) : 1.47
Consensus Log Po/w : 1.1

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.99
Solubility : 3.72 mg/ml ; 0.0103 mol/l
Class : Very soluble
Log S (Ali) : -0.72
Solubility : 68.6 mg/ml ; 0.19 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.01
Solubility : 0.356 mg/ml ; 0.000986 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.63

Safety of [ 100986-85-4 ]

Signal Word:Danger Class:N/A
Precautionary Statements:P261-P264-P270-P280-P301+P312-P302+P352 UN#:N/A
Hazard Statements:H302-H317-H334 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 100986-85-4 ]

* 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 [ 100986-85-4 ]

[ 100986-85-4 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 109-01-3 ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
97.1% With potassium hydroxide; In water; at 55℃; for 24h; ,3-dihydro-3-methyl-7-oxo-7H-pyrido [1,2,3-Delta] - [1,4] Benzoxazine-6-carboxylate, 4.5 g of water, 4.5 g of N-methylpiperazine and 0.22 g (81%) of potassium hydroxide were added and the reaction was incubated at 55 C and the alcohol , And the reaction was allowed to proceed for about 6 hours.The reaction was warmed to reflux for about 18 hours.N-methylpiperazine was replaced by N-methylpiperazine.The residue of levofloxacin crude, dissolved with chloroform and water, after acid and alkali pH adjustment, extraction, washing, concentration and other steps.(Methanol: dichloromethane = 1: 8), and the solid was combined with the cold methanol rinse to obtain the finished product of levofloxacin Yield: 97.1%.The compound was confirmed to be levofloxacin product by the same method as the product obtained in Example 1, by measuring the melting point, determining the molecular weight by high resolution mass spectrometry, and confirming the product by NMR.
96% With nano iron oxide on ZrO2 coated sulfonic acid; In water; for 0.366667h;Reflux; General procedure: A mixture of 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1a (1 mmol) and Nethylpiperazine2y (1.5 mmol) and n-FZSA (0.06 g) as catalystin H2O (5 ml) were heated under reflux for the appropriatetime. The reaction was monitored by TLC. After appropriatetime, the catalyst was separated using an externalmagnet and washed with hot ethanol (5 mL). The reactionmixture was then cooled to room temperature. The precipitatedsolid was collected by filtration, and recrystallized fromethanol 96% to give desired compound in high yields.
89% at 150℃;Microwave irradiation; General procedure: A mixture of 6-chloro-4-cyclopropyl-7-fluoro-1-oxo-1,4-dihydronaphthalene-2-carboxylic acid 1a (1 g, 3.5 mmol) with N-ethylpiperazine 2c (0.6 g, 5.25mmol) was loaded in a small flask fitted with a micro condenser, placed in the microwave reactor and irradiated for 25 min at 150C under solvent free conditions. The reaction progress was monitored by TLC. Upon completion of the process, addition of hot absolute ethanol (10 mL) to the reaction mixture was followed by filtration. The filtrate was concentrated and stored at room temperature for precipitation. The solid was filtered off and recrystallized from absolute ethanol to give compound 3c.
55% With BF3 etherate; triethylamine; In hydrogenchloride; methanol; diethyl ether; dimethyl sulfoxide; Example 8 (S)-(-)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid 7 Ml of BF3 etherate were added dropwise to a suspension of 1.41 g of <strong>[100986-89-8](S)-(-)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid</strong> in 150 ml of diethyl ether while stirring at room temperature. The reaction mixture was stirred for 5 hours, then the precipitate was collected by suction, washed with diethyl ether and dried under reduced pressure. The resulting chelate was dissolved in 15 ml of dry dimethylsulfoxide, and 1.42 ml of triethylamine and 0.8 g of N-methylpiperazine were added to the solution. The mixture was stirred at room temperature for 18 hours, followed by concentration to dryness under reduced pressure. The residue was treated with diethyl ether and dissolved in 40 ml of methanol and 1.42 ml of triethylamine and the solution was heated at reflux temperature for 24 hours. After cooling the reaction mixture was concentrated to dryness, the residue was dissolved in 50 ml of 10% hydrochloric acid and the solution was extracted three times with chloroform. The aqueous layer was separated and adjusted to pH=11 with 4N sodium hydroxide and then to pH=7.3 with 1N hydrochloric acid. The solution was extracted three times with 200 ml portions of chloroform, the extract was dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The resulting powder was recrystallized from ethanol-diethyl ether to afford 1.0 g of the title product. Yield: 55%. M.p. 240-245C. (dec). [alpha] [22/D ] = -77.8 (c=0.2, 0.05N NaOH).
In acetonitrile;Heating / reflux; [0040] S (-)-9,10-difluoro-7-oxo 2,3-dihydro 7H-pyrido [1,2,3-DE] [1,4] Benzoxazine-6-carboxylic acid (75 grams), N-Methyl piperazine (67 grams) were suspended in Acetonitrile (525 ml) and heated to the reflux temperature, further stirred till the reaction substantially completes. The solvent was distilled off completely from the reaction mixture to get the residual mass. Thus resulted residual mass was refluxed with toluene (75 ml) for about 5-6 hours then cooled to a temperature of 0-5 C. and stirred for 2-4 hours. The obtained solid mass was filtered and washed with toluene (75 ml) and dried at a temperature of 40-50 C. to a constant weight (45 grams). The dried compound was further refluxed with acetonitrile (675 ml) for 30-60 minutes and filtered the undissolved compound and washed with acetonitrile (45 ml). Thus obtained undissolved compound was dried at a temperature of 40-50 C. to a constant weight to afford desired Novel anhydrous crystalline form of Levofloxacin.
5.86 g (91.3%) In dimethyl sulfoxide; isopropyl alcohol; Example 1 Synthesis of Levofloxacin in DMSO 5 g (17.8 mmole) of (S)-(-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid was put in suspension in 2.5 mL of DMSO and 4.2 mL (37.9 mmole) of N-methyl piperazine. The reaction mixture was heated to 120 C. and the suspension became soluble. After 2.5 h the reaction was completed. The mixture was then cooled to 70 C. and isopropanol (25 mL) was then added at this temperature. The reaction mixture was slurried for 1 h at ambient temperature, filtered, and dried overnight to obtain 5.86 g (91.3%) of levofloxacin.
106 g (92%) In dimethyl sulfoxide; isopropyl alcohol; Example 15 Dry A 1 liter reactor equipped with mechanical stirrer, condenser and thermometer, was charged with (S)-9,10,difluoro-3methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4] benzoxazine-6-carboxylic acid (87.5 g), DMSO (61.3 ml) and N-methylpiperazine (86.3 ml) at ambient temperature. The slurry was then heated to 80 C. and stirred at a rate of 250 rpm under nitrogen atmosphere. The heating was continued for 4.5 hours until completion of the reaction. Then the slurried mixture was cooled to 75 C. and isopropanol (700 ml) was added at once. At the end of the addition, the mixture was stirred at a rate of 300 rpm. The reaction mixture was cooled over 2 hours until 7 C. The stirring was maintained for 2 hours at this temperature and at a rate of 350 rpm. The reaction mixture was then filtrated under vacuum and washed with isopropanol (175 ml). The wet material (162 g) was mixed with isopropanol (180 ml). The slurry was stirred at 40 C. for 1 hour at a rate of 250 rpm. The slurry was then filtrated under vacuum and washed with isopropanol (60 ml). The polymorph of the wet sample was H. The solid was dried in a vacuum oven at 60 C. for 14 hours to obtain 106 g (92%) of dry levofloxacin Form B.
106 g (92%) In dimethyl sulfoxide; isopropyl alcohol; Example 16 Dry A 1 liter reactor equipped with mechanical stirrer, condenser and thermometer, was charged with (S)-9,10,difluoro-3methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid (87.5 g), DMSO (61.3 ml) and N-methylpiperazine (86.3 ml) at ambient temperature. The slurry was then heated to 80 C. and stirred at a rate of 250 rpm under nitrogen atmosphere. The heating was continued for 4.5 hours until completion of the reaction. Then the slurried mixture was cooled to 75 C. and isopropanol (700 ml) was added at once. At the end of the addition, the mixture was stirred at a rate of 300 rpm. The reaction mixture was cooled over 2 hours until 7 C. The stirring was maintained for 2 hours at this temperature and at a rate of 350 rpm. The reaction mixture was then filtrated under vacuum and washed with isopropanol (175 ml). The wet material (162 g) was mixed with isopropanol (180 ml). The slurry was stirred at 40 C. for 1 hour at a rate of 250 rpm. The slurry was then filtrated under vacuum and was washed with isopropanol (60 ml). The polymorph of the wet samples was G. The solid was dried in a vacuum oven at 60 C. for 14 hours to obtain 106 g (92%) of dry levofloxacin Form B.
2.83 g (77.3%) In 2-methyl-propan-1-ol; Example 3 Synthesis of Levofloxacin in Isobutanol 3 g (10.67 mmole) of (S)-(-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid was put in suspension in 21 mL of isobutanol and 4.75 mL (43 mmole) of N-methyl piperazine. The reaction mixture was heated to reflux for 6 hours, then slurried at ambient temperature for 60 hours and heated again to reflux for 7 hours until completion of the reaction. During that time, the reaction mixture became soluble at reflux temperature. The mixture was then cooled to 0 C., filtered under vacuum, washed with 7 mL isobutanol and 10 mL n-heptane, and dried overnight to obtain 2.83 g (77.3%) of levofloxacin.
11.48 g (89.3%) In DMA (dimethyl acetamide); Example 5 Synthesis of Levofloxacin in DMA 10 g (35.6 mmole) of (S)-(-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid was put in suspension in 5 mL of DMA (dimethyl acetamide) and 8.3 mL (75 mmole) of N-methyl piperazine. The reaction mixture was heated to 110 C. until the complete conversion of the starting material, about 1.5 h. The reaction mixture was then cooled to 80 C. and 60 ml of isopropyl alcohol was added. The reaction mixture was then slurried for 3 hours at ambient temperature filtered under vacuum, washed with 40 ml IPA and dried in vacuum oven overnight to obtain 11.48 g (89.3%) of levofloxacin.
In butan-1-ol; at 120 - 125℃; for 6h; Example; Preparation of Levofloxacin hemihydrate; Step-1; (S)-(-) 9, 10-difluoro-3-methyl-7-oxo-2, 3-dihydro-7H-pyrido[l ,2,3-de] [1 ,4]benzoxazine- 6-carboxylic acid (100 g) is suspended in n-Butanol (80 ml), N-methyl piperazine (80 g) is added and the temperature is raised to 12O0C- 1250C. Reaction mass is maintained at temperature of 12O0C- 1250C for 6 hrs and cooled to below 1000C, distilled off the solvent under vacuum at temperature below 1000C. Toluene (100 ml) is added and. again distilled off under vacuum to remove traces of n-Butanol. Reaction mass is cooled to 6O0C - 650C, toluene (200 ml) and chloroform (1000 ml) are added and mixed for about 60 min at 250C - 3O0C. The reaction mass is filtered to remove insolubles. Clear filtrate is collected and the solvents are distilled off under vacuum at temperature below 650C. Isopropanol (500ml) is added to the reaction mass, temperature is raised to reflux and maintained at reflux temperature for about 15 min at 75C-80C. Reaction mass is cooled to 250C- 3O0C, maintained for 1 hr at 250C - 30C,the product is filtered and washed the wet cake with isopropanol (50 ml). ' ?The weight of the wet cake is about 150 g and the wet cake as such is preceded to next step without drying.
With triethylamine; In dimethyl sulfoxide; at 90℃; for 8h; 500ml three-necked flask was added 55.5g (), 28gDMSO, 111gN- methylpiperazine, triethylamine 28g, stirMix was heated to 90 , the reaction was kept 8h. Bi insulation, vacuum recovery DMSO, keeping the temperature <90 , vacuum <-. 098MPa,Until no liquid outflow, adding 150ml water, 150ml of chloroform was added a small amount of ammonia to adjust pH = 7.0, solution temperature with stirringAfter the solution was added activated charcoal 1g. 45 filtration rested stratification. The chloroform layer was separated, the aqueous layer was extracted three times with 50ml of chloroform,The combined chloroform layer was concentrated to dryness and recrystallized added 150ml of alcohol, drying the wet product was 63.8g levofloxacin ().The yield was 127.6% by weight.
In water; at 110℃; for 10.5h;Green chemistry; 20g of leucovorin and 70ml of water were put into the reaction flask, heated to 110 C with stirring, and 33ml of N-methylpiperazine was added dropwise. After half an hour dripping finished, the mixture was incubated for 10 hours, sampled and analyzed, and transformed into 94%. The mixture was cooled to 70-80 C and then distilled under reduced pressure to recover water and methylpiperazine. After steaming, 200 ml of ethanol was added and 15 ml of hydrochloric acid was added under stirring to reflux for 2 hours. The mixture was cooled to room temperature and filtered to obtain 56 g of tide (incomplete pumping Dry), do not dry direct secondary beating, add water, 9% ethanol 165ml heat reflux 1h. Cooling filtration, too tidal goods 28.14g, do not dry directly to the third beating, adding 95% ethanol 180ml, heated to reflux1h, cooled and filtered, washed with a small amount of anhydrous ethanol, dried, to obtain 19.86g liquid phase content of 99.43% levofloxacin hydrochlorideProducts, like white solid. Beating mother liquor was concentrated and recovered to obtain 4.13g of crude product, the content of 93.3%. Total yield of 86%, of which finished products receivedRate of 72.7%. Products can be further recovered from the secondary mother liquor, the cumulative yield of up to 90%.
In water; at 120℃; for 15.5h; 20g left oxycyclic acid, 70ml water into the reaction flask, heated to 120 C with stirring,38 ml of N-methylpiperazine are initially added dropwise,End half an hour, insulation 15 hours, sampling analysis, conversion 95%. After cooling to 70-80 C and distillation under reduced pressure,Recovering water and methylpiperazine, steaming and adding 200 ml of ethanol, adding 15 ml of hydrochloric acid while stirring, heating and refluxing for 2 hours, cooling to room temperature, filtering to obtain tide product 60g (not completely drained), not directly drying and performing secondary beating , Adding 165ml of 9% aqueous ethanol and heating to reflux for 3h. Cooled and filtered to obtain tide product 29.02g, do not directly dry the third beating, add 95% ethanol 180ml, heated to reflux 3h, cooled and filtered, a small amount of ethanol washing and drying, to obtain 21.03g liquid content of 99.56% Levofloxacin hydrochloride finished product, white-like solid. Beating mother liquor was concentrated and recovered, to obtain 4.34g crude, content of 92.8%. The total yield of 88%, of which yield of 72.7%. Products can be further recovered from the secondary mother liquor, the cumulative yield of up to 90%
In water; at 110℃; for 10.5h; 20g of L-Oxalaconic acid,70ml water is put into the reaction bottle,Heat to 110C with stirring33 ml of N-methylpiperazine was added dropwise.After half an hour drip, keep warm for 10 hours.Sampling analysis, conversion 94%.After cooling to 70-80 deg.] C under reduced pressure by distillation,And recovering water-methylpiperazine,200ml of ethanol was added after steaming.15ml of hydrochloric acid was added under stirring.Heat reflux 2h,Cool to room temperature, filter,56g (not completely drained)Direct drying without drying165 ml of 9% aqueous ethanol was added and the mixture was heated at reflux for 1 h.Cooled and filtered, the product was 28.14g.Do not dry directly for the third time,Add 95% ethanol 180ml, heated to reflux for 1h,Cooling filtration, a small amount of anhydrous ethanol washing,After drying, 19.86 g of finished levofloxacin hydrochloride with a liquid phase content of 99.43% was obtained.White solid.Beating mother liquor is concentrated and recovered.4.13 g of crude product are obtained with a content of 93.3%.Total yield 86%Wherein product yield 72.7%. The product can be further recovered from the secondary mother liquor,The cumulative yield of 90%.

  • 2
  • [ 82419-36-1 ]
  • [ 100986-85-4 ]
  • [ 100986-86-5 ]
YieldReaction ConditionsOperation in experiment
With O,O'-dibenzoyl-D-tartaric acid; 1-ethyl-3-methylimidazolium hydrogen (2R,3R)-tartrate; In water; for 2h; The racemate ofloxacin and ethyl-3-methylimidazolium L-tartrate was dissolved in deionized water to form a solution containing 1-ethyl-3-methylimidazole L-tartrate at a concentration of 0.05 mol/L, Ofloxacin racemate concentration of 1000ppm of water phase, D-dibenzoyltartaric acid is dissolved in n-decanol to form an organic phase containing D-dibenzoyltartaric acid at a concentration of 0.2 mol/L, The organic phase and the aqueous phase were mixed in a volume ratio of 1:1 and placed in an oscillator, shock 2h, and the concentration of L-ofloxacin and D-ofloxacin was detected by taking water phase clear solution, and the separation factor reached 3.17.
  • 3
  • [ 109-01-3 ]
  • (3S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid-boron difluoride chelate complex [ No CAS ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
The (3S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid-boron difluoride chelate complex (310 mg), which had been obtained in Example 13, was dissolved in dimethyl sulfoxide (6 mL), followed by the addition of triethylamine (0.32 mL) and N-methylpiperazine (0.13 mL). The thus-obtained mixture was stirred at room temperature for 17 hours, and was then evaporated to dryness under reduced pressure. After the residue was washed with diethyl ether, the residue was dissolved in 95% ethanol (20 mL) which contained triethylamine (0.5 mL). The solution so obtained was heated under reflux for 8 hours. The reaction mixture was allowed to cool, and was then evaporated to dryness under reduced pressure. The residue was dissolved in dilute hydrochloric acid (5%). Subsequent to addition of chloroform, the resultant mixture was allowed to separate into layers. The water layer was adjusted to pH 11 with sodium hydroxide (1 mol/L), and then to pH 7.4 with hydrochloric acid (1 mol/L). The thus-prepared mixture was extracted with chloroform (50 mL x 3). The extracts were combined and dried over sodium sulfate, and the chloroform was distilled off. Resulting powder was recrystallized from ethanol-diethyl ether to afford the title compound as transparent fine needles (120 mg). Melting point: 225-227C. [] Elemental analysis for C18H20FN3O4·1/2H2O:
  • 4
  • [ 100986-85-4 ]
  • (S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% In water; ethyl acetate; for 1h;Heating / reflux;Purification / work up; Example 4. Purification with mixed solvent containing ethyl acetate and water; 2.0 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 80 ml of a mixed solvent containing ethyl acetate and water (97 : 3). The reaction mixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 4 ml of the mixed solvent containing ethyl acetate and water (97 : 3). The resulting wet cake was dried under reduced pressure to provide 1.8 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 90 %).
89.6% In 2,8-dimethylnonan-5-one; water; for 1h;Heating / reflux;Purification / work up; Example 3. Purification with mixed solvent containing isobutyl methyl ketone and water; 1.15 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 35.7 ml of a mixed solvent containing isobutyl methyl ketone and water (98.5 : 1.5). The reaction mixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 2.3 ml of the mixed solvent containing isobutyl methyl ketone and water (98.5 : 1.5). The resulting wet cake was dried under reduced pressure to provide 1.03 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 89.6 %).
85.6% In acetic acid methyl ester; water; for 1h;Heating / reflux;Purification / work up; Example 2. Purification with mixed solvent containing methyl acetate and water; 1.18 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 59 ml of a mixed solvent containing methyl acetate and water (97 : 3). The reaction mixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 2.4 ml of the mixed solvent containing methyl acetate and water (97 : 3). The resulting wet cake was dried under reduced pressure to provide 1.01 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 85.6 %).
84.5 - 87.5% In water; ethyl acetate; tert-butyl alcohol; for 1h;Heating / reflux;Purification / work up; Example 8. Purification with mixed solvent containing t-butanol, ethyl acetate, and water; 2.0 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 54 ml of a mixed solvent containing t-butanol, ethyl acetate, and water (64.7 : 32.3 : 3). The reaction mixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 4.0 ml of the mixed solvent containing t-butanol, ethyl acetate, and water (64.7 : 32.3 : 3). The resulting wet cake was dried under reduced pressure to provide 1.69 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 84.5 %).Example 9. Purification with mixed solvent containing t-butanol, ethyl acetate, and water2.0 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 54 ml of a mixed solvent containing t-butanol, ethyl acetate, and water (48.5 : 48.5 : 3). The reaction mixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 4.0 ml of the mixed solvent containing t-butanol, ethyl acetate, and water (48.5 : 48.5 : 3). The resulting wet cake was dried under reduced pressure to provide 1.72 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 86 %).Example 10. Purification with mixed solvent containing t-butanol, ethyl acetate, and water2.0 g of the crude <strong>[100986-85-4]levofloxacin</strong> prepared in Example 1 was added to 64 ml of a mixed solvent containing t-butanol, ethyl acetate, water (32.3 : 64.7 : 3). The reactionmixture was refluxed for 1 hour and then cooled to room temperature. The resulting precipitate was filtered under reduced pressure and then washed with 4.0 ml of the mixed solvent containing t-butanol, ethyl acetate, and water (32.3 : 64.7 : 3). The resulting wet cake was dried under reduced pressure to provide 1.75 g of <strong>[100986-85-4]levofloxacin</strong> hemihydrate (yield: 87.5 %).

  • 5
  • [ 100986-89-8 ]
  • [ 50-81-7 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
5.63 g (87.6%) In dimethyl sulfoxide; Example 13 DMSO/Ascorbic Acid In a three necks flask equipped of a condenser were put in suspension in 3.5 ml of DMSO at 80 C. under nitrogen atmosphere 5 g (17.8 mmol) of (S)-(-)-9,10-Difluoro-3-Methyl-7-oxo-2,3-Dihydro-7H-Pyrido[1,2,3-de][1,4]Benzoxazine-6-Carboxylic Acid, 4.46 g (44.6 mmol), 31 mg (0.17 mmol) of ascorbic acid. The reaction mixture was heated at this temperature (4h30) until completion of the reaction. Then the solution was cooled to 70 C. and IPA (40 ml) was added dropwise. The mixture was cooled to 0 C. in 1 hour and then stirred at this temperature for 30 minutes. The precipitate was filtrated under vacuum, washed with IPA (10 ml) and dried at 60 C. in a vacuum oven to give 5.63 g (87.6%) of pure levofloxacin.
  • 6
  • sodium metabisulfite [ No CAS ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
11.8 g (92.4%) In dimethyl sulfoxide; Example 14 DMSO/Metabisulfite In a three necks flask equipped of a condenser were put in suspension in 7 ml of DMSO at 80 C. under nitrogen atmosphere 10 g (35.5 mmol) of (S)-(-)-9,10-Difluoro-3-Methyl-7-oxo-2,3-Dihydro-7H-Pyrido[1,2,3-de][1,4]Benzoxazine-6-Carboxylic Acid, 9.0 g (90 mmol), 34 mg (0.17 mmol) of sodium metabisulfite. The reaction mixture was heated at this temperature (5h30) until completion of the reaction. Then the solution was cooled to 70 C. and IPA (40 ml) was added dropwise. The mixture was cooled to 0 C. in 1 hour and then stirred at this temperature for 30 minutes. The precipitate was filtrated under vacuum, washed with IPA (10 ml) and dried at 60 C. in a vacuum oven to give 11.8 g (92.4%) of pure levofloxacin.
  • 7
  • [ 109-01-3 ]
  • [ 107-98-2 ]
  • [ 142-82-5 ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
2.98 g (77.3%) Example 2 Synthesis of Levofloxacin in PGME 3 g (10.67 mmole) of (S)-(-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid was put in suspension in 30 mL of PGME and 4.75 mL (43 mmole) of N-methyl piperazine. The reaction mixture was heated to reflux for 23 hours until completion of the reaction. During that time, the reaction mixture became soluble. The mixture was then cooled to 90 C. and n-Heptane (10 mL) was added at this temperature. The reaction mixture was then cooled to 0 C. and the precipitation occurred around 65 C. The reaction was left at 0 C. for 3 hours, filtrated under vacuum and dried overnight to obtain 2.98 g (77.3%) of levofloxacin.
  • 8
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-piperazine; n-heptane; Example 4 Synthesis of Levofloxacin (Neat) 5 g (17.79 mmole) of (S)-(-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid was put in suspension in 6.8 mL (0.06 mole) of N-methyl piperazine. The reaction mixture was heated to reflux for 40 minutes until completion of the reaction. The mixture was then cooled to 80 C. IPA (10 mL) and n-heptane (10 mL) were added at this temperature. The solid was filtrated under vacuum and rinsed with n-heptane. The mother liquor also gave a precipitate after addition of n-heptane. Both precipitates were filtrated under vacuum and dried overnight to yield 4.9 g (76%) levofloxacin.
  • 9
  • [ 109-01-3 ]
  • [ 109-63-7 ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In hydrogenchloride; methanol; diethyl ether; dimethyl sulfoxide; EXAMPLE 16 Preparation of S-(-)-9-Fluoro-3-Methyl-10-(4-Methyl-1-Piperazinyl)-7-oxo-2,3-Dihydro-7H-Pyrido[1,2,3-de][1,4]Benzoxazine-6-Carboxylic Acid (VI) (S-(-)-Isomer of Ofloxacin) In 600 ml of diethyl ether was suspended 14.3 g of the carboxylic acid obtained in Example 15, and 70 ml of boron trifluoride diethyl etherate was added thereto, followed by stirring at room temperature for 5 hours. The supernatant liquid was removed by decantation, and to the residue was added diethyl ether, followed by filtration. The solid was washed with diethyl ether and dried. The product was dissolved in 100 ml of dimethyl sulfoxide, and 14.2 ml of triethylamine and 7.3 ml of N-methylpiperazine were added to the solution. After the mixture was stirred at room temperature for 18 hours, the solvent was removed by distillation. Diethyl ether was added to the residue, followed by filtration. The collected yellow powder was suspended in 400 ml of 95% methanol, and 25 ml of triethylamine was added thereto. The mixture was heated at reflux for 25 hours. The solvent was distilled off under reduced pressure, and the residue was dissolved in 500 ml of 10% hydrochloric acid and washed three times with chloroform. The washed solution was adjusted to a pH of 11 with a 4N sodium hydroxide aqueous solution and then to a pH of 7.3 with 1N hydrochloric acid. The solution was extracted three times with 2 liter portions of chloroform, and the combined extract was dried over sodium sulfate. The chloroform was removed by distillation, and the resulting crystal was recrystallized from ethanol/diethyl ether to obtain 12.0 g of the titled compound having a melting point of 226-230 C. (with decomposition). [alpha]D =-76.9 (c=0.655, 0.05N NaOH).
  • 10
  • [ 109-01-3 ]
  • chloroform-methanol-water [ No CAS ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
In ethanol; dimethyl sulfoxide; Example 102 (3S)-(-) -9-Fluoro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid (levofloxacin) (S)-(-)-9,10-Difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid (21 mg) and N-methylpiperazine (30 mg) were dissolved in anhydrous dimethyl sulfoxide (3 ml) and stirred at 130 to 140C for 1 hour. After evaporating the solvent, ethanol (2 ml) was added to the residue. The solid thus precipitated was collected by filtration and washed successively with a small amount of ethanol and ether. 14 mg of the obtained powder was subjected to silica gel column chromatography with the use of 5 g of silica gel and eluted with a lower layer solution of chloroform-methanol-water (7:3:1) to thereby give (S)-(-)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid.
  • 11
  • G of N-methylpiperazine [ No CAS ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
74.3% In pyridine; diethyl ether; Example 9 (S)-(-)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid 1.2 G of N-methylpiperazine were added to 1.15 g of <strong>[100986-89-8](S)-(-)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid</strong> dissolved in 6 ml of pyridine. Next, the mixture was heated at 120C for 10 hours, while stirring. After cooling the workup was carried out as described in example 8. In this case diethyl ether was added to the residue, obtained by evaporating the chloroform extract. The crystalline material thus formed was filtered off, washed and dried to afford 1.3 g of crude material. Recrystallization from isopropanol afforded 1.1g of the title product. Yield: 74.3%. [alpha] [22/D ] = -78.1 (c=0.2, 0.05N NaOH). M.p. 225-226C. 1H NMR (CDCl3, ppm) delta = 1.62 (d, 3H), 2.38 (s, 3H), 2.58 (br.s, 4H), 3.41 (m, 4H), 4.44 (ABq, 2H), 4.59 (m, 1H), 7.67 (d, 1H), 8.65 (s, 1H).
  • 12
  • [ 1036016-10-0 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
76% EXAMPLE 9 (S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid (levofloxacin) 2.5 g (6.5 mmol) of (S)-6,8-difluoro-1-(1-hydroxypropan-2-yl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid were added to a solution of 1.3 g (23 mmol) of potassium hydroxide in 20 mL of ethanol 96% and heated at reflux for 3 hours. 1.25 mL of acetic acid were added to the mixture at room temperature and after cooling to 0-5C it was filtered to obtain 1.8 g (76%) of levofloxacin hemihydrate.
  • 13
  • [ 177472-29-6 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
78% EXAMPLE 10; (S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid (levofloxacin) Alternatively, the title compound could be obtained in a one pot process starting from (S)-ethyl 6,8-difluoro-1-(1-hydroxypropan-2-yl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate: 3.0 g (7.3 mmol) of (S)-ethyl 6,8-difluoro-1-(1-hydroxypropan-2-yl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate were added to a solution of 1.56 g (27.8 mmol) of potassium hydroxide in 80 mL of ethanol 96 %. After hydrolysis of the ester at room temperature, the reaction mixture was heated at reflux for 2 hours and a half. The reaction was cooled to room temperature and neutralised, with approximately 1.5 mL of glacial acetic acid, to pH 7. After neutralisation, 10 mL of water were added to the mixture and then it was cooled at 0-5 C for 2 hours and finally filtered to obtain 2.1 g (78%) of levofloxacin hemihydrate.
  • 14
  • [ 100986-85-4 ]
  • C18H19ClFN3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; In dichloromethane;Cooling with ice; Inert atmosphere; LF-NA-DP conjugates were prepared by chemical grafting chlorinated <strong>[100986-85-4]levofloxacin</strong> (LF-Cl) to NA-DP through amide formation as previously described with minor modifications (Hu et al., 2015; Tomii,Kujundi, Krajai, Vinjevac, & Koji-Prodi, 2002). In detail, to obtain LF-Cl, LF (722 mg, 2 mmol) was dissolved in 50 mL anhydrous CH2Cl2, and an appropriate amount of SOCl2 was added dropwise in an ice bath, followed by stirring overnight under N2 atmosphere. Eventually, the mixture was concentrated under reduced pressure using a rotary evaporator at 45 C to remove unreacted CH2Cl2 in dispersions.The freshly prepared LF-Cl (380 mg, 1 mmol) and moderate content of DIEA were then added to CH2Cl2 solution containing NA-DP (330 mg,1.2 mmol) and stirred overnight at room temperature to ensure complete reaction. And the resulting solution was passed through a silica gel column chromatography (eluted with CH2Cl2/CH3OH) to give the pure LF-NA-DP (422 mg, yield: 68.3%).
  • 15
  • [ 50398-09-9 ]
  • [ 100986-89-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
92% Example 5 9-Fluoro-(3S)-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid An acetonitrile solution (30 mL) containing 9,10-difluoro-(3S)-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acids (3 g), 4-methylpiperazine dihydrochloride (2.22 g), triethylamine (1.43 mL), and boron trifluoride-tetrahydrofuran complex (2.84 g) was stirred at room temperature for 30 minutes. Triethylamine (5.71 mL) was further added to the reaction mixture, followed by stirring at room temperature for 24 hours. The solvent was evaporated under reduced pressure, and methanol (30 mL) was added to the residue. The mixture was refluxed for 24 hours, and the solvent was evaporated under reduced pressure. Ethanol (15 mL) was added to the residue, and the mixture was stired at room temperature for 16 hours. The thus-produced crystals were recovered through filtration and dried, to thereby yield 3.55 g of the title compound (yield: 92%). 1H-NMR(400MHz,CDC13) deltappm: 1.63(3H,d,J=7Hz),2.38(3H,s),2.54-2.60(4H,m),3.40-3.44(4H,m),4.35-4.52(3H,m),7.76(1H,d,J=11.8Hz),8.64(1H,s) Elemental analysis: Calc. C;59.82%, H;5.58%, N;11.63% Obsd.C; 60.01%, H;5.69%, N;11.53%
  • 16
  • [ 100986-85-4 ]
  • (S)-9-fluoro-3-methyl-10-(4-methylpiperidin-1-yl)-2,3,5,6-tetrahydro-[1,4]oxazine[2,3,4-ij]quinolin-7-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
76.3% General procedure: The quinolone compound II (1.0 mmol) was suspended in 15 mL of anhydrous methanol and cooled to 0 C.A solution of NaBH4 (4.0 mmol) in 2 mL of cold anhydrous methanol was slowly added, and the mixture was reacted for 1 hour, and 3.4 mg of p-toluenesulfonic acid was added thereto, and the mixture was reacted at 60-65 C for 0.5 h.Evaporation to dryness under reduced pressure, the residue was dissolved in 15 mL of chloroform, washed with water, dried over magnesium sulfate and filtered.Concentration and purification by silica gel column chromatography (chloroform: ethyl acetate 3:1) to afford intermediate (IIIa-e).
EXAMPLE 1 - FLUOROQUINOLONE DERIVATIVES; Formation of fluoroquinolone aldehyde derivatives have been undertaken by modifying a reduction/ decarboxylation/ Claisen addition/ oxidation protocol reported by Kondo et al. (Kondo, H.; Sakamoto, F.; Kawakami, K.; Tsukarnoto, G. J. Med. Chem., 1988, 31, 221.); Fluoroquinolone Aldehyde Synthesis; To a 0 0C stirring solution of fluoroquinolone in anhydrous methanol under inert atmosphere was added solid sodium borohydride (4.5 eq.) slowly over 30 minutes. The mixture was allowed to warm to room temperature and p-toluene sulfonic acid (0.1 eq.) was added. After heating at reflux for 3.5 hours, the mixture was allowed to cool and the solvent removed in vacuo. The crude solid was washed with hot chloroform and water and then extracted with chloroform (* 3). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated under reduced pressure. The crude mixture was subjected to flash column chromatography (20 % methanol/ chloroform) to afford the intermediate.
  • 17
  • [ 33657-49-7 ]
  • [ 100986-85-4 ]
  • [ 55696-44-1 ]
  • [ 1261134-52-4 ]
YieldReaction ConditionsOperation in experiment
59% Stage #1: levofloxacin With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 0.333333h; Stage #2: chloromethyl n-butyrate In N,N-dimethyl-formamide at 90℃; for 1h;
  • 18
  • [ 124-09-4 ]
  • [ 100986-85-4 ]
  • [ 1350462-80-4 ]
YieldReaction ConditionsOperation in experiment
50% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 19
  • [ 462-94-2 ]
  • [ 100986-85-4 ]
  • [ 1350462-79-1 ]
YieldReaction ConditionsOperation in experiment
54% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 20
  • [ 646-19-5 ]
  • [ 100986-85-4 ]
  • [ 1350462-86-0 ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 21
  • [ 373-44-4 ]
  • [ 100986-85-4 ]
  • [ 1350462-81-5 ]
YieldReaction ConditionsOperation in experiment
68% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 22
  • [ 646-24-2 ]
  • [ 100986-85-4 ]
  • [ 1350462-82-6 ]
YieldReaction ConditionsOperation in experiment
50% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 23
  • [ 646-25-3 ]
  • [ 100986-85-4 ]
  • [ 1350462-83-7 ]
YieldReaction ConditionsOperation in experiment
52% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 24
  • [ 2783-17-7 ]
  • [ 100986-85-4 ]
  • [ 1350462-84-8 ]
YieldReaction ConditionsOperation in experiment
64% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 25
  • [ 100986-85-4 ]
  • [ 110-60-1 ]
  • [ 1350462-85-9 ]
YieldReaction ConditionsOperation in experiment
60% With triethylamine; trichloroacetonitrile; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; General procedure: To a solution of TPP (0.46 g, 1.8 mmol), diamine (0.45 mmol) and triethylamine (0.25 mL, 1.8 mmol) in 3 mL of CH2Cl2 under argon were added LV (0.32 g, 0.9 mmol) then TCA (0.18 mL, 1.8 mmol) dropwise. The mixture was stirred at room temperature for 2 h. The mixture was directly purified by 10% activated alumina gel chromatography (CH2Cl2/MeOH (0-1.5%)).
  • 26
  • gold(III) tetrachloride trihydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [AuCl2(levofloxacin)]Cl.2H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% In methanol; at 20℃; for 24h; General procedure: [AuCl2(LEVO)]Cl (2) and [AuCl2(SPAR)]Cl (3) were obtained by the reaction of appropriate quantities of the ligands (0.25 mmol), dissolved in methanol (40 mL), which were then added to the solutions of HAuCl4 (0.25 mmol) in methanol (5 mL). Immediately after the addition of the ligand, a precipitate formed. The reaction mixture remained stirring at room temperature for 24 h. The solids obtained were filtered under vacuum, washed with diethyl ether, and dried.
  • 27
  • zinc(II) nitrate hexahydrate [ No CAS ]
  • [ 100986-85-4 ]
  • C20H12N2O6Zn*2H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In methanol; at 20℃; [Zn(C10H6NO3)]·2H2O: Potassium hydroxide (5 mg, 0.08 mmol) was added to a stirred methanolic solution of the quinolone 3 (0.16 mmol in 3 mL) and the resulting mixture was filtered to remove solid particles in suspension. A methanolic solution of Cu(NO3)2·6H2O or Zn(NO3)2·6H2O (0.08 mmol in 5 mL) was added to the filtered and stirring was continued for 2 h. After this period, the solution was kept at room temperature to allow a complete evaporation of the solvent. The green crystals were collected by filtration, washed with water and ether, and dried in a desiccator containing phosphorous pentoxide. (white solid), IR (KBr): numax 1624 (COO), 1593 (C=O) cm-1; 1H NMR (CF3CO2D, 500MHz) delta 9.36 (s, 1H), 8.69 (d, J=8.3Hz, 1H), 8.25 (t, J=7.6Hz, 1H), 8.14 (d, J=8.5Hz, 1H), 8.00 (t, J=7.8Hz, 1H); 13C NMR (CF3CO2D, 125MHz) delta 176.3 (C=O), 172.7 (C=O), 148.2 (CH), 141.9 (C0), 140.7 (CH), 132.8 (CH), 127.3 (CH), 122.4 (C0), 122.3 (CH), 106.3 (C0). Elemental Anal. Calc. for C20H12ZnN2O6: C, 54.38; H, 2.74; N, 6.34. Found: C, 54.27; H, 2.71; N, 6.38%.
  • 28
  • copper(II) nitrate hexahydrate [ No CAS ]
  • [ 100986-85-4 ]
  • C20H12CuN2O6*2H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In methanol; at 20℃; [Cu(C10H6NO3)]·2H2O: Potassium hydroxide (5 mg, 0.08 mmol) was added to a stirred methanolic solution of the quinolone 3 (0.16 mmol in 3 mL) and the resulting mixture was filtered to remove solid particles in suspension. A methanolic solution of Cu(NO3)2·6H2O or Zn(NO3)2·6H2O (0.08 mmol in 5 mL) was added to the filtered and stirring was continued for 2 h. After this period, the solution was kept at room temperature to allow a complete evaporation of the solvent. The green crystals were collected by filtration, washed with water and ether, and dried in a desiccator containing phosphorous pentoxide. (green solid), IR (KBr): numax 1639 (COO), 1587 (C=O) cm-1. Elemental Anal. Calc. for C20H12CuN2O6: C, 54.58; H, 2.81; N, 6.35. Found: C, 54.61; H, 2.75; N, 6.37%.
  • 29
  • [ 100986-85-4 ]
  • [ 877-66-7 ]
  • [ 1469737-21-0 ]
YieldReaction ConditionsOperation in experiment
General procedure: To a solution of fluoroquinolone (e.g. <strong>[100986-85-4]levofloxacin</strong> hemihydrate, 200. mg, 0.5500mmol) in DCM (2ml_) was added triethylamine (0.08ml_, 0.5500mmol) followed by ethyl chloroformate (0.05ml_, 0.5500mmol) at 0C under Ar. This was allowed to stir at that temperature for 5 minutes. After which time the reaction mixture was allowed to warm to room temperature and hydrazine (0.5500mmol) was added in one portion. This was then allowed to stir at that temperature for 18 hours. After which time the reaction mixture was directly purified by automated flash chromatography (Grace Reveleris) using an eluent system of DCM:MeOH.; (BB) MS (m/z, rel. intensity) 531 (M+ H+, 100). Compound BB was prepared using method B.
  • 30
  • [ 121-91-5 ]
  • [ 5743-04-4 ]
  • [ 100986-85-4 ]
  • [Cd2(levofloxacin)(1,3-benzenedicarboxylate)2(H2O)2] [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With Adipic acid; triethylamine; In water; at 150 - 160℃; for 128h;Autoclave; A mixture of Cd(OAc)22H2O (0.5 mmol), LevofH (0.25 mmol),1,3-bdc (0.25 mmol), adipic acid (0.25 mmol), Et3N (0.5 mL), anddistilled water (8 mL) was stirred for 30 min in air, then sealed inan 18 mL Teflon-lined autoclave, which was heated at 150C for48 h and then heated at 160 C for 80 h under autogenous pressure.After slow cooling to room temperature, yellow block crystals of 3were filtered off, washed with distilled water and dried at ambienttemperature (55 mg, yield: 46% based on 1,3-bdc). Anal. Calc. forC34H32Cd2F2N3O14 (3): C, 42.97; H, 3.39; N, 4.42; Cd, 23.65. Found:C, 42.77; H, 3.54; N, 4.62; Cd, 23.49%. FT/IR data (cm1): 3386 (br),2860(w), 2658(w), 2523(w), 2483(w), 1902(w), 1630(s), 1606(s),1582(w), 1561(w), 1474(m), 1456(w), 1442(w), 1425(w), 1384(s),1347(w), 1268(m), 1185(w), 1151(w), 1126(s), 1092(w),1051(m), 1023(m), 977(m), 951(s), 914(w), 875(w), 838(w),819(s), 755(m), 737(w), 724(s), 690(w), 657(w), 631(w), 594(w),497(w), 464(m), 434(w), 413(w).
  • 31
  • [ 82419-36-1 ]
  • Cu(II)-coordinated G-rich oligonucleotides [ No CAS ]
  • [ 100986-85-4 ]
  • [ 100986-86-5 ]
  • 32
  • [ 366-18-7 ]
  • copper(II) choride dihydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [Cu(levofloxacin)(2,2-bipyridine)Cl]2*10.84H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium methylate; In methanol; for 0.5h;pH Ca. 8;Heating; A solution of CuCl2*2H2O (23.9 mg, 0.14 mmol) in methanol (5 ml) was added to a solution of 2,2-bipyridine (bipy) (21.9 mg,0.14 mmol) in methanol (5 ml), followed by the addition of a previously prepared solution of LVX (50.0 mg, 0.14 mmol) in methanol (5 ml) in the presence of CH3ONa. The pH was adjusted to ~8 using diluted CH3ONa solution (0.1 M). The resulting solution was stirred for half hour while heating, followed by concentration to its half volume. A fine amorphous product of green color was obtained, filtered off and washed with cold methanol and dried in vacuum desiccator over silica gel. Yield: 65%, (M.W: 1426.37) Recrystallization of the above amorphous product provides green crystals after few weeks suitable for X-ray crystallography (2). Selected bands: IR (KBr) vmax 3421 (OH), vasym 1614 (CO), vsym 1385(COO), v 1579 (COO), v 515 (Cu-O), v 554 (Cu-N). Elemental Anal. Calc. for C56H75.68Cl2Cu2F2N10O18.44 (2): C, 47.37; H, 5.37; N,9.87. Found: C, 48.27; H, 5.25; N, 10.04% (Average of 3).
  • 33
  • [ 366-18-7 ]
  • copper(II) choride dihydrate [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • [Cu2(levofloxacin(-1))2(bipy)2Cl2]*10.84H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium methylate; In methanol; for 0.5h;pH Ca. 8;Heating; A solution of CuCl2 2H2O (23.9 mg, 0.14 mmol) in methanol(5 ml) was added to a solution of 2,2-bipyridine (bipy) (21.9 mg,0.14 mmol) in methanol (5 ml), followed by the addition of a previouslyprepared solution of LVX (50.0 mg, 0.14 mmol) in methanol(5 ml) in the presence of CH3ONa. The pH was adjusted to 8 usingdiluted CH3ONa solution (0.1 M). The resulting solution was stirredfor half hour while heating, followed by concentration to its halfvolume. A fine amorphous product of green color was obtained, filteredoff and washed with cold methanol and dried in vacuum desiccatorover silica gel. Yield: 65%, (M.W: 1426.37) Recrystallizationof the above amorphous product provides green crystals after fewweeks suitable for X-ray crystallography (2).Selected bands: IR (KBr) vmax 3421 (OH), vasym 1614 (CO), vsym1385(COO), v 1579 (COO), v 515 (Cu-O), v 554 (Cu-N). Element Anal. Calc. for C56H75.68Cl2Cu2F2N10O18.44 (2): C, 47.37; H, 5.37; N,9.87. Found: C, 48.27; H, 5.25; N, 10.04% (Average of 3).
  • 34
  • [ 67-56-1 ]
  • copper(II) choride dihydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [Cu2(levofloxacin(-1))4]*1.6MeOH*1.2H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% A solution of CuCl2 2H2O (48.0 mg, 0.28 mmol) in water(5 ml) was added to a previously prepared solution of LVX(100.0 mg, 0.28 mmol) in water (5 ml). The pH was adjusted to8 using diluted NH3 (2 M). The resulting solution was stirredunder reflux for at least three hours. A fine amorphous productof green color was obtained, filtered off and washed with coldwater and dried in vacuum desiccator over silica gel. Yield: 43%,(M.W: 857,15) Recrystallization of the amorphous product frommethanol and slow evaporation at 4 C afforded X-ray quality crystalsafter ten days (1).Selected bands: IR (KBr) vmax 3421 (OH), vasym 1617 (CO), vsym1365(COO), v 1586 (COO), v 520 (Cu-O). Elemental Anal. Calc. forC37.6H46.8CuF2N6O10.8 (1): C, 52.69; H, 5.50; N, 9.81. Found: C,51.40; H, 5.08; N, 9.88% (Average of 3)
  • 35
  • [ 366-18-7 ]
  • copper(II) choride dihydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [Cu(levofloxacin)(2,2-bipyridine)Cl]*10.84H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium methylate; In methanol; for 0.5h;pH Ca. 8;Heating; A solution of CuCl2 2H2O (23.9 mg, 0.14 mmol) in methanol(5 ml) was added to a solution of 2,2-bipyridine (bipy) (21.9 mg,0.14 mmol) in methanol (5 ml), followed by the addition of a previouslyprepared solution of LVX (50.0 mg, 0.14 mmol) in methanol(5 ml) in the presence of CH3ONa. The pH was adjusted to 8 usingdiluted CH3ONa solution (0.1 M). The resulting solution was stirredfor half hour while heating, followed by concentration to its halfvolume. A fine amorphous product of green color was obtained, filteredoff and washed with cold methanol and dried in vacuum desiccatorover silica gel. Yield: 65%, (M.W: 1426.37) Recrystallizationof the above amorphous product provides green crystals after fewweeks suitable for X-ray crystallography (2).Selected bands: IR (KBr) vmax 3421 (OH), vasym 1614 (CO), vsym1385(COO), v 1579 (COO), v 515 (Cu-O), v 554 (Cu-N). Elemental Anal. Calc. for C56H75.68Cl2Cu2F2N10O18.44 (2): C, 47.37; H, 5.37; N,9.87. Found: C, 48.27; H, 5.25; N, 10.04% (Average of 3).
  • 36
  • [ 7717-76-2 ]
  • [ 5970-45-6 ]
  • [ 100986-85-4 ]
  • [Zn2(levofloxacin)2(4,4'-oxydiphthalate)]·5.5H2O [ No CAS ]
  • 37
  • copper(II) choride dihydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [ 2848-01-3 ]
  • C33H33CuFN3O6P*H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
54.2% With sodium methylate; In methanol; for 3h;pH Ca. 6.8;Reflux; General procedure: Methanolic solution of CuCl2 2H2O (1.5 mmol) was added to a methanolic solution of 3-(diphenylphosphino)-propionic acid (L) (1.5 mmol) followed by the addition of a previously prepared methanolic solution of sparfloxacin (SFLH) (1.5 mmol) in presence of CH3ONa (1.5 mmol). The pH of the reaction mixture was adjusted to ?6.8. The resulting solution was refluxed for 3 h on a water bath, followed by concentrating to half of its volume. A fine, green amorphous product obtained was washed with ether/hexane/chloroform and dried in vacuum desiccators. The proposed reaction for the synthesis of complexes is shown in scheme 1 .
  • 38
  • [ 109-63-7 ]
  • [ 100986-85-4 ]
  • difluoroboron complexes of levofloxacin [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% In dichloromethane; N,N-dimethyl-formamide; for 24h;Reflux; General procedure: The fluoroquinolones (2.0 mmol) were dissolved in 20 mL DMF-CH2Cl2 (1:1) solution, and boron trifluoride diethyl etherate (2.0 mL, 15.8 mmol) was added dropwise to this solution. The reaction mixture was stirred and refluxed for 24 h. The solution was then cooled to room temperature and the yellow solid was precipitated. The precipitates were filtered and washed with dichloromethane. The products were recrystallized from DMF-CHCl3 (1:1) solution to obtain difluoroboron complexes 1-6 in good yields.
  • 39
  • oxovanadium(IV) sulfate [ No CAS ]
  • [ 100986-85-4 ]
  • [ 2848-01-3 ]
  • C33H33FN3O7PV [ No CAS ]
YieldReaction ConditionsOperation in experiment
64.26% In methanol; for 10h;pH Ca. 6.8;Reflux; General procedure: To a hot solution of VOSO4 (2) (5 mmol) in MeOH(25.0 mL), previously prepared methanolic solution ofligand 3-(diphenylphosphino)-propionic acid (1) (5 mmol)was added, with constant stirring. Then, alkaline methanolicsolution of ciprofloxacin (5 mmol) was added. The pH of thereaction mixture was adjusted to*6.8. The resulting greensolution was refluxed for 10 h and concentrated under vacuum.Upon addition of Et2O, a green solid precipitate wasobtained, which was collected by filtration, washed withEt2O and dried in vacuo (Gajera et al., 2015). General synthesisof complexes is shown in Scheme 1. Yield: 62.61 %.M.P:[300. Anal. Calcd (%). for C32H33FN3O6PV: C, 58.54;H, 5.07; N, 6.40; V, 7.76. Found (%): C, 58.24; H, 4.76; N,6.89; V, 7.26. UV-VIS in DMSO [kmax/nm (e/M-1 cm-1)]:421 (23,729), 584 (17,100), 807 (12,391). FT-IR: tmax(cm-1) m(C=O)pyridone 1628, m(CO2)asym 1586, m(CO2)-sym 1384, m = m(CO2)asym-m(CO2)sym = 202, m(V=O)952, m(M-O) 513 cm-1. ESI-MS (m/z):654.62 [M?].
  • 41
  • ruthenium trichloride [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • C54H60Cl3F3N9O12Ru*8H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With ammonium hydroxide; In methanol; at 70 - 80℃; General procedure: A hot methanolic solution (3 mmol, 20 mL) of LEV (1.09 g) was added to an aqueous solution (20 mL) of RuCl3 (1 mmol, 0.21 g) andIrCl3·xH2O (1 mmol, 0.3 g), then the solutions were neutralized using aqueous (1M) ammonia solution. The reaction mixtures were refluxed for 1-2 h at ~70-80 C. The solutions were filtered off and left for slow evaporation. After a one day left a dark green-to-yellow microcrystalline products were deposited, collected with filtration, washed with methanol and dried under vacuum. The same procedure was repeated for platinum(IV) complex with molar ratio 1:2 (H2PtCl6·6H2O (1 mmol,0.34 g) and LEV (2 mmol, 0.722 mg).
  • 42
  • dihydrogen hexachloroplatinate(IV) hexahydrate [ No CAS ]
  • [ 100986-85-4 ]
  • C36H40Cl4F2N6O8Pt*4H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With ammonium hydroxide; In methanol; water; at 70 - 80℃; General procedure: A hot methanolic solution (3 mmol, 20 mL) of LEV (1.09 g) was added to an aqueous solution (20 mL) of RuCl3 (1 mmol, 0.21 g) andIrCl3·xH2O (1 mmol, 0.3 g), then the solutions were neutralized using aqueous (1M) ammonia solution. The reaction mixtures were refluxed for 1-2 h at ~70-80 C. The solutions were filtered off and left for slow evaporation. After a one day left a dark green-to-yellow microcrystalline products were deposited, collected with filtration, washed with methanol and dried under vacuum. The same procedure was repeated for platinum(IV) complex with molar ratio 1:2 (H2PtCl6·6H2O (1 mmol,0.34 g) and LEV (2 mmol, 0.722 mg).
  • 43
  • iridium(III) chloride n-hydrate [ No CAS ]
  • [ 100986-85-4 ]
  • C54H60Cl3F3IrN9O12*6H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With ammonium hydroxide; In methanol; water; at 70 - 80℃; General procedure: A hot methanolic solution (3 mmol, 20 mL) of LEV (1.09 g) was added to an aqueous solution (20 mL) of RuCl3 (1 mmol, 0.21 g) andIrCl3·xH2O (1 mmol, 0.3 g), then the solutions were neutralized using aqueous (1M) ammonia solution. The reaction mixtures were refluxed for 1-2 h at ~70-80 C. The solutions were filtered off and left for slow evaporation. After a one day left a dark green-to-yellow microcrystalline products were deposited, collected with filtration, washed with methanol and dried under vacuum. The same procedure was repeated for platinum(IV) complex with molar ratio 1:2 (H2PtCl6·6H2O (1 mmol,0.34 g) and LEV (2 mmol, 0.722 mg).
  • 44
  • [ 50893-36-2 ]
  • [ 100986-85-4 ]
  • C23H28FN3O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 70℃; for 3h;Inert atmosphere; 10146] To a DMF (80 mL) solution of Levofloxacin (3.62 g, 10 mmol) in a 200-mL eggplant-shaped flask (a stirring bar contained) were added Nal (3.6 g, 24 mmol) and K2C03 (3.3 g, 24 mmol), and the mixture was stirred. Subsequently, 1 -chloroethyl -ethyl carbonate (8.6 mL, 64 mmol) was added thereto, and the mixture was stirred at 70 deg. C for 3 hours under argon gas flow. Warming was stopped and water (about 70 mL) and ice (optimum amount) were added for quenching the reaction. AcOEt (70 mL) was added for extraction, and the oil layer and the aqueous layer were separated. The extraction operation was carried out for the aqueous layer twice (50 mLx2 times) by new AcOEt; the combined organic layer was dehydrated by Mg504 after one wash with water, one wash with a 1percent sodium thiosulfate solution, and two wash with a saturated saline solution; and the filtered solution was concentrated in vacuum. A crude product (4.0 g) was obtained, and purified by silica gel column chromatography (an eluent is CHC13: MeOH=2: 1), and the object product was obtained in a yield of 2.58 g (54percent). The results of analyses of this product are listedbelow, and the product was confirmed to be the aimedLevofloxacin ethoxycarbonyl- 1-ethyl hemiacetal-type ester(LVFX-EHE).10147] m.p.: 167 to 173 deg. C.10148] ?H-NMR (400 MHz, CDC13); 1.31 (t, 3H, J=7.0Hz, CH3), 1.56 (d, 3H, J=7.0 Hz, CH3), 1.66 (d, 3H, J=6.0Hz, CH3), 2.36 (s, 3H, CH3), 2.56 (m, 4H, CH2x2), 3.36 (m,4H, CH2x2), 4.23 (q, 2H, J=7.0 Hz, CH2), 4.31 (m, 1H),4.36 (s, 2H, CH2x2), 7.00 (q, 1H, J=5.5 Hz, CH), 7.60*,7.65* (d, 1H, J=5.5 Hz), 8.26*, 8.27*(s, 1H, CH);10149] Note: Signal * indicates a separated diastereoisomer peak.10150] ?3C-NMR, (100 MHz, CDC13); 1418.3, 19.7, 46.4-50.5*, 50.6*, 547.557*, 55.8*, 64.3, 68.0, 91.5*, 91.6*,105.1, 107.9, 108.0, 123.0*, 123.1*, 123.5, 131.8*, 131.9*,139.6*, 139.7*, 145.3, 145.8, 153.0*, 153.1*, 154.5*, 155.0*, 156.9*, 157.1*, 162.4, 163.2, 172.3*, 172.5*. Note:Signal * indicates a separated diastereoisomer peak.10151] HR-MS; Calcd. for C23H28FN307: 477.1911.Found: 477.1909.
  • 45
  • [ 98298-66-9 ]
  • [ 100986-85-4 ]
  • C24H30FN3O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 70℃; for 3h; 10153] In a 300-mL eggplant-shaped flask, a DMF (110 mL) solution of Levofloxacin (10.0 g, 27.6 mmol) is prepared, and Nal (2.4 g, 66.24 mmol) and K2C03 (4.8 g, 132.5 mmol) were added thereto, and the mixture was stirred. Subsequently, 1 -chioroethyl-isopropyl-carbonate (27.0 mL, 176.64 mmol) was measured by a measuring cylinder, and was added to the flask with a pipette. After a Dimroth reflux condenser was attached, the reaction mixture was warmed at 70 deg. C and stirring was continued for 3 h. Then, water (about 100 mL) was slowly added to the mixture, and the reaction was quenched. After a proper quantity of ice was added also, the mixture solution was moved to a 300-mL separating funnel. AcOEt (70 mL) was added to the funnel, and it was shaken well, then, the AcOEt layer was separated. The aqueous layer was extracted twice by new AcOEt (50 mL), and the organic layers were combined. The combinedorganic layer was dehydrated with MgSO4 afier one wash with a 1% sodium thiosulfate solution, and one wash with saturated saline solution; the solution was filtered and the filtered solution was concentrated in vacuum. The residue (10.1 g) was obtained. Purification by colunm chromatography (developing solvent CHC13 :MeOH=2: 1) of the residue afforded the product (7.8 g; yield: 58%). The results of analyses of the product are described below, and the product was confirmed to be a Levofloxacin isopropoxycarbonyl 1-ethyl hemiacetal-type ester derivative (LVFX-isoPrHE).10154] m.p.: 132 to 133 deg. C.10155] ?H-NMR (400 MHz, CDC13); 1.30*, 1.32* (d, 6H, J=6.2 Hz), 1.53*, 154* (d, 3H, J=4.0 Hz), 1.65 (d, 3H, J5.5 Hz), 2.36 (s, 3H), 2.54 (m, 4H), 3.35 (m, 4H), 4.30-4.41 (m, 3H), 4.91 (sept, 1H, J=6.2 Hz), 7.00*, 7.01 (q, 1H, J=5.5 Hz), 7.56*, 759* (d, 1H, J=13.0 Hz), 8.24*, 8.25* (s, 1H).Note: Signal * indicates a separated diastereoisomer peak.10156] ?3C-NMR, (100 MHz, CDC13); 50.5*, 50.6*, 54.8,55.7 64.3* 64.4*, 68.1, 91.6*, 91.7*, 105.4*, 105.5*,105.6* 105.7* 108.2*, 108.4*, 123.28*, 123.30*, 123.36*,123.38* 123.53, 123.56*, 123.58*, 131.80*, 131.84*, 131.95* 131.98* 139.65*, 139.71*, 145.46*, 145.72*, 153.06*,153.17*, 154.61*, 154.69*, 157.08*, 157.16*, 162.72*, 163.27*, 172.46*, 172.48*, 172.61*, 172.64*. Note: Signal *indicates a separated diastereoisomer peak.10157] HR-MS: Calcd. for C24H30 FN307: 491.2068;Found: 491.2069.
  • 46
  • [ 100986-85-4 ]
  • (S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-6-(5-oxo-4,5-dihydro-1H-tetrazol-1-yl)-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinolin-7-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Preparation of (S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-6-(5-oxo-4,5-dihydro-1H-tetrazol-1-yl)-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinolin-7-one Diphenyl phosphoryl azide (323 muL, 1.5 mmol) was added to a stirred solution of <strong>[100986-85-4]Levofloxacin</strong> (361 mg, 1.0 mmol) and Et3N (280 muL, 2.0 mmol) in CH2Cl2 (10 mL) at 0 C. under an atmosphere of nitrogen. The mixture was stirred at 0 C. for 15 min, then allowed to warm to room temperature and stirred for 4 hr. Further aliquots of diphenyl phosphoryl azide (323 muL, 1.0 mmol) and Et3N (280 muL, 2.0 mmol) were added and the mixture was stirred at room temperature overnight. H2O (20 mL) and CH2Cl2 (15 mL) were added and the aqueous and organic layers were partitioned. The aqueous layer was extracted with CH2Cl2 (2*20 mL), and the combined organic layers were dried over Na2SO4, filtered and the solvent was removed under vacuum to leave a crude residue. The residue was suspended in azidotrimethylsilane (5 mL) and 1,4-dioxane (5 mL), then placed under an atmosphere of nitrogen. The mixture was slowly heated from room temperature to 100 C., and then stirred at 100 C. for 4 hr. After cooling, the mixture was dry-loaded on to silica gel and purified by column chromatography on silica gel using CHCl3/(MeOH/NH4OH; 7:1) [1:0 to 7:3] as eluent to give the product as a solid. 1H NMR (DMSO-d6, 300 MHz): delta 8.51 (s, 1H), 7.39 (d, J=12.3 Hz, 1H), 4.62-4.54 (m, 1H), 4.47 (dd, J=11.4, 1.5 Hz, 1H), 4.34 (dd, J=11.4, 2.1 Hz, 1H), 3.25 (br. s, 8H), 2.24 (s, 3H), 1.41 (d, J=6.3 Hz, 3H) 19F NMR (DMSO-d6, 282 MHz): delta -122.9 (d, J=12.3 Hz) m/z=402.91 [M+H]+ HRMS (EI): [M+H]+ calc'd for C10H8N6O2 m/z 402.1701. found 402.1690. HRMS (EI): [M-H]+ calc'd for C10H8N6O2 m/z 400.1527. found 400.1534.
  • 47
  • 2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-hydroxybenzoate [ No CAS ]
  • [ 100986-85-4 ]
  • 4-(((2-(prop-2-yn-1-yl)pent-4-yn-1-yl)oxy)carbonyl)phenyl 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% To an ice cod soution of evofoxacin (500.0 mg, 1.38 mmo) and NEt3 (250 pL, 178 mmo) in anhydrous DCM (30 mL), ethy choroformate (158 pL, 165 mmo)was added in one portion. The reaction mixture was stirred at 0C for 1 h and to it was added 2-(prop-2-yn-l -y)pent-4-yn-1 -y-4-hydroxybenzoate (368 m g 1 ,S2mmo), The reaction was aowed to warm to room temperature and then stirred further for 18 h. The reaction was quenched with H20 (20 mL), extracted with CH2C2 (2x 20 mL), washed with H20 (2 x 20 mL) and brine (20 mL). Combined organic extracts dried over anhydrous Na2SO4, fi[tered and concentrated under reduced pressure. Rash chromatography over sihca g& (030% DCM/MeOH gradient &ution) gave the tit?e compound as a pa?e yeflow sohd(375 mg, 0.64 mmo, 46%).
  • 48
  • 2-hydroxypropane-1,3-diyl bis(hex-5-ynoate) [ No CAS ]
  • [ 100986-85-4 ]
  • 2-((9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carbonyl)oxy)propane-1,3-diyl bis(hex-5-ynoate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.718 g With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 72h; 2hydroxypropane-13diy bis(hex-5-ynoate) (0.667 g, 2.38 mmo, 1.0 eq.),evofioxacin (1.03 g, 2.86 mmo, 1.2 eq.), HBTU (1.08 g, 2.86 mmo, 1.2 e.q) were dissoved in 25 mL anhydrous dichoromethane. Triethyamine (0.963 g, 9.52 mrno, 4.0 eq.) was added sowy into the reaction mixture and stirred for 72 hours at room temperature. The crude materia was purified directy via coumn chromatography on sihca ge (10% methano in DCM) to give the product as ayeflow oi (0.718 g).
  • 49
  • 1-chloroethyl (2-(prop-2-yn-1-yl)pent-4-yn-1-yl) carbonate [ No CAS ]
  • [ 100986-85-4 ]
  • 1-((((2-(prop-2-yn-1-yl)pent-4-yn-1-yl)oxy)carbonyl)oxy)ethyl (3S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 96h;Darkness; To a suspension & <strong>[100986-85-4]levofloxacin</strong> (0.280 g, 0.88 mmol) in anhydrous DMF, potassium carbonate (0.475 g, 3.44 mmol) and a solution & 1-chloroethyl (2- (prop-2-yn-1-yl)pent-4-yn-1-yl) carbonate (0.339 g, 1.5 mmol) in anhydrous DMF (5 mL) was added. The reaction mixture was stirred at room temperature for 4days with the exdusion from light The reaction mixture was extracted with ethyl acetate and washed with water and brine. The organic phase was then dried over Na2SO4, filtered and concentrated and dried in vacuo. The crude residue was purified on the automated flash chromatography using 0%-30% MeOH in DOM gradient elution to give a 1:1 diastereomer & the title compound as a dearcolourless oil (0.1148 g, 27% yield).
  • 50
  • [ 76-87-9 ]
  • [ 100986-85-4 ]
  • (S)-triphenylstannyl 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With sulfuric acid; In ethanol; acetone;Reflux; General procedure: The organotin derivatives (3a-3n) were obtained from the reaction of Ph3SnOH/ (Bu3Sn) 2O with ligand acid in 1:1 and 1:2M ratio, respectively. All the newly synthesized compounds are air stable, crystalline solids and soluble in common organic solvents. The general chemical reaction is given as Scheme 1. For the preparation of organotin ester equimolar amounts of ligand acid (2.33g, 10mmol) and triphenyltin hydroxide (3.17g 10mmol), while for the preparation of tributyltin amounts (2:1) of ligand acid (2.33g, 10mmol) and bis (tributyltin) oxide (3.17g 10mmol) respectively were suspended in 100mL of dry ethanol/acetone (8:2) solvent mixture and refluxed for 8h. After cooling to room temperature, the reaction mixture was filtered and solvents were rotary evaporated. The solids obtained was recrystallized from chloroform with few drops of n-hexane. 2.2.11 (S)-triphenylstannyl 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3, 7-dihydro-2H-[1, 4] oxazino [2, 3, 4-ij] quinoline-6-carboxylate (3k) Yield 62%, Rf = 0.60; m.p.: 293 C. FTIR data (KBr, cm-1): 3133 (Csp2-H), 2969, 2938 (Csp3-H), 1650 (C=O) 1H NMR data (DMSO-d6), delta: 8.51 (s, 1H, 5'aryl H), 7.73-7.71 and 7.48-7.44 (m, 15H, SnPh), 6.34 (d, 1H, 8'aryl H, J = 13.1), 3.61; 2.59 (m, 8H, piperznyl H), 2.34 (s, 3H of piperazinyl CH3), 4.31-4.22 (m, 3H, oxazine H), 3.65 (d, 3H of oxazinering CH3, J = 6.1), 13C NMR data (DMSO-d6) delta: 178.9, 173.5, 152.4, 140.2, 137.5, 135.4, 133.2, 131.6, 130.5, 129.2, 128.5, 127.4, 124.2, 123.5, 121.3, 65.5, 59.2, 57.1, 45.4, 18.2, Anal. Calcd. For C36H34FN3O4Sn: C, 60.87; H, 4.82; N, 5.92; found C, 60.85; H, 4.78; N, 5.90; found: 711.
  • 51
  • [ 1066-45-1 ]
  • [ 100986-85-4 ]
  • C21H28FN3O4Sn [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% General procedure: <strong>[100986-85-4]Levofloxacin</strong>(5 mmol) was stirred in an aqueous solution of NaHCO3 at room temperature for 30 min (Scheme 1).After formation of clear solution which indicated the corresponding salt formation [20, 21], the solvent was evaporated under vacuum and the salt was air dried. The sodium salt (5 mmol) of <strong>[100986-85-4]levofloxacin</strong> was loaded in a two neck round bottom flask containing toluene(30 mL) as a solvent. Triorganotin chloride (5 mmol) (for complexes 1 and 2) or diorganotin dichloride(2.5 mmol) (for complexes 3 and 4), respectively, was added dropwise upon refluxing and constant stirring for 6-7 h. The reaction mixture was stored over night for efficient precipitation of NaCl followed by its filtering off. The solid complexes precipitated upon vacuum evaporation of the solvent, were recrystallized from a 2 : 8 (v/v) mixture of petroleum ether with methanol. However, all attempts of obtaining single crystals suitable for XRD analysis were unsuccessful. (CH3)3SnL (1). Yellow solid, yield 76%, mp 235-237C, soluble in chloroform, toluene, DMSO, DMF,methanol, and ethanol. FT-IR, nu, cm-1: 1680 (C=O),1606 (C=CAr), 1575 (COOasym), 1463 (C=CAr), 1339(COOsym), 551 (Sn-C), 450 (Sn-O). 1H NMRspectrum, delta, ppm: 0.50 s (3H, Halpha, 2J[119Sn-1Halpha] = 66.6,64.2 Hz, thetaC-Sn-C = 115); 1.53 d (3H, H16); 2.17 s (3H,H15); 2.64 t (4H, H14,14); 3.40 t (4H, H13,13); 4.53 m(1H, H4); 4.67 d.d (1H, H5); 7.55 d (1H, H9, 3JH-F =13 Hz); 8.58 s (1H, H3). 13C NMR spectrum, delta, ppm:-0.40 (Calpha, 1J[119/117Sn-13Calpha] = 448.5, 422 Hz, thetaC-Sn-C =116); 16.8 (C16); 29.0 (C15); 49.9 (C13,13); 53.9(C14,14); 55.3 (C4); 68.9 (C5); 104.0 d (C9, 2JCF =24 Hz); 110.2 (C2); 121.3 (C10); 124.5 (C11); 132.3 d(C7, 2JCF = 15 Hz); 140.3 d (C8, 1JCF = 7 Hz); 145.5(C6); 153.1 (C3); 168.8 (C1); 173.3 (C12). Found, %: C48.01, H 52.32, N 7.80. C21H28FN3O4Sn. Calculated,%: C 48.12, H 5.48, N 8.02
  • 52
  • [ 1461-22-9 ]
  • [ 100986-85-4 ]
  • C30H46FN3O4Sn [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% General procedure: <strong>[100986-85-4]Levofloxacin</strong>(5 mmol) was stirred in an aqueous solution of NaHCO3 at room temperature for 30 min (Scheme 1).After formation of clear solution which indicated the corresponding salt formation [20, 21], the solvent was evaporated under vacuum and the salt was air dried. The sodium salt (5 mmol) of <strong>[100986-85-4]levofloxacin</strong> was loaded in a two neck round bottom flask containing toluene(30 mL) as a solvent. Triorganotin chloride (5 mmol) (for complexes 1 and 2) or diorganotin dichloride(2.5 mmol) (for complexes 3 and 4), respectively, was added dropwise upon refluxing and constant stirring for 6-7 h. The reaction mixture was stored over night for efficient precipitation of NaCl followed by its filtering off. The solid complexes precipitated upon vacuum evaporation of the solvent, were recrystallized from a 2 : 8 (v/v) mixture of petroleum ether with methanol. However, all attempts of obtaining single crystals suitable for XRD analysis were unsuccessful.
  • 53
  • [ 753-73-1 ]
  • [ 100986-85-4 ]
  • C38H44F2N6O8Sn [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% General procedure: <strong>[100986-85-4]Levofloxacin</strong>(5 mmol) was stirred in an aqueous solution of NaHCO3 at room temperature for 30 min (Scheme 1).After formation of clear solution which indicated the corresponding salt formation [20, 21], the solvent was evaporated under vacuum and the salt was air dried. The sodium salt (5 mmol) of <strong>[100986-85-4]levofloxacin</strong> was loaded in a two neck round bottom flask containing toluene(30 mL) as a solvent. Triorganotin chloride (5 mmol) (for complexes 1 and 2) or diorganotin dichloride(2.5 mmol) (for complexes 3 and 4), respectively, was added dropwise upon refluxing and constant stirring for 6-7 h. The reaction mixture was stored over night for efficient precipitation of NaCl followed by its filtering off. The solid complexes precipitated upon vacuum evaporation of the solvent, were recrystallized from a 2 : 8 (v/v) mixture of petroleum ether with methanol. However, all attempts of obtaining single crystals suitable for XRD analysis were unsuccessful.
  • 54
  • [ 1135-99-5 ]
  • [ 100986-85-4 ]
  • C48H48F2N6O8Sn [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% General procedure: <strong>[100986-85-4]Levofloxacin</strong>(5 mmol) was stirred in an aqueous solution of NaHCO3 at room temperature for 30 min (Scheme 1).After formation of clear solution which indicated the corresponding salt formation [20, 21], the solvent was evaporated under vacuum and the salt was air dried. The sodium salt (5 mmol) of <strong>[100986-85-4]levofloxacin</strong> was loaded in a two neck round bottom flask containing toluene(30 mL) as a solvent. Triorganotin chloride (5 mmol) (for complexes 1 and 2) or diorganotin dichloride(2.5 mmol) (for complexes 3 and 4), respectively, was added dropwise upon refluxing and constant stirring for 6-7 h. The reaction mixture was stored over night for efficient precipitation of NaCl followed by its filtering off. The solid complexes precipitated upon vacuum evaporation of the solvent, were recrystallized from a 2 : 8 (v/v) mixture of petroleum ether with methanol. However, all attempts of obtaining single crystals suitable for XRD analysis were unsuccessful.
  • 55
  • [ 29122-68-7 ]
  • [ 100986-85-4 ]
  • C32H40FN5O6 [ No CAS ]
  • C32H40FN5O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dicyclohexyl-carbodiimide; In dichloromethane; at 40 - 50℃; for 2.5h; (RS)-Atenolol was derivatizated with chiral reagent <strong>[100986-85-4]levofloxacin</strong> using dicyclohexylcarbodiimide (DCC) as dehydrating agent. The derivatization procedure is discussed as follows: The solution of (RS)-atenolol (10-2 M) was added to solution of <strong>[100986-85-4]levofloxacin</strong> (10-2 M) in dichloromethane (DCM). Thedicyclohexylcarbodiimide (DCC) (2 mM) was added to this solution. The reaction mixture was kept on magnetic stirrer at 40-50 C for 2.5 h with constant stirring. The completion of derivatization reaction (i.e. reaction progress) was carried out by continuous TLC monitoring before workup. After completion of reaction the mixture was cooled at room temperature followed by filtration and evaporation on rotavapor.
  • 56
  • [ 100986-85-4 ]
  • Levofloxacin hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In ethanol; for 2h;Reflux; Green chemistry; 20g of leucovorin and 70ml of water were put into the reaction flask, heated to 110 C with stirring, and 33ml of N-methylpiperazine was added dropwise. After half an hour dripping finished, the mixture was incubated for 10 hours, sampled and analyzed, and transformed into 94%. The mixture was cooled to 70-80 C and then distilled under reduced pressure to recover water and methylpiperazine. After steaming, 200 ml of ethanol was added and 15 ml of hydrochloric acid was added under stirring to reflux for 2 hours. The mixture was cooled to room temperature and filtered to obtain 56 g of tide (incomplete pumping Dry), do not dry direct secondary beating, add water, 9% ethanol 165ml heat reflux 1h. Cooling filtration, too tidal goods 28.14g, do not dry directly to the third beating, adding 95% ethanol 180ml, heated to reflux1h, cooled and filtered, washed with a small amount of anhydrous ethanol, dried, to obtain 19.86g liquid phase content of 99.43% <strong>[100986-85-4]levofloxacin</strong> hydrochlorideProducts, like white solid. Beating mother liquor was concentrated and recovered to obtain 4.13g of crude product, the content of 93.3%. Total yield of 86%, of which finished products receivedRate of 72.7%. Products can be further recovered from the secondary mother liquor, the cumulative yield of up to 90%
With hydrogenchloride; In ethanol; water; for 8h;Reflux; 20g left oxycyclic acid, 70ml water into the reaction flask, heated to 120 C with stirring,38 ml of N-methylpiperazine are initially added dropwise,End half an hour, insulation 15 hours, sampling analysis, conversion 95%. After cooling to 70-80 C and distillation under reduced pressure,Recovering water and methylpiperazine, steaming and adding 200 ml of ethanol, adding 15 ml of hydrochloric acid while stirring, heating and refluxing for 2 hours, cooling to room temperature, filtering to obtain tide product 60g (not completely drained), not directly drying and performing secondary beating , Adding 165ml of 9% aqueous ethanol and heating to reflux for 3h. Cooled and filtered to obtain tide product 29.02g, do not directly dry the third beating, add 95% ethanol 180ml, heated to reflux 3h, cooled and filtered, a small amount of ethanol washing and drying, to obtain 21.03g liquid content of 99.56% <strong>[100986-85-4]Levofloxacin</strong> hydrochloride finished product, white-like solid. Beating mother liquor was concentrated and recovered, to obtain 4.34g crude, content of 92.8%. The total yield of 88%, of which yield of 72.7%. Products can be further recovered from the secondary mother liquor, the cumulative yield of up to 90%
With hydrogenchloride; In ethanol; water; for 2h;Reflux; 20g of L-Oxalaconic acid,70ml water is put into the reaction bottle,Heat to 110C with stirring33 ml of N-methylpiperazine was added dropwise.After half an hour drip, keep warm for 10 hours.Sampling analysis, conversion 94%.After cooling to 70-80 deg.] C under reduced pressure by distillation,And recovering water-methylpiperazine,200ml of ethanol was added after steaming.15ml of hydrochloric acid was added under stirring.Heat reflux 2h,Cool to room temperature, filter,56g (not completely drained)Direct drying without drying165 ml of 9% aqueous ethanol was added and the mixture was heated at reflux for 1 h.Cooled and filtered, the product was 28.14g.Do not dry directly for the third time,Add 95% ethanol 180ml, heated to reflux for 1h,Cooling filtration, a small amount of anhydrous ethanol washing,After drying, 19.86 g of finished <strong>[100986-85-4]levofloxacin</strong> hydrochloride with a liquid phase content of 99.43% was obtained.White solid.Beating mother liquor is concentrated and recovered.4.13 g of crude product are obtained with a content of 93.3%.Total yield 86%Wherein product yield 72.7%. The product can be further recovered from the secondary mother liquor,The cumulative yield of 90%.
  • 57
  • [ 94695-48-4 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: triethylamine / toluene / 3 h / 40 °C / Green chemistry 2: 1 h / 40 - 90 °C / Green chemistry 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C / Green chemistry 4: sulfuric acid; acetic acid / N,N-dimethyl-formamide / 1 h / Reflux; Green chemistry 5: water / 10.5 h / 110 °C / Green chemistry
Multi-step reaction with 5 steps 1: triethylamine / toluene / 6 h / 60 °C 2: toluene / 2 h / 60 - 90 °C 3: potassium carbonate / N,N-dimethyl-formamide / 8 h / 150 °C 4: sulfuric acid; acetic acid / water / 3 h / 20 °C / Reflux 5: water / 15.5 h / 120 °C
Multi-step reaction with 5 steps 1: triethylamine / toluene / 3 h / 55 °C 2: 1 h / 40 - 90 °C 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C 4: sulfuric acid; acetic acid / N,N-dimethyl-formamide / 1 h / Reflux 5: water / 10.5 h / 110 °C
Multi-step reaction with 5 steps 1: triethylamine / toluene / 4 h / 27 °C 2: triethylamine / 0.5 h / 20 °C / pH 5 - 6 3: 24 h / 120 °C 4: potassium carbonate / 16 h / 140 °C 5: hydrogenchloride / ethanol; water / 36 h / 83 °C
Multi-step reaction with 5 steps 1: triethylamine / toluene / 4 h / 27 °C 2: 16 h / 50 °C 3: acetic acid / 0.5 h / 20 °C / pH 5 - 6 4: potassium carbonate / water / 4 h / 140 °C 5: hydrogenchloride / water; ethanol / 36 h / 83 °C

  • 58
  • titanium(IV) sulfate [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • [Ti(levofloxacin)2(H2O)2]SO4*6H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; In ethanol; at 20℃; for 24h; The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator.
  • 59
  • yttrium(III) chloride [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • [Y(levofloxacin)2(H2O)2]Cl*4H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With sodium hydroxide; In methanol; acetone; at 20℃; for 24h; General procedure: The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator. The apple-green, yellowish, canary-yellow,pale brown and yellow solid complexes of[VO(Levo)2(H2O)]·5H2O, [Y(Levo)2(H2O)2]Cl·4H2O,[ZrO(Levo)2(H2O)]·6H2O, [Ce(Levo)2(H2O)2]SO4·5H2Oand [UO2(Levo)2(H2O)2]·2H2O were prepared in a similarmanner described above by using methanol and acetone assolvents and VOSO4·H2O, YCl3,ZrOCl2·8H2O, Ce(SO4)2and UO2(NO3)2·6H2O as a metal salts in 1:2 molar ratio (M:Levo). The complexes are stable in their solid case at roomtemperature and their integrity in solution state were goodand stable enough within 3 weeks (in DMSO-d6 and DMFsolvents) considering that we have used these solutions duringthat time to measure molar conductivity, antibacterialactivity and 1H NMR spectra. The chemical structures of thesynthesized metal complexes were confirmed as follows.
  • 60
  • cerium(IV) sulphate [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • [Ce(levofloxacin)2(H2O)2]SO4*5H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With sodium hydroxide; In methanol; acetone; at 20℃; for 24h; General procedure: The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator. The apple-green, yellowish, canary-yellow,pale brown and yellow solid complexes of[VO(Levo)2(H2O)]·5H2O, [Y(Levo)2(H2O)2]Cl·4H2O,[ZrO(Levo)2(H2O)]·6H2O, [Ce(Levo)2(H2O)2]SO4·5H2Oand [UO2(Levo)2(H2O)2]·2H2O were prepared in a similarmanner described above by using methanol and acetone assolvents and VOSO4·H2O, YCl3,ZrOCl2·8H2O, Ce(SO4)2and UO2(NO3)2·6H2O as a metal salts in 1:2 molar ratio (M:Levo). The complexes are stable in their solid case at roomtemperature and their integrity in solution state were goodand stable enough within 3 weeks (in DMSO-d6 and DMFsolvents) considering that we have used these solutions duringthat time to measure molar conductivity, antibacterialactivity and 1H NMR spectra. The chemical structures of thesynthesized metal complexes were confirmed as follows.
  • 61
  • [ 12440-03-8 ]
  • [ 100986-85-4 ]
  • [VO(levofloxacin)2(H2O)]*5H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With sodium hydroxide; In methanol; acetone; at 20℃; for 24h; General procedure: The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator. The apple-green, yellowish, canary-yellow,pale brown and yellow solid complexes of[VO(Levo)2(H2O)]·5H2O, [Y(Levo)2(H2O)2]Cl·4H2O,[ZrO(Levo)2(H2O)]·6H2O, [Ce(Levo)2(H2O)2]SO4·5H2Oand [UO2(Levo)2(H2O)2]·2H2O were prepared in a similarmanner described above by using methanol and acetone assolvents and VOSO4·H2O, YCl3,ZrOCl2·8H2O, Ce(SO4)2and UO2(NO3)2·6H2O as a metal salts in 1:2 molar ratio (M:Levo). The complexes are stable in their solid case at roomtemperature and their integrity in solution state were goodand stable enough within 3 weeks (in DMSO-d6 and DMFsolvents) considering that we have used these solutions duringthat time to measure molar conductivity, antibacterialactivity and 1H NMR spectra. The chemical structures of thesynthesized metal complexes were confirmed as follows.
  • 62
  • zirconyl chloride octahydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [ZrO(levofloxacin)2(H2O)]*6H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
78.6% With sodium hydroxide; In methanol; acetone; at 20℃; for 24h; General procedure: The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator. The apple-green, yellowish, canary-yellow,pale brown and yellow solid complexes of[VO(Levo)2(H2O)]·5H2O, [Y(Levo)2(H2O)2]Cl·4H2O,[ZrO(Levo)2(H2O)]·6H2O, [Ce(Levo)2(H2O)2]SO4·5H2Oand [UO2(Levo)2(H2O)2]·2H2O were prepared in a similarmanner described above by using methanol and acetone assolvents and VOSO4·H2O, YCl3,ZrOCl2·8H2O, Ce(SO4)2and UO2(NO3)2·6H2O as a metal salts in 1:2 molar ratio (M:Levo). The complexes are stable in their solid case at roomtemperature and their integrity in solution state were goodand stable enough within 3 weeks (in DMSO-d6 and DMFsolvents) considering that we have used these solutions duringthat time to measure molar conductivity, antibacterialactivity and 1H NMR spectra. The chemical structures of thesynthesized metal complexes were confirmed as follows.
  • 63
  • uranyl nirate hexahydrate [ No CAS ]
  • [ 100986-85-4 ]
  • [UO2(levofloxacin)2(H2O)2]*2H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
81.4% With sodium hydroxide; In methanol; acetone; at 20℃; for 24h; General procedure: The complexes have been prepared by direct reactionbetween Levo with the corresponding metal cations in theform of water-soluble salts, such as sulphate, nitrate andchloride. Complex of [Ti(Levo)2(H2O)2]SO4·6H2O wassynthesized as follows: 0.5 mmol (1.32 mL) of titaniumsulphate was added to a magnetically stirred solution containing1 mmol (0.370) Levo and 1 mmol (0.40) NaOH in25 mL ethanol. The mixture was stirred at room temperaturefor 1 day. The mixture was left for slow evaporationto concentrate the reaction mixture; the reddish brown precipitate formed was filtered off, washed several times byethanol and dried under vacuum over CaCl2 in a desiccator. The apple-green, yellowish, canary-yellow,pale brown and yellow solid complexes of[VO(Levo)2(H2O)]·5H2O, [Y(Levo)2(H2O)2]Cl·4H2O,[ZrO(Levo)2(H2O)]·6H2O, [Ce(Levo)2(H2O)2]SO4·5H2Oand [UO2(Levo)2(H2O)2]·2H2O were prepared in a similarmanner described above by using methanol and acetone assolvents and VOSO4·H2O, YCl3,ZrOCl2·8H2O, Ce(SO4)2and UO2(NO3)2·6H2O as a metal salts in 1:2 molar ratio (M:Levo). The complexes are stable in their solid case at roomtemperature and their integrity in solution state were goodand stable enough within 3 weeks (in DMSO-d6 and DMFsolvents) considering that we have used these solutions duringthat time to measure molar conductivity, antibacterialactivity and 1H NMR spectra. The chemical structures of thesynthesized metal complexes were confirmed as follows.
  • 64
  • [ 109-01-3 ]
  • [ 106939-34-8 ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
85.7% With acetic acid; In water; N,N-dimethyl-formamide; at 70 - 105℃; for 10h; 20 g of (S) -9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7h-pyrido [1,2,3-de] -1,4-benzoxazine-6-carboxylate and 65 g of N-methylpiperazine were introduced into a 250 mlIn a reaction flask with a reflux device,Then 20 grams of N, N-dimethylformamide and 10 grams of water were added,The reaction was incubated at 105 C for about 8 hours until N-methylpiperazine was substituted completely and the solvent was evaporated to dryness under reduced pressure and dissolved in 80 g of water.Then add 7.4 g of acetic acid, warmed to 70 C , stirred for 2 hours,After acid and alkali pH adjustment, by extraction, washing, concentration, crystallization and other steps, 20.53 g of levofloxacin finished product,Molar yield 85.7%.
  • 65
  • [ 91759-32-9 ]
  • [ 100986-85-4 ]
  • levofloxacinium 2-thiobarbiturate [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% In water; at 80℃; A mixture of 0.54 mmol of LevoH 1/2H2O and 0.54 mmol of H2tba was dissolved in 5 ml of water at 80 C. The solution was cooled to room temperature and then kept in a refrigerator at 4 C for 2 days. A pale pink precipitate in the form of platy crystals was filtered off, washed with 1 ml of water, 1 ml of acetone, and dried in the air until constant weight. The yield was 43%. A single crystal for XRD was selected from the bulk precipitate.
  • 66
  • [ 2231-57-4 ]
  • [ 100986-85-4 ]
  • [ 1215036-47-7 ]
YieldReaction ConditionsOperation in experiment
65% In ethanol; for 6h;Reflux; A mixture of (0.36 g, 0.001 mol) of <strong>[100986-85-4]levofloxacin</strong> and 0.1g (0.001mol) of thiocarbohydrazide with absolute ethanol as a solvent was refluxed for6 h and then cooled and separated by filtration and the solid was recrystallized from ethanol in order to obtain the desired result in the form of crystals with yellow colour and with a yield of (65%) and melting point (211-213C). TLC method was used to determine the purity of the prepared compound.
  • 67
  • [ 109-01-3 ]
  • C21H22BF2NO8 [ No CAS ]
  • [ 100986-85-4 ]
YieldReaction ConditionsOperation in experiment
7.38 g Take 20g (43mmol) of intermediate 1, 100ml of acetonitrile, 5.9 g (58.64 mmol) of triethylamine, 8.8 g (88 mmol) of N-methyl piperazine was sequentially placed in a 500 ml flask. Replaced with nitrogen three times, The reaction was stirred at a temperature of 50 C for 1.5 h. TLC detection reaction was completed (developing agent was DCM: MeOH = 10:1); After the reaction is completed, the solvent is distilled off under reduced pressure; the solution is stirred and dissolved by adding 200 ml of methanol. Cool down to 0-10 C; add 13.2 g of concentrated hydrochloric acid to adjust the pH, The system was allowed to warm to room temperature (20-30 C) and stirred for 1.5 h. The system was cooled to 0-10 C and stirred for 1.5 h, suction filtered, and the filter cake was washed with a small amount of methanol. The mixture was dried to constant weight at 40 C in a blast oven to obtain 13 g (33 mmol) of levofloxacin hydrochloride in a yield of 76%. 10 g (25.14 mmol) of levofloxacin hydrochloride, 100 ml of ethyl acetate, and 30 ml of water were placed in a 250 ml flask, and a sodium carbonate aqueous solution was added dropwise to the pH to 8, and the mixture was stirred at room temperature for 0.5 h; The system was poured into a separatory funnel, and the layers were allowed to stand, and the organic phase was taken; the aqueous phase was extracted with 10 ml of ethyl acetate, and the organic phase was combined. Evaporate the solvent under reduced pressure, add 70 ml of isopropanol, heat under nitrogen to 80 C, until the solution is clarified and cooled to 0-10 C, stir 0.5h, suction filtration. Drying to constant weight gave a finished product of 7.38 g with a yield of 81%.
  • 68
  • [ 1201939-89-0 ]
  • [ 100986-85-4 ]
  • (S)-N-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; General procedure: A mixture of 4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluoroaniline (11, 315mg, 1mmol), Nadifloxacin (433mg, 1.2mmol), HATU (570mg, 1.5mmol), and DIEA (0.5mL, 3mmol) in DMF (20mL) was stirred at rt overnight. Next, water was added to the mixture, and the precipitates was filtrated. The filter cake was washed with water, diluted with DCM, and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel to get the product as a white solid (460mg, 70%).
  • 69
  • [CoIII(tris(2-pyridylmethyl)amine)Cl2]Cl [ No CAS ]
  • sodium perchlorate [ No CAS ]
  • [ 7732-18-5 ]
  • [ 100986-85-4 ]
  • C36H37CoFN7O4(2+)*2ClO4(1-)*3H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% [Co(tpa)Cl2]Cl (72.91 mg, 0.16 mmol) and levH (57.82 mg,0.16 mmol) were dissolved in 10 mL water and NaOH (6.4 mg,0.16 mmol) was added. The reaction mixture was stirred at 60 Covernight and it was cooled at 4 C for one day. Some solid was filteredoff using cotton wool, and NaClO4 (39.18 mg, 0.32 mmol) was added.The complex was isolated as a red crystalline solid. The crystals werefiltered off and dried in vacuo. Yield: 59.15 mg (38%). 1H NMR(400 MHz, D2O): delta/ppm=9.36 (d, 1H, py-H isomer A); 9.19 (d, 1H, py-H isomer B); 9.06 (s, 1H, Ar-H isomer A); 8.91 (s, 1H, Ar-H isomer B);8.60 (d, 1H, Ar-H isomer A); 8.45 (d, 2H, py-H); 8.31 (m, 2H, Ar-Hisomer B, py-H); 8.09-7.99 (m, 4H, py-H); 7.98-7.88 (m, 2H, py-H);7.79-7.66 (m, 7H, py-H); 7.53 (m, 2H, py-H); 7.44 (m, 2H, py-H); 7.31(m, 2H, py-H); 5.78-5.60 (m, 1H, tpa-CH2); 5.05 (m, 1H, tpa-CH2);4.92-4.81 (m, 9H, tpa-CH2, lev-CH2); 4.63 (d, 1H, tpa-CH2); 4.53-4.43(m, 3H, tpa-CH2); 4.33 (d, 1H, tpa-CH2); 3.58 (t, 4H, -CH2 isomer A);3.38 (t, 4H, -CH2 isomer B); 2.84 (t, 4H, -CH2 isomer A); 2.72 (t, 4H,-CH2 isomer B); 2.47 (s, 3H, -CH3 isomer A); 2.40 (s, 3H, -CH3 isomerB); 1.58 (d, 3H, -CH3 isomer A); 1.50 (d, 3H, -CH3 isomer B). IR (KBr)/cm-1: 3439, 1633, 1519, 1448, 1272, 1094, 624. Anal. Required forC36H43Cl2CoFN7O15: C, 44.92, H, 4.50, N, 10.19%. Found: C, 44.65, H,4.15, N, 10.14%. MS (ESI, positive ion): m/z: 354.612 ([Co(tpa)(lev)]2+).
  • 70
  • ammonium hexafluorophosphate [ No CAS ]
  • [ 20023-19-2 ]
  • [ 100986-85-4 ]
  • C24H37CoFN7O4(2+)*2F6P(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% LevH (115.63mg, 0.32mmol) was dissolved in 15mL 96% 14 ethanol and 1 equiv. 1M 15 KOH (320muL) was added. 16 [Co(tren)Cl2]Cl (100.00mg, 0.32mmol), dissolved in 5mL 17 water, was added and the pH was adjusted to 9, using 1M KOH. The purple reaction mixture was stirred at 60C overnight. The colour of the solution turned deep red and after cooling, 18 NH4PF6 (104.38mg, 0.64mmol) was added. Orange crystalline solid appeared after few days, by slow evaporation at room temperature. The solid was filtered off and dried in vacuo. Yield: 106.28mg (39%). 1H NMR (400MHz, DMSO): delta/ppm=9.18 (s, 1H, Ar-H); 7.86 (d, 1H, Ar-H); 5.51 (m, 2H, -CH2); 5.18 (m, 5H, -CH, -NH2); 4.68 (m, 1H, -NH2); 4.34 (m, 1H, -NH2); 3.54 (m, 2H, tren-H); 3.33 (m, 8H, tren-H, -CH2); 3.18 (t, 2H, tren-H); 2.92 (m, 3H, -CH2); 2.73 (m, 5H, tren-H); 2.27 (s, 3H, -CH3) 1.47 (d, 3H, -CH3). IR (KBr)/cm-1: 3434, 3221, 3120, 1636, 1520, 1472, 1281, 843, 558. Anal. Required for C24H37CoF13N7O4P2: C, 33.70, H, 4.36, N, 11.46%. Found: C, 33.77, H, 4.63N, 11.03%. MS (ESI, positive ion): m/z: 282.608 ([Co(tren)(lev)]2+).
  • 71
  • [ 849585-22-4 ]
  • [ 100986-85-4 ]
  • levofloxacin lactate [ No CAS ]
YieldReaction ConditionsOperation in experiment
94.3% In ethanol; at 80℃; for 1h; The preparation method of <strong>[100986-85-4]levofloxacin</strong> lactate monohydrate crystal form is as follows: 1) 10 g of <strong>[100986-85-4]levofloxacin</strong> and a mass concentration of 95% ethanol 32.5 g into a three-necked bottle, stirred, and heated to 80 C;2) 7.4 g of a 33% by mass lactic acid solution was added dropwise to the mixture obtained in the step 1).The dropping time is 1 min, the stirring is kept for 1 h, and the temperature is lowered to 50 C at a rate of 1 C/min.The crystal was allowed to stand for 2 hours; the stationary crystal was finished.Stir at 100-150r/min,Cooling to 8 C at a rate of 0.5 C / min;3) After filtering the crystals in the obtained mixture of the step 2), it is washed with absolute ethanol, and then the crystals are dried under vacuum at 45 C to obtain. The yield of the preparation method is 94.34%;It was detected by PXRD as the crystal form of <strong>[100986-85-4]levofloxacin</strong> monohydrate. The purity of the product was 99.96% by HPLC, the content of <strong>[100986-85-4]levofloxacin</strong> was 80.3%, and the moisture was 3.9% by TGA.
  • 72
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C22H29FN6O4 [ No CAS ]
  • 73
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C26H37FN8O5 [ No CAS ]
  • 74
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C30H45FN10O6 [ No CAS ]
  • 75
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C34H53FN12O7 [ No CAS ]
  • 76
  • [ 71989-18-9 ]
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C33H42FN7O12 [ No CAS ]
  • 77
  • [ 71989-18-9 ]
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C38H49FN8O15 [ No CAS ]
  • 78
  • [ 71989-18-9 ]
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • C28H35FN6O9 [ No CAS ]
  • 79
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • [ 128917-74-8 ]
  • C34H52FN7O5 [ No CAS ]
  • 80
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • [ 128917-74-8 ]
  • C38H60FN9O6 [ No CAS ]
  • 81
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • [ 128917-74-8 ]
  • C42H68FN11O7 [ No CAS ]
  • 82
  • [ 100986-85-4 ]
  • [ 125238-99-5 ]
  • [ 128917-74-8 ]
  • C46H76FN13O8 [ No CAS ]
  • 83
  • [ 52462-29-0 ]
  • [ 100986-85-4 ]
  • C28H33ClFN3O4Ru [ No CAS ]
YieldReaction ConditionsOperation in experiment
63.8% In methanol; dichloromethane; at 20℃; General procedure: [Ru(p-cym)(Flq1-3)Cl] (RAFlq-1-3) were prepared by a typical mu-chlorido-bridge splitting reaction of [Ru(eta6 -p-cymene)Cl 2 ] 2 . To a solution of [Ru(eta6 -p-cymene)Cl 2 ] 2 (in 2.5ml CH 2 Cl 2 ), a solution of the ligand Flq-1-3 in 2.5ml methanol was added with stirring in 1:2 ratio, respectively. The reaction mixture was left on stirring overnight (20-24h) at room temperature and then left for slow evaporation at r.t. The reddish brown crystalline precipitate was filtered, washed with pet ether and CH 2 Cl 2 and dried in air. The com-plexes so obtained were recrystallized from dichloromethane and ether which resulted in reddish brown crystals but not of the single-crystal quality. Figure2 shows the general syn-thetic route for the preparation of RAFlq-1-3 complexes.
  • 84
  • dichlorobis(1,10-phenanthroline)ruthenium(II) dihydrate [ No CAS ]
  • sodium perchlorate [ No CAS ]
  • [ 100986-85-4 ]
  • C42H35FN7O4Ru(1+)*ClO4(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
66.78% General procedure: [Ru(phen) 2 Cl 2 ] 2H 2 O and the fluoroquinolone ligands Flq-1-3 in 1:1mol ratio were mixed and refluxed in 3ml of ethanol/water (2:1) mixture for 7h to yield a clear red solu-tion. After cooling, a saturated aqueous solution of NaClO 4 was added drop-wise and stirred for 2h at r.t. The reaction mixture was sealed under nitrogen and cooled at 0C for overnight. On addition of water, immediate reddish brown precipitates were obtained which were filtered, washed with water and diethyl ether and dried. Figure1 shows the general synthetic route of complexes RPFlq-1-3.
  • 85
  • [ 100986-85-4 ]
  • [ 74-88-4 ]
  • C19H23FN3O4(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Add 100 mL of acetonitrile and 10.038 g of ammonium bicarbonate to a round bottom flask and stir at room temperature for 1 minute.Then 1.5 g of <strong>[100986-85-4]levofloxacin</strong> was added to the mixture and stirred at room temperature for 1 minute. Subsequently, 48.6 mmol CH3I was added dropwise within 3 minutes, and the mixture was stirred at room temperature for 180 h.After the reaction, vacuum distillation was performed, and the obtained powder was vacuum dried at 80 C. Approximately 1.0 g of product was dissolved in 60 mL of chloroform containing 1.6 g of N-hydroxysuccinimide (NHS).Under dry conditions, 40 ml of acetonitrile containing 5.3 g of 1-ethyl- (3-dimethylaminopropyl)ethylenediimide hydrochloride (EDC·HCl) was slowly added, and the round bottom flask was wrapped with tin foil.The mixture was stirred at room temperature for 26 hours.After the reaction, it was distilled under reduced pressure and recrystallized from absolute ethanol to obtain CH3-ALSF as pale yellow. The synthesis process of CH2D / CHD2 / 13CD3 / CD3 / C2H5 / C2H3D2 / C2H2D3 / C2D5-ALSF can only be replaced by CH2DI, CHD2I, 13CD3I, CD3I, C2H5Br, C2H3D2I in the "dropwise addition of 48.6 mmol CH3I in 3 minutes". C2H2D3I and C2D5I reagents, the rest of the experimental steps are the same.In addition, the synthesis process of C3H7-ALSF is also the CH3I in the above part is replaced with C3H7Br, and other experimental steps are also completely the same as the above process. The synthetic yields of CH3 / CH2D / CHD2 / 13CD3 / CD3 / C2H5 / C2H3D2 / C2H2D3 / C2D5 / C3H7-ALSF are all between 55% and 65%.
With ammonium bicarbonate; In acetonitrile; at 20℃; for 150h; Used in the present invention is based on a multi-channel mass <strong>[100986-85-4]levofloxacin</strong> derivatizing reagent synthesis is as follows:. A 1.5g of <strong>[100986-85-4]levofloxacin</strong> was dissolved in 100mL of acetonitrile chromatography, sonicated for 2 minutes, 10.038g ammonium bicarbonate, 48.6mmolCH. 3the I, into the magnetic After sealing, the mixture was stirred at room temperature for 150 hours.The solid obtained by suction filtration was dried in a vacuum oven at 50 C for 7-8h.The white solid obtained was: CH3-LFC.
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