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Chemical Structure| 127294-70-6
Chemical Structure| 127294-70-6
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Product Details of [ 127294-70-6 ]

CAS No. :127294-70-6 MDL No. :MFCD00864925
Formula : C20H24FN3O4 Boiling Point : -
Linear Structure Formula :- InChI Key :MGQLHRYJBWGORO-UHFFFAOYSA-N
M.W : 389.42 Pubchem ID :65958
Synonyms :
Q-35
Chemical Name :1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-(methylamino)piperidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Calculated chemistry of [ 127294-70-6 ]

Physicochemical Properties

Num. heavy atoms : 28
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.5
Num. rotatable bonds : 5
Num. H-bond acceptors : 6.0
Num. H-bond donors : 2.0
Molar Refractivity : 107.44
TPSA : 83.8 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.26 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.73
Log Po/w (XLOGP3) : 0.58
Log Po/w (WLOGP) : 2.35
Log Po/w (MLOGP) : 1.44
Log Po/w (SILICOS-IT) : 2.21
Consensus Log Po/w : 1.86

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.55
Solubility : 1.09 mg/ml ; 0.00279 mol/l
Class : Soluble
Log S (Ali) : -1.91
Solubility : 4.76 mg/ml ; 0.0122 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -4.03
Solubility : 0.0366 mg/ml ; 0.000094 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.58

Safety of [ 127294-70-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 127294-70-6 ]

* 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 [ 127294-70-6 ]

[ 127294-70-6 ] Synthesis Path-Downstream   1~37

  • 1
  • 3-methylaminopiperidine dihydrochloride [ No CAS ]
  • (PhO)3 B [ No CAS ]
  • [ 112811-72-0 ]
  • 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.90 g (48.8%) With sodium hydroxide; triethylamine; In acetonitrile; Example 7 Synthesis of 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid using (PhO)3 B A mixture of 2.95 g of <strong>[112811-72-0]1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid</strong> (10 mmol), 3.75 g of 3-methylaminopiperidine 2HCl (20 mmol), 5.80 g of (PhO)3 B (20 mmol), 4.4 g of triethylamine (43 mmol) and 20 ml of acetonitrile was refluxed with heating for 6 hours. The reaction solution was cooled to room temperature, made acid with 6N--HCl and extracted with 10 ml of ethyl acetate twice. The pH of the water layer was adjusted to 8 to 9 with 25% NaOH, and separated crystals were filtered and dried to obtain 1.90 g (48.8%) of the objective compound.
  • 2
  • 3-methylaminopiperidine dihydrochloride [ No CAS ]
  • [ 112811-72-0 ]
  • 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% Example 3 1-Cyclopropyl-1,4-dihydro-6-fluoro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxo-3-quinolinecarboxylic acid dihydrate An acetonitrile solution (30 mL) containing <strong>[112811-72-0]1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid</strong> (3 g), 3-methylaminopiperidine dihydrochloride (2.1 g), triethylamine (1.43 mL), and boron trifluoride-tetrahydrofuran complex (2.84 g) was stirred at room temperature for 2 hours. 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 6 hours, and the solvent was evaporated under reduced pressure. 80% Hydrated methanol (30 mL) was added to the residue, and the pH of the product was adjusted to 8 by use of 5N aqueous sodium hydroxide solution, followed by stirring at room temperature for 16 hours. The thus-produced crystals were recovered through filtration and dried, to thereby yield 3.98 g of the title compound (yield: 92%). 1H-NMR(400MHz,DMSO-d6) deltappm: 0.90-1.31(4H,m),1.31-2.12(4H,m),2.67-3.71(5H,m),3.77(3H,s),3.98-4.09(1H,m),7.85(1H,d,J=11.1Hz),8.78(1H,s) Elemental analysis: Calc. C;56.69%, H;6.62%, N;9.74% Obsd. C;56.48%, H;6.63%, N;9.86%
With triethylamine; In acetonitrile; EXAMPLE 13 A mixture of <strong>[112811-72-0]1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid</strong> (2.95 g), 3-methylaminopiperidine dihydrochloride (6.69 g) and triethylamine (10 g) in acetonitrile (50 ml) was refluxed with stirring for 12 hours. The reaction mixture was concentrated in vacuum, and the residue was extracted with chloroform. The extract was washed with a saturated NaCl solution and concentrated in vacuo. The residue was purified by silica gel column chromatography (chloroform:methanol:ammoniumhydroxide=15:5:1) to give 1.28 g of 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline-3-carboxylic acid, which was recrystallized from acetonitrile-water, colorless needles. m.p. 134-135 C.
  • 3
  • [ 1016680-64-0 ]
  • [ 127294-70-6 ]
  • [ 1236145-63-3 ]
YieldReaction ConditionsOperation in experiment
57% With potassium carbonate In N,N-dimethyl-formamide at 40℃;
  • 4
  • [ 4290-78-2 ]
  • [ 127294-70-6 ]
  • [ 1236145-62-2 ]
YieldReaction ConditionsOperation in experiment
59% With potassium carbonate In N,N-dimethyl-formamide at 40℃; for 27.5h;
  • 5
  • [ 16773-42-5 ]
  • [ 127294-70-6 ]
  • [ 1643323-92-5 ]
YieldReaction ConditionsOperation in experiment
91% With potassium hydroxide In ethanol; water for 12h; Reflux;
  • 6
  • [ 166734-83-4 ]
  • [ 127294-70-6 ]
  • [ 1643323-96-9 ]
YieldReaction ConditionsOperation in experiment
68% With potassium hydroxide In ethanol; water for 12h; Reflux;
  • 7
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium dodecyl-sulfate In aq. buffer at 20℃; for 0.25h;
  • 8
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium dodecyl-sulfate In aq. buffer at 20℃; for 0.25h;
  • 9
  • [ 127294-70-6 ]
  • [ 2216786-17-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / dichloromethane / 0.33 h / Cooling with ice 1.2: Cooling with ice 2.1: triethylamine / toluene 2.2: 110 - 120 °C
  • 10
  • [ 98-97-5 ]
  • [ 4635-59-0 ]
  • [ 127294-70-6 ]
  • [ 2216786-18-2 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid With sodium hydrogencarbonate In dichloromethane for 0.333333h; Cooling with ice; Stage #2: 4-Chlorobutanoyl chloride In dichloromethane Cooling with ice; Stage #3: 2-pyrazylcarboxylic acid Further stages; 21 Example 21 Add 1 mmol of banofloxacin and 2 mL of DCM to a 100 mL round bottom flask. Cooled in the ice bath, Magnetic stirring, Add 3mmol NaHCO3, After 20 minutes, A solution of 2.5 mmol of 4-chlorobutanoyl chloride in DCM (2 mL) was added dropwise with a constant pressure dropping funnel (drip acceleration of about 1d/2s). Continue to react under the ice bath. TLC was monitored until the end of the reaction. Stop stirring, Add 15 mL of H2O and 20 mL of DCM. Adjust pH=3-4 with 1N HCl solution with stirring. If there is a solid, it will stand still. Filtering, The filter cake was washed 3 times with DCM. The filter cake is left for further purification; The filtrate was transferred to a separatory funnel. Liquid separation, The aqueous phase was extracted with DCM (15 mL×1). Combine the organic phase, Wash with saturated NaCl solution (15 mL × 1), Collect organic phase, Dry with anhydrous Na2SO4. Rotary evaporator to spin dry to obtain a crude product. Column chromatography to obtain a pure product, Vacuum drying, An intermediate is obtained.1 mmol of the above intermediate was added to a 100 mL round bottom flask. 5mL toluene, 2mmol Et3N, Stir for 20-30min, Add 2mmol of pyrazinecarboxylic acid (POA), After 10 minutes, move to 110 ° C ~ 120 ° C oil bath to reflux reaction, TLC was monitored until the reaction was complete. The reaction solution was spun dry using a rotary evaporator rotary evaporator. Add 30mL DCM and stir to dissolve. Filtering, The filter cake was washed 3 times with DCM. The filtrate was washed with 10% citric acid solution (15 mL x 1). Collect organic phase, Dry with anhydrous Na2SO4. Rotary evaporator to spin dry to obtain a crude product. Column chromatography to obtain a pure product.
  • 11
  • [ 79-04-9 ]
  • [ 127294-70-6 ]
  • [ 2216786-08-0 ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine In N,N-dimethyl-formamide at 20℃; for 24h; Synthesis of compound 2a-g General procedure: 0.32 g (1.0 eq, 1 mmol) 1a was dissolved in 10 mL waterfreeDMF, and 150 μL (1.5 eq, 1.5 mmol) TEA and 169 μL(2.2 eq, 2.2 mmol) chloroacetyl chloride were added insequence. The solution was stirred at room temperature for24 h, After the reaction completion detected by TLC, 30 mLof deionized water was added. After filtration, the filter cakewas washed with deionized water and dried overnight in thevacuum chamber, 0.27 g of the target compound 2a wasobtained in a yield of 73%.Compound 2b-g was synthesized in the same way ascompound 2a in yields of 70-88%.
88% With triethylamine In N,N-dimethyl-formamide at 20℃; for 24h; Synthesis of compound 2a-g General procedure: 0.32 g (1.0 eq, 1 mmol) 1a was dissolved in 10 mL waterfreeDMF, and 150 μL (1.5 eq, 1.5 mmol) TEA and 169 μL(2.2 eq, 2.2 mmol) chloroacetyl chloride were added insequence. The solution was stirred at room temperature for24 h, After the reaction completion detected by TLC, 30 mLof deionized water was added. After filtration, the filter cakewas washed with deionized water and dried overnight in thevacuum chamber, 0.27 g of the target compound 2a wasobtained in a yield of 73%.Compound 2b-g was synthesized in the same way ascompound 2a in yields of 70-88%.
73.12% In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 14 Example 14 Synthesis of triazole Balofloxacin Take 0.389g of Balofloxacin, placed in a round bottom flask, add 10 mL DMF at 0 °C, stirring reaction at a constant rate for 10 min, slowly add chloroacetyl chloride 153µL, stir at 0 °C for 30 min, stir at room temperature for another 24 h, into the reaction solution add 3 times the volume of water, a large amount of insoluble matter was formed, stirred for another 1 hour, and filtered, the filter cake was dried to obtain an intermediate of 0.34 g, yield 73.12%. Weigh 0.1 g of intermediate, dissolved in 10mL acetonitrile, again added 22mg of sodium triazole, the reaction was carried out at 50 ° C for 48 h, and the reaction solution was concentrated, silica gel column chromatography and obtained new quinolone compound 0.078g, yield 58.33% (Synthetic route is shown in Figure 17)
Stage #1: 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid With Sodium hydrogenocarbonate In dichloromethane for 0.333333h; Cooling with ice; Stage #2: chloroacetyl chloride In dichloromethane Cooling with ice; 10 Example 10 Add 1 mmol of banofloxacin and 2 mL of DCM to a 100 mL round bottom flask. Cooled in the ice bath, Magnetic stirring, Add 3mmol NaHCO3, After 20 minutes, A 2.5 mmol solution of 2-chloroacetyl chloride in DCM (2 mL) was added dropwise with a constant pressure dropping funnel (drip acceleration was about 1 d / 2 s). Continue to react under the ice bath. TLC was monitored until the end of the reaction. Stop stirring, Add H2O15mL and DCM 20mL, Adjust pH=3-4 with 1N HCl solution with stirring. If there is a solid, it will stand still. Filtering, The filter cake was washed 3 times with DCM. The filter cake is left for further purification; The filtrate was transferred to a separatory funnel. Liquid separation, The aqueous phase was extracted with DCM (15 mL×1). Combine the organic phase, Wash with saturated NaCl solution (15 mL × 1), Collect organic phase, Dry with anhydrous Na2SO4. Rotary evaporator to spin dry to obtain a crude product. Column chromatography to obtain a pure product, Vacuum drying, Get the product.

  • 12
  • [ 638-29-9 ]
  • [ 127294-70-6 ]
  • [ 2278358-26-0 ]
YieldReaction ConditionsOperation in experiment
41.18% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 6 Example 6 Synthesis of valeric balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 100 μL of triethylamine and 122 μL of valeryl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and react to the reaction. was added 4 volumes of water, extracted with dichloromethane, washed with water three times and concentrated organic phase was washed with cold ether, and concentrated to give the novel quinolone compound 0.10g, yield of 41.18% (see Scheme 9)
  • 13
  • [ 142-61-0 ]
  • [ 127294-70-6 ]
  • [ 2278358-27-1 ]
YieldReaction ConditionsOperation in experiment
47.92% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 7 Example 7 Synthesis of hexanoyl balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 100 μL of triethylamine and 132 μL of hexanoyl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and then react to the reaction solution. 2 times by volume of water was added, extracted with dichloromethane, washed three times with water, and the organic phase was concentrated, washed with cold diethyl ether, and concentrated to precipitate a precipitated product to obtain a novel quinolone compound (0.12 g, yield 47.92% (see Figure 10 for the synthetic route)
  • 14
  • [ 2528-61-2 ]
  • 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid [ No CAS ]
  • C27H36FN3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
34.94% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 8 Example 8 Synthesis of heptanoyl balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 100 μL of triethylamine and 142 μL of heptanoyl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and react to the reaction, three times the volume of water was added to the solution, extracted with dichloromethane, washed three times with water, and the organic phase was concentrated, washed with cold diethyl ether, and then concentrated to precipitate, to give a novel quinolone compound, 0.09 g, yield 34.94% (see Figure 11 for the synthetic route)
  • 15
  • [ 111-64-8 ]
  • [ 127294-70-6 ]
  • [ 2278358-29-3 ]
YieldReaction ConditionsOperation in experiment
49.09% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 9 Example 9 Synthesis of octanoyl balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 100 μL of triethylamine and 159 μL of octanoyl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and react to the reaction. 4 times by volume of water was added to the solution, extracted with dichloromethane, washed with water three times, and the organic phase was concentrated, washed with cold diethyl ether, and concentrated to give a white quinolone compound (0.13 g) (yield: 49.09%)
  • 16
  • [ 764-85-2 ]
  • 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid [ No CAS ]
  • C29H40FN3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
55.15% With triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 24.5h; Take 0.2g balofloxacin, round-bottom flask, 0 added 10mL DMF, the reaction constant stirring 10min, and 100muL of triethylamine was slowly added dropwise 190 l of nonanoyl chloride, stirred for 30min 0 , at room temperature and then stirred for 24h, to the reaction 2 volumes of water were added to the solution, extracted with dichloromethane, washed three times with water, and the organic phase was concentrated, washed with cold diethyl ether, and concentrated to give 0.15 g of a novel quinolone compound, yield 55.15% (see Figure 13 for the synthetic route)
  • 17
  • [ 112-13-0 ]
  • [ 127294-70-6 ]
  • [ 2278358-31-7 ]
YieldReaction ConditionsOperation in experiment
42.98% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 11 Example 11 Synthesis of decanoyl barofloxacin Take 0.2 g of balofloxacin, place in a round bottom flask, add 10 mL of DMF at 0 ° C, and stir the reaction for 10 min at a constant rate. Slowly add 100 μL of triethylamine and 205 μL of decanoyl chloride, stirrer at 0 ° C for 30 min, stir at room temperature for 24 h. Add 3 volumes of water to the reaction solution, extracted with dichloromethane, washed with water three times, the organic phase was washed with cold diethyl ether was concentrated, and concentrated to give the novel quinolone compound 0.12g, yield of 42.98% (see Scheme 14)
  • 18
  • [ 16130-58-8 ]
  • [ 127294-70-6 ]
  • [ 2278358-32-8 ]
YieldReaction ConditionsOperation in experiment
0.1 g With triethylamine In N,N-dimethyl-formamide at 20℃; for 12h; 12 Example 12 Synthesis of cyanoparoxacin derivatives 1.1 g of cyanoacetic acid was dissolved in anhydrous dichloromethane, stirred at -10 ° C for 10 min, 1.04 mL of oxalyl chloride and a catalytic amount of DMF were slowly added. After completion of the reaction, the oxalyl chloride and the solvent were removed by a rotary evaporator, and the product was added to contain 0.389 g. Add 200 μL of triethylamine to the DMF solution of balofloxacin, react at room temperature for 12 h, add 4 volumes of water to the reaction solution, extract with dichloromethane, wash three times with water, concentrate the organic phase, wash with cold ether, concentrate and precipitate. Precipitation gave 0.1 g of a novel quinolone compound in a yield of 22.10% (see Figure 15 for the synthetic route)
  • 19
  • [ 1310878-66-0 ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide for 24h; 13 Example 13 Synthesis of alanine balofloxacin Take 0·15mg boc-alanine dissolved in 5mL DMF, stir for 5min, added triethylamine 232µL and ethyl chloroformate 151µL, stir the reaction for 30 min, again added 25 mL of DMF solution containing 0.2 g of Balofloxacin, stirring reaction for 24h, into the reaction solution added 2times volumes of water, extracted with dichloromethane, washed three times with water, concentrated organic phase, add 10 mL of trifluoroacetic acid and stir the reaction for 12 h, the trifluoroacetic acid was removed under reduced pressure, wash with diethyl ether, obtained 0.2 g of a new quinolone compound, yield 69.47% (Synthetic route is shown in Figure 16)
  • 20
  • [ 4023-34-1 ]
  • [ 127294-70-6 ]
  • [ 2278358-35-1 ]
YieldReaction ConditionsOperation in experiment
67.57% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 15 Example 15 Synthesis of cyclopropionyl balofloxacin Take 0.2g of Balofloxacin, placed in a round bottom flask, add 10 mL DMF at 0 °C, stirring reaction at a constant rate for 10 min, slowly add triethylamine 108µL and cyclopropionyl chloride 120µL, stir at 0 °C for 30 min, stir at room temperature for another 24 h, into the reaction solution add 4 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold ether, concentrated and then precipitated, obtained a new quinolone compound 0.15g, yield 67.57% (Synthetic route is shown in Figure 18)
  • 21
  • [ 64-18-6 ]
  • [ 127294-70-6 ]
  • [ 2278358-24-8 ]
YieldReaction ConditionsOperation in experiment
33% at 20 - 110℃; for 24.17h; 4 Example 4 Synthesis of formyl balofloxacin Take 0.2g of balofloxacin, place it in a round bottom flask, add 10mL of formic acid at room temperature, stir the reaction for 10min at a constant speed, heat and reflux at 110 °C, stir for 24h, add 2 volumes of water to the reaction solution, extract with dichloromethane, wash with water three times, the organic phase was concentrated washed with cold diethyl ether, and concentrated to give the novel quinolone compound 0.07g, 33% yield (see Scheme 7)
  • 22
  • [ 2278358-20-4 ]
  • [ 127294-70-6 ]
  • [ 2278358-36-2 ]
YieldReaction ConditionsOperation in experiment
0.2 g In N,N-dimethyl-formamide for 24h; 16 Example 15 Synthesis of cyclopropionyl balofloxacin Take 0.2g of Balofloxacin, placed in a round bottom flask, add 10 mL DMF at 0 °C, stirring reaction at a constant rate for 10 min, slowly add triethylamine 108µL and cyclopropionyl chloride 120µL, stir at 0 °C for 30 min, stir at room temperature for another 24 h, into the reaction solution add 4 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold ether, concentrated and then precipitated, obtained a new quinolone compound 0.15g, yield 67.57% (Synthetic route is shown in Figure 18)
  • 23
  • [ 2719-27-9 ]
  • [ 127294-70-6 ]
  • [ 2278358-37-3 ]
YieldReaction ConditionsOperation in experiment
85.94% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 17 Example 17 Synthesis of cyclohexanol acyl balofloxacin Take 0.2g of balofloxacin, placed in a round bottom flask, add 10 mL DMF at 0 °C, stirring reaction at a constant rate for 10 min, slowly add triethylamine 107µL and cyclohexanoyl chloride 150µL, stir at 0 °C for 30 min, stir at room temperature for another 24 h, into the reaction solution add 4 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold ether, concentrated, obtained a new quinolone compound 0.22g, yield 85.94% (Synthetic route is shown in Figure 20)
  • 24
  • [ 64531-95-9 ]
  • [ 127294-70-6 ]
  • [ 2278358-39-5 ]
YieldReaction ConditionsOperation in experiment
0.18 g In N,N-dimethyl-formamide for 24h; 19 example 19 Synthesis of pyridine-3-formyl balofloxacin Take 0.1g pyridine-3-carboxylic acid dissolved in 5mL DMF, stir for 5 min, and added 261μL of triethylamine and 170μL of ethyl chloroformate, stir the reaction for 30 min, again added 20mL of DMF solution containing 0.2 g of Balofloxacin, stirring reaction for 24h, into the reaction solution add 3 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold diethyl ether, concentrated, obtained a new quinolone compound 0.18g, yield 58.06% (Synthetic route is shown in Figure 22)
  • 25
  • [ 50-00-0 ]
  • [ 127294-70-6 ]
  • [ 2245159-01-5 ]
YieldReaction ConditionsOperation in experiment
82.13% Stage #1: 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid With formic acid at 20℃; for 0.166667h; Stage #2: formaldehyd at 100℃; for 24h; 1 Example 1 Synthesis of methyl balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of formic acid at room temperature, stir the reaction for 10 min at a constant speed, slowly add 200 μL of formaldehyde, heat and reflux at 100 ° C, stir for 24 h, add 2 volumes of water to the reaction solution. The mixture was extracted with dichloromethane, washed with water three times, and the organic phase was concentrated, washed with cold diethyl ether, and concentrated to precipitate a precipitated product to obtain a novel quinolone compound (0.17 g, yield: 82.13% (see Figure 1 for the synthetic route and Figure 2 for the characterization)
  • 26
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
  • [ 2278358-41-9 ]
YieldReaction ConditionsOperation in experiment
0.21 g In N,N-dimethyl-formamide for 24h; 21 Example 21 Synthesis of 2-tetrahydrofuranformyl balofloxacin Take 0.1g 2-tetrahydrofuran formic acid in 5mL DMF, stir for 5 min, and added 252μL of triethylamine and 164μL of ethyl chloroformate, stir the reaction for 30 min, again added 20mL of DMF solution containing 0.2 g of Balofloxacin, stirring reaction for 24h, into the reaction solution add 2 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold diethyl ether, concentrated and then Precipitate, obtained a new quinolone compound 0.21g, yield 70.02% (Synthetic route is shown in Figure 24)
  • 27
  • [ 2278358-21-5 ]
  • [ 127294-70-6 ]
  • [ 2278358-42-0 ]
YieldReaction ConditionsOperation in experiment
0.21 g In N,N-dimethyl-formamide for 24h; 22 Example 22 Synthesis of pyrrole-2-formyl balofloxacin Take 0.1g pyrrole formic acid in 5mL DMF, stir for 5 min, and added 125μL of triethylamine and 94μL of ethyl chloroformate, stir the reaction for 30 min, again added 20mL of DMF solution containing 0.25 g of Balofloxacin, stirring reaction for 24h, into the reaction solution add 4 times the volume of water, extract with dichloromethane and wash three times with water, concentrated organic phase, washed with cold diethyl ether, concentrated and then Precipitate, obtained a new quinolone compound 0.21g, yield 67.74% (Synthetic route is shown in Figure 25)
  • 28
  • [ 75-36-5 ]
  • [ 127294-70-6 ]
  • [ 2278358-22-6 ]
YieldReaction ConditionsOperation in experiment
67.57% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 2 Example 2 Synthesis of acetyl baloxycin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 208 μL of triethylamine and 141 μL of acetyl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and react to the reaction. Add 3 volumes of water to the solution, extract with dichloromethane, wash three times with water, and concentrate the organic phase, After washing with cold diethyl ether, the precipitate was precipitated to obtain 0.15 g of a novel quinolone compound, the yield was 67.57% (the synthetic route is shown in Fig. 3, and the characterization map is shown in Fig. 4).
  • 29
  • [ 79-03-8 ]
  • [ 127294-70-6 ]
  • [ 2278358-23-7 ]
YieldReaction ConditionsOperation in experiment
61.14% With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.5h; 3 Example 3 Synthesis of propionyl balofloxacin Take 0.2 g of balofloxacin, place it in a round bottom flask, add 10 mL of DMF at 0 ° C, stir the reaction for 10 min at a constant rate, slowly add 190 μL of triethylamine and 90 μL of propionyl chloride, stir at 0 ° C for 30 min, stir at room temperature for another 24 h, and react to the reaction. 4 times volume of water was added to the solution, extracted with dichloromethane, washed three times with water, concentrated organic phase, washed with cold diethyl ether and concentrated to give a new quinolone compound 0.14 g, yield 61.14% (the synthetic route is shown in Fig. 5, the characterization map is shown in Fig. 6)
  • 30
  • [ 2417332-18-2 ]
  • [ 127294-70-6 ]
  • [ 2417332-10-4 ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine In 1,4-dioxane at 20℃; stereoselective reaction;
  • 31
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide at 20℃; General protocol for the preparation of compounds 5a-e General procedure: Compound 4 (28 mg, 0.025 mmol, 1 equiv) was mixed with 2 equiv of ciprofloxacin, pazufloxacin, garenoxacin, balofloxacin, or moxifloxacin in DMF (1 mL). The mixture was stirred at room temperature for 24 h, concentrated in vacuo and then purified on a silica gel column. Compounds were eluted with DCM/MeOH (20:1 to 2:1). Compounds 5a-e were obtained as dark blue solids with purities of ≥ 95%. The identity of each hybrid was verified by HRESIMS: 5a calcd m/z for C73H83FN5O23 (M + H+) 1416.5462, found m/z 1416.5485; 5b calcd m/z for C72H80FN4O24 (M + H+) 1403.5147, found m/z 1403.5152; 5c calcd m/z for C79H85F2N4O24 (M + H+) 1511.5522, found m/z 1511.5513; 5d calcd m/z for C76H89FN5O24 (M + H+) 1474.5882, found m/z 1474.5872. The lead compound from this set, 5c, was further characterized by NMR. 1H NMR (600 MHz, DMSO-d6): δ 8.91 (s, 1H), 8.37 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 6.3 Hz, 1H), 7.67 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 6.84 (m, 1H), 6.72 (t, J = 72.6 Hz, 1H), 6.54 (m, 1H), 5.90 (d, J = 11.0 Hz, 1H), 5.85 (s, 1H), 5.56 (br s, 1H), 5.32 (m, 1H), 5.26 (m, 1H), 5.14 (br s, 1H), 5.10 (s, 1H), 4.94 (t, J = 10.3 Hz, 1H), 4.78 (s, 1H), 4.73 (m, 1H), 4.50 (d, J = 6.3 Hz, 1H), 4.16 (m, 1H), 4.06 (m, 1H), 3.62 (dd, J = 8.4 Hz, 5.0 Hz, 1H), 3.54 (m, 1H), 3.51 (s, 1H), 3.42 (m, 1H), 3.28 (m, 1H), 2.81 (t, J = 8.1 Hz, 1H), 2.38 (m, 1H), 2.33 (d, J = 16.2 Hz, 1H), 2.18 (m, 1H), 2.16 (s, 3H), 2.08 (s, 3H), 2.01 (m, 1H), 1.96 (m, 1H), 1.95 (s, 3H), 1.80 (m, 1H), 1.74 (m, 1H), 1.70 (s, 3H), 1.63 (m, 1H), 1.56 (d, J = 5.26 Hz, 3H), 1.25 (m, 2H), 1.19 (m, 2H), 1.17 (d, J = 6.1 Hz, 3H), 1.08 (s, 3H), 1.05 (s, 3H), 1.03 (d, J = 6.3 Hz, 3H), 0.85 (m, 3H), 0.82 (m, 3H), 0.57 (br s, 3H); 13C NMR (150 MHz, DMSO-d6): δ 192.3, 181.7, 177.1, 175.1, 173.8, 172.0, 171.0, 169.9, 169.8, 165.2, 156.1, 155.9, 153.5, 152.5, 144.1, 143.7, 142.3, 138.2, 137.1, 136.7, 135.6, 135.4, 131.2, 130.9, 129.7, 129.6, 128.9, 128.8, 128.7, 124.3, 122.8, 122.7, 117.2, 115.5, 113.8, 113.6, 111.3, 108.3, 106.2, 104.9, 96.8, 93.9, 77.4, 77.3, 74.8, 73.8, 72.2, 72.1, 69.8, 69.4, 68.1, 60.3, 51.7, 43.4, 42.1, 41.1, 32.4, 31.3, 25.3, 24.5, 22.1, 21.0, 20.9, 20.8, 18.4, 17.3, 12.5, 11.9, 11.1, 9.57, 7.53.
In N,N-dimethyl-formamide at 20℃; General protocol for the preparation of compounds 5a-e General procedure: Compound 4 (28 mg, 0.025 mmol, 1 equiv) was mixed with 2 equiv of ciprofloxacin, pazufloxacin, garenoxacin, balofloxacin, or moxifloxacin in DMF (1 mL). The mixture was stirred at room temperature for 24 h, concentrated in vacuo and then purified on a silica gel column. Compounds were eluted with DCM/MeOH (20:1 to 2:1). Compounds 5a-e were obtained as dark blue solids with purities of ≥ 95%. The identity of each hybrid was verified by HRESIMS: 5a calcd m/z for C73H83FN5O23 (M + H+) 1416.5462, found m/z 1416.5485; 5b calcd m/z for C72H80FN4O24 (M + H+) 1403.5147, found m/z 1403.5152; 5c calcd m/z for C79H85F2N4O24 (M + H+) 1511.5522, found m/z 1511.5513; 5d calcd m/z for C76H89FN5O24 (M + H+) 1474.5882, found m/z 1474.5872. The lead compound from this set, 5c, was further characterized by NMR. 1H NMR (600 MHz, DMSO-d6): δ 8.91 (s, 1H), 8.37 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 6.3 Hz, 1H), 7.67 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 6.84 (m, 1H), 6.72 (t, J = 72.6 Hz, 1H), 6.54 (m, 1H), 5.90 (d, J = 11.0 Hz, 1H), 5.85 (s, 1H), 5.56 (br s, 1H), 5.32 (m, 1H), 5.26 (m, 1H), 5.14 (br s, 1H), 5.10 (s, 1H), 4.94 (t, J = 10.3 Hz, 1H), 4.78 (s, 1H), 4.73 (m, 1H), 4.50 (d, J = 6.3 Hz, 1H), 4.16 (m, 1H), 4.06 (m, 1H), 3.62 (dd, J = 8.4 Hz, 5.0 Hz, 1H), 3.54 (m, 1H), 3.51 (s, 1H), 3.42 (m, 1H), 3.28 (m, 1H), 2.81 (t, J = 8.1 Hz, 1H), 2.38 (m, 1H), 2.33 (d, J = 16.2 Hz, 1H), 2.18 (m, 1H), 2.16 (s, 3H), 2.08 (s, 3H), 2.01 (m, 1H), 1.96 (m, 1H), 1.95 (s, 3H), 1.80 (m, 1H), 1.74 (m, 1H), 1.70 (s, 3H), 1.63 (m, 1H), 1.56 (d, J = 5.26 Hz, 3H), 1.25 (m, 2H), 1.19 (m, 2H), 1.17 (d, J = 6.1 Hz, 3H), 1.08 (s, 3H), 1.05 (s, 3H), 1.03 (d, J = 6.3 Hz, 3H), 0.85 (m, 3H), 0.82 (m, 3H), 0.57 (br s, 3H); 13C NMR (150 MHz, DMSO-d6): δ 192.3, 181.7, 177.1, 175.1, 173.8, 172.0, 171.0, 169.9, 169.8, 165.2, 156.1, 155.9, 153.5, 152.5, 144.1, 143.7, 142.3, 138.2, 137.1, 136.7, 135.6, 135.4, 131.2, 130.9, 129.7, 129.6, 128.9, 128.8, 128.7, 124.3, 122.8, 122.7, 117.2, 115.5, 113.8, 113.6, 111.3, 108.3, 106.2, 104.9, 96.8, 93.9, 77.4, 77.3, 74.8, 73.8, 72.2, 72.1, 69.8, 69.4, 68.1, 60.3, 51.7, 43.4, 42.1, 41.1, 32.4, 31.3, 25.3, 24.5, 22.1, 21.0, 20.9, 20.8, 18.4, 17.3, 12.5, 11.9, 11.1, 9.57, 7.53.
  • 32
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With triethylamine; O-(7-azabenzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluoro-phosphate In N,N-dimethyl-formamide at 25℃; for 1h; General protocol for the preparation of compounds 2a-i General procedure: Fluoroquinolones were purchased from Sigma. Compound 1 (3 mg, 1 equiv) was dissolved in 50 µL DMF. To this was added 2 equiv each of HATU, TEA, and finally a fluoroquinolone. Reactions were performed at 25 °C and allowed to proceed for 1 h with gentle agitation. The resultant hybrids 2a-i were purified by HPLC using a 10 mm x 150 mm C18 column (Waters) using the following method: 30-95% acetonitrile:water with 0.1% formic over 30 min at a flow rate of 3.5 mL/min. All hybrids were assayed for activity at purities of 95% or greater. The identity of each hybrid was verified by HRESIMS: 2a calcd m/z for C67H80FN4021 (M + H+) 1295.5299, found m/z 1295.5277; 2b calcd m/z for C66H77FN3O22 (M + H+) 1282.4983, found m/z 1282.4960; 2c calcd m/z for C73H82F2N3O22 (M + H+) 1390.5358, found m/z 1390.5289; 2d calcd m/z for C69H84FN4O22 (M + H+) 1339.5561, found m/z 1339.5537; 2e calcd m/z for C70H77F3N5O21 (M + H+) 1380.5063, found m/z 1380.5041; 2f calcd m/z for C70H86FN4O22 (M + H+) 1353.5718, found m/z 1353.5688; 2g calcd m/z for C69H83ClFN4O21 (M + H+) 1357.5222, found m/z 1357.5175; 2h calcd m/z for C68H82FN6O22 (M + H+) 1353.5466, found m/z 1353.5435; 2i calcd m/z for C71H86FN4O22 (M + H+) 1365.5718, found m/z 1365.5652.
With triethylamine; O-(7-azabenzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluoro-phosphate In N,N-dimethyl-formamide at 25℃; for 1h; General protocol for the preparation of compounds 2a-i General procedure: Fluoroquinolones were purchased from Sigma. Compound 1 (3 mg, 1 equiv) was dissolved in 50 µL DMF. To this was added 2 equiv each of HATU, TEA, and finally a fluoroquinolone. Reactions were performed at 25 °C and allowed to proceed for 1 h with gentle agitation. The resultant hybrids 2a-i were purified by HPLC using a 10 mm x 150 mm C18 column (Waters) using the following method: 30-95% acetonitrile:water with 0.1% formic over 30 min at a flow rate of 3.5 mL/min. All hybrids were assayed for activity at purities of 95% or greater. The identity of each hybrid was verified by HRESIMS: 2a calcd m/z for C67H80FN4021 (M + H+) 1295.5299, found m/z 1295.5277; 2b calcd m/z for C66H77FN3O22 (M + H+) 1282.4983, found m/z 1282.4960; 2c calcd m/z for C73H82F2N3O22 (M + H+) 1390.5358, found m/z 1390.5289; 2d calcd m/z for C69H84FN4O22 (M + H+) 1339.5561, found m/z 1339.5537; 2e calcd m/z for C70H77F3N5O21 (M + H+) 1380.5063, found m/z 1380.5041; 2f calcd m/z for C70H86FN4O22 (M + H+) 1353.5718, found m/z 1353.5688; 2g calcd m/z for C69H83ClFN4O21 (M + H+) 1357.5222, found m/z 1357.5175; 2h calcd m/z for C68H82FN6O22 (M + H+) 1353.5466, found m/z 1353.5435; 2i calcd m/z for C71H86FN4O22 (M + H+) 1365.5718, found m/z 1365.5652.
  • 33
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide; water monomer / 50 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
  • 34
  • [ 83948-53-2 ]
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In water monomer; N,N-dimethyl-formamide at 50℃; General protocol for the preparation of compounds 6a-e General procedure: Fluoroquinolone-linker conjugates were prepared as follows. To a stirred solution of K2CO3, (2 equiv) in DMF/H2O (1:1), a fluoroquinolone (1 equiv) was added, followed by N-Boc-3-bromopropylamine (2 equiv). The reaction mixture was stirred at 50 °C for 1-3 days, at which point it was concentrated in vacuo and then diluted in H2O (5 mL). The pH was adjusted to 4-5 using aqueous 2N HCl. The solution was then extracted in DCM (2 x 10 mL). The organic fractions were washed with brine (10 mL), dried over Na2SO4, filtered, and dried under vacuum to obtain a white residue. The residue was purified by silica gel column chromatography (DCM/MeOH, 9:1) to obtain a white solid. Removal of the Boc group was subsequently completed by dissolving the intermediate in TFA/DCM (1:1, 1 mL) and stirring at room temperature for 2 h. The solvent was removed under vacuum. The solution was then neutralized with addition of 1 mL TEA followed by concentration in vacuo. Each fluoroquinolone-linker conjugate was obtained as a white solid and used directly in the synthesis of compounds 6a-e using the general procedure used to generate compounds 5a-e. The identity of each hybrid was verified by HRESIMS: 6a calcd m/z for C76H90FN6O23 (M + H+) 1473.6041, found m/z 1473.6028; 6b calcd m/z for C75H87FN5O24 (M + H+) 1460.5725, found m/z 1460.5723; 6c calcd m/z for C82H91F3N5O24 (M + H+) 1586.6006, found m/z 1586.6028; 6d calcd m/z for C79H96FN6O24 (M + H+) 1531.6461, found m/z 1531.6454.
With potassium carbonate In water monomer; N,N-dimethyl-formamide at 50℃; General protocol for the preparation of compounds 6a-e General procedure: Fluoroquinolone-linker conjugates were prepared as follows. To a stirred solution of K2CO3, (2 equiv) in DMF/H2O (1:1), a fluoroquinolone (1 equiv) was added, followed by N-Boc-3-bromopropylamine (2 equiv). The reaction mixture was stirred at 50 °C for 1-3 days, at which point it was concentrated in vacuo and then diluted in H2O (5 mL). The pH was adjusted to 4-5 using aqueous 2N HCl. The solution was then extracted in DCM (2 x 10 mL). The organic fractions were washed with brine (10 mL), dried over Na2SO4, filtered, and dried under vacuum to obtain a white residue. The residue was purified by silica gel column chromatography (DCM/MeOH, 9:1) to obtain a white solid. Removal of the Boc group was subsequently completed by dissolving the intermediate in TFA/DCM (1:1, 1 mL) and stirring at room temperature for 2 h. The solvent was removed under vacuum. The solution was then neutralized with addition of 1 mL TEA followed by concentration in vacuo. Each fluoroquinolone-linker conjugate was obtained as a white solid and used directly in the synthesis of compounds 6a-e using the general procedure used to generate compounds 5a-e. The identity of each hybrid was verified by HRESIMS: 6a calcd m/z for C76H90FN6O23 (M + H+) 1473.6041, found m/z 1473.6028; 6b calcd m/z for C75H87FN5O24 (M + H+) 1460.5725, found m/z 1460.5723; 6c calcd m/z for C82H91F3N5O24 (M + H+) 1586.6006, found m/z 1586.6028; 6d calcd m/z for C79H96FN6O24 (M + H+) 1531.6461, found m/z 1531.6454.
  • 35
  • [ 127294-70-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: triethylamine / N,N-dimethyl-formamide / 24 h / 20 °C 2.1: potassium carbonate / acetonitrile / 0.17 h / 20 °C 2.2: 24 h / 50 °C
  • 36
  • [ 127294-77-3 ]
  • [ CAS Unavailable ]
  • [ 127294-70-6 ]
YieldReaction ConditionsOperation in experiment
44.1% With triethylamine In chloroform for 20h; Reflux; 1.S2; 2.S2; 3.S2 Step S2: Crude balofloxacin(1-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoQuinoline-3-carboxylate ·Synthesis of boron diacetate (DFQ-B complex). Operation: In a 5L three-necked flask, add 215g (1.15mol) of 3-methylaminopiperidine dihydrochloride, 400g (0.95mol) of compound (DFQ-Bcomplex), 400mL of triethylamine and 3000mL of chloroform, stir, and heat up to Reflux and react for 20h. Cooled, concentrated under reduced pressure, diluted with water, extracted with chloroform (800 mL×3), dried and concentrated to obtain 156.4 g of crude balofloxacin as a yellow solid, with a yield of 42.5%.
  • 37
  • [ 127294-70-6 ]
  • [ 151060-21-8 ]
YieldReaction ConditionsOperation in experiment
76.3% Stage #1: 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-7-(3-methylaminopiperidin-1-yl)-3-quinolinecarboxylic acid In ethanol for 0.5h; Reflux; Stage #2: With water monomer at 50 - 60℃; 1.S3; 2.S3; 3.S3 Step S3: product refining. Operation: 6000 mL of ethanol was added to 150 g of balofloxacin crude product, and the mixture was heated and refluxed under stirring until the solid was completely dissolved. Slightly cool, add 10.0g activated carbon, continue to reflux for 30min, and filter while hot. The filtrate was concentrated to about 500 mL under reduced pressure at 50-60° C., 500 mL of water was added, and the mixture was cooled to room temperature with continued stirring, and crystals were precipitated. It was left overnight, filtered, and dried at 45°C to obtain 122.7 g of white crystals, yield 74.9%,
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