113028-17-4|Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 113028-17-4 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 113028-17-4 ]

CAS No. :	113028-17-4
Formula :	C₁₈H₂₀FN₃O₃S
M.W :	377.43
SMILES Code :	O=C(C1=C(SC2C)N2C3=C(C=C(F)C(N4CCNCC4)=C3)C1=O)OCC
MDL No. :	MFCD08063938
InChI Key :	XWZXETKTFKCCPB-UHFFFAOYSA-N
Pubchem ID :	10249018

Safety of [ 113028-17-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 113028-17-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	26
Num. arom. heavy atoms	10
Fraction Csp3	0.44
Num. rotatable bonds	4
Num. H-bond acceptors	5.0
Num. H-bond donors	1.0
Molar Refractivity	106.48
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	88.87 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.87
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.72
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.69
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.78
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.77
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.37

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.91
Solubility	0.046 mg/ml ; 0.000122 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.24
Solubility	0.0217 mg/ml ; 0.0000575 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-4.52
Solubility	0.0114 mg/ml ; 0.0000302 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.67 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	3.8

Application In Synthesis of [ 113028-17-4 ]

* 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.

Upstream synthesis route of [ 113028-17-4 ]
Downstream synthetic route of [ 113028-17-4 ]

[ 113028-17-4 ] Synthesis Path-Upstream 1~1

1
[ 113028-17-4 ]
[ 123447-62-1 ]

References: [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 25, p. 4727 - 4738.
[2] Patent: WO2012/1357, 2012, A1, .

[ 113028-17-4 ] Synthesis Path-Downstream 1~16

1
[ 110-85-0 ]
[ 113046-72-3 ]
[ 113028-17-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	In dimethyl sulfoxide; at 60℃; for 4h;	50 g of ethyl 6,7-difluoro-1-methyl-4-oxo-4H- [1,3] thiazine [3,2-a] Dissolve in 5 volumes of DMSO at 60C, add 40 g of piperazine, and stir at 60C for 4 hours. The mixture was cooled to room temperature, then 5 volumes of acetonitrile were added and stirring was continued for 4 hours at room temperature. The precipitate was collected by filtration and dried to give 6-fluoro-7-piperazine-1-methyl-4-oxo- [1,3] thiazacyclo [3,2-a] Ethyl acid 52.8g, yield 87%. The yield of 6-fluoro-7-piperazine-1-methyl-4-oxo- [1,3] thiazacyclo [3,2-a] quinoline-3-carboxylic acid B Ester purity 99%.
87%	In dimethyl sulfoxide; at 60℃; for 4h;	Take the ethyl 6,7-difluoro-1-methyl-4-oxo-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate 50g,Dissolve in 5 volumes of DMSO at 60C.Then add 40 g of piperazine,Stir at 60C for 4 hours.Cool the mixture to room temperatureThen add 5 volumes of acetonitrile,Stirring was continued for 4 hours at room temperature.Filter, collect the precipitate, dry,This gives 52.8 g of ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate.Yield 87%.HPLC detection, ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate purity 99% .
	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide;	EXAMPLE 4 Ethyl 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-(1,3)thiazeto(3,2-a)quinoline-3-carboxylate Ethyl 6,7-difluoro-1-methyl-4-oxo-4H-(1,3)thiazeto(3,2-a)quinoline-3-carboxylate (5.0 g) was suspended in 150 ml of N,N-dimethylformamide and the suspension was stirred with 4.6 g of piperazine at room temperature for 48 hours. N,N-Dimethylformamide was evaporated in vacuo and to the residue was added ice water to collect the crystals by filtration. Purification by a column chromatography (silica gel/chloroform-methanol (1:1)) gave 3.0 g of desired compound, m.p. 224 C. (decompn.). Elementary analysis calculated for C18 H20 FN3 O3 S.3/4H2 O. Calcd (%): C 55.30, H 5.54, N 10.74. Found (%): C 55.29, H 5.52, N 10.37.

In N,N-dimethyl-formamide; at 20 - 25℃;Product distribution / selectivity;

Example 7: Preparation of Ulifloxacin ethyl ester; Method A: Dimethylformamide (13.94 It), ethyl 6,7-difluoro-l-methyl-4-oxo-4H- (l,3)thiazeto(3,2-a)quinoline-3-carboxylate (1.39kg) and piperazine (1.39kg) were stirred at 20- 25C for 20-22 hours. Reaction completion was checked by TLC. Water (69.5 It) was added and the reaction mixture was filtered, washed with water and dried to obtain 1.11kg of ulifloxacin ethyl ester having purity 97.47 % by HPLC.

References: [1]Patent: CN107383069,2017,A .Location in patent: Paragraph 0061; 0062.
[2]Patent: CN107501298,2017,A .Location in patent: Paragraph 0055; 0056.
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.
[4]Patent: US4843070,1989,A .
[5]Patent: WO2009/93268,2009,A1 .Location in patent: Page/Page column 15.

2
[ 80715-22-6 ]
[ 113028-17-4 ]
ethyl 6-fluoro-1-methyl-7-<4-<(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl>-1-piperazyl>-4-oxo-4H-<1,3>thiazeto<3,2-a>-quinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydrogencarbonate; In N,N-dimethyl-formamide;	EXAMPLE 1 Ethyl 6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolen-4yl)methyl-1-piperazinyl]-4oxo-4H-[1,3-]thiazeto[3,2-a]quinoline-3-carboxylate. Ethyl 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate (3.88 g) and 1.23 g of potassium bicarbonate were suspended in 20 ml of N,N-dimethylformamide, 2.38 g of 4-bromomethyl-5-methyl-1,3-dioxolen-2-one was dropped thereinto with ice cooling, and the mixture was stirred for 3 hours. After the reaction, the solvent was evaporated in vacuo therefrom at 50 C. and the residue was extracted with chloroform containing a few amount of methanol. The extract was washed with water, dried, the solvent was evaporated therefrom and the residue was purified by a column chromatography (chloroform-methanol/silica gel) to give 3.32 g of desired product. M.p. 241-243 C. (decompn.) Elem. Anal. for C23 H24 FN3 O6 S; Calcd. (%) C: 56.43 H: 4.94 N: 8.58; Found (%) C: 56.13 H: 4.99 N: 8.26. IR (KBr) nu (cm-1): 1820, 1720 (carbon-yl). NMR (CF3 CO2 D)(ppm) 1.51(3H, COOCH2 CH3, t), 2.31(3H, STR10 s), 2.35(3H, STR11 d), 3.40~4.30(8H, proton in piperazine ring, m), 4.55(2H, STR12 s), 4.65(2H, COOCH2 CH3, q), 6.51(1H, STR13 q), 7.05(1H, 8-proton, d), 8.11(1H, 5-proton, d).

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.
[2]Patent: US5086049,1992,A .

3
[ 113028-17-4 ]
[ 112984-60-8 ]

Yield	Reaction Conditions	Operation in experiment
97%		Ethyl-6-fluoro-1 -methyl-4-oxo-7-(1 -piperazinyl)-4H-(1 ,3)-thiazeto-[3,2-a]-quinoline-3- carboxylate (100 gms, 0.265 moles) was stirred in water (600 ml) at 25-30C. To this potassium hydroxide solution (50 gms of potassium hydroxide flakes is dissolved in 200 ml of water) was added and the reaction mass was heated to 80-85C. The contents were stirred for 1 hour and after completion of reaction, the reaction mass was cooled to 25-30C. The pH of the reaction mass was adjusted to 6.5-7.0 using 1:1 aqueous acetic acid solution. The contents were stirred at room temperature for 1 hour. The precipitated solid was filtered, washed with water (2 x 100 ml). The solid was slurried in methanol (300 ml) for 1 hour at 25-30C, filtered, washed with methanol (2 x 50 ml) and dried under vacuum at 70-75C to yield the title compound [90 gms, 97% yield, 96% HPLC purity].
97.3%	With water; potassium hydroxide; at 60 - 70℃;Large scale;	the reaction vessel 8. 0kg a compound of formula (II), 112kg water, 6. 0kg potassium hydroxide, and heated to 60~ 70 C the hydrolysis reaction, 2 to 3 hours. After completion of the reaction, was cooled to room temperature, 30. 4kg washed with ethyl acetate, the aqueous layer was separated, stirred, adjusted with concentrated hydrochloric acid rhoEta 6~7, stirring was continued for 0.5 hours, the filter cake was suction filtration, an appropriate amount of ethyl washing the filter cake drying, cake was collected, 60~70 C hot air circulation drying, to obtain a compound of formula (III) finished 7. 36kg, yield (mol) 96.4%, purity 97.3%;
90%	With potassium hydroxide; at 20℃; for 5h;	30 g of ethyl 6-fluoro-7-piperazine-1-methyl-4-oxo- [1,3] thiazepino [3,2-a] 120ml concentration of 1mol / L of potassium hydroxide solution dissolved, And stirred at room temperature for 5 hours. The solution was neutralized with a 20% (v/v) acetic acid solution and the pH was adjusted to 7-8 and stirred well. The precipitate was collected by filtration, and the precipitate was washed three times with deionized water and acetonitrile, respectively. The precipitate was then dried in vacuo at 60 C to give 6-fluoro-7-piperazine-1-methyl-4-oxo- [1,3] thiazacyclo [3,2-a] 3-carboxylic acid 29g, 90% yield. The obtained 6-fluoro-7-piperazine-1-methyl-4-oxo- [1,3] thiazepino [3,2-a] quinoline-3-carboxylic acid was 99.1% pure.

Example 8: Preparation of Ulifloxacin;Tertiary butanol (5.55It), 6-fluoro-l-methyl-4-oxo-7-(l-piperazinyl)-4H-[l,3]thiazeto [3,2- a]quinoline-3-carboxylic acid ethyl ester (1.1 lkg), potassium hydroxide (0.37kg) and water (2.75 It) were added at room temperature. The reaction mixture was heated to 600C and maintained for 1.5 hours. Reaction completion was checked by TLC. This was followed by the addition of water (22.2 It) and acetic acid (0.39 It). The reaction mixture was filtered, washed with water followed by slurry wash with acetone (2.22 It) twice and dried to obtain 0.95 kg of ulifloxacin having purity 97.56% by HPLC.

References: [1]Patent: WO2012/1357,2012,A1 .Location in patent: Page/Page column 22.
[2]Patent: CN103113392,2016,B .Location in patent: Paragraph 0024; 0037; 0038; 0039.
[3]Patent: CN107383069,2017,A .Location in patent: Paragraph 0063; 0064.
[4]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.
[5]Patent: WO2009/93268,2009,A1 .Location in patent: Page/Page column 15.

4
[ 113028-17-4 ]
[ 598-31-2 ]
ethyl 7-(4-acetonyl-1-piperazinyl)-6-fluoro-1-methyl-4-oxo-4H-<1,3>thiazeto<3,2-a>quinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide;	EXAMPLE 5 Ethyl 7-(4-acetonyl-1-piperazinyl)-6-fluoro-1-methyl-4-oxo-4H-(1,3)thiazeto(3,2-a)quinoline-3-carboxylate Ethyl 6-fluoro-1-methyl-7-(1-piperazinyl)-4-oxo-4H-(1,3)thiazeto(3,2-a)quinoline-3-carboxylate (3.8 g) was suspended in 50 ml of N,N-dimethylformamide, 1.66 g of potassium carbonate was added thereto, 1.65 g of bromoacetone was dropped in with ice cooling and stirring, and the mixture was stirred at room temperature for 20 hours. The reaction solution was poured over into ice water and the crystals separated out were collected by filtration, washed with water, dried and recrystallized from ethanol to give 3.7 g of desired compound in colorless powdery crystals, m.p. 196-200 C. (decompn.). Elementary analysis calculated for C21 H24 FN3 O4 S: Calcd (%): C 58.18, H 5.58, N 9.69. Found (%): C 57.93, H 5.39, N 9.46.

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.
[2]Patent: US4843070,1989,A .

5
[ 113028-75-4 ]
[ 113028-17-4 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 4727 - 4738.

6
[ 84339-06-0 ]
[ 113028-17-4 ]