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天空之痕

金虫 (著名写手)

药物小博士

[求助] 求助印度专利一篇

Indian Pat. Appl. (2010), IN 2008MU01781 A 20100813
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研究透了，你就开始懂了
1楼 2012-12-01 15:37:04
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wjswift

至尊木虫 (职业作家)

看文献，做实验......

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★ ★ ★ ★ ★ ★
天空之痕: 金币+5, ★★★★★最佳答案 2012-12-03 22:38:49
chemistryer: 金币+1, SPI+2, 感谢贡献 2012-12-04 08:33:11
http://good.gd/2333012.htm
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Darwin said, a scientific man ought to have no wishes, no affections, - a mere heart of stone.
6楼2012-12-03 10:21:04
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muziyongxin

木虫之王 (文坛精英)

无名小帅

文献杰出贡献

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http://good.gd/2330539.htm
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木子李也
2楼2012-12-01 15:54:19
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huzguo

铁杆木虫 (著名写手)

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http://1000eb.com/dfwr
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提供高品质、权威的民商法律、著作权、专利权和商标权等法律技术解决方案
3楼2012-12-01 15:56:20
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天空之痕

金虫 (著名写手)

药物小博士
引用回帖:
3楼: Originally posted by huzguo at 2012-12-01 15:56:20
http://1000eb.com/dfwr

这篇专利怎么没有内容呢？只有一个封面啊
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研究透了，你就开始懂了
4楼2012-12-01 16:15:45
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huzguo

铁杆木虫 (著名写手)

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★ ★ ★ ★ ★
天空之痕: 金币+5, 辛苦了，但楼下的是pdf版的 2012-12-03 22:39:15
Complete Specification
DESCRIPTION:

The invention provides 8,9-Disubstituted-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido [3,2,1-ij]quinoline-2-carboxylic acid, isomers and salts thereof. The invention also provides pure nadifloxacin. The invention further provides composition of 8,9-Disubstituted-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinolone-2-carboxylic acid and salts thereof.

Nadifloxacin is chemically known as 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid having Formula I.


Racemic Nadifloxacin is marketed under the names Acuatim, Nadoxin and Nadixa. It is used for the treatment of acne vulgaris and to treat bacterial skin infections.

There are several patents and patent applications cited in the literature, which refer to the process for the preparation of nadifloxacin such as U.S. Patent No. 4,399,134. S-(-)-Nadifloxacin and its salts are disclosed in U.S. Patent No. 6,750,224, U.S. Patent No. 6,878,713, U.S. Patent No. 7,247,642 and U.S. Patent No. 7,393,957. Chem. Pharm. Bull 44 (1996), discloses the synthesis of (S)(O-ß-Diacetoxy-(8,9-difluoro-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]-quinolizine-2-carboxy) borane, an intermediate useful in synthesis of Nadifloxacin, using toluene.

The inventors provide benzoquinolizine carboxylic acid of compound of Formula II,

wherein,
R1 is alkyl, substituted alkyl, aryl, substituted aryl and arylalkyl;
R2 is H, alkyl, substituted alkyl, aryl, substituted aryl and arylalkyl; or
(R1)(R2)N- may combine together to form a structure of formula,

wherein,
X is O, CHR4, NR4 or S;
R3/R3' are the same or different and represent H, alkyl, substituted alkyl, alkylamino, or arylalkyl;
R4 is H, alkyl, alkylamino, dialkylamino, aryl, arylalkyl, trihaloalkyl, -OR5 or NR6R7;
wherein,
R5 is H, alkyl, glycosyl, arylalkyl, alkanoyl, aminoalkanoyl or an acid residue derived from one of the 20 naturally occurring amino acids, or the optically active isomers thereof, or the racemic mixtures thereof, or
R5 is 1-aminocyclohexylcarbonyl; or
R5 is C6H11O6, PO2(CH3)H, PO3H2, PO2(OCH3)H or SO3 H;
R6 is H, alkyl, C3-6 cycloalkyl, arylalkyl, alkanoyl, alkoxycarbonyl, arylalkyloxycarbonyl, aminoalkanoyl or an amino acid residue derived from one of the 20 naturally occurring amino acids or the optically active isomers thereof, or the racemic mixtures thereof; or
R6 is C6H11O6;
R7 is H, alkyl, C3-6cycloalkyl, arylalkyl, alkanoyl, arylalkyloxycarbonyl or aminoalkanoyl; or an amino acid residue derived from one of the 20 naturally occurring amino acids or the optically active isomers thereof, or the racemic mixtures thereof, or
R7 is C6H11O6;
and pharmaceutically acceptable salts thereof.

The specific compounds of invention include;

8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethyl-4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-isopropyl-5-ethyl-4-hydroxypiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-4-dimethyaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-3-ethyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-isopropyl-5-ethyl-4-hydroxypiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethyl-4-ethylaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-ethyl-3-methyl-5-ethyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethy-5-methyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof and
8,9-Bis(3-ethyl,-3-methyl-4-dimethylaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof.

In this disclosure, “C1-C6 alkyl” refer to saturated, straight, or branched chain hydrocarbon radicals derived from a hydrocarbon moiety containing between one and six carbon atoms by removal of a single hydrogen atom. The non-limiting examples of C1-C6 alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, neopentyl, and n-hexyl and the like.

The term “substituted alkyl” refers to the alkyl group as defined previously, wherein one or more hydrogens on the designated carbon is replaced with a substituent selected from the group consisting of hydroxy, amino, cyano, F, Cl, Br, I and carboxy.

The term “aryl” refers to a mono-, fused bicyclic or fused tricyclic carbocyclic ring system having one or more aromatic rings including, but not limited to, phenyl, naphthyl, indanyl, indenyl, tetrahydronaphthyl, anthracenyl, phenanthrenyl, biphenylenyl and fluorenyl.

The term “substituted aryl” refers to an aryl group as defined previously, wherein one or more hydrogens on a designated carbon is replaced with a substituent selected from the group consisting of mono, fused bicyclic or fused tricyclic carbocyclic ring system having one or more aromatic rings.

The term “arylalkyl” refers to a radical in which an aryl group as defined previously, is substituted for an alkyl group as defined previously. For eg : toluene, xylene etc.

The term “alkylamino” refers to an alkyl group, as previously defined, attached to the parent molecular moiety through a nitrogen atom. Examples of alkyl-amino include, but are not limited to methylamino, ethylamino, and propylamino, butylamino.

The term “dialkylamino” refers to two alkyl group, as previously defined, attached to the parent molecular moiety through a nitrogen atom. Examples of dialkyl-amino include, but are not limited to dimethylamino and diethylamino.

The term “trihaloalkyl” refers to an alkyl group, as defined above, having three halogen atoms attached thereto. Examples of trihaloalkyl include, but are not limited to trichloromethyl, tribromoethyl, trifluoromethyl.

The term “alkanoyl” refers to -C(O)-C1-C6 alkyl groups wherein "C1-C6 alkyl group" is as defined above.

The term “aminoalkanoyl” refers to an alkanoyl group as previously defined, attached to the parent molecular moiety through a nitrogen atom.

The term “naturally occuring amino acid” include the 20 naturally occurring amino acids alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine , threonine, tryptophan, tyrosine or valine.

The term “C3-6 cycloalkyl” refers to a monovalent group derived from a monocyclic or bicyclic saturated carbocyclic ring compound by the removal of a single hydrogen atom. Examples include, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
The term “alkoxyl” refers to an alkyl (carbon and hydrogen chain) group linked to
oxygen.The range of alkoxy groups is as great, the simplest being methoxy (-OCH3) and ethoxy group (-OCH2CH3).

The term “alkoxycarbonyl” refers to alkoxy group, as defined above, attached to a carbonyl moiety. For example : (OC-OCH3) and (OC-OCH2CH3).

The term “arylalkyloxycarbonyl” refers to an aryl group as defined above, attached to an alkoxycarbonyl group as defined above. For example : (OC-OCH2-aryl).

The term “pharmaceutically acceptable salts” refers to those salts derived from one of the 20 naturally occurring amino acids. The term also include acid and base addition salts of compound of Formula II. Preferred acid addition salts are those of hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate and salts of organic acids such as acetate, lactate, succinate, oxalate, maleate, fumarate, malate, tartrate, citrate, ascorbate, cinnamate, gluconate, benzoate, methane sulfonateand p-toluene sulfonate. Preffered base addition salts are lithium, sodium and potassium salts, alkaline earth salts are magnesium, and calcium salts.

Numerous asymmetric centers may exist in the compounds of the invention. The invention contemplates the various stereoisomers and mixtures thereof.

In another aspect, the invention provides pure 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid.

In this disclosure, pure 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid refer to 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid having the content of 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij]quinoline-2-carboxylic acid or salts thereof 1% or less.

In yet another aspect of the invention there is provided a pharmaceutical composition containing 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido [3,2,1-ij]quinoline-2-carboxylic acid and salts thereof of Formula II in association with a pharmaceutically acceptable excipient and/or carrier.

In yet another aspect of the invention there is provided a pharmaceutical composition containing pure 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H -pyrido[3,2,1-ij]quinoline-2-carboxylic acid in association with a pharmaceutically acceptable excipient and/or carrier.

In the disclosure composition includes a preparation such as solid compositions, liquid compositions or other compositions for oral administration or compositions meant for topical or parenteral or body cavities administration.

Solid composition may be present in the form of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet . Topical composition may be in the form of lotion, cream, ointment, paste, gel, spray, suspension, emulsion, foam, patch, powder or liniment. Parenteral composition may be injection etc.

In yet another aspect, the invention provides a process for preparation of compound 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij] quinoline-2-carboxylic acid and salts thereof of Formula II, wherein the process includes the steps of;
(a) converting compound of Formula III to compound of Formula IV,

b) treating the compound of Formula IV with an amine of formula (R1)(R2)NH and
c) isolating compound of Formula II from the reaction mass thereof.

The compound of Formula II is produced by the reaction of compound of Formula IV with an amine of Formula (R1)(R2)NH, as depicted in scheme 1.

The compound of Formula II can be prepared by treating compound of Formula III with a mixture of acylating agents, such as acetic acid and acetic anhydride and boric oxide at temperature of 120-130 oC, to obtain compound of Formula IV. The compound of Formula IV is further refluxed with an amine of Formula (R1)(R2)NH, in presence of base using an organic solvent. The reaction mass is further stirred with caustic lye for 1 hour. The reaction mass obtained is filtered and pH adjusted with concentrated hydrochloric acid between 5-15 oC and isolating the compound of Formula II from the reaction mass thereof.

The non limiting examples of amine of Formula (R1)(R2)NH include methylamine, dimethylamine, aniline, 4-hydroxypiperidine, 3-methyl-4-hydroxypiperidine, 3-methyl amino-4-hydroxypiperidine, 3,3-dimethyl-4-hydroxypiperidine, 3,5-dimethyl-4-hydroxy piperidine, 4-aminopiperidine, 3-methyl-4-dimethyaminopiperidine, 3,3-dimethy-4-aminopiperidine, 3-methyl-3-ethyl-4-aminopiperidine, 3,3-dimethyl-5-methyl-4-hydroxy piperidine, 3-isopropyl-5-ethyl-4-hydroxypiperidine, 3-isobutyl-5-ethyl-4-hydroxy piperidine, 3-methyl-4-ethylaminopiperidine,3-methyl-4-methylamino piperidine, 3-ethyl-4-aminopiperidine, 3-ethyl-4-methylaminopiperidine, 3-ethyl-4-ethylamino piperidine, 3-ethyl-4-dimethylaminopiperidine, 3,3-dimethyl-4-aminopiperidine,3,3-dimethyl-4-methyl aminopiperidine,3,3-dimethyl-4-ethylaminopiperidine,3,3-dimethyl-4-dimethylamino piperidine,3,3-dimethyl-4-acetamidepiperidine, 3-ethyl,-3-methyl-4-methylamino
piperidine , 3-ethyl-3-methyl-4-dimethylaminopiperidine,3,3-diethyl-4-amino piperidine, 3,5-dimethyl-4-amino piperidine, 3,5-dimethyl-4-methylaminopiperidine, 3,5-dimethyl-4-ethylamino piperidine, 3,5-dimethyl-4-dimethylaminopiperidine, 3,3-dimethy-5-methyl-4-aminopiperidine, 3-ethyl-3-methyl-5-methyl-4-aminopiperidine, 3-ethyl-3-methyl-5-ethyl-4-aminopiperidine.

The non limiting examples of base include triethylamine, 2-(dimethylamino)ethanol pyrrolidone and pyridine.

The non limiting examples of organic solvents include acetonitrile, propionitrile, benzonitrile, glutaronitrile, malononitrile, butyronitrile, adiponitrile, caprinitrile, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, sec-butyl acetate, tert-butyl acetate, isoamyl acetate, isobutyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, methyl iso-butyl ketone, dioxane, tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and mixture thereof.

The invention is further illustrated by the following example which is provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLE-1
Preparation of 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid.
To a mixture of Acetic acid (45.0 Kg) and Acetic anhydride (110.0 Kg) was added boric oxide (14.2Kg). The reaction mass was heated to 125°C and maintained under stirring for 6 hours. (S)-8,9-Difluoro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzoi,j
quinolozine-2-carboxylicacid (64.0 Kg) was charged at 75°C and rewarmed to 125 °C and monitored the reaction to completion. The reaction mass was cooled and vacuum distilled to remove the acetic acid and acetic anhydride. Toluene (400 litre) was charged to the residue and stirred for 2 hours. The solids were collected by filtration and washed with toluene. The wet solid was charged to acetonitrile (300 litre) at room temperature under stirring. The triethylamine (19 Kg) followed by 4-hydroxypiperidine (41.0 Kg) was charged. The reaction mass was heated to reflux. The acetonitrile was recovered completely under vacuum at <60°C. Water (750 litre) and acetonitrile (300 litre) and caustic lye (77.0 Kg) (~50%w/w) were charged to the reaction mass and stirred to completion of reaction. The reaction mass was filtered and pH adjusted with concentrated hydrochloric acid to 7 at ~10°C. The precipitate was filtered and washed with water. The solids were charged in chloroform (1040 litre) and warmed to reflux for 30 minutes and cooled to room temperature. The insoluble mass was filtered out and the clear chloroform layer was washed with dilute dilute hydrochloric acid (~3%) and water. The chloroform was removed by distillation completely. Methanol (1040 litre) was charged and stirred to dissolve the solids. The reaction mass was treated with charcoal and filtered. Methanol was recovered by atmospheric distillation leaving behind 200 litre volume. The reaction mass was stirred at room temperature for 30 minutes and filtered to collect the solids. The wet solid was dried under vacuum to get the titled product.
Yield: 32Kg.
HPLC purity : 99.87%.


EXAMPLE-2
Isolation of (S)-8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetra hydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid.
The pH of mother liquor obtained from the Example-1 was adjusted to 6.5 with sodium carbonate. The solid precipitated out was filtered and suspended in methanol (150 ml). The suspension was warmed to reflux and filtered hot. The solid obtained was dissolved in mixture of methanol:dichloromethane (1:1), (100 ml). The solution was filtered to remove any suspended matter. The filtrate was cooled to 10 oC and the pH was adjusted to 2 using 2-propanol-HCl solution. After stirring for 30 minutes, the precipitated solid was filtered and washed with methyl tert-butyl ether. The solid so obtained was dried under vaccum to get the titled product.
Yield : 2.5 g.
Mass: (m/e): 442.3 (M+1)
HPLC Purity: 99.5 %.
We Claim:

1. A compound of Formula (II),

wherein,
R1 is alkyl, substituted alkyl, aryl, substituted aryl and arylalkyl;
R2 is H, alkyl, substituted alkyl, aryl, substituted aryl and arylalkyl; or
(R1)(R2)N- may combine together to form a structure of formula,

wherein,
X is O, CHR4, NR4 or S;
R3/R3' are the same or different and represent H, alkyl, substituted alkyl, alkylamino, or arylalkyl;
R4 is H, alkyl, alkylamino, dialkylamino, aryl, arylalkyl, trihaloalkyl, -OR5 or NR6R7;
wherein,
R5 is H, alkyl, glycosyl, arylalkyl, alkanoyl, aminoalkanoyl or an acid residue derived from one of the 20 naturally occurring amino acids, or the optically active isomers thereof, or the racemic mixtures thereof, or
R5 is 1-aminocyclohexylcarbonyl; or
R5 is C6H11O6, PO2(CH3)H, PO3H2, PO2(OCH3)H or SO3 H;
R6 is H, alkyl, C3-6 cycloalkyl, arylalkyl, alkanoyl, alkoxycarbonyl, arylalkyloxycarbonyl, aminoalkanoyl or an amino acid residue derived from one of the 20 naturally occurring amino acids or the optically active isomers thereof, or the racemic mixtures thereof; or
R6 is C6H11O6;
R7 is H, alkyl, C3-6cycloalkyl, arylalkyl, alkanoyl, arylalkyloxycarbonyl or aminoalkanoyl; or an amino acid residue derived from one of the 20 naturally occurring amino acids or the optically active isomers thereof, or the racemic mixtures thereof, or
R7 is C6H11O6 and

pharmaceutically acceptable salts thereof.

2. A compound of claim 1, selected from the group comprising of;
8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethyl-4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-isopropyl-5-ethyl-4-hydroxypiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-4-dimethyaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-methyl-3-ethyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-isopropyl-5-ethyl-4-hydroxypiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethyl-4-ethylaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3-ethyl-3-methyl-5-ethyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof;
8,9-Bis(3,3-dimethy-5-methyl-4-aminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof and
8,9-Bis(3-ethyl,-3-methyl-4-dimethylaminopiperidine)-5-methyl-1-oxo-1,5,6,7-tetrahydro pyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof.

3. A pure 9-fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido [3,2,1-ij]quinoline-2-carboxylic acid having the content of 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij]quinoline-2-carboxylic acid and salts thereof 1% or less.

4. A process for preparation of compound 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij] quinoline-2-carboxylic acid and salts thereof of Formula II, wherein the process comprises steps of;
(a) converting compound of Formula III to compound of Formula IV,

b) treating the compound of Formula IV with an amine of formula (R1)(R2)NH and
c) isolating compound of Formula II from the reaction mass thereof.

5. The process of claim 4, wherein a compound of Formula III is converted to compound of Formula IV using acetic anhydride, acetic acid and boric oxide mixture.

6. The process of claim 4, wherein treating the compound of Formula IV with an amine of formula (R1)(R2)NH is carried out in presence of base.
7. A pharmaceutical composition comprising compound 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido[3,2,1-ij] quinoline-2-carboxylic acid and salts thereof of Formula II in association with a pharmaceutically acceptable excipient and/or carrier.

8. A pharmaceutical composition of 9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid having the content of compound 8,9-Bis(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1,5,6,7-tetrahydropyrido [3,2,1-ij]quinoline-2-carboxylic acid or salts thereof of Formula II 1% or less in association with a pharmaceutically acceptable excipient and/or carrier.

9. The pharmaceutical composition of claim 7 or 8, comprises solid compositions, liquid compositions or other compositions for oral administration or compositions meant for topical or parenteral or body cavities administration.

10. The pharmaceutical composition of claim 9, comprises of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet, lotion, cream, ointment, paste, gel, spray, suspension, emulsion, foam, patch, powder, liniment or injection.
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