Field of the Invention:
The present invention relates to novel crystalline form of 5-fiuoro-3-phenyl-2-[(IS)-l-
(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one compound of formula-1, represented by
the.following structural formula:
Background of the Invention:
Several compounds have been identified as PI3K inhibitors. For example, compounds capable of inhibiting the biological activity of human P.I3K, including 5-fluoro-3-phenyl-2-[(lS)-l-(9H-Purin-6-ylamino)propyl]quinazoIin-4(3H)-one) and their uses are disclosed in U.S. Patent No. 6,518,277, U.S. Patent No. 6,667,300, and U.S. Patent No. 7,932,260.
Each of these references is hereby incorporated herein by reference in its entirety In July 20.4, ZYDELIG (Ide.alisib), a first-in-class inhibitor of POK delta, was approved by the U.S. Food and Drug Administration for the treatment of three B-cell blood cancers.
ZYDELIG has also been approved by the European Commission for two blood cancers, chronic lymphocytic leukemia (CLL) and follicular lymphoma (PL),
International (PCT) Publication No. WO2005/113556 Al discloses quinazolones as mh.bitors of phosphoinositide 3-kinase (PI3K) delta and provides preparation of Idelalisib and related compounds but does not discuss about its polymorphic form.
International (PCT) Publication No. WO2013/134288 Al discloses various crystalline polymorphic forms of Idelalisib, Form I, Form II, Form III, Form IV, Form V, Form VI and
Form VII.

International (PCT) Publication No. WO2015/014315 Al discloses various crystalline polymorphic forms of Idelalisib, Form II, Form III, Form IV, Form V (THF solvate), Form VI (tetrahydrate), Form VII (tert-butyl ether solvate), Form VIII, Form IX and Form X (dioxane
solvate).
International (PCT) Publication No. WO2015/095605 Al discloses hydrochloric acid salt of Idelalisib and its polymorphic forms.
IPCOM000244272D publication discloses the crystalline forms of Idelalisib hydrochloric acid salt.
Brief description of the Invention:
The first aspect of the present invention is to provide a novel crystalline form of 5-
fluoro-3-PhenyI-2-[(lS)-l-(9H-purin.6-ylamino)Propyl]quinazolin-4(3H)-one compound of formula-1 herein after designated as form-M.
The second aspect of the present invention is to provide a process for the preparation of crystalline form-M of 5-fluoro-3-Phenyl-2-[(lS)-l-(9H-purin-6-ylamino)proPyl] quinazolin-4 (3H)-one compound of formula-1.
. . ■ The third aspect of the present invention is to provide a process for the preparation of
amorphous form of 5-fluoro-3-Phenyl-2-[(lS)-l-(9H-Purin-6-ylamino)ProPyl]quinaZolin-4 (3H)-one compound of formula-1.
Brief description of the Drawings:
Figure 1: Illustrates the PXRD pattern of crystalline form-M of 5-fluoro-3-phenyl-2-[(lS)-l-
(9H-Purin-6-ylamino)proPyl]quinazolin-4(3H)-one compound of formula-1.
Figure 2: Illustrates the DSC thermogram of crystalline form-M of 5-fluoro-3-phenyl-2-
[(lS)-l-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one compound of formula-1.
Figure 3: Illustrates the IR spectrum of crystalline form-M of 5-fluoro-3-phenyl-2-[(lS)-l-
(9H-purin-6-ylamino)proPyl]quinazolin-4(3H)-one compound of formula-1.

Detailed description of the Invention:
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point 5 thermal behaviors (e.g. measured by thermogravimetric analysis - "TGA" or differential scanning calorimetry - "DSC"), X-ray powder diffraction (XRPD or powder XRD) pattern mfrared absorption fingerprint, and solid state nuclear magnetic resonance (NMR) spectrum One or more of these techniques may be used to distinguish different polymorphic forms of a compound. 10
Discovering new polymorphic forms and solvates of a pharmaceutical product can prov.de materials having desirable processing properties, such as ease of handling ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New polymorphic forms and
5 solvates of a pharmaceutical^ useful compound or salts thereof can also provide an opportunity to improve the performance characteristics of a pharmaceutical product It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e g better processing or handling characteristics, improved dissolution profile, or improved shelf-life.
3 For at least these reasons, there is a need for additional solid state forms of Idelalisib.
As used herein the term "suitable solvent" used in the present invention refers to "hydrocarbon solvents" such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane cycloheptane, methylcyclohexane, m-, o-, or p-xylene, and the like; "ether solvents" such as ■ chmethoxy methane, tetrahydrofuran, . ,3-dioxane, 1,4-dioxane, furan, diethyl ether ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether d.ethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether 1,2-dimethoxy ethane and the like; "ester solvents" such as methyl acetate, ethyl acetate' ■sopropyl acetate, n-butyl acetate and the like; "polar-aprotic solvents such as d.methylacetamide (DMA), dimethylformamide (DMF), dimethyl sulfoxide (DMSO) N-methylpyrrolidone (NMP) and the like; "chloro solvents" such as dichloro methane

■sobutylketone and the like; "nitrile solvents" such as acetonitrile, propionitrile ■sobutyronitrile and the like; "alcoholic solvents" such as methanol, ethanol, n-propanol' -sopropanoi; n-butanol, isobutanol, ,-butanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoro 5 ethanol, ethylene glycol, 2-methoxyethanol, 1, 2-ethoxyethanol, Methylene glycol 1 2 or 3 pentano., neo-pentyl alcohol, t-pentyl alcohol, diethy.ene glycol monoethylether cyclohexanol or glycerol and the like; "polar solvents" such as water or mixtures thereof.
The first aspect of the present invention provides a novel crystalline form-M of 5-
) ^-o-S-phenyl^Kl^-.^H-purin-Mamino^opylJquinazolin^O^-one compound of formula-1, characterized by its powder x-ray diffraction pattern having peaks at 8 8 .4 8 19.2, 22.5, 23.6, 25.5, 30.0, 30.5 and 32.2 ±0.2 degrees two theta.
The crystalline form-M of 5-fluoro-3-phenyl-2-[(IS)-.-(9H-purin-6-ylamin0)proPyl] qumazolin-4(3H)-one is further characterized by 11.4, 12.6, 13.5, 15.5, .7.4, 18.0 20 1 20 6 22.0, 23.2, 23.7, 25.6, 26.1, 26.9, 28.0, 31.3, 33.4 and 39.4 ±0.2 degrees two theta.
The crystalline form-M of 5-fluoro-3-phenyl-2-[(lS)-l-(9H-purin-6-ylamino)propyl] qmnazolin-4(3H)-one further characterized by powder x-ray diffraction pattern as depicted in
figure 1.
The crystalline form-M of 5-fluoro-3-Phenyl-2-[(lS)-l-(9H-purin-6-ylamino)propyl] qumazo.in^-one further characterized by differentia, scanning ca.orimetry (DSC) thermogram as depicted in flgure-2.
The crystalline form-M of 5-fluoro-3-phenyl-2-[(,S)-,-(9H-purin-6-ylamino)proPyl] qumazol1n-4(3H)-one further characterized by Infrared Spectrum (IR) as depicted in figure-3.
The second aspect of the present invention provides a process for the preparation of
crystalhne form-M of 5-fluoro-3-phenyl-2-[(.S)-l-(9H-pUrin-6-ylamino)propy.]quinazolin-4 (3H)-one compound of formula-1, comprising of:
a) Adding 5-fluoro-3-Phenyl-2-[(lS)-l-(9H-purin-6-ylamino)proPyl]quinazolin-4 (3H)-one compound of formula-1 to a suitable solvent at a suitable temperature,
5
* L-- t~- .•''M I."- ..I-*- TV .-"• .IT--. ;--■-- 1. I T— k I t 1 tr- T ' ..».. ' . j-. ;--_ ..-.■_.- .... . ..... . _

b) stirring the reaction mixture at a suitable temperature,
c) filtering the precipitated solid and drying to get crystalline form-M of 5-fiuoro-3-phenyI-2-[( IS)-1 -(9H-Purin-6-ylamino)propyl]quinazolin-4(3H)-one.
Wherein,
in step-a) the suitable solvent is selected from alcohol solvents, ketone solvents ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile so.vents and polar solvents like water or mixture thereof;
in step-a) and steP-b) the suitable temperature is ranging from 0°C to reflux temperature of
the solvent used in the reaction.
The preferred embodiment of the present invention provides a process for the preparat.on of crystalline form-M of 5-flUoro-3-pheny.-2-r(,S)-,-(9H-purin-6-yropyl]quinazolin-4 (3H)-one compound of formula-1, comprising of:
a) Adding 5-fluoro-3-Phenyl-2-[(lS)-l-(9H-purin-6-ylamino)propyl] quinazolin-4(3H)-one compound of formula-1 to acetonitrile at 25-30°C,
b) stirring the reaction mixture at 25-30°C,
c) filtering the precipitated solid and drying to get crystalline form-M of 5-fluoro-3-pheny l-2-[( 1S)-1 -(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one.
Crystalline form-M of 5-fluoro-3-pheny.-2-[(1S)-.-(9H-purin-6-ylamino)propyl] u-nazohn^-one compound of formula-, obtained according to the present invention is ibstantially free from residual solvents.
The third aspect of the present invention provides a process for the preparation of
norphous form of 5-fluoro-3-phenyl-2-[(lS)-,-(9H-purin-6-ylamino)propyl]quinaZo.in-3H)-one compound of formula-1, comprising of:
a) Dissolving 5-fluoro-3-phenyl-2-[(lS)-l.(9H-purin-6-ylamino)propyl]quinazo,in-4 (3H)-one compound of formula-1 in a suitable solvent
b) stirring the reaction mixture at a suitable temperature,
c) distilling off the solvent completely under reduced pressure,
d) adding a suitable solvent to the compound obtained in step-c),

e) stirring the reaction mixture,
f) filtering the solid and drying to get the amorphous form of 5-f1uoro-3-phenyl-2-[(lS)-l-(9H-purin-6-ylamino)propyl]quinazoIin-4(3H)-one compound of formula-1.
5 Wherein,
in step-a) and d) the suitable solvent is selected from alcohol solvents, ketone solvents ester so.vents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents and polar solvents like water or mixture thereof;
in step-b) the suitable temperature is ranging from 0°C to reflux temperature of the solvent
0 used in the reaction.
The preferred embodiment of the present invention provides a process for the preparafon of amorphous form of 5-fluoro-3-phenyl-2.[(lS>K9H-p„rin-6.ylamino)propy|] quinazohn-4(3H)-one compound of formula-1, comprising of:
5 a) Dissolving 5-fluoro-3-phenyI.2-[(lS)-l-(9H-purin-6-ylamino)proPyl]quinazolin-4
(3H)-one compound of formula-1 in methanol,
b) stirring the reaction mixture at 25-30°C,
c) distilling off the solvent completely under reduced pressure,
d) adding water to the compound obtained in step-(c),
1 e) stirring the reaction mixture,
f) filtering the solid and drying to get the amorphous form of 5-f1uoro-3-phenyl-2-[(lS)-l-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one compound of formula-1.
5-fluoro-3-phenyl-2-[(lS)-l-(9H-Purin-6-ylamino)proPyl]quinazolin-4(3H)-one compound of formula-] produced by the present invention can be further micronized or nulled m a conventiona. techniques to get the desired particle size to achieve desired so.ub.lity profi.e based on different forms of pharmaceutical composition requirements Techmques that may be used for particle size reduction include, but not limited to ball roller and hammer mills, and jet mills. Milling or micronization may be performed before drying, or after the completion of drying of the product.

5-fluoro-3.phenyl.2-[(lS)-l.(9H-pUrin.6-ylamino)propyl]quinazolin-4(3H)-one compound of formula-1 used in the present invention is prepared according to any of the process known in the art.
5 The crystalline form-M and amorphous form of 5-fluoro-3-phenyl-2-[(lS)-l-(9H-
purin-6-ylamino)propyI]quinazolin-4(3H)-one compound of formula-1 obtained according to the present inventions are stable at accelerated and long term stability conditions.
The invention also encompasses pharmaceutical compositions comprising compound 10 of formu.a-1 or salts thereof of the present invention. As used herein, the term "pharmaceutical compositions" or "pharmaceutical formulations" include tablets pills powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.
15 P-XRD Method of Analysis:
PXRD analysis of compounds produced by the present invention were carried out using BRUKER/AXS X-Ray diffractometer using Cu Ka radiation of wavelength 1.5406 A° and continuous scan speed of 0.037min.
0 DSC method of Analysis:
Differential scanning calorimetric (DSC) analysis was performed with Q10 V9 6 Build 290 calorimeter. Samples of about 2 to 3 milligrams held in a closed pan were analyzed at a heating rate of 10° per minute.
5 The process described in the present invention was demonstrated in examples
illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.
Examples: ) Example-l:
Preparation of crystalline form-M of 5-fluoro-3-phe„vl-2-[(lS)-i-(9H-puri„-6-ylami„o) propyl]quinazolin-4(3H)-one (Formula-1)

Acetonitrile (20 ml) was added ,o 5-W3-phenyl-24(.SHK9H-purin-6-ylamino) propyl]quinazo.in-4(3H)-one (1.0 gms) at 25-30°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid, washed with acetonitrile and dried to get the title compound.
Yield: 0.7 gms; M.R: 250-252°C.
The P-XRD pattern of the obtained compound was depicted in figure-1.
ExampIe-2:
Preparation of amorphous form of 5-f]uoro.3-phe„yI.2-[(lS)-l-(9H-Pun„-6-y.ami„o) propyl]quinazolin-4(3H)-one(Formula-l)
Methanol (300 ml) was added to 5-fluoro-3-pheny.-2-r(IS)-l-(9H-purin-6y