The Quinolin-2(1H)-one derivative is a heterocyclic compound having a specific substituent or substituents is known as an active ingredient that has serotonin uptake inhibitory activity (or serotonin re-uptake inhibitory activity) in addition to dopamine D2 receptor partial agonistic activity (D2 receptor partial agonistic activity), serotonin 5-HT2A receptor antagonistic activity (5-HT2A receptor antagonistic activity), and adrenaline α1 receptor antagonistic activity (α1 receptor antagonistic activity). This active ingredient has a wide therapeutic spectrum for central nervous system diseases (particularly schizophrenia). In the pharmaceutical field, the development of pharmaceutical preparations that are suitable according to the severity of disease in various patients in need of treatment, patient predisposition, and other factors, has been desired.
Brexpiprazole, which is a Quinolin-2(1H)-one derivative, having the chemical name 7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one a compound of formula I has been approved under the trade name Rexulti® as an Tablet, oral having the following dosage forms 0.25 MG, 0.5 MG, 1 MG, 2 MG, 3 MG, 4 MG.

U.S. Pat. No. 7,888,362 B2 (U.S. Pat. No. '362) discloses Brexpiprazole and its pharmaceutically acceptable salts. U.S. Pat. No. '362 discloses the following scheme for the preparation of Brexpiprazole.
wherein X, Lg represents a halogen atom or a group, which causes a substitution reaction the same as in halogen atom.
The key intermediates in the preparation of Brexpiprazole are 7-Hydroxyquinoline-2(1H)-one a compound of formula II and 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride of formula IV. One of the intermediate in the preparation of Brexpiprazole, 7-Hydroxyquinoline-2(1H)-one a compound of formula II was synthesized from Journal of Medicinal Chemistry Volume 58 Issue 14 Pages 5561-5578, WO 2014085284 A1, WO 2012003418 A2, WO 2002002108 A1 wherein discloses the preparation of Formula II by the reaction of N-(3-methoxyphenyl)cinnamamide with aluminum chloride at reflux temperature.
The provided prior art processes involves higher temperatures for the cyclization reaction as well as involves class 2 solvents, such as chlorobenzene, which have limitations in the use of these solvents as per the FDA ICH guidelines.
CN 104844585 A discloses the following scheme for the preparation of Brexpiprazole:

CN 104447723 A discloses the following scheme for the preparation of Brexpiprazole:

The present inventors have followed the above provided process and observed that if DDQ used in the final stages of the reaction impurities are formed, which are difficult to be removed and in turn results in low yield and low purity of the obtained product.
Another key intermediate involved in the preparation of Brexpiprazole is 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride and was synthesized as follows:
wherein X is a leaving group.
However the above reaction involves in the formation of dimer of formula X as impurity during the condensation of compound of formula XI and XII.

U.S. Pat. No. '362, WO 2007026959 A2, WO 2008047883 A1, JP 4540700 B2, JP 4785881 B1, Organic Process Research & Development, Volume: 19, Issue: 4, Pages: 555-558, CN 104529998 A, WO 2015054976 A1, CN 104829602 A, CN104892589 A discloses the reaction of 1-(benzo[b]thiophen-4-yl)piperazine with conc. hydrochloric acid, wherein the purity of the obtained 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt is low with significant amount of dimer impurity, which inevitably decreases the yield of final compound i.e., Brexpiprazole.
Further the prior art processes discloses the column purification methods to increase the purity of Brexpiprazole, however it is not commercially and industrially feasible.
U.S. Pat. No. 9,206,169 B2 (U.S. Pat. No. '169) discloses the preparation of 1-(benzo[b]thiophen-4-yl)piperazine by reacting compound of formula XI and XII in the presence of (a) a palladium compound and a tertiary phosphine or (b) a palladium carbene complex, in an inert solvent or without a solvent in order to suppress the by-product impurity. However, the process is not economical and cost-effective as the used palladium complexes are not easily available. Further after the reaction, the removal of by-products is not easy.
US 20150087655 A1 discloses Brexpiprazole dihydrate, anhydride and its process for the preparation thereof.
CN 104844586 A discloses Brexpiprazole amorphous form and its process for the preparation thereof.
CN 104829603 A discloses Brexpiprazole hydrochloride monohydrate and process for the preparation, wherein designated as Form A.
Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Thus, in the strict sense, polymorphs are different crystalline structures of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules”. Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Infrared spectrometry (IR).
Brexpiprazole and its hydrochloride salt can exist in different polymorphic forms which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation. However, there is still a need for novel crystalline forms, which are more stable, reproducible and free of other polymorphic forms.
In view of the above the present inventors have now found a polymorph of Brexpirpazole hydrochloride, which is stable, having high purity and can be used as an intermediate in the preparation of Brexpiprazole.
Further the present inventors have observed that by incorporating these prior art processes the obtained yields of intermediates are low with the formation of by-products which thereby led to the low yields and low purity of Brexpiprazole.
Further there is a need for the improved, cost-effective, industrially applicable process for the preparation of Brexpiprazole having high yields and purity.
The present inventors have now found a process for preparation of Brexpiprazole, which resolves above referred issues and industrially suitable.