KR20040085846A - Novel process for preparing high purity finasteride - Google Patents

Abstract

PURPOSE: Provided are a process for preparing finasteride with excellent therapeutic effect on positive prostatomegaly and male-type alopecia, and intermediate compounds useful for the preparation of finasteride. CONSTITUTION: The process for preparing finasteride represented by the formula (I) is prepared by the process comprising the steps of: reacting a compound of the formula (II) with 2,2'-dithiobis(benzothiazole) to produce a reactive derivative compound of the formula (III) and then reacting the compound of the formula (III) with t-butylamine or reacting a compound of the formula (IV) with mercapto benzothiazole to produce an intermediate compound of the formula (V); and converting the compound of the formula (V) obtained in the preceding step into an intermediate compound of the formula (VI) and then heating the compound of the formula (VI) in an organic solvent to dehydrogenate.

Description

Novel process for preparing high purity finasteride

The present invention relates to a novel process for the preparation of finasterides and to intermediate compounds of novel chemical structures useful in the production of finasterides.

Finasteride is a 4-aza steroid compound of the following structural formula (I) (17β- (Nt-butylcarbamoyl) -5α-4-aza-andro-1--1--3-one based on androstene) ), The drug shows excellent therapeutic efficacy against benign prostatic hyperplasia and androgenetic alopecia.

(I)

Prostatic hyperplasia and masculine alopecia are expressed by the binding of an excess of 5α-dihydrotestosterone (DHT) with the androgen receptor. This 5α-dihydrotestosterone is obtained from testosterone, where testosterone 5α-reductase is directly involved in converting testosterone to 5α-dihydrotestosterone. Finasteride is an inhibitor of testosterone 5α-reductase, which inhibits the conversion of testosterone to 5α-dihydrotestosterone in plasma and cells, thereby drastically lowering DHT concentrations and rapidly restoring prostates or increasing hair. The drug is not only potent, but also very well tolerated, and most of the side effects are mild and temporary. Furthermore, it is the only oral product among the two hair loss treatments approved by the US FDA so far.

Method for preparing finasteride is disclosed in US Patent No. 4,760,071 and Korean Patent Registration No. 1990-0001206. Looking at this in detail with reference to Scheme (1), Reactivity by reacting the starting material 3-oxo-4-aza-5α-androstan-17β-carboxylic acid (2) with 2,2'-pyridyl disulfide After conversion to pyridylthio ester (3) as a derivative, it was reacted with t-butylamine to prepare 17β-t-butylcarbamoyl compound (4), and dehydrogenation of the azasteroid by benzene selenide anhydride method to obtain the desired finasteride ( It is characterized by manufacturing 1).

However, in the above method, the 2,2′-pyridyl disulfide used for the preparation of the pyridylthio ester compound (3), which is a reactive derivative in the first step, is an expensive reagent, which puts a considerable burden on the production cost. The disadvantage is that it is uneconomical for industrial use.

In particular, various methods have been disclosed to solve the problem of converting the carboxy group of the 17β-position to t-butyl carbamoyl is difficult electronically and steric.

Documents describing the introduction of t-butylcarbamoyl at the 17β-position are described. A method of introducing butylcarbamoyl is disclosed, which has the advantage of proceeding to the next reaction without separating the intermediate acid chloride, but it is difficult to handle and pollutes the environment due to the use of highly toxic thionyl chloride. Has

Meanwhile, U.S. Patent Nos. 5,468,860, 5,652,365 and European Patent 599,376 disclose t-butylaminomagnesium halides by reacting organic magnesium halides with t-butylamine and then reacting them with 17β-carboalkoxy compounds to achieve 17β-t A method of preparing butylcarbamoyl is disclosed. This method uses an organic magnesium halide that is extremely sensitive to moisture, and thus has to be reacted under anhydrous conditions, thereby preventing mass production.

In addition, International Patent Application No. PCT / ESOO / 0239 discloses a method for producing 17β-t-butylcarbamoyl by reacting lithium t-butylamide with 17β-carboalkoxy compound, which is used as a reaction reagent. Lithium t-butylamide, which is highly flammable, needs to be synthesized directly under difficult conditions, and requires special care in handling.

European Patent No. 271,200 discloses a method of introducing 17β-t-butylcarbamoyl by converting 17β-carboxy group to hydroxybenzothiazolyl ester or imidazolide and then reacting with t-butylamine. In the case of hydroxy benzothiazolyl esters, it is not easy to remove hydroxy benzothiazole which has fallen off after the acylation reaction from the reaction solution, resulting in a lower purity of the target product obtained, and in the case of imidazolide Since the imidazolide in the form is easily decomposed to moisture, there is a problem that the reaction solvent or the reaction environment must proceed with the reaction in which water is completely excluded.

In addition, the process of dehydrogenating 17 (beta) -t- butyl carbamoyl compound (4) and converting it to finasteride (1) which is a target compound as a 3rd step process in reaction formula (1) is made using expensive benzene selenide anhydride. It was found that the yield was poor and the content of impurities was large. In addition, there is a problem that the use of selenium catalyst, which is uneconomical and very expensive and highly toxic, such as the use of column chromatography for separation of the final product.

Therefore, in order to secure this disadvantage, a process of forming a double bond by dehydrogenating positions 1 and 2 is also disclosed in various methods to solve the problem.

For example, European Patent No. 298,652, US Patent No. 5,084,574, US Patent No. 5,116,983 and Korean Patent Registration No. 1996-0015038 disclose methods for introducing Δ ¹ double bonds by reacting with silylating agents in the presence of quinones. This method also discloses an expensive oxidizing agent (2,3-dichloro-5,6-dicyano-1,4-benzoquinone; DDQ) and an expensive silylating agent (bistrimethylsilylfluoroacetamide; BSTFA). There is a disadvantage that it is not suitable for mass production by using and obtaining the desired product through a complicated process.

In addition, U. S. Patent No. 5,091, 534, EP 428, 366 and EP 473, 225 disclose reaction with a silylating agent in the presence of a base and then introduce a halogen at position 2 and a strong base (e.g., potassium-t-butoxide). (potassium tert-butoxide; t-BuOK), tetrabutylammonium fluoride, 1,8-diazabicyclo [5.4.0] -7-ene (1,8-diazabicyclo [5.4.0] -7 -ene; DBU) and 1,5-diazabicyclo [4.3.0] non-5-ene (1,5-diazabicyclo [4.3.0] none -5-ene; is reacted with DBN)) △ ¹ double bond The method of introducing the present invention is disclosed, and these methods also have a high content of various impurities such as impurities (1) (EP regulation: impurity A) having the following chemical structure in which unstable halogen groups self-decompose by using strong bases. Low (e.g., for Example 1 of European Patent 428,366, crude yield: 80.2%, purity: 78.8% purification yield: 60.2%, purity: 98%), Given that the yield has the disadvantage that the overall yield of introducing a double bond reduced to 48%.

(One)

J. Med. Chem , 1984, Vol . 27 , No. 12, 1690, disclose a method for dehydrogenating a 3-oxo-4- azasteroid compound by a complex five step method comprising sulfinate intermediates. Looking at this in detail with reference to Scheme (2), after reacting the compound (2) of the starting material with dimethyl sulfate to prepare a compound (3) protected with an amide group, a strong base (lithium diisopropylamide) LDA), reacted with diphenyl disulfide under the conditions of -78 ° C.) to introduce a phenyl sulfide group at position 2, deprotect the amide group under strong acid conditions, and prepare a sulfinate compound (4) using an oxidizing agent. It is then characterized in that the target compound (1) is prepared by heating.

However, this method involves difficult reaction conditions and unnecessary steps to protect and remove amide groups to introduce Δ ¹ double bonds, and consists of a five-step complex process that is not only economically feasible for industrial use but also mass production. There are disadvantages that are difficult to apply to.

As described above, the conventional finasteride manufacturing method has a problem of burdening manufacturing costs or polluting the environment by using expensive or highly toxic reagents, in particular, it is not easy to remove by-products, so the purity of the target product is reduced, Mass production is difficult by using reagents or active derivatives which are easily decomposed to moisture.

Accordingly, the inventors of the present invention have studied the method for preparing finasteride which can be easily produced in high purity and high yield under mild conditions, excluding the disadvantages of the prior art, and by using a novel and stable benzothiazolyl reactive derivative t-butyl carbamoyl can be introduced more easily, and a new intermediate compound in which benzothiazole which is separated in the process of introducing t-butyl carbamoyl is substituted with an iodine group can be easily obtained. The present invention has been completed by finding that finasteride, which is the target compound of the present invention, can be obtained in high purity and high yield by heating in a solvent to dehydrogenation.

It is an object of the present invention to provide a novel process for preparing finasteride that exhibits excellent therapeutic efficacy against benign prostatic hyperplasia and masculine alopecia and an intermediate compound of novel chemical structure useful for the preparation of the compound.

In order to achieve the above object, the present invention

Novel Reactivity by Reacting 2-iodine-3-oxo-4-aza-5α-androstan-17β-carboxylic acid of Structural Formula (II) as Starting Material with 2,2′-dithiobis (benzothiazole) A benzothiazolyl 2-iodine-3-oxo-4-aza-5α-androstan-17β-thiocarboxylate of the following structural formula (III) as a derivative is produced, and then reacted with t-butylamine to form a novel intermediate compound. To form 17β- (Nt-butylcarbamoyl) -2-benzothiazolylthio-4-aza-5α-androstan-3-one of formula (V) or to a compound of formula (IV): mercapto benzo Reacting with thiazole to produce the compound of formula (V); And

Converting the compound of formula (V) obtained in the above step into a new intermediate compound of formula (VI), which is a sulfinate compound, in the presence of an oxidant, and then performing a third step of heating in an organic solvent to dehydrogenate continuously. It provides a process for preparing finasteride of the following structural formula (I).

(Ⅰ)

(Ⅱ)

(Ⅲ)

(Ⅳ)

(Ⅴ)

(Ⅵ)

The present invention is also characterized by providing compounds of the formulas (III) and (V) having novel chemical structures as intermediates useful in the preparation of finasteride, and methods for their preparation.

Hereinafter, the manufacturing process of the present invention will be described in detail by the following scheme.

The preparation process of the present invention may be chemically synthesized by the method shown in the following scheme, but is not limited to this example, and may be prepared by appropriate changes of reagents and starting materials known to those skilled in the art.

Preparation Step 1: Preparation of Benzothiazolyl 2-iodine-3-oxo-4-aza-5α-androstan-17β-thiocarboxylate of formula (III)

As shown in Scheme (3) below, the compound of formula II was prepared according to the method described in EP 473,225 (Example 6) under 2,2′-dithiobis (benzothiazole) under basic conditions. And benzothiazolyl 2-iodine-3-oxo-4-aza-5α-androstan-17β-thiocarboxylate of the following structural formula (III) which is a novel reactive derivative.

Specifically, 2-iodine-3-oxo-4-aza-5α-androstan-17β-carboxylic acid, 2,2′-dithiobis (benzothiazole) and triphenylphosphine of formula (II) After suspending in a suitable organic solvent, triethyl amine was slowly added thereto and reacted for 3 to 4 hours at room temperature to filter the crystals thus formed, thereby obtaining a high yield (93% or more) of the compound of formula (III). Can be.

In this case, the amount of 2,2'-dithiobis (benzothiazole) and triphenylphosphine may be used in an amount of 1.0 to 2.0 equivalents, preferably 1.1 to 1.2 equivalents, based on 1 equivalent of the compound of formula (II).

Moreover, as a base which can be used for the said reaction, triethylamine, a pyridine, etc. are preferable, and triethylamine is more preferable. In this case, the amount of the base used is 1.0 to 3.0 equivalents, preferably 1.0 to 1.5 equivalents based on 1 equivalent of the compound of formula (II).

In addition, as the organic solvent usable in the reaction, a conventional one can be used.

Preparation Step 2: Preparation of 17β- (N-t-butylcarbamoyl) -2-benzothiazolylthio-4-aza-5α-androstan-3-one of formula (V)

As shown in the following Reaction Scheme (4), the benzothiazole which is separated while converting the reactive derivative of Structural Formula (III) obtained from the production process (1) in the presence of t-butylamine is a novel compound substituted with an iodine group (V) A compound can be prepared.

Specifically, the compound of formula (III), which is a reactive derivative, is suspended in an appropriate organic solvent, and then t-butylamine is added to react at room temperature for 4 to 5 hours, and water is added, followed by filtering the resulting crystals. The compound of V) can be prepared in high yield (85% or more).

In this case, the amount of t-butylamine used is 1.0 to 10.0 equivalents, preferably 3.0 to 5.0 equivalents, based on 1 equivalent of the compound of formula (III).

In addition, examples of the organic solvent usable in the reaction include carbon chlorides such as dichloromethane, chloroform and 1,2-dichloroethane; Ethers such as tetrahydrofuran and dioxane; Ketones such as methyl isobutyl ketone; Nitriles such as acetonitrile; And one or more selected from the group consisting of amides such as dimethylacetamide and dimethylformamide, and particularly preferably a solvent capable of reacting the reactants in a homogeneous state.

In the reaction, the reaction temperature is 0 to 50 ℃, preferably 25 to 35 ℃, the time required to complete the reaction may vary depending on the reaction temperature, the amount of base used, but approximately 3 to 6 hours is sufficient.

In addition, the compound of formula (V), which is a novel intermediate compound, may be prepared by another manufacturing process.

Looking specifically at this with reference to Scheme (5), 17β- (Nt-butylcarbamoyl) -2-iodine-4-aza-5α-andro of the following formula (IV) which is a compound disclosed in European Patent No. 473,225 By reacting stan-3-one with mercapto benzothiazole under basic conditions, the compound of formula (V) can be readily prepared in quantitative yield.

The base usable in the reaction is preferably triethylamine, pyridine, sodium bicarbonate, sodium carbonate, potassium carbonate, and the like, more preferably potassium carbonate. The amount used is 1.0 to 5.0 equivalents, preferably 2.0 to 3.0 equivalents based on 1 equivalent of the compound of formula (IV).

Further, the amount of mercapto benzothiazole used is 1.0 to 2.0 equivalents, preferably 1.1 to 1.2 equivalents, relative to 1 equivalent of the compound of formula (IV).

Preparation Process 3: Preparation of Finasteride of Structural Formula (I)

As shown in the following Reaction Scheme (6), the compound of Structural Formula (V) obtained from the second manufacturing process is converted into a novel compound of the following Structural Formula (VI) which is a sulfinate compound in the presence of an oxidizing agent, and then heated in an organic solvent to dehydrate. By extinguishing, the finasteride of the following structural formula (I) as a target compound can be prepared.

Specifically, the compound of formula (V) obtained from the second production process is dissolved in a suitable organic solvent and then reacted with an oxidizing agent to synthesize a sulfinate compound, which is then heated in a suitable organic solvent and then cooled to produce a crystal. By filtration, finasteride as a target compound can be efficiently produced in high yield (75% or more) without undergoing a purification step such as column chromatography.

The oxidizing agent that can be used at this time, m-chloroperbenzoic acid (m-CPBA), peroxyacetic acid (peroxyacetic acid), trifluoroperacetic acid, permaleic acid, sodium bromate (NaBrO ₃ ), Sodium hypochlorite (NaOCl), hydrogen peroxide, sodium periodate (NaIO ₄ ), iodosomethylbenzene and iodosobenzene (C ₆ H ₅ IO) are preferred, and more preferably Preferably m-chloroperbenzoic acid.

In this case, the amount of oxidizing agent used is 1.0 to 1.5 equivalents, preferably 1.1 to 1.2 equivalents, respectively, relative to 1 equivalent of the compound of formula (V).

Moreover, as an organic solvent which can be used, Aromatic hydrocarbons, such as benzene, toluene, xylene, etc. which can deposit the target material finasteride; Esters such as isopropyl acetate; Ethers such as isopropyl ether, methyl t-butyl ether and dioxane; And ketones, such as methyl isobutyl ketone; It is preferable that it is selected from the group which consists of, More preferably, it is toluene or diisopropyl acetate.

According to the production method of the present invention, t-butyl carbamoyl can be introduced more easily by using a novel and stable benzothiazolyl reactive derivative of formula (III), and is separated from the process of introducing t-butyl carbamoyl. The compound of formula (V), which is a novel intermediate compound in which benzothiazole is substituted with iodine group, can be easily obtained, and after deoxidation by heating in an organic solvent through an oxidation process, the reaction solution is cooled and filtered to obtain high yield and high purity. You can get Pinasteride (above 98%).

In particular, the above mentioned reaction scheme (2), including the unnecessary reaction conditions (strong base (LDA), low temperature (-78 ℃)) and unnecessary steps for the introduction of Δ ¹ double bonds and unnecessary steps are included and Compared with the prior art, which consists of a complex process, the production method of the present invention is a process that is quite simple, economical and mass-producible. In addition, a method of introducing a halogen at position 2 and reacting with a strong base (t-BuOK) to introduce a Δ ¹ double bond (Example 1 of European Patent No. 428,366) includes impurities in which an unstable halogen group is self-decomposed (EP regulation: While various impurities are produced, including impurity A), the yield is low as 48% including the purification step, but the present invention can prevent the generation of impurities in advance by using no strong base, and crystals formed in the reaction solution. By filtering, finasteride can be obtained in high yield (75%) and high purity (98% or more) without purification process such as column chromatography.

Hereinafter, the present invention will be described in more detail with reference to Examples, which are only intended to assist in understanding the configuration and operation of the present invention, and the scope of the present invention is not limited to these Examples.

Reference example. Preparation of 2-iodine-3-oxo-4-aza-5α-androstan-17β-carboxylic acid (II) (see Example 6 of European Patent 473,225)

100 g (0.31 mol) of 3-oxo-4-aza-5α-androstan-17β-carboxylic acid was dispersed in 2 L of toluene, and then 189 mL (4 equivalents) of tetramethylene ethylenediamine was added, and 117.5 mL of trimethylsilyl chloride ( 3 equivalents) was slowly added dropwise to the reaction solution. After the reaction solution was stirred at room temperature for 1 hour, the reaction solution was cooled to 0 ° C., and then 157.4 g (2 equivalents) of iodine was slowly added dropwise to the reaction solution, followed by stirring for 3 hours under cooling. After the reaction was completed, 1L of 10% sodium thiosulfate solution was added dropwise to the reaction solution, stirred at room temperature for 4 hours, and the resulting crystals were filtered and washed sequentially with water, toluene, acetonitrile, and washed with 100 ml of desired white color. 120 g (yield: 86.9%) of the title compound were obtained.

¹ H-NMR (300 MHz, ¹ H-NMR CDCl ₃ ) δ 12.0 (Brs, 1H), 7.74 (s, 1H, NH), 4.81 (dd, 1H), 3.07 (dd, 1H), 2.57 (dd, 1H ), 2.33 (t, 1H), 2.08-2.01 (m, 3H), 1.70-1.67 (m, 4H), 1.40-0.92 (m, 9H), 0.86 (s, 3H), 0.70 (s, 3H)

Example 1 Preparation of Benzothiazolyl 2-iodine-3-oxo-4-aza-5α-androstan-17β-thiocarboxylate (III)

120 g of 2-iodine-3-oxo-4-aza-5α-androstan-17β-carboxylic acid, 107.7 g (2,2′-dithiobis (benzothiazole)) and triphenyl in 1.5 L of methylene chloride 85 g (1.2 equiv) of phosphine was added and then stirred. A solution obtained by diluting 45.2 ml of triethylamine in 120 ml of methylene chloride was slowly added thereto, followed by stirring at room temperature for 3 hours. The resulting solid was filtered, washed with 300 ml of methylene chloride, and dried in a hot air to obtain 150 g (yield: 93.4%) of the title compound as pale yellow.

Melting Point: 187 ℃ ~ 188 ℃

¹ H-NMR (300 MHz, ¹ H-NMR CDCl ₃ ) δ 8.02 (d, 1H), 7.92 (d, 1H), 7.46 (m, 2H), 5.57 (brs, 1H), 4.78 (t, 1H), 3.22 (dd, 1H), 2.77 (t, 1H), 2.60 (t, 1H), 0.89 (s, 3H), 0.77 (s, 3H)

Example 2. Preparation of 17β- (N-t-butylcarbamoyl) -2-benzothiazolylthio-4-aza-5α-androstan-3-one (V)

To 1.5 L of dimethyl formamide was added dropwise 150 g of benzothiazolyl 2-iodine-3-oxo-4-aza-5α-androstan-17β-thiocarboxylate obtained in Example 1, followed by t-butylamine 132.6 at room temperature. ML (5 equiv) was added dropwise and stirred for 4 h. The reaction mixture was lowered to 0 ° C to 5 ° C and 3L of water was added to the reaction solution to form a solid. After stirring for 30 minutes, the mixture was filtered, washed with 500 ml of water, and then with 500 ml of isopropyl ether, and then air-dried to obtain 118.8 g (yield: 88%) of the title compound as light white crystals.

Mass: m / z = 540.4 (M + l), 307.7. 172.4

Melting Point: 102 ℃ ~ 104 ℃

¹ H-NMR (300 MHz, ¹ H-NMR CDCl ₃ ) δ 7.86 (d, 1H), 7.78 (d, 1H), 7.43 (t, 1H), 7.34 (t, 1H) 5.75 (s, 1H), 5.05 (s, 1H), 4.32 (m, 1H), 3.22 (dd, 1H), 3.41 (dd, 1H), 2.52 (m, 1H), 2.16 (m, 1H), 1.35 (s, 9H) 1.07 (s , 3H), 0.71 (s, 3H)

Example 3. Preparation of 17β- (N-t-butylcarbamoyl) -2-benzothiazolylthio-4-aza-5α-androstan-3-one (V)

50 g (0.17) of β- (Nt-butylcarbamoyl) -2-iodine-4-aza-5α-androstan-3-one (compound of formula (IV) prepared with reference to Example 3 of European Patent No. 473,225) mol), 18.4 g (1.1 equivalents) of mercapto benzothiazole and 27.6 g (2 equivalents) of potassium carbonate were dispersed in 750 ml of acetone and then heated at a temperature of 60 ° C. to 70 ° C. for 3 hours. The reaction solution was distilled under reduced pressure to remove the solvent, and 1 liter of water was added thereto, followed by extraction twice with 300 ml and 100 ml of methylene chloride. The organic layer was washed with 300 ml of water, dried over anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure distillation to give 53.44 g (yield: 99%) of the title compound.

Mass, melting point and ¹ H-NMR obtained the same analysis results as in Example 2.

Example 4. Preparation of 17β- (N-t-butyl) -4-aza-5α-androst-1-en-3-one (I; finasteride)

118.8 g (0.22 mol) of 17β- (Nt-butylcarbamoyl) -2-benzothiazolylthio-4-aza-5α-androstan-3-one was dissolved in 1.2 L of methylene chloride, and the reaction solution was cooled to 0 ° C. 54.2 g (1.1 equiv) of m-chloroperbenzoic acid (77%) were added thereto, followed by stirring at the same temperature for 3 hours. The reaction solution was washed twice with 1 L of saturated sodium bicarbonate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure distillation to obtain a foamy sulfoxide compound. Then, 356 ml of toluene was added to the residue, which was then warmed to 100 ° C. and stirred at the same temperature for 3 hours. The reaction solution was slowly cooled to room temperature and then stirred overnight. The resulting crystals were filtered and the crystals thus obtained were dispersed in 600 ml of IPA (Isopropyl alcohol), stirred for 30 minutes, and the insoluble materials were filtered off through celite, and 1.8 L of water was added thereto. After stirring for 1 hour, the mixture was filtered to give 61.5 g (yield: 75%) of the title compound (pinasteride) as white crystals.

Melting Point: 250 ℃

Purity: 99.3% (HPLC)

¹ H-NMR (300 MHz, ¹ H-NMR CDCl ₃ ) δ 6.82 (d, 1H), 5.81 (d, 1H), 5.49 (brs, 1H), 5.10 (brs, 1H), 3.34 (ddd, 1H), 2.21 (t, 1H), 2.01 (m, 2H), 1.80-1.60 (m, 7H), 1.34 (s, 9H), 1.50-1.26 (m, 5H), 1.07-1.00 (m, 3H), 0.98 ( s, 3H), 0.71 (s, 3H)

According to the production method of the present invention, t-butyl carbamoyl can be introduced more easily by using a novel and stable benzothiazolyl reactive derivative, and benzothiazole which is released in the process of introducing t-butyl carbamoyl is iodine Intermediate compounds having a novel chemical structure substituted with a group can be easily obtained, and high yield and high purity finasteride can be obtained by heating and dehydrogenating in an organic solvent through an oxidation process. In addition, the manufacturing method of the present invention is simple to process, economical to use industrially, and can be used for mass production of finasteride.

Claims (8)

Reacting a compound of the following structural formula (II) as a starting material with 2,2'-dithiobis (benzothiazole) to produce a compound of the following structural formula (III) which is a novel reactive derivative, and then reacting with t-butylamine Generating a compound of formula (V) by producing a compound of formula (V) which is a novel intermediate compound or reacting a compound of formula (IV) with mercapto benzothiazole; And The compound of formula (V) obtained in the above step in the presence of an oxidizing agent is converted into a novel intermediate compound of formula (VI), followed by heating in an organic solvent to dehydrogenation, characterized by the following formula (I) Method for preparing finasteride: (Ⅰ) (Ⅱ) (Ⅲ) (Ⅳ) (Ⅴ) (Ⅵ) The method according to claim 1, wherein the 2,2'-dithiobis (benzothiazole) is used in an amount of 1.0 to 2.0 equivalents based on 1 equivalent of the compound of formula (II). The method according to claim 1, wherein the t-butylamine is used in an amount of 1.0 to 10.0 equivalents based on 1 equivalent of the compound of formula (III). The method of claim 1 wherein the oxidizing agent is m-chloroperbenzoic acid, peracetic acid, trifluoroperacetic acid, permaleic acid, sodium bromite, sodium hypochlorite, hydrogen peroxide, sodium periodate, iodosomethylbenzene and io Process for the production, characterized in that selected from the group consisting of dosobenzene. The method according to claim 1, wherein the oxidizing agent is used in an amount of 1.0 to 1.5 equivalents based on 1 equivalent of the compound of formula (V). The organic solvent of claim 1, wherein the organic solvent is selected from aromatic hydrocarbons such as benzene, toluene and xylene; Esters such as isopropyl acetate; Ethers such as isopropyl ether, methyl t-butyl ether and dioxane; And ketones such as methyl isobutyl ketone; characterized in that it is selected from the group consisting of. In the process for preparing finasteride, the compound of formula (III) having the novel chemical structure: (Ⅲ) In the process for preparing finasteride, the compound of formula (V) having the novel chemical structure: (Ⅴ)