DESC:The following specification particularly describes the application and the manner in which it is to be performed:
FIELD OF THE INVENTION
The present application provides novel intermediates of Suvorexant and synthetic processes for their preparation.
BACKGROUND OF THE INVENTION
Suvorexant chemically described as [(R)-4-(5-Chlorobenzoxazol-2-yl)-7-methyl-[1,4]diazepan-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)methanone is an antagonist of orexin receptor. It may be structurally represented by the following formula I:

US7951797 discloses suvorexant and process for the preparation wherein 5-methyl-2-(1,2,3-triazol-2-yl) benzoic acid is coupled with 1-benzyloxycarbonyl-5(R)-methyl-1,4-diazepane hydrochloride using EDC, HOAt and NMM to produce benzyl (5R)-5-methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepane-1-carboxylate, which is N-deprotected using H2 over Pd(OH)2/C to obtain (7R)-7-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepane [amine]. Subsequently amine is condensed with 2,5-dichlorobenzoxazole in the presence of triethyl amine to obtain suvorexant (Formula I).
WO2012148533 and Org. Process Res. Dev. 2011, 15, 367-375 (OPRD) discloses 5-Chloro-2-(5-methyl-[1,4] diazepan-1-yl)-benzoxazole (diazepine intermediate) as an intermediate for the synthesis of suvorexant. The preparation of diazepine intermediate is carried out by racemic direct reductive amination of 4-[(2-Amino-ethyl)-(5-chlorobenzoxazol-2-yl)amino]butan-2-one-bis-methane sulfonic acid salt with a reducing agent in the presence of a weak base, followed by chiral resolution. According to OPRD reference, weak base is added to prevent cleavage of benzoxazole moiety under the conditions of reductive amination. (R)-5-Chloro-2-(5-methyl-[1,4] diazepan-1-yl)-benzoxazole is reacted with 5-methyl-2-(1,2,3-triazol-2-yl)benzoic acid after its conversion into corresponding acid chloride, in presence of base to obtain suvorexant.
Org. Lett., Vol. 14, No. 13, 2012 discloses an asymmetric transamination of 4-[(2-amino-ethyl)-(5-chlorobenzoxazol-2-yl)amino]butan-2-one-bis-methane sulfonic acid salt by biocatalytic transamination technology.
Chinese Chemical Letters, 26 (2015), 103-107 disclosed a process for the preparation of (R)-1-benzyl-5-methyl-1,4-diazepane, in which (R)-3-amino butanoic acid is used as a starting material.
There remains a need to provide a novel processes for the preparation of suvorexant (formula I), its related compounds and its intermediates that are simple, economical and commercially viable.
SUMMARY OF THE INVENTION
In the first embodiment, the present application provides a process for the preparation of a compound of formula II or pharmaceutically acceptable salts thereof comprising:
a) reductive amination of a compound of formula V with a compound of formula VI to obtain a compound of formula IV,

b) converting the compound of formula IV to a compound of formula III,

c) reducing the compound of formula III to a compound of formula II,

d) optionally converting formula II into its pharmaceutically acceptable salts.
wherein R may be selected from H or an amino protecting group, R1 is a lower alkyl group and R2 may be selected from H or an amino protecting group.
In the second embodiment, the present application provides a process for preparing a compound of formula IV comprising reductive amination of a compound of formula V with a compound of formula VI to obtain a compound of formula IV:

wherein R, R1 and R2 are as defined above.
In the third embodiment, the present application provides a process for preparing a compound of formula III comprising conversion of a compound of Formula IV to a compound of formula III:

wherein R, R1 and R2 are defined above.
In the fourth embodiment, the present application provides a process for preparing a compound of formula II or pharmaceutically acceptable salts thereof comprising:
a) reducing a compound formula III:

wherein R is as defined above.
b) optionally converting a compound of formula II in to pharmaceutically acceptable salts thereof.
In the fifth embodiment the present application provides, a process for the purification of a compound of formula II or a pharmaceutically acceptable salt thereof comprising:
a) converting a compound of formula II to a pharmaceutically acceptable salt thereof,
b) isolating the resulting salt in pure form,
c) optionally, neutralizing the salt obtained in step b) to obtain pure compound of formula II.
In the sixth embodiment, the present application provides a compound of formula III,

wherein R is as defined above.
In the seventh embodiment, the present application provides a process for the preparation of Suvorexant comprising using a compound of formula III.
DETAILED DESCRIPTION
The term "about" when used in the present application preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1% of its value. For example "about 10" should be construed as meaning within the range of 9 to 11, preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1.
The term "pure" when used in the present application with reference to a compound of formula II refers to a purity of at least about 98% or about 98.5% or about 99% or about 99.5% or about 99.8% or about 99.9% or 100%.
Optionally, in carrying out the processes according to the present application, the reaction product of a given step may be carried forward to the next step without the isolation of the product i.e., one or more reactions in a given process may be carried out in-situ as one pot process optionally in the presence of the same reagent/s used in a previous step wherever appropriate to do so, to make the process of the present application economical and commercially more viable.
Optionally, in carrying out the processes according to the present application, the reaction product of a given step may be isolated and purified by the methods described herein or the methods known to a person skilled in the art before using in a subsequent step of the process.
In the present application, the isolation of products after completion of the reactions may be effected by removing the solvent. Suitable techniques which may be used for the removal of the solvent include evaporation techniques such as a Büchi® Rotavapor®, spray drying, thin film drying, nauta drying, tray drying, freeze drying (lyophilization) or any other suitable technique.
Isolated product may be optionally further dried. Drying may be suitably carried out in a tray dryer, vacuum oven, Büchi® Rotavapor®, air oven, fluidized bed dryer, spin flash dryer, flash dryer, cone dryer, agitated nutsche filter cum dryer, nauta dryer or the like or any other suitable dryer. The drying may be carried out at atmospheric pressure or under reduced pressures at temperatures of less than about 150°C, less than about 100°C, less than about 60°C, less than about 40°C, less than about 20°C, less than about 0°C, less than about -20°C, or any other suitable temperatures. The drying may be carried out for any time period required for obtaining a desired quality, such as from about 15 minutes to several hours.
In different embodiments of the present application, R and R2 in compounds formulae II, III, IV, V and VI represent an amino-protecting group. The term "N-protecting group" or “amino-protecting group” as used herein refers to those groups intended to protect a nitrogen atom against undesirable reactions during synthetic procedures. N-protecting group includes, aryloxycarbonyl such as benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc); alkoxycarbonyl such as methyloxycarbonyl, acetoxycarbonyl, propoxycarbonyl, tert-butyloxycarbonyl (Boc); acyl such as acetyl, propanoyl, iso-butyryl, tert-butyryl, t-butylacetyl, pivaloyl; aroyl groups such as benzoyl; silyl such as trimethylsilyl, ter-butyldimethylsilyl; sulphonyl such as methanesulphonyl, p-tolylsulphonyl; sulphenyl such as 2-nitorphenylsulfenyl; urea; urethane; nitroso; nitro and the like.
In the first embodiment of the present application, in step a) the reductive amination of compound of formula V may be carried out using sodiumborohydride, sodium triacetoxyborohydride, sodium cyanoborohydride or Raney Ni. The reaction may be carried out in the presence or absence of a solvent. The solvent that may be used in the said reaction includes, water; C1-C10 straight or branched chain alcohol such as methanol, ethanol, isopropyl alcohol, 1-butanol, 2-butanol, 2-methyl-2-propanol; ethers such as tetrahydrofuran, 1,4-dioxane, diisopropylether, diethylether, 2-methyltetrahydrofuran, or methyl tert-butyl ether; esters such as ethyl acetate or isopropyl acetate; halogenated solvents such as dichloromethane, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; aliphatic hydrocarbon solvents such as methylcyclohexane, cyclohexane, heptane or hexane; aromatic hydrocarbon solvents such as toluene, o-xylene, m-xylene or p-xylene; dimethyl sulphoxide, amide such as N,N-dimethyl formamide, N,N-dimethyl acetamide or mixtures thereof.
The reaction time should be sufficient to complete the reaction, as is commonly known to one skilled in the art. Typically, the reduction reaction time can vary from about few minutes to several hours. For example the reaction time may be from about 10 minutes to about 24 hours, or any other suitable time period.
The reaction can take place at a temperature of about -20°C to about 150°C, about -10°C to about 100°C, about 0°C to about 30°C, about room temperature, about reflux temperature of the solvent used in the reaction, or any other suitable temperature. Optionally the compound of formula IV may be isolated.
In the first embodiment of the present application, in step b) the compound of formula IV first deprotected and then insitu cyclized to a compound of formula III. The deprotection of compound formula IV for example, when protecting group is alkoxycarbonyl, may be carried out using an acid or base. The acid that may be used includes hydrochloric acid, trifluoacetic acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid or aqueous phosphoric acid. The deprotected compound insitu cyclized to compound of formula III in the presence of a suitable base. The suitable base may be selected from organic or inorganic bases; organic base such as TEA (Triethyl amine), DIPEA (N,N-diisopropylethylamine), DIEA (Diethylamine), pyridine; alkoxides like sodium methoxide or potassium methoxide; or an inorganic base includes, hydroxides of alkali metals such as sodium hydroxide, lithium hydroxide or potassium hydroxide; carbonates of alkali metals such as sodium carbonate or potassium carbonate; bicarbonates of alkali metals such as sodium bicarbonate or potassium bicarbonate.
The reaction may be carried out in the presence or absence of a solvent. The solvent that may be used in the said reaction includes, water; C1-C10 straight or branched chain alcohol such as methanol, ethanol, isopropyl alcohol, 1-butanol, 2-butanol, 2-methyl-2-propanol; ethers such as tetrahydrofuran, 1,4-dioxane, diisopropylether, diethylether, 2-methyltetrahydrofuran, or methyl tert-butyl ether; esters such as ethyl acetate or isopropyl acetate; halogenated solvents such as dichloromethane, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; aliphatic hydrocarbon solvents such as methylcyclohexane, cyclohexane, heptane or hexane; aromatic hydrocarbon solvents such as toluene, o-xylene, m-xylene or p-xylene; dimethyl sulphoxide, amide such as N,N-dimethyl formamide, N,N-dimethyl acetamide or mixtures thereof. Optionally the compound of formula III may be isolated.
In the first embodiment of the present application, in step c) the compound of formula III may be reduced using reducing agent to obtain the compound of formula II. The suitable reducing agent includes, borohydrides such as sodium borohydride, potassium borohydride, lithium borohydride, sodium cyanoborohydride, potassium cyanoborohydride, lithium cyanoborohydride, sodium triacetoxyborohydride, potassium triacetoxyborohydride, also in the presence of suitable additives such as sulfuric acid, methanesulfonic acid, acetic acid, titanium chloride, zinc chloride, cobalt (II) chloride, aluminium chloride, tin chloride, nickel chloride, phosphorus oxychloride, methanesulfonic anhydride, trifluoromethanesulfonic anhydride, pyridine, iodine, trifluoroethanol or 1,2-ethanedithiol; boranes such as borane, diborane or catechol borane, also in the form of complexes with ethers, sulfides or amines such as BH3.SMe2, BH3.Et2O, BH3.THF, BH3-t-butylamine, BH3-dimethylamine or BH3.diethylaniline; silanes such as triethylsilane, diphenylsilane or trichlorosilane, optionally in the presence of one or more Lewis acids, such as trifluoroborane, titanium chloride, aluminium chloride, zinc iodide or trifluoroacetic acid, also in form of complexes with ethers, such as boron trifluoride diethyl etherate; aluminium hydrides such as aluminium hydride (alane), LiAlH4, iBu2AIH, sodium bis(2-methoxyethoxy)aluminium hydride (Red-Al) or LiHAI(OCH3)2, optionally in the presence of one or more Lewis acids, such as trifluoroborane, titanium chloride, aluminium chloride, zinc iodide or trifluoroacetic acid.
The reduction of the compound of formula III to provide the compound of formula II may be carried out in the presence or absence of a solvent. The suitable solvent includes, C1-C10 straight or branched chain alcohol such as methanol, ethanol, isopropyl alcohol, 1-butanol, 2-butanol, 2-methyl-2-propanol; ethers such as tetrahydrofuran, dioxane, diisopropylether, diethylether, 2-methyltetrahydrofuran, cyclopentyl methyl ether or methyl tert-butyl ether; esters such as ethyl acetate, isopropyl acetate; halogenated solvents such as dichloromethane, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; aliphatic hydrocarbon solvents such as methylcyclohexane, cyclohexane, heptane or hexane; aromatic hydrocarbon solvents such as toluene, xylene, 4-chlorotoluene, trifluorotoluene, or mixtures thereof.
The reduction reaction time should be sufficient to complete the reaction, as is commonly known to one skilled in the art. Typically, the reduction reaction time may vary from about few minutes to several hours. For example the reaction time may be from about 10 minutes to about 24 hours, or any other suitable time period.
The reduction of the compound of formula III to provide the compound of formula II may take place at a temperature of about -20°C to about 150°C, about -10°C to about 100°C, about 0°C to about 30°C, about room temperature, about reflux temperature of the solvent used in the reaction, or any other suitable temperature.
Optionally, the steps (a) and (b) of the process according to the first embodiment may be carried out as one-pot without isolation of the product. Optionally, converting compound of formula II into pharmaceutically acceptable salts.
The reductive amination process of the second embodiment may be carried out as per the reaction conditions herein discussed in step a) of the first embodiment.
The process of the third embodiment may be carried out as per the reaction conditions herein discussed in step b) of the first embodiment.
The reduction of compound of formula III of the fourth embodiment may be carried out as per the reaction conditions herein discussed in step c) of the first embodiment.
Step a) of the fifth embodiment involves formation of a pharmaceutically acceptable salt of compound of formula II. The pharmaceutically acceptable salt in step (a) may be inorganic or organic acid addition salt. Inorganic acids for salt formation may be selected from but not limited to hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid. Organic acids for salt formation may be selected from but not limited to formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, fumaric acid and succinic acid. In one variant it may be hydrochloride salt.
The step b) of fifth embodiment, the salt of compound of formula II may be isolated.
Optionally, in step c) of the fifth embodiment, salt obtained in step a) or step b) involves neutralization of salt of compound of formula II in the presence of a base and solvent. The said process involves addition of salt of compound of formula II to a solvent and then adding base. The suitable base includes but not limited to, alkali metal hydroxide such as sodium hydroxide, lithium hydroxide or potassium hydroxide; carbonates of alkali metals such as sodium carbonate, lithium carbonate or potassium carbonate; or bicarbonates of alkali metals such as sodium bicarbonate or potassium bicarbonate or mixtures thereof.
The neutralization may be carried out at atmospheric pressure or under a reduced pressure, at temperatures of less than about 55°C, or less than about 45°C, or less than about 35°C, or any other suitable temperatures. In one variant step (a) may be preferably carried out at room temperature.
The present application further provides intermediate compound of formula III

wherein R is as defined above.
The present application further provides a process for the preparation of Suvorexant by using compound of formula III.
The starting materials used in the present application may be prepared by known methods in the art or may be prepared by the methods disclosed here.
Certain specific aspects and embodiments of the present application will be explained in more detail with reference to the following examples, which are provided for purposes of illustration only and should not be construed as limiting the scope of the present application in any manner.
Example 1: Preparation of tert-butyl (R)-(4-hydroxybutan-2-yl)carbamate

In a round bottom flask (R)-3-aminobutanol (50 gm) and 1,4-dioxane (500 ml) are charged and stirred at room temperature for 10 minutes. The reaction mixture is cooled to 15-20oC and slowly added 5M sodiumhydroxide (125 ml), di-t-butyl dicarbonate (134.5 gm) and DMAP (0.25 gm). Raise the temperature of reaction mixture to 27oC and stirred for 2 hours. Check the TLC, if R-3-aminobutanol still present in the reaction mixture add di-t-butyl dicarbonate (12.3 gm) and stir for 45 minutes. Now charge DM water (1500 ml) and ethylacetate (500 ml) stirred for 15 minutes and separate the layers. Aqueous layer was extracted with ethylacetate (500 ml) and layers were combined and washed with DM water (500 ml). Distilled under vacuum below 50oC to give title product (104 gm).
Example 2: Preparation of tert-butyl (R)-(4-oxobutan-2-yl)carbamate

In a round bottom flask tert-butyl (R)-(4-hydroxybutan-2-yl)carbamate (80 gm), dichloromethane (1200 ml), sodiumbromide (8.71 gm) and DM water (200 ml) are charged at room temperature and stirred for 10 minutes. The reaction mixture is cooled to 5oC and TEMPO (1.65 gm) is added.
In another round bottom flask sodium hypochlorite (37.7 gm) was taken and the pH is adjusted to 9-9.5 using 10% sodiumbicarbonate (1200 ml).
This solution is slowly added drop wise to above reaction mass over period of 1-2 hours and stirred for 30 minutes at 4oC. Raise the temperature of the reaction mass to room temperature and separate the layers. Aqueous layer was extracted with dichloromethane (400 ml) and the layers were combined. Wash with hypo (37.7 gm) and DM water (800 ml). Distilled under vacuum below 50oC to give title product (56.2 gm).
Example 3: Preparation of ethyl (R)-N-benzyl-N-(3-((tert-butoxycarbonyl) amino)butyl) glycinate

In a round bottom flask tert-butyl (R)-(4-oxobutan-2-yl)carbamate (20 gm), methanol (200 ml), acetic acid (12.8 gm) and N-benzylglycine ethylester (18.5 gm) are charged at room temperature. Sodium triacetoxyborohydride (56.4 gm) added slowly lot wise over a period of 35-40 minutes. Maintain the reaction mass at room temperature overnight. Quench the reactions mass with 10% ammoniumchloride (200 ml) solution and distill the organic layer under vacuum below 50oC. The obtained crude was dissolved in ethylacetate (200 ml) and DM water (200 ml) and stirred for 15 minutes. The layers were separated and aqueous layer was extracted with ethylacetate (100 ml) and combine the organic layers. The combined layers were washed with DM water (200 ml) and distill the organic layer under vacuum below 45oC to give title compound as oil (37.2g).
Example 4: Preparation of (R)-4-benzyl-7-methyl-1,4-diazepan-2-one
In a round bottom flask ethyl (R)-N-benzyl-N-(3-((tert-butoxycarbonyl) amino)butyl) glycinate (37 gm) and methanol (185 ml) were taken and stirred for 10 minutes at room temperature. To the reaction mass methanolic hydrochloric acid (370 ml) was added and stirred for one hour at room temperature. The reaction mass was concentrated under vacuum and charged methanol (400 ml). The reaction mass was stirred for 10 minutes at room temperature and sodium methoxide (20.4 gm) slowly added. The reaction mass was heated to 55oC and maintained at this temperature for 1-2 hours. Cool the reaction mass to room temperature and add saturated ammoniumchloride (200 ml) solution. The reaction mass distilled to complete evaporation of methanol to give crude. The crude was dissolved in dichloromethane (800 ml), DM water (400 ml) and stir for 15 minutes at room temperature. Separate the layers and aqueous layer was extracted with dichloromethane (800 ml) and combine the layers. Wash the layers with DM water (400 ml) and distill the organic layer under vacuum to get crude. To the crude heptane (80 ml) was added and stirred for 1-2 hours at room temperature and filter the titled compound (11.5 gm).
1H NMR (400 MHz, CDCl3): d 7.33-7.24 (m, 5H), 5.67 (s, 1H), 3.77-3.74 (d, 2H, J=5.6Hz), 3.69-3.64 (m, 1H), 3.58-3.40 (m, 2H), 3.03-3.0(m, 1H), 2.81-2.74 (m, 1H), 1.89-1.80 (m, 1H), 1.57-1.52 (m, 1H), 1.25-1.23 (d, 3H, J=6.4Hz).

Example 5: Preparation of (R)-4-benzyl-7-methyl-1,4-diazepane
In a round bottom flask (R)-4-benzyl-7-methyl-1,4-diazepan-2-one (11 gm), THF (55 ml) and sodiumborohydride (2.86 gm) were charged under nitrogen atmosphere and stirred for 10-15 minutes at room temperature. Dropwise add BF3.Et2O (14.33 gm in 55 ml of THF) solution to the reaction mixture and stir for 30-45 minutes at 40oC. Raise the temperature to 60oC and maintained for 30 hours. Now cool the reaction mass to 15-20oC and methanol (22 ml), 17%HCl solution (88 ml) slowly over 20-30 minutes. Maintain the reaction mass at 60oC for 4-5 hours and stop maintenance and keep the reaction mass overnight. Now adjust pH to 12-13 with 25% NaOH solution (88 ml) and filter the reaction mass and add ethylacetate (22 ml) and separate the layers. Organic layer was kept aside and aqueous layer was extracted with ethylacetate (22 ml). The layers were combined and wash with DM water (110 ml) followed by NaCl solution (110 ml). Distill the organic layer under vacuum to give (R)-4-benzyl-7-methyl-1,4-diazepane as oil (9.79 gm).
A portion of the above liquid (5.5 gm) was taken in a round bottom flask and cooled to 2oC and Ethanolic HCl (27.5 ml) slowly for 10-15 minutes. Maintain the reaction mass at 6oC for 10 minutes. Slowly raise the temperature to 25oC and maintain for 4 hours. The reaction mass was distilled under vacuum at below 50oC and ethylacetate (18 ml) was added and stirred for 1-2 hours at room temperature. Filter the solid and washed with ethylacetate (11 ml) and dried to give (R)-4-benzyl-7-methyl-1,4-diazepane hydrochloride salt (5.6 gm).
(R)-4-benzyl-7-methyl-1,4-diazepane hydrochloride salt (500 mg) and isopropyl alcohol (2.5 ml) were taken into a round bottom flask and stirred and maintained for 2-3 hours at room temperature. Now filter the solid washed with isopropyl alcohol (1.5 ml) and dry to give (R)-4-benzyl-7-methyl-1,4-diazepane hydrochloride salt (400 mg).
(R)-4-benzyl-7-methyl-1,4-diazepane hydrochloride salt (0.38 gm), DM water (0.8 ml) and dichloromethane (1.9 ml) were taken into a round bottom flask and stirred for 10 minutes at room temperature. Adjust the pH to 12.4 by adding 25% NaOH solution (0.5 ml) and stirred for 10 minutes at room temperature. Separate the layers and organic layer was kept aside and aqueous layer was extracted with dichloromethane (1.9 ml). Combine the organic layers and washed with DM water (1.9ml) and distilled under vacuum at 40oC to give titled product (0.29 gm).
,CLAIMS:We Claim:
1) A process for the preparing a compound of formula II or pharmaceutically acceptable salts thereof comprising:
a) reductive amination of a compound of formula V with a compound of formula VI to obtain a compound of formula IV,

b) converting the compound of formula IV to a compound of formula III,

c) reducing the compound of formula III to a compound of formula II,

d) optionally converting formula II to its pharmaceutically acceptable salts.
wherein R may be selected from H or an amino protecting group, R1 is a lower alkyl group and R2 can be selected from H or an amino protecting group.
2) A process for preparing a compound of formula IV comprising reductive amination of a compound of formula V with a compound of formula VI to obtain a compound of formula IV:

wherein R, R1 and R2 are as defined in claim 1.
3) A process for preparing a compound of formula III comprising conversion of a compound of Formula IV to a compound of formula III:

wherein R, R1 and R2 are as defined in claim 1.
4) A process for preparing a compound of formula II or pharmaceutically acceptable salts thereof comprising:
a) reducing a compound formula III:

wherein R is as defined in claim 1.
b) optionally converting a compound of formula II in to pharmaceutically acceptable salts thereof.
5) A process for the purification of a compound of formula II or a pharmaceutically acceptable salt thereof comprising:
a) converting a compound of formula II to a pharmaceutically acceptable salt thereof,
b) isolating the resulting salt in pure form,
c) optionally, neutralizing the salt obtained in step b) to obtain pure compound of formula II.
6) A compound of formula III,

wherein R is as defined in claim 1.
7) A process for the preparation of Suvorexant comprising converting a compound of formula III to Suvorexant.