MX2008007151A

MX2008007151A - Processes for the preparation of modafinil and analogs thereof

Info

Publication number: MX2008007151A
Application number: MXMX/A/2008/007151A
Authority: MX
Inventors: R Duchek John; Liang Sidney; J Schaefer Carl
Original assignee: R Duchek John; Liang Sidney; Mallinckrodt Inc; J Schaefer Carl
Priority date: 2005-12-09
Filing date: 2008-06-04
Publication date: 2008-09-02

Abstract

The present invention generally relates to an improved process for preparing modafinil and analogs thereof. The process minimizes impurities and improves the overall yield by oxidizing a modafinil intermediate compound in a reaction mixture including an alcohol and an organic acid at a ratio of from about 1:1 to about 80:1 (by volume).

Description

PROCESSES FOR THE PREPARATION OF MODAFINIL AND ANALOGS OF THE SAME FIELD OF THE INVENTION The present invention relates in general to processes prepared to improve modafinil and analogs thereof. More specifically, the processes include the oxidation of a modafinil intermediate compound and a reaction mixture including an alcohol and an organic acid, BACKGROUND OF THE INVENTION Modafinil, also known as benzhydrylsulfinylacetamide or 2- [(diphenyl) sulfinyl] acetamide, corresponds to the structure: Modafinil is a derivative of synthetic acetamide and exerts a wake-promoting effect. Modafinil has been approved by the Food and Drug Administration of the United States for use in the treatment of excessive daytime sleepiness associated with narcolepsy. Synthetic preparations of modafinil and similar compounds were first described by Lafon in U.S. Patent No. 4,177,290 ('290). Ref .: 191520 The compounds were described as possessing useful pharmaceutical activity on the central nervous system. In Example 1 of 290, modafinil was prepared by reacting the benzhydrylthioacetic acid with thionyl chloride to produce the benzhydrylthioacetyl chloride. The chloride was then converted to benzhydrylthioacetamide by reaction with ammonia in methylene chloride. The sulfur atom of benzhydrylthioacetamide was then oxidized with hydrogen peroxide in the presence of acetic acid to produce modafinil. The example of '290 describes an alternative synthetic method for the production of modafinil on an industrial scale. According to this process, benzhydrol is reacted with thiourea to form a compound that is subsequently hydrolyzed to benzhydrithioacetic acid. The acid is then oxidized with hydrogen peroxide in a mixture of chloroacetic acid and water. The resulting modafinil sulfoxide intermediate is treated with dimethyl sulfate to methylate the carboxylic acid group, and the resulting ester is derivatized with ammonia to produce modafinil. In the processes described by Lafon in (? 290), the sulfide atoms in the modafinil intermediary compounds, namely, benzhydrylthioacetamide and benzhydrylthioacetic acid, are oxidized with hydrogen peroxide. This oxidation process is carried out in acetic acid to solubilize modafinil intermediate compounds. Singer et al., However, described in U.S. Patent No. 6,849,120 that this process tends to over-oxidize the sulfur atom to produce the sulfone impurity, benzhydrylsulfonyl acetamide: The over-oxidation of the sulfur to sulfone atom occurs relatively consistently and strongly, particularly near the end of the reaction. In addition, the sulfone impurity, benzhydrylsulfonylacetamide, is not easily removed from the pure modafinil product, resulting in high levels of impurities and reduced overall yield. In addition to over-oxidation, the use of substantial amounts of glacial acetic acid during the oxidation process is undesirable, due to handling problems with the associated materials. For example, the management of glacial acid waste after oxidation requires relatively large amounts of base and relatively long periods of time to safely neutralize. In U.S. Patent No. 6,849,120, Singer et al. described a process for the preparation of modafinil with purity = 99.5% after a simple recrystallization. The process comprised the oxidation of 2- [(diphenylmethyl) thio] acetamide (for example, benzhydrylthioacetamide) with hydrogen peroxide in the presence of a mineral acid (preferably sulfuric acid) and a linear, branched or cyclic alcohol, or a phase transfer. An inert liquid organic medium (such as methanol), ethanol, and ethylene glycol) was also used as a diluent for the oxidation reaction. Singer et al., Described the contacting of 2- [(diphenylmethyl) thio] acetamide with about 1.5 to about 4 molar equivalents of hydrogen peroxide. The mineral acid was described as present only in a catalytic amount, preferably from about 0.002 to about 0.2 molar equivalents with respect to acetamide. The alcohol or phase transfer catalyst was described as being used in an amount of about 2 to about 4 equivalents with respect to acetamide. While this process is generally effective in the production of modafinil, there are a number of associated problems of performance and material handling in the use of relatively toxic sulfuric acid as a preferred mineral acid. The volume of water and sodium bisulfite necessary to neutralize the highly acidic mineral acid, can tend to negatively affect productivity (for example, water and bisulfite dilute the reaction mixture, reducing the yield and the additional volume of reagents occupy reactor space, affecting the manufacturing economy). In addition, the use of the phase transfer catalysts in the reaction mixture can result in the presence of difficult to remove metallic impurities in the final product. There is a need for methods of producing modafinil and analogues thereof, wherein the presence of impurities is minimized. It may be particularly necessary to provide an improved process for the synthesis of modafinil and analogs thereof, which substantially minimizes the over-oxidation of the sulfur atom to sulfone and provides a highly pure modafinil product before recrystallization. In addition, it would be desirable to provide a process for producing modafinil and analogs thereof that minimize the use of acetic acid and other dangerous or toxic reagents in the oxidation reaction.

BRIEF DESCRIPTION OF THE INVENTION Among the various aspects of the present invention is the provision of a process for the preparation of modafinil and analogues thereof. More specifically, the process involves the oxidation of a modafinil intermediate compound in a mixture of reagents. The process minimizes the over-oxidation of the sulfur atom to sulfone, thereby minimizing impurities and improving overall performance. The process also uses relatively small amounts of an organic acid, compared to known methods. In summary, therefore, the present invention is directed to a process for the preparation of modafinil or analogs thereof, the process comprising: oxidizing an ordinary modafinil compound in a reaction mixture comprising an alcohol, an organic acid, and an oxidizing agent; and recovering modafinil or analogs thereof from the reaction sample; wherein the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 80: 1 (by volume); the modafinil intermediate compound corresponds to formula (1): A-S-Y (1); The recovered modafinil or the analogue thereof corresponds to the formula (10): or A-S-Y (10).

A is substituted alkyl, substituted aryl, substituted heteroaryl, or a substituted or unsubstituted tricyclic ring; and Y is hydrocarbyl or substituted hydrocarbyl. Other objectives and characteristics will be partly apparent and partly signaled later in the present.

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to a process for the preparation of modafinil and analogs thereof. The process includes oxidation of a modafinil intermediate compound in a reaction mixture that includes an alcohol, an organic acid and an oxidizing agent, wherein the alcohol and the organic acid are present in the reaction mixture at a ratio of about 1. : 1 to approximately 80: 1 (in volume). It has been found that by oxidizing a modafinil intermediate compound in a reaction mixture including an alcohol and an organic acid at these proportions, the over-oxidation of the sulfur atom to sulfone is reduced to a minimum, and modafinil or analogs thereof can be recovered from the reaction mixture having high purity before recrystallization. Modafinil and analogs thereof can be prepared according to the process of the present invention correspond in general to formula (10): O A-S-Y (10). wherein A is substituted alkyl, substituted aryl, substituted heteroaryl, or a substituted or unsubstituted tricyclic ring; and Y is hydrocarbyl or substituted hydrocarbyl. The process for producing modafinil and analogues thereof described above comprises the oxidation of a modafinil intermediate compound corresponding to formula (1): in a reaction mixture comprising an alcohol, an organic acid and an oxidizing agent, wherein A and Y are as defined above. The oxidation of the modafinil intermediate compound corresponding to formula (1) to produce modafinil and analogs thereof, corresponding to formula (10), proceeds in general according to Reaction Scheme 1: Reaction Scheme 1 O I I - s Y ^ ~ A S Y 1) alcohol: organic acid '' 2) oxidizing agent * ' The designation "alcohol: organic acid" in the various reaction schemes herein, refers to a ratio of the alcohol to the organic acid in the reaction mixture according to those described herein (for example from about 1: 1 to about 80: 1 (by volume). modafinil intermediates can be oxidized according to the process of the present invention to produce modafinil and analogs thereof according to Reaction Scheme 1. In one embodiment, A is an alkylene substituted with two phenyl groups and Y is - (CH2) -C (= 0) -Yi, where Yi is hydrocarbyl, hydroxyl, halo, alkoxy, or amino According to this embodiment, the intermediate compound of modafinil corresponds to Formula (2): and the recovered modafinil or the analogue thereof corresponds to the formula (20): where Yi is as defined above.

In a preferred embodiment, Yi is -NH2-. According to this embodiment, the intermediate compound of modafinil is benzhydrylthioacetamide (2A): and the recovered modafinil or the analogue thereof is modafinil (200): The modafinil intermediate compound, benzhydrylhoacetamide (2A) can be produced according to various processes, such as those described in U.S. Patent Nos. 4,177,290, 4,098,824, and 4,066,686 to Lafon; Patent of the United States No. 6,875,893 to Largeu et al .; U.S. Patent No. 6,649,796 to Naddaka et al., And WO2004 / 075841 and WO2005 / 042479 to Liang, each of which are incorporated by reference herein. To produce benzhydrylthioacetamide (2A), several of these references first describe the formation of a benzhydrylthiouronium salt (A) from the reaction of the benzhydrol, thiourea, and an acid (typically a hydrogen halide such as HCl or HBr), as illustrated in Reaction Scheme 2: Reaction Scheme 2 where X ~ is the counter ion of the corresponding acid. The aforementioned references then describe different synthesis routes that use the benzhydrylthiouronium salt (A) to reach the end of the modafinil intermediate compound, benzhydrylhoacetamide (2A), which can then be oxidized according to the process of the present invention. Reaction Scheme 3 (a) - (d) illustrate the various synthetic routes by which benzhydrylhoacetamide (2A) can be synthesized from the benzhydrylthiouronium salt (A). Reaction Scheme 4 illustrates the oxidation of benzhydrylhoacetamide (2A) to produce modafinil (200) according to the process of the present invention.

Reaction Scheme 3 (a) - (d¡ Reaction Scheme 4 As noted above, when the modafinil intermediate compound corresponds to formula (2), Yi may also be hydrocarbyl, hydroxyl, halo, or alkoxy.

According to this embodiment, modafinil intermediates may correspond to Formulas (2B), (2C), or (2D), which illustrate benzhydrylthioacetic acid, benzhydrylthioacetyl halide, or alkyl benzhydrylthioacetate, respectively.

Reaction Schemes 5-8 illustrate the processes for producing modafinil (200), wherein the intermediate modafinil (2B), (2C), (2D) intermediates are oxidized according to the process of the present invention to produce various modafinil-sulfoxide intermediates. In Reaction Schemes 5-8, the general processes for producing various intermediate compounds are the same or similar to those shown in Reaction Schemes 3 (a) - (d), the only difference being that the oxidation step according to the present invention is carried out in different steps (for example, as described at the beginning) in the synthesis process. After oxidation, the modafinyl sulfoxide intermediates can then be optionally derivatized to produce modafinil (200).

Reaction Scheme 5 halide NH3 10 Reaction Scheme 6 Reaction Scheme 7 Reaction Scheme 8 1) alcohol: organic acid 2) oxidizing agent In various other embodiments, modafinil analogs can also be produced according to the process of the present invention by oxidation of a modafinil intermediate compound in a reaction mixture comprising an alcohol, an organic acid and a oxidizing agent, wherein the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 80: 1 (by volume). In one embodiment, the modafinil intermediate compounds correspond to formula (3): the recovered modafinil or the analogue thereof corresponds to the Formula (30): Ari and Ar2 are each independently selected from aryl or heteroaryl of 6 to 10 carbon atoms; wherein each of Ai or Ar2 can be independently optionally with 1-3 substituents independently selected from: a) H, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, -CF3, -N02, -OH, -0R7, -0 (CH2) PNR9 Rio, -OC (= 0) R7, -OC (= 0) NR9R10, -0 (CH2) POR8, -CH2OR8, -NR9R10, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH2ORn; c) -NR8C (= 0) NR9R? o, -NR8C (= S) NR9R10, -C02R? 2, -C (= 0) R? 3, -C (0) NR9R? O, -C (= S) NR9R? 0, -CH = N0Ri2, -CH = NR7, - (CH2) PNR9R10, - (CH2) pNHRu, -CH = NNR12R12A, -C (-NR8) NR8AR8B, NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) pS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -0R7, -CH2OR8, -NR9R10, -0- (CH2) p-OH, -S- (CH2) p-OH, -Xi (CH2) POR7, -Xj. (CH2) PNR9R10, -Xi (CH2) PC (= 0) NR9R? O, -Xi (CH2) PC (= S) NR9R10, -Xi (CH2) POC (= 0) NR9R10, -Xi (CH2) PC02R8. -Xi (CH2) PS (0) XR7, -XXS (CH2) PNR8C (= 0) NR9R? 0, -C (= 0) R? 3, -C02R? 2, -OC (= 0) R7, -C (= 0) NR9R? O, -OC (= 0) NR? 2Ri2A, 0- 1 et rahidropi rani lo, C (= S) NR9R? Or, -CHNNR12R12A, -CHNOR12, -CHNR7, CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= O) NR9R10, -NR8C (= S) NR9R10, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR12RI2A, -P (= 0) (0R8) 2, -OR11, and a monosaccharide of 5 to 7 carbon atoms where each hydroxyl group of the monosaccharide is independently either unsubstituted or it is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or -0-C (= 0) R7; Xi is -0-, -S-, or -N (R8) -; Z is selected from alkylene of 1 to 4 carbon atoms, -C (R?) (R2) -, arylene of 6 to 10 carbon atoms, heteroarylene, cycloalkylene of 3 to 8 carbon atoms, heterocyclylene, -0-, -N (R8) -, -S (0) y, -CR9A = CR8B-, -CH = CH-CH (R8) -, -CH (R8) - CH = CH-, or -C = C-; Ri, R2, R3 and R4 are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, -OH, and -CH (R6) -CONR8AR8B; or R3 and R, together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclyl ring; R is hydrogen, alkyl of 1 to 4 carbon atoms, or the side chain of an α-amino acid; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; R8, R8A and RβB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; R9 and Rio are each independently selected from H, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or R9 and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclyl ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and R12A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or Ri2 and RI? A, together with the nitrogen atom to which they are bound, form a heterocyclyl ring of 5-7 members; Ri3 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; m is O, 1, 2 or 3; n is 0, 1, 2 or 3; p is 1, 2, 3 or 4; t is 2, 3 or 4; and y is O, 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to formula (4): the recovered inil fashion or the analogue thereof corresponds to the Formula (40): Ari and Ar2 are each independently selected from thiophene, isothiazole, phenyl, pyridyl, oxazole, isoxazole, thiazole, imidazole, and other five or six membered heterocycles comprising heteroatoms of 1-3 atom of -N-, -O-, or -S-; Ri, R2, R3 and R4 are each independently selected from hydrogen, lower alkyl, -OHi -CH (R6) -C0NR6AR6B, or any of Ri, R2, R3 and R4 can be taken together to form a carboxylic or heterocyclic ring of 3-7 members; and each of Ari or Ar2 can be independently optionally substituted with one or more substituents independently selected from: a) H, aryl, heterocyclyl, F, Cl, Br, I, -CN, -CF3, -N02, -OH, - OR, -0 (CH2) pNR9R? O, -OC (= 0) R7, -OC (= 0) NR9R? 0, -0 (CH2) pOR8, -CH2OR8, -NR9R? O, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH20Rn, wherein Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; c) -NR8C (= O) NR9R? 0, -NR8C (= S) NR9R? 0, -C02R12, -C (= 0) Ri2, -C (= 0) NR9R? o, -C (= S) NR9R ? 0, -CH-NOR12, -CH-NR7, - (CH2) NR9R? O, - (CH2) pNHRn, or CH-NNR? 2R? 2A, wherein Ri2 and Ri2A are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, -OH, alkoxy of 1 to 4 carbon atoms, -OC (= 0) R7, -OC (= 0) NR9R? 0, -OC (= S) NR9R? 0, -0 (CH2) pNRgRio, -0 (CH2) POR8, arylalkyl substituted or unsubstituted having 6 to 10 carbon atoms, and substituted or unsubstituted heterocyclylalkyl; d) -S (0) and R? 2, - (CH2) pS (0) and R7, -CH2S (0) and Ru where y is 0, 1 or 2; and e) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkinyl of 2 to 8 carbon atoms, where: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is substituted with 1 to 3 groups selected from aryl of 6 to 10 carbon atoms, heterocyclyl, arylalkoxy, heterocycloalkoxy, hydroxylalkoxy, alkyloxy alkoxy, hydroxyalkylthio, alkoxy-alkylthio, F, Cl, Br, I, -CN, -N02, -OH, -OR7, -X2 (CH2) PNR9R? O, -X2 (CH2) PC (= 0) NR9R? 0, -X2 (CH2) pC (= S) NRgR? O, -X2 (CH2) P0C (= 0) NR9R10, -X2 (CH2) PC02R7 > -X2 (CH2) pS (0) and R7, -X2 (CH2) PNR8C (= 0) NR9R? O, -0C (= 0) R7, -OC (= 0) NHR12, O-tetrahydropyranyl, -NR9R? 0, -NR8C02R7, -NR8 (C = 0) NR9R? 0, -NR8C (= S) NR9R10, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -C02R? 2, -C (= 0) NR9R? 0, -C (= S) NR9R? 0, -C (= 0) Ri2, -CH2OR8, -CH = NNR? 2Ri2A, -CH = N0Ri2, -CH = NR7, -CH = NNHCH (N = NH) NH2, -S (= 0) 2NR? 2R? 2A, -P (= 0) (0R8) 2, -ORu , and a monosaccharide of 5 to 7 carbon atoms where each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkylcarbonyloxy of 2 to 5 carbon atoms, or alkoxy of 1 to 4 carbon atoms, where X2 is 0, S, or NR8; wherein R7 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclyl; R8 is hydrogen or alkyl having 1 to 4 carbon atoms; p is 1, 2, 3 or 4; and wherein 1) R9 and Rio are each independently hydrogen, unsubstituted alkyl of 1 to 4 carbon atoms, or substituted alkyl; or 2) R9 and Rio together form a linking group of the Formula - (CH2) 2-X? ~ (CH2) 2-, wherein Xi is selected from -0-, -S-, and -CH2-, In yet another embodiment, the modafinil intermediate compound corresponds to Formula (5): the recovered modafinil or the analogue thereof corresponds to the Formula (50): X is a bond, -CH2CH2-, -O-, S (0) y-, -N (R8) -, -CHN (R8) -, -CH = CH-, -CH2-CH = CH-, C ( = 0), -C (R8) = N-, -N = C (R8) -, -C (= 0) -N (R8) -, or -NR8-C (= 0) -; The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with a oxygen atom, nitrogen or sulfur; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein ring A and ring B can each be independently substituted with 1-3 substituents selected from: a) hydrogen, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, - CF3, -N02, -OH, -OR7, -0 (CH2) P NR9R? O, -0C (= 0) R7, -OC (= 0) NR9R? O, -0 (CH2) P0R8, -CH2OR8, - NR9R10, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH2ORn; c) -NR8C (= O) NR9R? 0, -NR8C (= S) NR9R? 0, -C02Ri2, -C (= 0) R? 3, -C (= O) NRgR? 0, -C (= S) NR9R10, -CH = NOR? 2, -CH = NR7, - (CH2) PNR9R10, - (CH2) pNHR?, -CH = NNR12R? 2A, -C (= NR8) NR8AR8B- NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 6 carbon atoms, alkenyl of 2 8 carbon atoms or alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -OR7, -CH2OR8, -NRgRio, -O- (CH2) P-OH, -S- (CH2) P-OH, -Xi (CH2) POR7, X? (CH2) PNR9R? O, -Xi (CH2) ) PC (= 0) NR9R10, -Xx (CH2) PC (= S) NR9R? 0, -X? (CH2) POC (O) NR9R10, -Xi (CH2) PC02R8, -Xx (CH2) PS (O) R7, -X? (CH2) pNR8C (= 0) NR9R? O, -C (= 0) R13, -C02R? 2, -OC (= 0) R7, -C (= 0) NRgRio, -OC (= 0) NR? 2Ri2A. O-tetrahydropyranyl, -C (= S) NR9R? 0, -CH = NNR? 2R? 2A, -CH = N0RX2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C ( = O) NRgR? 0, -NR8C (= S) NR9R? 0, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, - S (0) and R7, -S (= 0) 2NR12R? 2A, -P (= 0) (0R8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently is unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or -0-C (= 0) R7; R3 and R4 are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, -OH, -CH (R6) -C0NR8AR8B, or R3 and R4, together with the nitrogen atom to which they are bonded, form a ring heterocyclic 3-7 members; Re is hydrogen, alkyl of 1 to 4 carbon atoms, or the side chain of an α-amino acid; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Rs, RTA and RβB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; Rg and Rio are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or Rg and R10 together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and RI2A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or R12 and R? 2A, together with the nitrogen atom to which they are linked, form a 5-7 membered heterocyclic ring; R13 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; Xi is -O-, -S-, or -N (R8) -; Z is selected from alkylene of 1 to 4 carbon atoms, arylene of 6 to 10 carbon atoms, heteroarylene, cycloalkylene of 3 to 8 carbon atoms, heterocyclylene, -O-, -N (R8) -, -S (0) y, -CR8A = CR8B -, -CH = CH-CH (R8) -, -CH (R8) -CH = CH-, or -C = C-; m is O, 1, 2 or 3; n is 0, 1, 2 or 3; p is 1, 2, 3 or; q is 0, 1 or 2; t is 2, 3 or 4; and y is 0, 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to Formula (6): the recovered modafinil or the analogue thereof corresponds to the Formula (60): Ri and Ar2 are each independently selected from aryl of 6 to 10 carbon atoms or heteroaryl; wherein each of Arx or Ar can be independently optionally substituted with 1-3 substituents independently selected from: a) hydrogen, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, -CF3 , -N02, -OH, -OR7, -0 (CH2) P NRgRio, -OC (= 0) R7, -OC (= 0) NR9R? O, -0 (CH2) POR8, -CH2OR8, -NR9R? 0, -NR8S (= 0) 2R7, -NR8C (= 0) R7 , or -NR8C (= S) R7; b) -CH20Rn; c) -NR8C (= O) NR9R10, -NR8C (= S) NR9R? or, -C02R? 2, -C (= 0) R? 3, -C (= 0) NR9R? o, -C (= S) ) NR9R? 0, -CH = NOR12, -CH = NR7, - (CH2) pNR9R? O, - (CH2) pNHR?, -CH = NNR12R12A, -C (= NR8) NR8AR8B-NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 6 carbon atoms, alkenyl of 2 8 carbon atoms or alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms. carbon, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH, -0R7, -CH2OR8, -NR9R? or, -0- (CH2) P-0H, -S- (CH2) P-0H, -Xx (CH2) P0R7, X? (CH2) PNR9R? Or, -X? (CH2) pC (= O) NR9R10, -Xi (CH2) pC (= S) NR9R10, -X? (CH2 ) POC (0) NR9R? O, -Xx (CH2) PC02R8, -Xx (CH2) PS (0) R7, -X1 (CH2) pNR8C (= 0) NR9R? O, -C (= 0) R13, - C02R? 2, -0C (= 0) R7, -C (= O) NRgR? 0, -OC (= 0) NR? 2Ri2A, O-tetrahydropyranyl, -C (= S) NR9R10, -CH = NNR? 2R ? 2A, -CH = NOR? 2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= O) NR9R? 0, -NR8C (= S) NR9R? 0, - NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR? 2R? 2A, -P (= 0) (0R8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms carbon, alkoxy of 1 to 4 carbon atoms or -0-C (= 0) R; Xi is -0-, -S-, or -N (R8) -; J is alkylene of 2 to 4 carbon atoms or Q-C0-; Q is alkylene of 1 to 3 carbon atoms; R2A is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R 4A is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Re? RßA and RdB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to carbon atoms; Rg and Rio are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or Rg and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and R12A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or Ri2 and R? 2ñ, together with the nitrogen atom to which they are bound, form a 5-7 membered heterocyclic ring; Ri3 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; p is 1, 2, 3 or 4; q e s 0, 1 or 2; t s 2, 3 or 4; and y is 0, 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to Formula (7): the recovered modafinil or analogous thereof corresponds to Formula (70): X is a bond, -CH2CH2-, -O-, S (0) y-, -N (R8) -, -CHN (R8) -, -CH = CH-, -CH2-CH = CH-, C ( = 0), -C (R8) = N-, -N = C (R8) -, -C (= 0) -N (R8) -, or -NR8-C (= 0) -; The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with an oxygen, nitrogen or sulfur atom; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein ring A and ring B can each be independently substituted with 1-3 substituents selected from: a) hydrogen, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, - CF3, -N02, -OH, -0R7, -0 (CH2) P NR9R? O, -OC (= 0) R7, -OC (= O) NRgR? 0, -0 (CH2) POR8, -CH2OR8, -NR9R? 0, -NR8S (= 0) 2R7, -NR8C (= 0 ) R7, or -NR8C (= S) R7; b) -CH2ORn; c) -NR8C (= O) NRgR? 0, -NR8C (= S) NR9R? 0, -C02R? 2, -C (= 0) Ri3, -C (= 0) NR9R? o, -C (= S) ) NR9R? 0, -CH = NORi2, -CH = NR7, - (CH2) pNR9R? O, - (CH2) pNHRn, -CH = NNR? 2R? 2A, -C (= NR8) NR8AR8B- NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 6 carbon atoms, alkenyl of 2 8 carbon atoms or alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -OR7, -CH2OR8, -NR9R? 0, -O- (CH2) P-OH, -S- (CH2) P-OH, -Xi (CH2) POR7, X? (CH2) PNR9R? O, -X ! (CH2) pC (= O) NR9R10, -Xi (CH2) PC (= S) NR9R? 0, -X? (CH2) POC (0) NRgR? O, -Xi (CH2) PC02R8, -Xx (CH2) ) PS (O) R7, -X? (CH2) pNR8C (= 0) NR9R? O, -C (= 0) R? 3, -C02R? 2, -OC (= 0) R7, -C (= 0) ) NR9R? O, -OC (= 0) NR12R12A, O-tetrahydropyranyl, -C (= S) NR9R? 0, -CH = NNR12R? 2A, -CH = NORi2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= 0) NR9R? Or, -NR8C (= S) NR9R? 0, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR? 2R? 2A, -P (= 0) (OR8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon or -0-C (= 0) R7; J is alkylene of 2 to 4 carbon atoms or Q-C0-; Q is alkylene of 1 to 3 carbon atoms; R2 is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R 4A is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Rβ RTA and RβB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; R9 and Rio are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or Rg and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and RI2A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or R 2 and R 2A, together with the nitrogen atom to which they are bound, form a 5-7 membered heterocyclic ring; R 3 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R 7, -C (= 0) NR 9 R 0, or -C ( = S) NR9R? 0; Xi is -O-, -S-, or -N (R8) -; p is 1, 2, 3 or; q is 0, 1 or 2; t is 2, 3 or 4; Y and is O, 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to Formula (8): The recovered modafinil or analogous thereof corresponds to the Formula (80): The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with an oxygen, nitrogen or sulfur atom; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein the rings are optionally substituted with one to three R20 groups; X is not present, it is a bond, 0, S (0) and, NR10, alkylene of 2 carbon atoms, alkenylene of 2 to 3 carbon atoms, C (= 0), C (R2p2NR10, C (R2p = N , N = C (R2p, C (= 0) N (R10), or NR10C (= O), wherein the alkylene and alkenylene groups are optionally substituted with one to three R20 groups, R is hydrogen or alkyl of 1 to 6 carbon atoms; Y is selected from: a) (C 1-6 -alkylene) -R 1; b) (C 1-6 -alkylene) -R 2; c) (C 1-4 -alkylene) ) mZ- (alkylene of 1 to 4 carbon atoms) n-R1; d) (alkylene of 1 to 6 carbon atoms) - e) alkyl of 1 to 6 carbon atoms substituted with one to two OR21 groups; and f) CH2CR21 = C (R21) 2; wherein the alkyl and alkylene groups are optionally substituted with one to three R20 groups; Z is O, S (0) y, CR21 = CR21, C = C (R21) 2, C = C, arylene of 6 to 10 carbon atoms, heteroarylene of 5-10 O members, cycloalkylene of 3 to 6 carbon atoms carbon, or 3-6 membered heterocycloalkylene; wherein the arylene, heteroarylene, cycloalkylene and heterocycloalkylene groups are optionally substituted with one to three R20 groups; R1 is selected from NR12R13, C (= 0) R15, C02R, OC (= 0) Rn, C (= 0) NR12R13, C (= 0) NR21OR14 C (= NRn) NR12R13, NR21S (0) 2R, S (0) 2NR12R13, NR21S ( 0) 2NR12R13, and PO (OR21) 2; R2 is 5-6 membered heteroaryl, wherein the heteroaryl group is optionally substituted with one to three R20 groups; R10 and R10? at each occurrence they are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, C (= 0) R15, and S (0) and R14; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, and arylalkyl; wherein the alkyl, aryl and arylalkyl groups are optionally substituted with one to three R20 groups; R15 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, arylalkyl, and heteroaryl; in wherein the alkyl, aryl, arylalkyl, and heteroaryl groups are optionally substituted with one to three R20 groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OR21, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, spirocycloalkyl of 3 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3 to 7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, = 0, C (= 0 ) R22, C02R21, 0C (= 0) R22, C (= 0) NR23R24, NR21C (= 0) R22. NR21C02R22. OC (= 0) NR23R24, NR21C (0) R22, NR21C (= S) R22, and S (0) and R22; R21 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R23 and R24, together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring; R25 in each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and y is 0, 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to Formula (9): the recovered modafinil or the analogue thereof corresponds to the Formula (90): Ar is aryl of 6 to 10 carbon atoms substituted with 0-5 R3; cycloalkenyl of 5 to 10 carbon atoms substituted with 0-5 R3; or a 5- to 14-membered heteroaryl group substituted with 0-5 R3, wherein the heteroaryl group comprises one, two or three heteroatoms selected from nitrogen, oxygen sulfur or selenium; Y is alkylene of 1 to 6 carbon atoms substituted with 0-3 R20A; R1 is selected from H, C (= 0) NR12R13, C (= N) NR12R13, OC (= 0) NR, 1i2¿pR1I 3 NR iS (= 0) 2NR > 112Z pR13, 'a ri l de 6 carbon atoms) -NR12R13 wherein the aryl is substituted with 0-3 R2p NR21C (= 0) R14, C (= 0) R14, C (= 0) OR, 0C (= 0) Rn, and NR21S (= 0) 2R; R2 is selected from hydrogen, F, Cl, Br, and OR16, OR25, NR17R18, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, C (= 0) R16, C (= 0) 0R16, 0C (= 0) R16, C (= 0) NR17R18, NR15C (= 0) R16, NR15C02Rld, OC (= 0) NR17R18, NR15C ( = S) R16, SR16; S (= 0) R16; and S (= 0) 2R16; alternatively, two R2 groups can be combined to form a methylenedioxy group, an ethylenedioxy group or a propylenedioxy group; R3 is selected from hydrogen, F, Cl, Br, I, OR16, OCF3, OR25, NR17R18, NHOH, N02, CN, CF3, CH2OR16, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3-7 members, phenyl, heteroaryl of 5 or 6 members, aplalkyl of 7 to 10 carbon atoms, C (= 0) R16, C (= 0) OR16, OC (= 0) R16, C (= 0) NR17R18, NR15C (= 0) R16, NR15C02R16, OC (= 0) NR17R18, NR15C (= S) R16, SR16; S (= 0) R16; and S (= 0) 2R16, and NR15S (= 0) zR "; R4 and R5 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl from 2 to 6 carbon atoms, alternatively, R4 and R5, together with the carbon to which they are linked, form a spirocyclic ring of 3 to 7 members; R11 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms substituted with 0-3 R20; and aryl of 6 to 10 carbon atoms substituted with 0-3 R20; R12 and R13 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms substituted with 0-3 R20 and aryl of 6 to 10 carbon atoms substituted with 0-3 R20; alternatively, R12 and R13, together with the nitrogen atom to which they are linked, form a 3-7 membered heterocyclic ring substituted with 0-3 R20; R14 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms substituted with 0-3 R20; aryl of 6 to 10 carbon atoms substituted with 0-3 R20; and arylalkyl of 7 to 10 carbon atoms substituted with 0-3 R20; R15 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R16 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms; R17 and R18 in each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or alternatively, R17 and R18, together with the nitrogen atom to which they are bonded, form a heterocyclic ring of 3-7 members, wherein the 3-7 membered heterocyclic ring is substituted with 0-2 oxo groups; R20 in each occurrence is independently selected from F, Cl, Br, I, OH, OR22, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, (alkyl of 1 to 6 carbon atoms ) -OH, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3 to 7 members, phenyl substituted with 0-1 R2d; 5 or 6 membered heteroaryl, arylalkyl of 7 to 10 carbon atoms, = 0, C (= 0) R22, C (= 0) OR22, 0C (= 0) R22, C (= 0) NR23R24, NR21C (= 0) R22, NR21C02R22, OC (= 0) NR23R24. NR21C (= S) R22. SR22; S (= 0) R22; and S (= 0) 2R22; R20A at each occurrence is independently selected from F, Cl, OH, alkoxy of 1 to 4 carbon atoms, CF3, alkyl of 1 to 4 carbon atoms, (alkyl of 1 to 4 carbon atoms) -OH, alkenyl of 2 to 4 carbon atoms, alkynyl of 2 to 4 carbon atoms, and cycloalkyl of 3 to 5 carbon atoms; R21 in each occurrence is independently selected from H and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, (alkyl of 1 to 6 carbon atoms) -OH, and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl from 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or alternatively, R23 and R24, together with the nitrogen atom to which they are bonded, form a 3-7 membered heterocyclyl ring; R at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R26 at each occurrence is independently selected from hydrogen, F, Cl, Br, alkyl of 1 to 5 carbon atoms, and alkoxy of 1 to 6 carbon atoms; x is O, 1, 2, 3 or 4; and q is 1 or 2. In yet another embodiment, the modafinil intermediate compound corresponds to Formula (11): Ar-S-Y (11); the recovered modafinil or the analogue thereof corresponds to the Formula (110) Or Ar-S-Y (110). Ar is X is a bond, CH2, 0, S (0) and, or NR10; rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR21, 0R2p NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3-7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, C (= 0) R22 , C02R21, OC (= 0) R22, C (= 0) NR23R24, NR21C (= 0) R22, NR21C02R22, OC (= 0) NR23R24, NR21C (= S) R22, and S (0) 7R22; Ring B is optionally substituted with one to three groups selected from alkyl of 1 to 6 carbon atoms, phenyl, and 5-6 membered heteroaryl; Y is (alkylene of 1 to 6 carbon atoms) -R1; or (alkylene of 1 to 4 carbon atoms) n-R1; wherein the alkylene groups are optionally substituted with one to three R20 groups; Z is 0, NR10A, S (0) y, CR21 = CR21, C = C (R21) 2, C = C, arylene of 6 to 10 carbon atoms, heteroarylene of 5-10 members, cycloalkylene of 3 to 6 atoms carbon, or 3-6 membered heterocycloalkylene; wherein the arylene, heteroarylene, cycloalkylene, and heterocycloalkylene groups are optionally substituted with one to three R20 groups; R1 is NR12R13, NR21C (0) R14, C (= 0) R15, COOH, C02R14, 0C (= 0) R, C (= 0) NR12R13, C (= N) NR12R13, OC (= 0) NR12R13, NR21S (0) 2RU, S (0) 2NR12R13, NR21C (= 0) NR12R13, NR21S (0 ) 2NR12R13, or PO (OR21) 2; R10 and R10A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, C (= 0) R15, and S (0) and R14; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R11 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R12 and R13 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R12 and R13, together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring; wherein the alkyl and aryl groups and the heterocycloalkyl ring are optionally substituted with one to three R20 groups; R14 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, and arylalkyl; wherein the alkyl, aryl and arylalkyl groups are optionally substituted with one to three R20 groups; R15 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, arylalkyl, and heteroaryl; wherein the alkyl, aryl, arylalkyl and heteroaryl groups are optionally substituted with one to three R20 groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OR21, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, spirocycloalkyl of 3 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3-7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, = 0, C (= 0 ) R22, C02R21, 0C (= 0) R22, C (= 0) NR23R24. NR21C (= 0) R22, NR21C02R22, OC (= 0) NR23R24, NR21C (= 0) R22, NR21C (= S) R22, and S (0) and R22; R21 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R23 and R24, together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring; R25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; m is 0 or 1; n is 0 or 1; q is 0, 1 or 2; e and is 0, 1 or 2. Generally speaking, the modafinil intermediates and modafinil analogs described above (eg, the modafinil intermediate compounds corresponding to Formulas (3), (4), (5), ( 6), (7), (8), (9), and (11), and the modafinil analogs corresponding to Formulas (30), (40), (50), (60), (70), (80), (90), and (110)) correspond to the compounds produced according to the processes described in the Patents of the United States Nos. 6,492,396, 6,670,358, and 6,919,367 to Bacon et al., And United States Patent Applications.

Published Nos. 2005/0192313, 2005/0234040, 2005/20050245747, and 2005/0228040 to Bacon et al., Each of which is incorporated by reference herein. The processes for producing the various modafinil intermediates and modafinil analogs described by Bacon et al. (and other modafinil analogs described herein) typically correspond to the general scientific procedures illustrated in Reaction Schemes 9 (a) - (f), wherein A and Y are defined as described above.

Reaction Schemes 9 (a) - (Y (a) A-OH * - A-S-Y ",, ^., - A-S-Y 1) thiol formation ... 1) Substitution 2) substitution l '2) Oxidation (10) < b) A = 0 A-OH A-S-Y A-S-Y grignard reagent 1) thiol formation 1) Substitution 2) substitution 0) 2) Oxidation (10) OR II (C) A-X A-OH A-S-Y A-S-Y metal exchange 1) thiol formation 1) Substitution 2) substitution (D 2) Oxidation (10) (d) A-OH - ^ £ A-S-? 1) Substitution | 6n »A-S-Y \ 2) Oxidation; 10 ^ Y ° (?) A-SH * - A-S-Y .. ... .. * ~ A-S-Y jr, 1) Substitution (1 2) Oxidation (10) -NH2 O (f) A_OH formation of A_S ^ 1) thiol formation A_S_Y 1) Substitution A_S "And the thiourome salt 2) substitution (1) 2) Oxidation (io) As described in detail above, step 25 of oxidation does not necessarily need to be the last or almost the last step in the synthesis process. The various intermediates can be oxidized according to the process of the present invention at any practical point in the synthesis and the oxidized compounds recovered or subsequently derivatized to produce the desired compound. Modafinil and analogs thereof are produced according to the process of the present invention by the formation of a reaction mixture that includes a modafinil intermediate compound described in detail above., an alcohol, and an organic acid. The modafinil intermediate compound is then oxidized with an oxidizing agent. The ratio of the alcohol to the organic acid in the reaction mixture is preferably from about 1: 1 to about 80: 1 (by volume). More preferably, the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 40: 1 (by volume). For example, the ratio of alcohol to organic acid in the reaction mixture may be from about 1: 1 to about 5: 1 (by volume), from about 1: 1 to about 10: 1 (by volume), of about 1. : 1 to about 15: 1 (by volume), from about 1: 1 to about 20: 1 (by volume), from about 1: 1 to about 25: 1 (by volume), of about 1: 1 to about 30: 1 (by volume), from about 1: 1 to about 35: 1 (by volume), or from about 1: 1 to about 40: 1 (by volume). Still more preferably, the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 7: 1 (by volume). For example, the ratio of the alcohol to the organic acid in the reaction mixture may be from about 1: 1 to about 2: 1 (by volume), from about 1: 1 to about 3: 1 (by volume), of about 1. 1 to about 4: 1 (by volume), from about 1: 1 to about 5: 1 (by volume), from about 1: 1 to about 6: 1 (by volume), or from about 1: 1 to about 7: 1 (in volume). Most preferably, the ratio of the alcohol to the organic acid in the reaction mixture is about 3: 1 (by volume). In contrast to the dissolution of the modafinil intermediate compound, for example, acetic acid alone, these particular ranges of proportions of alcohol to the organic acid advantageously minimize the amount of sulfone impurity produced during the oxidation process and can produce modafinil and analogs thereof with high performance before recrystallization. Any suitable linear, branched or branched alcohol can be used in the process of this invention. Suitable alcohols include, for example, methanol, ethanol, propanol, isopropanol, butanol, sec-butanol, tert-butanol, 2-methyl-1-butanol, ethylene glycol, cyclohexanol, and the like. Preferably, the alcohol is methanol. Any suitable organic acid can be used in the process of the present invention. By way of example, the organic acid can be a carboxylic acid such as, for example, formic acid, acetic acid, propionic acid, butyric acid, oxalic acid, benzoic acid, carbonic acid, lactic acid, malic acid, tartaric acid, acid mandelic acid, citric acid, fumaric acid, sorbic acid, succinic acid, adipic acid, glycolic acid, glutaric acid and the like. The organic acid may also be a sulfonic acid such as, for example, methanesulfonic acid, benzenesulfonic acid, trifluoromethanesulfonic acid, and the like. Preferably, the organic acid is a carboxylic acid such as formic acid or acetic acid. Most preferably, the organic acid is acetic acid. Any suitable oxidizing agent can be used in the process of the present invention. Oxidizing agents suitable for use in the process of the present invention include, for example, 02, K2S208, Ca (OCI) 2, NaCl02, NaOCI, HN03, NaI04, m-chloroperoxybenzoic acid, acylnitrates, sodium perborate, hypochlorite tert-butyl, hydrogen peroxide, t-butylhydroperoxide, alkyl and acyl peroxides such as benzoyl peroxide, peracetic acid and the like. Preferably, the oxidizing agent is hydrogen peroxide. More preferably, the oxidizing agent is a solution of about 25% (by weight) to about 55% (by weight) of hydrogen peroxide in water. Still more preferably, the oxidizing agent is a solution of about 30% (by weight) to about 50% (by weight of hydrogen peroxide in water) Most preferably, the oxidizing agent is a solution of about 30% (by weight) of hydrogen peroxide in water The oxidizing agent is typically present in the reaction mixture from about 0.80 to about 1: 1 molar equivalents with respect to the modafinil intermediate compound.For example, the oxidizing agent may be present in the reaction mixture from about 0.80 to about 0.85 molar equivalents with respect to the modafinil intermediate compound, from about 0.80 to about 0.90 molar equivalents with respect to the modafinil intermediate compound, from about 0.80 to about 0.95 molar equivalents to the modafinil intermediate compound, of about 0.80 to approximately 1.0 equi valent molars with respect to the intermediate compound of modafinil, or from about 0.80 to about 1.05 molar equivalents with respect to the intermediate modafinil compound. More preferably, the oxidizing agent is present in the reaction mixture of about 0.95 to about 1.07 molar equivalents with respect to the modafinil intermediate compound. For example, the oxidizing agent may be present in the reaction mixture from about 0.95 to about 0.97 molar equivalents with respect to the modafinil intermediate compound, from about 0.95 to about 0.99 molar equivalents to the modafinil intermediate compound, of about 0.95 to about 1.01 molar equivalents with respect to the modafinil intermediate compound, from about 0.95 to about 1.03 molar equivalents with respect to the modafinil intermediate compound, or from about 0.95 to about 1.05 molar equivalents with respect to the modafinil intermediate compound. Most preferably, the oxidizing agent is present in the reaction mixture from about 0.98 to about 1.07 molar equivalents with respect to the modafinil intermediate compound. For example, the oxidizing agent may be present in the reaction mixture from about 0.98 to about 1.0 molar equivalents with respect to the modafinil intermediate compound, from about 0.98 to about 1.02 molar equivalents with respect to the modafinil intermediate compound, from about 0.98 to about 1.04 molar equivalents with respect to the modafinil intermediate compound, or from about 0.98 to about 1.06 molar equivalents with respect to the modafinil intermediate compound. Typically, the reaction mixture is formed by mixing the alcohol, the organic acid, and the modafinil intermediate compound, with the alcohol and the organic acid which are present in the proportions described above. The oxidizing agent is then charged to the reaction mixture to oxidize the modafinil intermediate compound. While the order of the addition of the various reagents is not narrowly critical, the oxidizing agent is preferably added at the end and slowly to minimize the over-oxidation of the sulfide atom to the sulfone. Preferably, the oxidizing agent is charged to the reaction mixture at a rate of about 1 kg / minute to about 2 kg / minute. In addition, the modafinil intermediate compound is preferably not added at the end, since over-oxidation to the sulfone probably occurs. Oxidation of the modafinil intermediate compound according to the process described herein is typically performed at a temperature of the reaction mixture of at least room temperature. Preferably, the temperature of the reaction mixture during oxidation is less than about 70 ° C. More preferably, the temperature of the reaction mixture during oxidation is from about 20 ° C to about 70 ° C. Still more preferably, the temperature of the reaction mixture during oxidation is from about 30 ° C to about 65 ° C. Most preferably, the temperature of the reaction mixture during oxidation is about 40 ° C. Alternatively, the reaction mixture is not maintained at a particular temperature throughout the entire oxidation reaction. For example, the temperature can be maintained at any of the above temperatures for about 24 hours to about 48 hours, and then the reaction mixture can be allowed to cool and proceed without any such maintenance of the temperature. The length of time to achieve that the oxidation reaction reaches the termination (for example, reaching a maximum yield for the desired modafinil or the analogue thereof) typically depends on the temperature at which the oxidation is carried out. In general, however, oxidation is typically allowed to proceed for about 1 hour to about 48 hours.

More preferably, the oxidation is allowed to proceed for about 18 hours to about 24 hours. Most preferably, the oxidation is allowed to proceed for approximately 24 hours. Once the oxidation is complete, the reaction mixture is typically cooled to about room temperature or colder. Any excess oxidizing agent present in the reaction mixture can be optionally removed with, for example, sodium metabisulfite, sodium thiobisulfite, sodium sulfite, ferrous sulfite or the like. If desired, from about 0.05 molar equivalents to about 0.2 molar equivalents with respect to the modafinil intermediate can be added to the reaction mixture to decompose any excess oxidizing agent present in the reaction mixture. After the termination of the oxidation reaction, the oxidized modafinil or the analogue thereof is recovered. Alternatively, if the oxidation reaction produces an intermediate of modafinil sulfoxide, the intermediate may undergo additional derivatization to produce other modafinil compounds and analogues thereof, as described in Reaction Schemes 5-8 above, which may be then recovered. Various methods for the recovery of modafinil and analogs thereof from the reaction mixture are known. Typically, modafinil or the analogue thereof can be recovered from the reaction mixture by cooling, precipitation, filtration and drying the precipitate. The recovered modafinil or the analogue thereof can be optionally purified by recrystallization methods known to those of ordinary skill in the art. For example, in U.S. Patent No. 4,177,290 to Lafon, methanol or a mixture of methanol: water is used to purify modafinil by recrystallization. The use of methanol as a recrystallization solvent, however, is often relatively inefficient, or in some cases, inadequate to obtain pharmaceutically pure modafinil. Often, this is the case where several impurities are present at more than 0.1% (by weight). Modafinil is often only slightly soluble in alcoholic solvents, even at reflux temperatures. Modafinil impurities are also relatively insoluble in alcoholic recrystallization solvents, therefore after filtration these are only moderately reduced. In addition, the processes of the present invention produce a highly pure recovered product prior to recrystallization, therefore a recrystallization step may not be necessary or desired. If desired, the recovered modafinil or analogue it can be recrystallized by mixing it with a halo-organic solvent such as, for example, dichloromethane, dichloroethane, chloroform and the like. Typically, the halo organic solvent is chloroform. Advantageously, modafinil and analogs thereof produced by the processes of the present invention tend to be relatively insoluble in chloroform, while larger impurities (such as, for example, modafinil acid, modafinil-sulfone acid, and modafinil-sulfone) are relatively soluble in chloroform. The mixture of recovered modafinil or analogs thereof / halo-organic solvent tends to form a relatively viscous suspension. To reduce the viscosity, the mixture is preferably charged first with a low-boiling aliphatic solvent, followed by the slow addition of the halo-organic solvent. Low-boiling aliphatic solvents include, for example, pentane, hexane, octane, heptane, and the like. Preferably, the low-boiling aliphatic solvent is heptane. The processes described herein are effective in minimizing the over-oxidation of the sulfur to sulfone atom in the preparation of modafinil and analogues thereof. In general, the general purity of the recovered modafinil or the analogs thereof (eg, the amount of modafinil or the analogue thereof, the sulfone impurity and other impurities) can be determined by chromatography (e.g., HPLC at approximately 225 nm). Typically, no more than about 0.1% (per area as determined by CLAR) of the sulfone impurity is present in the recovered modafinil or analogue thereof prior to recrystallization. Preferably, no more than about 0.05% (per area as determined by HPLC) of the sulfone impurity is present in the recovered modafinil or analogue thereof prior to recrystallization; more preferably, no more than about 0.02% (per area as determined by CLAR) is present. Most preferably, the recovered modafinil or the analogue thereof is substantially free of the sulfone impurity. As used herein, "substantially free of sulfone impurity" refers to a recovered modafinil or analogs thereof having less than about 0.05% (per area as determined by CLAR) of sulfone impurity prior to recrystallization The processes described herein are also effective to produce highly pure modafinil and analogs thereof, prior to any recrystallization of the recovered modafinil or analogue thereof. Preferably, the recovered modafinil or the analogue thereof is more than about 80% pure before recrystallization. More preferably, the recovered modafinil or the analogue of the same is more than about 85% pure before recrystallization. Still more preferably, the recovered modafinil or the analogue thereof is more than about 90% pure before recrystallization. Still more preferably, the recovered modafinil or the analogue thereof is more than about 95% pure before recrystallization. Still more preferably, the recovered modafinil or the analogue thereof is more than about 99% pure before recrystallization. Most preferably, the recovered modafinil or the analogue thereof is more than about 99.5% pure before recrystallization.

ABBREVIATIONS AND DEFINITIONS The following definitions and methods are provided to better define the present invention and to guide those of ordinary skill in the art in the practice of the present invention. Unless stated otherwise, the terms will be understood according to conventional use by those of ordinary experience in the relevant art. As used herein, the term "alkyl" refers to a branched or unbranched or linear unsubstituted hydrocarbon chain of 1 to 8 carbon atoms, which is formed by the removal of an atom of hydrogen. In certain preferred embodiments, the alkyl group contains from 1 to 6 carbon atoms. In other preferred embodiments, the alkyl group contains from 1 to 4 carbon atoms. A designation such as "alkyl of 1 to 4 carbon atoms" refers to an alkyl radical containing from 1 to 4 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl, 2-methylpentyl, hexyl, 2-methylhexyl, 2,3-dimethylhexyl, heptyl, octyl, etc. . As used herein, the term "lower alkyl" refers to a straight, branched or cyclic, saturated hydrocarbon of 1 to 6 carbon atoms, which are optionally substituted. Lower alkyl groups include, but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, cyclopentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl, -methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl and the like. As used herein "alkenyl" refers to a straight or branched hydrocarbon chain, substituted or unsubstituted, containing from 2 to 8 carbon atoms having one or more carbon-carbon double bonds that may occur at any point stable along the chain, and that is formed by the elimination of a hydrogen atom. A designation "alkenyl from 2 to 8 "carbon atoms" refers to an alkenyl radical containing from 2 to 8 carbon atoms Examples include ethenyl, propenyl, isopropenyl, 2,4-pentadienyl, etc. As used herein, "alkynyl" refers to a linear or branched hydrocarbon radical, substituted or unsubstituted containing 2 to 8 carbon atoms, having one or more triple carbon-carbon bonds that can appear at any stable point along the chain, and which is formed by the elimination of a hydrogen atom A designation "alkenyl of 2 to 8 carbon atoms" refers to an alkynyl radical containing from 2 to 8 carbon atoms Examples include ethynyl, propynyl, isopropynyl, 3, 5 hexadiinyl, etc. As used herein, the term "aryl" refers to a substituted or unsubstituted mono- or bicyclic hydrocarbon ring system having 6 to 12 carbon atoms in the ring. phenyl and naphthyl Preferred aryl groups include substituted or unsubstituted phenyl and naphthyl groups. Included within the definition of "aryl" are fused ring systems, which include, for example, ring systems in which an aromatic ring is fused to a cycloalkyl ring. Examples of such fused ring systems include, for example, indane, indene and tetrahydronaphthalene.

As used herein, the terms "carbocycle", "carbocyclic" or "carbocyclyl" refer to a stable monocyclic or bicyclic hydrocarbon ring system, substituted or unsubstituted, which is saturated, partially saturated or unsaturated, and contains 3 to 10 carbon atoms in the ring. Accordingly, the carbocyclic group can be aromatic or non-aromatic, and includes the cycloalkyl and aryl compounds defined herein. The bonds connecting the endocyclic carbon atoms of a carbocyclic group can be single, double, triple or part of a fused aromatic moiety. As used herein, the term "cycloalkyl" refers to a saturated or partially saturated mono- or bicyclic alkyl ring system containing from 3 to 10 carbon atoms. A designation such as "cycloalkyl of 5 to 7 carbon atoms" refers to a cycloalkyl radical containing from 5 to 7 carbon atoms in the ring. Preferred cycloalkyl groups include those containing 5 or 6 carbon atoms in the ring. Examples of cycloalkyl groups include groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenylene and adamantanyl. As used herein, the terms "heterocycle" or "heterocyclic" refer to a ring monocyclic or stable bicyclic 3- to 10-membered, saturated, partially unsaturated or unsaturated, substituted or unsubstituted, wherein at least one member of the ring is a heteroatom. Accordingly, the heterocyclic group can be aromatic or non-aromatic. Typically, heteroatoms include, but are not limited to, oxygen, nitrogen, sulfur, selenium and phosphorus. The preferred heteroatoms are the oxygen, nitrogen and sulfur atoms. The nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen may be optionally substituted on non-aromatic rings. The bonds connecting the endocyclic atoms of a heterocyclic group can be single, double, triple or part of a fused aromatic moiety. Heterocycles are intended to include the "heterocyclyl" and "heteroaryl" compounds defined herein. As used herein, "heterocyclyl" refers to a stable, saturated, or partially unsaturated, substituted or unsubstituted, 3 to 7 membered heterocyclic ring that is formed by the removal of a hydrogen atom. Examples include epoxyethyl, pyrrolidyl, pyrazolidinyl, piperidyl, pyranyl, oxazolinyl, morpholino, morpholinyl, piperazinyl, etc. Examples of heterocycles include, but are not limited to, 2-pyrrolidinyl, 2H-pyrrolyl, 4-piperidinyl, 6H-1, 2, 5-thiadiazinyl, 2H, 6H-1, 5, 2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, isoxazolyl, morpholinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1, 2,4-oxadiazolyl, 1, 2, 5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, tetrahydrofuranyl, 6H-1, 2, 5- thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1, 2, 5-thiadiazolyl, 1,3,4-thiadiazolyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, triazinyl, 1, 2, 3-triazolyl, 1,2,4-triazolyl, 1, 2, 5-triazolyl, 1, 3, 4-triazolyl, and tetrazole. Suitable heterocycles are also described in The Handbook of Chemistry and Physics, 76th Edition, CRC Press, Inc., 1995-1996, pages 2-25 to 2-26, the disclosure of which is incorporated by reference herein. Preferred heterocyclic groups formed with a nitrogen atom include, but are not limited to, pyrrolidinyl, piperidinyl, piperidino, morpholinyl, morpholino, thiomorpholino, N-methylpiperazinyl, indolyl, isoindolyl, imidazole, imidazoline, oxazoline, oxazole, triazole, thiazoline, thiazole, isothiazole, thiadiazoles, triazines, isoxazole, oxindole, indoxyl, pyrazole, pyrazolone, pyrimidine, pyrazine, quinoline, isoquinoline, and tetrazole.

Preferred heterocyclic groups formed with an oxygen atom include, but are not limited to, the furan, tetrahydrofuran, pyran, benzofuran, isobenzofuran, and tetrahydropyran groups. Preferred heterocyclic groups formed with a sulfur atom include, but are not tendered to, thiophene, tyaphthalene, tetrahydrothiophene, tetrahydrothiapyran, and benzothiophenes. Preferred aromatic heterocyclic groups include, but are not limited to, pyridyl, pyridyl, pyrrolyl, fuplo, thienyl, imidazolyl, tpazolyl, tetrazolyl, quinolyl, isoquinolyl groups. benzoimidazolyl, thiazolyl, pyrazolyl, and benzothiazolyl. As used herein the term "heterocycloalkyl" refers to a cycloalkyl group in which one or more carbon atoms in the ring are replaced by at least one heteroatom such as -O-, -N-, or -S- . Examples of heterocycloalkyl groups include pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, pyrazinyl, piperidyl, piperazyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, dithiolyl, oxathiolyl, dioxazolyl, oxathiazolyl, pyranyl, oxazinyl, oxathiazyl, and oxadiazyl. As used herein, the term "hetero-tile" refers to an aromatic group containing to 10 carbon atoms in the ring in which one or more carbon atoms in the ring are replaced by at least one heteroatom such as -O-, -N-, or -S-. Examples of heteroaryl groups include pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, isoxazolyl, oxazolyl, oxathiolyl, oxadiazolyl, triazolyl, oxatriazolyl, furazanyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, picolinyl, indolyl, isoindolyl, indazolyl, benzofliranyl, isobenzofuranyl, purinyl, quinazolinyl, quinolyl, isoquinolyl, benzoimidazolyl, benzothiazolyl, benzothiophenyl, tianaphtenyl, benzoxazolyl, benzisoxazolyl, cinolinyl, phthalazinyl, naphthyridinyl, and quinoxalinyl. Included within the definition of "heteroaryl" are fused ring systems that include, for example, ring systems in which an aromatic ring is fused to a heterocycloalkyl ring. Examples of such fused ring systems include, for example, phthalamide, italic anhydride, indoline, isoindoline, tetrahydroisoquinoline, chroman, isochroman, chromene, and isochromen. As used herein, the term "arylalkyl" refers to an alkyl group that is substituted with an aryl group. A designation "arylalkyl of 7 to 10 carbon atoms" refers to an alkyl group which is substituted with an aryl group with the combination thereof containing from 7 to 10 carbon atoms. Examples of arylalkyl groups include, but are not limited to, benzyl, phenethyl, phenpropyl, phenylbutyl, diphenylmethyl, triphenylmethyl, diphenylethyl, naphthylmethyl, etc. Preferred examples of arylalkyl groups include, but are not limited to, benzyl and phenethyl. As used herein, the term "spirocycloalkyl" refers to a cycloalkyl group linked to a carbon chain or carbon ring portion by a carbon atom common to the cycloalkyl group and the carbon chain or ring portion of carbon. For example, an alkyl group of 3 carbon atoms substituted with a group R wherein the group R is spirocycloalkyl containing 5 carbon atoms refers to: As used herein, the term "substituted" refers to the replacement of one or more hydrogen atoms on an indicated group, with a selected group referred to herein as a "substituent", with the proviso that the valence of the substituted atom is not exceeded, and that substitution results in a stable compound. A substituted group has 1 to 5, preferably 1 to 3, and more preferably 1, substituents independently selected. Preferred substituents include, but are not limited to F, Cl, Br, I, OH, OR, NH2, NR2, NHOH, N02, CN, CF3, CF2CF3, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocyclyl, aryl of 6 to 10 carbon atoms, heteroaryl, arylalkyl, C (= 0) ) R, COOH, C02R, 0-C (= 0) R, C (= 0) NRR ', NRC (= 0) R', NRC02RY 0C (= 0) NRR ', -NRC (= 0) NRR', -NRC (= S) NRR 'and -S02NRR', wherein R and R 'are each independently hydrogen, alkyl of 1 to 6 carbon atoms or aryl of 6 to 10 carbon atoms. As used herein, the term "alkylene" refers to a straight or branched chain hydrocarbon substituted or unsubstituted of 1 to 8 carbon atoms, which is formed by the removal of two hydrogen atoms. A designation such as "alkylene of 1 to 4 carbon atoms" refers to an alkylene radical containing from 1 to 4 carbon atoms. Examples include methylene (-CH2-), propylidene (CH3CH2CH =), 1,2-ethanediyl (-CH2CH2-), etc. As used herein, the term "heterocyclylene" refers to a stable 3 to 7 membered heterocyclic ring, saturated or partially unsaturated, substituted or unsubstituted, which is formed by the elimination of two hydrogen atoms. Examples include epoxyethylene, pyrrolidylene, pyrrolidylidene, pyrazolidinylene, piperidylene, pyranylene, morpholinylidene, etc. As used herein, the term "Arylene" refers to a substituted or unsubstituted aromatic carbocyclic ring containing from 6 to 10 carbon atoms, which is formed by the removal of two hydrogen atoms. Examples include phenylene (-C6H4-), naphthylene (-C? 0H6-), etc. The "phenylene" group has the following structure: As used herein, the term "heteroarylene" refers to a 5- to 10-membered aromatic heterocyclic ring, substituted or unsubstituted, formed by the removal of two hydrogen atoms. Examples include the heteroarylene groups corresponding to the respective heteroaryl groups described above, and in particular, include thienylene (-C4H2S-), pyridylene (-C5H3N-), pyrimidinylene (-C3H2N2-), quinolinylene (-C9H5N-), thiazolylene (-C3HNS-), etc. The "thienylene" group has the following structure: cP The "pyridylene" group has the following est structure As used herein, the term "alkoxy" refers to an oxygen radical substituted with an alkyl group. Preferably, the alkoxy group contains from 1 to 6 carbon atoms. A designation such as "C 1 -C 4 alkoxy" refers to an alkoxy radical containing 1 to 4 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, t-butoxy, etc. As used herein, "monosaccharide of 5 to 7 carbon atoms" refers to the simple sugars of the formula (CH20) n where n = 5-7. The monosaccharides can be straight chain or ring systems, and can include a sucrose unit of the formula -CH (OH) -C (= 0) -. Examples include erythrose, threose, ribose, arabinose, xylose, lyxose, alose, altrose, glucose, mannose, gulose, iodine, galactose, talose, eritulose, ribulose, xiulose, psychose, fructose, sorbose, tagatose, erythropentulose, treopentulose, glycerotetrulose , glucopyranose, fructofuranose, etc. As used herein, the term "amino acid" refers to a molecule that contains a amino group and a carboxyl group. Modes of amino acids include cx-amino, β-amino, α-amino acids. The -aminoacids have a general formula HOOC-CH (side chain) -NH2. In certain embodiments, substituents for the compounds of the present invention include the residue of an amino acid after removal of the hydroxide portion of the carboxyl group thereof; for example, the groups of the formula -C (= 0) CH (NH2) - (side chain). The amino acids can be in their D, L or racemic configurations. The amino acids include the portions of natural origin and not natural origin. Amino acids of natural origin include the 20 standard amino acids found in proteins, such as glycine, serine, tyrosine, proline, histidine, glutamine, etc. Amino acids of natural origin can also include non-amino acids such as "β-alanine, β-aminobutyric acid, homocysteine, etc.), rare amino acids (such as 4-hydroxyproline, 5-hydroxylysine, 3-methylis idina, etc.) and non-protein (such as citrulline, ornithine, canavanine, etc.) Amino acids not of natural origin are well known in the art, and include analogs of natural amino acids.Lehninger, AL Biochemistry, 2nd ed.; Worth Publishers: New York, 1975; 71-77.Amino acids not of natural origin also they include the a-amino acids wherein the side chains are replaced with synthetic derivatives. The representative side chains of the a-amino acids of natural origin and non-natural origin are shown in Table A below.

Table A Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in appended claims. In addition, it should be appreciated that all examples of the present disclosure are provided as non-limiting examples.

EXAMPLE 1 In this example, the intermediate compound of modafinil, benzhydrylthioacetamide was oxidized to produce modafinil according to the processes described herein, using various proportions of alcohol to the organic acid and various temperatures of the reaction mixture. First, benzhydrylthioacetamide (10 g, MW = 257.35, 1.0 equivalent), methanol and acetic acid were charged to a 250 ml flask. Hydrogen peroxide (4.3 ml, 1.05 equivalent) was then charged to the resulting mixture in the course of about 5 minutes. The reaction was allowed to proceed for approximately 24 hours, with samples periodically taken for HPLC analysis. Several different tests using particular ratios of methanol and acetic acid at particular temperatures were performed. The results are illustrated in the following Tables 1-7.

Table 1: 20 ml of methanol / 20 ml of acetic acid; 40 ° C Table 2: 30 ml of methanol / 10 ml of acetic acid; 40 ° C Table 3: 35 ml of methanol / 5 ml of acetic acid; 40 ° C Table 4: 39 ml of methanol / 1 ml of acetic acid; 40 ° C Table 5: 30 ml of methanol / 10 ml of acetic acid; 65 ° C Table 6: 39 ml of methanol / 1 ml of acetic acid; 65 ° C Table 7: 39.5 ml of methanol / 0.5 ml of acetic acid; 65 ° C lf 2( As illustrated in Tables 1-7 above, the processes of the present invention are effective in the production of modafinil with a high yield and with a relatively low sulfone impurity content.

Specifically, as illustrated in Table 2, a reaction mixture comprising 30 ml of methanol and 10 ml of acetic acid (for example, methanol and acetic acid are present in the reaction mixture at a ratio of about 3: 1) with the oxidation reaction proceeding at 40 ° C, is particularly effective, producing modafinil with a yield of about 96% with a sulphone impurity content of about 0.22%.

EXAMPLE 2 In this Example, the modafinil intermediate, benzhydrylthioacetamide was oxidized on a commercial scale to produce modafinil according to the processes described herein. Firstly, benzhydrylthioacetamide (100 g, PM = 257.35, 1.0 equivalent) was charged to a reaction chamber. The reaction chamber was purged with approximately 0.35 kg / cm2 (5 psig) of N2 and vented through a chemical scavenger. Approximately 155 kg of methanol (1.50-1.67 kg / kg of benzhydrylthioacetamide) was then charged to the reaction chamber. The temperature of the reaction chamber was adjusted to approximately 30 ° C-40 ° C and the resulting mixture was stirred at approximately 70-90 RPM. Then, 0.70 kg of acetic acid (0.68-0.72 kg / kg) was added to the reaction chamber. benzhydrylthioacetamide) was charged to the reaction chamber. The resulting mixture was then stirred for approximately 15 minutes, and the temperature was maintained at approximately 30 ° C-40 ° C. To the mixture of benzhydrylthioacetamide / methanol / acetic acid was then added about 0.472 kg of 30% hydrogen peroxide (0.448-0.496 kg / kg of benzhydrylthioacetamide) at a rate of about 1-2 kg / minute. The resulting mixture was then heated to and maintained at about 38 ° C-43 ° C and stirred for about 24 hours. After about 24 hours, the reaction mixture was cooled to approximately 20 ° C-30 ° C and the reaction chamber was pressurized to approximately 0.21-0.49 kg / cm2 (3-7 psig) with N being vented through a chemical scrubber The reaction mixture was subsequently cooled to approximately 0 ° C-5 ° C and stirred for about 2 hours. The reaction mixture was then charged to a centrifuge purged with N2 (content of 02 <7%). The centrifuge was cycled at low speed until the basket of the centrifuge was less than 3/4 full with the product modafinil crude (approximately 15 minutes). The load of the centrifuge was washed with approximately 113 liters of cold methanol, and the crude modafinil cake was removed from the liquor at a high speed centrifugation by approximately 15-30. minutes The white to off-white crude modafinil product (approximately 85.2 kg) was then loaded onto a tray coated with Teflon® and dried at approximately 60 ° C-70 ° C for at least about 6 hours (6-24 hours). After drying, a sample of 5 to 10 g was analyzed by HPLC. The results are illustrated in Table 8 below: Table 8 As illustrated in Examples 1 and 2, the processes of the present invention are effective in producing modafinil in a high yield with a relatively low impurity content, prior to recrystallization. It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A process for the preparation of modafinil or analogs thereof, characterized in that it comprises: oxidizing an ordinary modafinil compound in a reaction mixture comprising an alcohol, an organic acid, and an oxidizing agent; and recovering modafinil or analogs thereof from the reaction sample; wherein the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 80: 1 (by volume); the modafinil intermediate compound corresponds to formula (1): A-S-Y (1); the recovered modafinil or the analogue thereof corresponds to the formula (10): O A-S-Y (10). A is substituted alkyl, substituted aryl, substituted heteroaryl, or a substituted or unsubstituted tricyclic ring; and Y is hydrocarbyl or substituted hydrocarbyl.
2. The process according to claim 1, characterized in that the modafinil intermediate compound corresponds to Formula (2): and the recovered modafinil or the analogue thereof corresponds to the formula (20): Yi is hydrocarbyl, hydroxyl, halo, alkoxy, or amino.
3. The process according to claim 1, characterized in that the intermediate compound corresponds to the formula (2A): and the recovered modafinil or the analog thereof is modafinil (200 '
4. The process according to claim 1, characterized in that the modafinil intermediates correspond to the formula (3): the recovered modafinil or the analogue thereof corresponds to the Formula (30): Ari and Ar2 are each independently selected from aryl or heteroaryl of 6 to 10 carbon atoms; wherein each of Ax or Ar2 can be independently optionally with 1-3 substituents independently selected from: a) H, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, -CF3, -N02, -OH, -OR7, -0 (CH2) PNR9 Rio, -OC (= 0) R7, -OC (= 0) NR9R? 0, -0 (CH2) POR8, -CH2OR8, -NR9R? O, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH2ORu; c) -NR8C (= O) NRgR? 0, -NR8C (= S) NR9R? 0, -C02R? 2, -C (= 0) Ri3, -C (0) NR9R? o, -C (= S) NR9R10, -CH = NORX2, -CH = NR7, - (CH2) pNR9R? O, - (CH2) pNHRn, -CH = NNR? 2R12A, -C (-NR8) NR8AR8B, NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) pS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -0R7, -CH2OR8, -NR9R? Or, -O- (CH2) p-OH, -S- (CH2) P-OH, -Xi (CH2) POR7, -X? (CH2) PNR9R? Or, - X? (CH2) PC (= 0) NR9R? O, -Xx (CH2) PC (= S) NR9R? 0, -X? (CH2) POC (= 0) NR9R? O, -Xi (CH2) PC02R8. -Xx (CH2) PS (O) XR7, -X? S (CH2) pNR8C (= 0) NR9R? O, -C (= 0) Ri3, -C02R? 2, -OC (= 0) R7, -C (= O) NRgR? 0, -OC (= 0) NR12RI2A, O-tetrahydropyranyl, -C (= S) NR9R? 0, -CHNNR12R? 2A, -CHNORiz, -CHNR7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= O) NR9R? 0, -NR8C (= S) NRgRio, -NHC (= NH) NH2 , -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR12R12A, -P (= 0) (0R8) 2 , -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or -0-C (= 0) R7; Xi is -0-, -S-, or -N (R8) -; Z is selected from alkylene of 1 to 4 carbon atoms, -C (R?) (R2) -, arylene of 6 to 10 carbon atoms, heteroarylene, cycloalkylene of 3 to 8 carbon atoms, heterocyclylene, -0-, -N (R8) -, -S (0) y, -CR9A = CR8B-, -CH = CH-CH (R8) -, -CH (R8) - CH = CH-, or -C = C-; Ri, R2, R3 and R4 are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, -OH, and -CH (R6) -C0NR8AR8B; or R3 and R, together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclyl ring; R6 is hydrogen, alkyl of 1 to 4 carbon atoms, or the side chain of an α-amino acid; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Rdi RßA and RβB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; Rg and Rio are each independently selected from H, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or R9 and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclyl ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; Ri2 and R2A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or R 2 and R 2A, together with the nitrogen atom to which they are bound, form a heterocyclyl ring of 5-7 members; Ri3 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; m is O, 1, 2 or 3; n is 0, 1, 2 or 3; p is 1, 2, 3 or 4; t is 2, 3 or 4; y y e s O, 1 or 2.
5. The process according to claim 1, characterized in that the intermediate compound modafinil corresponds to formula (4): the recovered modafinil or the analogue thereof corresponds to the Formula (40): Ari and Ar2 are each independently selected from thiophene, isothiazole, phenyl, pyridyl, oxazole, isoxazole, thiazole, imidazole, and other five or six membered heterocycles comprising heteroatoms of 1-3 atom of -N-, -0-, or -S-; Ri R2 R3 and R4 are each independently selected from hydrogen, lower alkyl, -OHi -CH (Rβ) -C0NR? AR6B, or any of Ri, R2, R3 and R can be taken together to form a carboxylic or heterocyclic ring of 3-7 members; and each of Ari or Ar2 can be independently optionally substituted with one or more substituents independently selected from: a) H, aryl, heterocyclyl, F, Cl, Br, I, -CN, -CF3, -N02, -OH, -0R7, -0 (CH2) pNR9R? O, -0C (= 0) R7, -OC (= 0) NR9R10, -0 (CH2) P0R8, -CH2OR8, -NRgRio, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH20Rn, wherein Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; c) -NR8C (= 0) NR9R? o, -NR8C (= S) NR9R? 0, -C02Ri2, -C (= 0) R? 2, -C (= 0) NR9R? o, -C (= S) ) NRgRio, -CH-N0R12, -CH-NR7, - (CH2) NR9R? 0, - (CH2) pNHR ?, or CH-NNR? 2R? 2A, wherein Ri2 and Ri2A are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, -OH, alkoxy of 1 to 4 carbon atoms, -OC (= 0) R7, -OC (= 0) NR9R? 0, -OC (= S) NR9R? 0, -0 (CH2) pNR9R? o, -0 (CH2 ) POR8, substituted or unsubstituted arylakyl having from 6 to 10 carbon atoms, and substituted or unsubstituted heterocyclylalkyl; d) -S (0) and R12, - (CH2) PS (0) and R7, -CH2S (0) and Rn where y is 0, 1 or 2; and e) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkinyl of 2 to 8 carbon atoms, where: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is substituted with 1 to 3 groups selected from aryl of 6 to 10 carbon atoms, heterocyclyl, arylalkoxy, heterocycloalkoxy, hydroxylalkoxy, alkyloxy alkoxy, hydroxyalkylthio, alkoxy alkylthio, F, Cl, Br, I, -CN, -N02, -OH, -OR7, -X2 (CH2) pNR9R? O, -X2 (CH2) PC (= 0) NRgRio, -X2 (CH2) pC (= S) NR9R? O, -X2 (CH2) P0C (= 0) NR9R? 0, -X2 (CH2) PC02R7 > -X2 (CH2) pS (0) and R7, -X2 (CH2) PNR8C (= 0) NR9R? O, -0C (= 0) R7, -OC (= 0) NHR? 2, O-tetrahydropyranyl, -NR9R? 0, -NR8C02R7, -NR8 (C = 0) NRgRio, -NR8C (= S) NRgR? 0, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -C02R? 2, -C (= 0) NR9R? 0, -C (= S) NR9R? 0, -C (= 0) R? 2, -CH20R8 , -CH = NNR? 2R? 2A, -CH = N0R? 2, -CH = NR7, -CH = NNHCH (N = NH) NH2, -S (= 0) 2NRi2R? 2A, -P (= 0) ( 0R8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms where each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkylcarbonyloxy of 2 to 5 atoms carbon, or alkoxy of 1 to 4 carbon atoms, where X is 0, S, or NR8; wherein R7 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclyl; R8 is hydrogen or alkyl having 1 to 4 carbon atoms; p is 1, 2, 3 or 4; and wherein 1) R9 and Rio are each independently hydrogen, unsubstituted alkyl of 1 to 4 carbon atoms, or substituted alkyl; or 2) Rg and Rio together form a linking group of the Formula - (CH2) 2-X? ~ (CH2) 2-, wherein Xi is selected from -0-, -S-, and -CH2-.
6. The process according to claim 1, characterized in that the modafinil intermediate compound corresponds to Formula (5): the recovered modafinil or the analogue thereof corresponds to the Formula (50): X is a bond, -CH2CH2-, -0-, S (0) y-, -N (R8) -, -CHN (R8) -, -CH = CH-, -CH2-CH = CH-, C ( = 0), -C (R8) = N-, -N = C (R8) -, -C (= 0) -N (R8) -, or -NR8-C (= 0) -; The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with an oxygen, nitrogen or sulfur atom; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein ring A and ring B can each be independently substituted with 1-3 substituents selected from: a) hydrogen, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, - CF3, -N02, -OH, -OR7, -0 (CH2) PNR9R10, -OC (= 0) R7, -OC (= 0) NR9R? O, -0 (CH2) POR8, -CH2OR8, -NR9R? 0, -NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH20Rn; c) -NR8C (= 0) NR9R? o, -NR8C (= S) NR9R? 0, -C02R? 2, -C (= 0) Ri3, -C (= O) NRgR? 0, -C (= S) ) NR9R? 0, -CH = NORx2, -CH = NR7, - (CH2) pNR9R? O, - (CH2) pNHRn, -CH = NNR? 2R? 2A, -C (= NR8) NR8AR8B-NR8C (= NH ) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; Y e) alkyl of 1 to 6 carbon atoms, alkenyl of 2 8 carbon atoms or alkynyl of 2 to 8 carbon atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -OR, -CH2OR8, -NRgRio, -O- (CH2) P-OH, -S- (CH2) P-OH, -Xj. (CH2) POR7, X? (CH2) PNR9R? O, -X? (CH2) pC (= O) NR9R10, -Xi (CH2) PC (= S) NR9R? 0, -X? (CH2) POC (0 ) NR9R? O, -Xx (CH2) PC02R8, -Xx (CH2) PS (O) R7, -X1 (CH2) pNR8C (= 0) NR9R? O, -C (= 0) R13, -C02R? 2, -0C (= 0) R7, -C (= 0) NR9R? O, -OC (= 0) NR? 2Rx2A, O-tetrahydropyranyl, -C (= S) NR9R? 0, -CH = NNR? 2Rx2A, - CH = N0R? 2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= O) NR9R? 0, -NR8C (= S) NR9R? 0, -NHC (= NH NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR? 2R? 2A, -P (= 0) (0R8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or -0-C (= 0) R7; R3 and R4 are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, -OH, -CH (R6) -C0NR8AR8B, or R3 and R, together with the atom of nitrogen to which they are bound, form a 3-7 membered heterocyclic ring; Re is hydrogen, alkyl of 1 to 4 carbon atoms, or the side chain of an α-amino acid; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Rd / R8A and RβB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; Rg and Rio are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or R9 and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and RI2A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or Ri2 and R12A, together with the nitrogen atom to which they are bound, form a 5-7 membered heterocyclic ring; Ri3 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; Xi is -O-, -S-, or -N (R8) -; Z is selected from alkylene of 1 to 4 on atoms, arylene of 6 to 10 on atoms, heteroarylene, cycloalkylene of 3 to 8 on atoms, heterocyclylene, -O-, -N (R8) -, -S (0 ) and, -CR8A = CR8B-, -CH = CH-CH (R8) -, -CH (R8) - CH = CH-, or -C = C-; m is O, 1, 2 or 3; n is 0, 1, 2 or 3; p is 1, 2, 3 or 4; q is 0, 1 or 2; t is 2, 3 or 4; and y is 0, 1 or 2.
7. The process according to claim 1, characterized in that the modafinil intermediate compound corresponds to Formula (6): the recovered modafinil or the analogue thereof corresponds to the Formula (60): Ari and Ar2 are each independently selected from aryl of 6 to 10 on atoms or heteroaryl; wherein each of Ari or Ar2 can be independently optionally substituted with 1-3 substituents independently selected from: a) hydrogen, aryl of 6 to 10 on atoms, heteroaryl, F, Cl, Br, I, -CN, -CF3 , -N02, -OH, -OR7, -0 (CH2) P NR9R10, -OC (= 0) R7, -OC (= 0) NR9R? O, -0 (CH2) P0R8, -CH20R8, -NR9R10, - NR8S (= 0) 2R7, -NR8C (= 0) R7, or -NR8C (= S) R7; b) -CH20Rn; c) -NR8C (= O) NRgR? 0, -NR8C (= S) NR9R? 0, -C02R? 2, -C (= 0) Ri3, -C (= O) NR9R? 0, -C (= S) NR9R10, -CH = NORx2, -CH = NR7, - (CH2) pNR9R? O, - (CH2) pNHRn, -CH = NNR? 2R? 2A, -C (= NR8) NR8AR8B-NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 6 on atoms, alkenyl of 2 8 on atoms or alkynyl of 2 to 8 on atoms, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 groups independently selected from aryl of 6 to 10 on atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH, -0R7, -CH20R8, -NR9R10, -O- (CH2) P- 0H, -S- (CH2) P-0H, -Xx (CH2) POR7, X? (CH2) pNR9R? O, -X? (CH2) pC (= 0) NR9R? O, -Xi (CH2) PC ( = S) NR9R? 0, -XiíCHzJpOCÍOJNRgRio, -Xi (CH2) PC02R8, -Xx (CH2) PS (O) R7, -X? (CH2) pNR8C (= 0) NR9R? O, -C (= 0) R ? 3, -C02R12, -OC (= 0) R7, -C (= 0) NR9R? O, -OC (= 0) NR12R? 2A, O-tetrahydropyranyl, -C (= S) NR9R? 0, -CH = NNR? 2R? 2A, -CH = N0Ri2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= O) NRgR? 0, -NR8C (= S) NR9R? 0 , -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR? 2R? 2A, -P (= 0) (OR8) 2, -ORn, and a monosaccharide of 5 to 7 on atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl from 1 to 4 on atoms, alkoxy of 1 to 4 on atoms or -0-C (= 0) R7; Xi is -0-, -S-, or -N (R8) -; J is alkylene of 2 to 4 on atoms or Q-C0-; Q is alkylene of 1 to 3 on atoms; R2A is hydrogen, alkyl of 1 to 6 on atoms, aryl or heteroaryl; R 4A is hydrogen, alkyl of 1 to 6 on atoms, aryl or heteroaryl; R is alkyl of 1 to 6 on atoms, aryl of 6 to 10 on atoms, or heteroaryl; R8, R8A and R8B are each independently hydrogen, alkyl of 1 to 4 on atoms, or aryl of 6 to 10 on atoms; Rg and Rio are each independently selected from hydrogen, alkyl of 1 to 4 on atoms, and aryl of 6 to 10 on atoms; or Rg and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the oxyl group is removed; R 2 and R 2 A are each independently selected from hydrogen, alkyl of 1 to 6 on atoms, cycloalkyl, aryl of 6 to 10 on atoms, and heteroaryl; or Ri and R? 2ñ, together with the nitrogen atom to which they are bound, form a 5-7 membered heterocyclic ring; R13 is hydrogen, alkyl of 1 to 6 on atoms, cycloalkyl, aryl of 6 to 10 on atoms, heteroaryl, -C (= 0) R7, -C (= O) NR9R10, or -C (= S) NR9R ? 0; p is 1, 2, 3 or 4; q is 0, 1 or 2; t is 2, 3 or 4; and y is 0, 1 or 2.
8. The process according to claim 1, characterized in that the intermediate compound of modafinil corresponds to the Formula 10 the recovered modafinil or analogous thereof corresponds to Formula (70): X is a bond, -CH2CH2-, -O-, S (0) y-, -N (R8) -, -CHN (R8) -, -CH = CH-, -CH2-CH = CH-, C ( = 0), -C (R8) = N-, -N = C (R8) -, -C (= 0) -N (R8) -, or -NR8-C (= 0) -; The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with an oxygen, nitrogen or sulfur atom; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein ring A and ring B can each be independently substituted with 1-3 substituents selected from: a) hydrogen, aryl of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, -CN, - CF3, -N02, -OH, -OR7, -0 (CH2) PNR9R10, -OC (= 0) R7, -OC (= 0) NR9R? O, -0 (CH2) POR8, -CH2OR8, -NR9R? 0, -NR8S (= 0) 2R7, -NR8C (= 0) R, or -NR8C (= S) R7; b) -CH2ORn; c) -NR8C (= 0) NR9R? o, -NR8C (= S) NR9R10, -C02R? 2, -C (= 0) Ri3, -C (= 0) NR9R? O, -C (= S) NR9R? 0, -CH = NOR? 2, -CH = NR7, - (CH2) pNR9R? O, - ( CH2) pNHRn, -CH = NNR? 2R? 2A, -C (= NR8) NR8AR8B- NR8C (= NH) R8A, -NR8C (= NH) NR8AR8B, d) -S (0) and R7, - (CH2) PS (0) and R7, -CH2S (0) and R7; and e) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms carbon, wherein: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 independently selected aryl groups of 6 to 10 carbon atoms, heteroaryl, F, Cl, Br, I, CF3, -CN, -N02, -OH , -OR7, -CH20R8, -NRgRio, -O- (CH2) P-0H, -S- (CH2) P-0H, -Xi (CH2) POR, X? (CH2) PNR9R? O, -X? CH2) pC (= 0) NR9R? O, -Xi (CH2) PC (= S) NR9R? 0, -X? (CH2) POC (0) NR9R? O, -Xi (CH2) PC02R8, -Xx (CH2) ) PS (O) R7, -X? (CH2) pNR8C (= O) NR9R10, -C (= 0) R? 3, -C02R? 2, -OC (= 0) R7, -C (= 0) NRgRio , -OC (= 0) NR? 2R? 2A, O-tetrahydropyranyl, -C (= S) NR9R? 0, -CH = NNR? 2R? 2A, -CH = N0Ri2, -CH = N7, -CH = NNHCH (N = NH) NH2, -NR8C02R7, -NR8C (= 0) NR9R? Or, -NR8C (= S) NR9R10, -NHC (= NH) NH2, -NR8C (= 0) R7, -NR8C (= S) R7, -NR8S (= 0) 2R7, -S (0) and R7, -S (= 0) 2NR? 2R? 2A, -P (= 0) (OR8) 2, -ORn, and a monosaccharide of 5 to 7 carbon atoms wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon or -0-C (= 0) R7; J is alkylene of 2 to 4 carbon atoms or Q-CO-; Q is alkylene of 1 to 3 carbon atoms; R2A is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R4A is hydrogen, alkyl of 1 to 6 carbon atoms, aryl or heteroaryl; R7 is alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, or heteroaryl; Rs, RβA and RTB are each independently hydrogen, alkyl of 1 to 4 carbon atoms, or aryl of 6 to 10 carbon atoms; Rg and Rio are each independently selected from hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 6 to 10 carbon atoms; or Rg and Rio together with the nitrogen atom to which they are bound, form a 3-7 membered heterocyclic ring; Rn is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R 2 and R 2 A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, and heteroaryl; or R 2 and R 2A, together with the nitrogen atom to which they are bound, form a 5-7 membered heterocyclic ring; R13 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl, aryl of 6 to 10 carbon atoms, heteroaryl, -C (= 0) R7, -C (= 0) NR9R? O, or -C (= S) ) NR9R? 0; Xi is -O-, -S-, or -N (R8) -; p is 1, 2, 3 or 4; q is 0, 1 or 2; t is 2, 3 6 4; and y is 0, 1 or 2.
9. The process according to claim 1, characterized in that the modafinil intermediate compound corresponds to Formula (8): The recovered modafinil or analogous thereof corresponds to the Formula (80): The rings A and B, together with the carbon atoms to which they are linked, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms can be replaced by heteroatoms selected by oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which: i) a carbon atom is replaced with a oxygen atom, nitrogen or sulfur; ii) two carbon atoms are replaced with a sulfur atom and a nitrogen atom, an oxygen atom and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen atom and two nitrogen atoms or one sulfur atom and two nitrogen atoms; wherein the rings are optionally substituted with one to three R20 groups; X is not present, it is a bond, O, S (0) and, NR10, alkylene of 2 carbon atoms, alkenylene of 2 to 3 carbon atoms, C (= 0), C (R21) 2NR10, C (R21) ) = N, N = C (R21), C (= 0) N (R10), or NR10C (= O); wherein the alkylene and alkenylene groups are optionally substituted with one to three R20 groups; R is hydrogen or alkyl of 1 to 6 carbon atoms; Y is selected from: a) (alkylene of 1 to 6 carbon atoms) -R1; b) (alkylene of 1 to 6 carbon atoms) -R2; c) (alkylene of 1 to 4 carbon atoms) mZ- (alkylene of 1 to 4 carbon atoms) n-Rp-d) (alkylene of 1 to 6 carbon atoms) -0 (CH2) pOR21, e) alkyl from 1 to 6 carbon atoms substituted with one to two OR21 groups; and f) CH2CR21 = C (R21) 2; wherein the alkyl and alkylene groups are optionally substituted with one to three R20 groups; Z is O, NR10A, S (0) y, CR21 = CR21, C = C (R21) 2, C = C, arylene of 6 to 10 carbon atoms, heteroarylene of 5-10 members, cycloalkylene of 3 to 6 atoms of carbon, or 3-6 membered heterocycloalkylene; wherein the arylene, heteroarylene, cycloalkylene and heterocycloalkylene groups are optionally substituted with one to three R20 groups; R1 is selected from NR12R13, NR21C (= 0) R14, C (= 0) R15, C02Rn, 0C (= 0) R, C (= 0) NR12R13, C (= 0) NR210R14 C (= NR) NR12R13, NR21S (O) 2R11, S (0) 2NR12R13, NR21S (0) 2NR12R13, and P0 (0R21) 2; R2 is 5-6 membered heteroaryl, wherein the heteroaryl group is optionally substituted with one to three R20 groups; R10 and R10A at each occurrence are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, C (= 0) R15, and S (0) and R14; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R14 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, and arylalkyl; wherein the alkyl, aryl and arylalkyl groups are optionally substituted with one to three R20 groups; R15 in each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, arylalkyl, and heteroaryl; wherein the alkyl, aryl, arylalkyl, and heteroaryl groups are optionally substituted with one to three R20 groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OR21, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, spirocycloalkyl of 3 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3 to 7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, = 0, C (= 0 ) R22, C02R21, 0C (= 0) R22, C (= 0) NR23R24, NR21C (= 0) R22. NR21C02R22. OC (= 0) NR23R24, NR21C (0) R22, NR21C (= S) R22, and S (0) and R22; R21 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R23 and R24, together with the nitrogen atom to which they are attached, form a 3-7 heterocycloalkyl ring members; R25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and y is 0, 1 or 2.
10. The process according to claim 1, characterized in that the modafinil intermediate compound corresponds to Formula (9): the recovered modafinil or the analogue thereof corresponds to the Formula (90): Ar is aryl of 6 to 10 carbon atoms substituted with 0-5 R3; cycloalkenyl of 5 to 10 carbon atoms substituted with 0-5 R3; or a 5- to 14-membered heteroaryl group substituted with 0-5 R3, wherein the heteroaryl group comprises one, two or three heteroatoms selected from nitrogen, oxygen sulfur or selenium; And it is alkylene of 1 to 6 carbon atoms substituted with 0-3 R20A; R1 is selected from H, C (= 0) NR12R13, C (= N) NR12R13, 0C (= 0) NR12R13, NR21C (= 0) NR12R13, NR21S (= 0) 2NR12R13, - (aryl of 6 to 10 carbon atoms) -NR12R13 wherein the aryl is substituted with 0-3 R2p NR21C (= 0) R14, C (= 0) R14, C (= 0) 0R11, 0C (= 0) Rn, and NR21S (= 0) 2Rn; R2 is selected from hydrogen, F, Cl, Br, and OR16, OR25, NR17R18, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, C (= 0) R16, C (= 0) 0R16, OC (= 0) R16, C (= 0) NR17R18, NR15C (= 0) R16, NR15C02R16, OC (= 0) NR17R18, NR15C ( = S) R16, SR "; and S (= 0) 2R16; alternatively, two R2 groups can be combined to form a methylenedioxy group, an ethylenedioxy group or a propylenedioxy group; R3 is selected from hydrogen, F, Cl, Br, I, OR16, 0CF3, OR25, NR1 R18, NHOH, N02, CN, CF3, CH2OR16, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 atoms carbon, 3-7 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, arylalkyl of 7 to 10 carbon atoms, C (= 0) R16, C (= 0) 0R16, 0C (= 0) R16, C (= 0) NR17R18, NR15C (= 0) R16, NR15C02R15, OC (= 0) NR17R18, NR15C (= S) R16, SR16; S (= 0) R16; and S (= 0) 2R16, and NR15S (= 0) 2R16; R4 and R5 at each occurrence are each independently selected from hydrogen, alkyl from 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms; alternatively, R4 and R5, together with the carbon atom to which they are bonded, form a spirocyclic ring of 3 to 7 members; R11 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms substituted with 0-3 R20; and aryl of 6 to 10 carbon atoms substituted with 0-3 R20; R12 and R13 at each occurrence are each independently selected from hydrogen, alkyl from 1 to 6 carbon atoms substituted with 0-3 R20 and aryl of 6 to 10 carbon atoms substituted with 0-3 R20; alternatively, R12 and R13, together with the nitrogen atom to which they are linked, form a 3-7 membered heterocyclic ring substituted with 0-3 R20; R14 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms substituted with 0-3 R20; aryl of 6 to 10 carbon atoms substituted with 0-3 R20; and arylalkyl of 7 to 10 carbon atoms substituted with 0-3 R20; R15 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R16 in each occurrence is independently 13 selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms; R17 and R18 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or alternatively, R17 and R18, together with the nitrogen atom to which they are attached , form a 3-7 membered heterocyclic ring, wherein the 3-7 membered heterocyclic ring is substituted with 0-2 oxo groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OH, OR22, OR2p NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, (alkyl of 1 to 6 carbon atoms) -OH, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3 to 7 members, phenyl substituted with 0-1 R26; 5 or 6 membered heteroaryl, arylalkyl of 7 to 10 carbon atoms, = 0, C (= 0) R22, C (= 0) OR22, 0C (= 0) R22, C (= 0) NR23R24, NR21C ( = 0) R22, NR21C02R22, 0C (= 0) NR23R24. NR21C (= S) R22. SR22; S (= 0) R22; and S (= 0) 2R22; R20A at each occurrence is independently selected from F, Cl, OH, alkoxy of 1 to 4 carbon atoms, CF3, alkyl of 1 to 4 carbon atoms, (alkyl of 1 to 4 carbon atoms) -OH, alkenyl of 2 to 4 carbon atoms, alkynyl of 2 to 4 carbon atoms, and cycloalkyl of 3 to 5 carbon atoms; R21 at each occurrence is independently selected from H and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, (alkyl of 1 to 6 carbon atoms) -OH, and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl from 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or alternatively, R23 and R24, together with the nitrogen atom to which they are bonded, form a 3-7 membered heterocyclyl ring; R25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R26 at each occurrence is independently selected from hydrogen, F, Cl, Br, alkyl of 1 to 5 carbon atoms, and alkoxy of 1 to 6 carbon atoms; x is O, 1, 2, 3 or 4; and q is 1 or 2. The process according to claim 1, characterized in that the intermediate modafinil compound corresponds to Formula (11): Ar-S-Y (11); the recovered modafinil or the analogue thereof corresponds to the Formula (110) Or Ar-S-Y (110). Ar is X is a bond, CH2, 0, S (0) and, or NR10; rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR21, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, alkenyl from 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3-7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, C (= 0) R22, C02R21, 0C (= 0) R22, C (= 0) NR23R24, NR21C (= 0) R22, NR21C02R22, OC (= 0) NR23R24, NR21C (= S) R22, and S (0) 7R22; Ring B is optionally substituted with one to three groups selected from alkyl of 1 to 6 carbon atoms, phenyl, and 5-6 membered heteroaryl; Y is (alkylene of 1 to 6 carbon atoms) -R1; or (alkylene of 1 to 4 carbon atoms) n-R1; wherein the alkylene groups are optionally substituted with one to three R20 groups; Z is 0, NR10A, S (0) y, CR21 = CR21, C = C (R21) 2, C = C, arylene of 6 to 10 carbon atoms, heteroarylene of 5-10 members, cycloalkylene of 3 to 6 atoms carbon, or 3-6 membered heterocycloalkylene; wherein the arylene, heteroarylene, cycloalkylene, and heterocycloalkylene groups are optionally substituted with one to three R20 groups; R1 is NR12R13, NR21C (0) R14, C (= 0) R15, COOH, C02R14, OC (= 0) R, C (= 0) NR1R13, C (= N) NR12R13, OC (= 0) NR12R13, NR21S (0) 2R
11, S (0) 2NR12R13, NR21C (= 0) NR12R13, NR21S (0 ) 2NR12R13, or P0 (0R21) 2; R10 and R10A are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, C (= 0) R15, and S (0) and R14; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R11 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms; wherein the alkyl and aryl groups are optionally substituted with one to three R20 groups; R12 and R13 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R12 and R13, together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring; wherein the alkyl and aryl groups and the heterocycloalkyl ring are optionally substituted with one to three R20 groups; R14 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, and arylalkyl; wherein the alkyl, aryl and arylalkyl groups are optionally substituted with one to three R20 groups; R15 at each occurrence is independently selected from alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, arylalkyl, and heteroaryl; wherein the alkyl, aryl, arylalkyl and heteroaryl groups are optionally substituted with one to three R20 groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OR21, OR25, NR23R24, NHOH, N02, CN, CF3, alkyl of 1 to 6 carbon atoms, spirocycloalkyl of 3 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, heterocycloalkyl of 3-7 members, phenyl, heteroaryl of 5 or 6 members, arylalkyl, = 0, C (= 0 ) R22, C02R21, OC (= 0) R22, C (= 0) NR23R2. NR21C (= 0) R22, NR21C02R22, 0C (= 0) NR23R24, NR21C (= 0) R22, NR21C (= S) R22, and S (0) and R22; R21 at each occurrence is independently selected from hydrogen and alkyl of 1 to 6 carbon atoms; R22 at each occurrence is independently selected from hydrogen, alkyl of 1 to 6 carbon atoms and aryl of 6 to 10 carbon atoms; R23 and R24 at each occurrence are each independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, and aryl of 6 to 10 carbon atoms, or R23 and R24, together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring; R25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; m is 0 or 1; n is 0 or 1; q is O, 1 or 2; e and is 0, 1 or 2.
12. The process according to any of claims 1-11, characterized in that the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 40: 1 (in volume).
13. The process according to any of claims 1-12, characterized in that the ratio of the alcohol to the organic acid in the reaction mixture is from about 1: 1 to about 7: 1 (by volume).
14. The process according to any of claims 1-13, characterized in that the ratio of alcohol to organic acid in the reaction mixture is about 3: 1 (by volume).
15. The process according to any of claims 1-14, characterized in that the alcohol is selected from the group consisting of linear, branched or cyclic alcohols.
16. The process according to any of claims 1-15, characterized in that the alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, sec-butanol, tert-butanol, 2-methyl-1- butanol, ethylene glycol, cyclohexanol and combinations thereof.
17. The process according to any of claims 1-16, characterized in that the alcohol is methanol.
18. The process according to any of claims 1-17, characterized in that the organic acid is selected from the group consisting of carboxylic acids, sulfonic acids and combinations thereof.
The process according to any of claims 1-18, characterized in that the organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, oxalic acid, benzoic acid, carbonic acid, lactic acid , malic acid, tartaric acid, mandelic acid, citric acid, fumaric acid, sorbic acid, acid succinic, adipic acid, glycolic acid, glutaric acid, methanesulfonic acid, benzenesulfonic acid, trifluoromethanesulfonic acid and combinations thereof.
20. The process according to any of claims 1-19, characterized in that the organic acid is acetic acid.
21. The process according to any of claims 1-20, characterized in that the oxidizing agent is selected from the group consisting of 02, K2S2? 8, Ca (0CI) 2, NaCl02, NaOCI, HN03, NaI04, acid m- chloroperoxybenzoic, acyl nitrates, sodium perborate, tert-butyl hypochlorite, hydrogen peroxide, t-butylhydroperoxide, alkyl and acyl peroxides, benzoyl peroxide, peracetic acid, and combinations thereof.
22. The process according to any of claims 1-21, characterized in that the oxidizing agent is hydrogen peroxide.
23. The process according to any of claims 1-22, characterized in that the oxidizing agent is a solution of hydrogen peroxide and water.
24. The process according to any of claims 1-23, characterized in that the oxidizing agent is a solution of about 25% (by weight) to about 55% (by weight) of hydrogen peroxide in water.
25. The process according to any of claims 1-24, characterized in that the oxidizing agent is a solution of about 30% (by weight) to about 50% (by weight) of hydrogen peroxide in water.
26. The process according to any of claims 1-25, characterized in that the oxidizing agent is a solution of about 30% (by weight) of hydrogen peroxide in water.
27. The process according to any of claims 1-26, characterized in that the reaction mixture comprises from about 0.80 to about 1.1 molar equivalents of oxidizing agent with respect to the modafinil intermediate compound.
28. The process according to any of claims 1-27, characterized in that the reaction mixture comprises from about 0.95 to about 1.07 molar equivalents of oxidizing agent with respect to the modafinil intermediate compound.
29. The process according to any of claims 1-28, characterized in that the reaction mixture comprises from about 0.98 to about 1.07 molar equivalents of oxidizing agent with respect to the modafinil intermediate compound.
30. The process of compliance with any of claims 1-29, characterized in that the temperature of the reaction mixture during oxidation is at least about room temperature.
31. The process according to any of claims 1-30, characterized in that the temperature of the reaction mixture during oxidation is less than about 70 ° C.
32. The process according to any of claims 1-31, characterized in that the temperature of the reaction mixture during oxidation is from about 20 ° C to about 70 ° C.
33. The process according to any of claims 1-32, characterized in that the temperature of the reaction mixture during oxidation is from about 30 ° C to about 65 ° C.
34. The process according to any of claims 1-33, characterized in that the temperature of the reaction mixture during oxidation is about 40 ° C.
35. The process according to any of claims 1-34, characterized in that the reaction mixture is not maintained at a particular temperature during oxidation.
36. The process according to any of claims 1-35, characterized in that the Oxidation is allowed to proceed for approximately 1 hour to approximately 48 hours.
37. The process according to any of claims 1-36, characterized in that the oxidation is allowed to proceed for about 18 hours to about 24 hours.
38. The process according to any of claims 1-37, characterized in that the oxidation is allowed to proceed for approximately 24 hours.
39. The process according to any of claims 1-38, characterized in that it further comprises recrystallization of the recovered modafinil or analogs thereof.
40. The process according to any of claims 1-39, characterized in that the recovered modafinil or analogs thereof, is substantially free of sulfone impurities before recrystallization.
41. The process according to any of claims 1-40, characterized in that the recovered modafinil or the analogue thereof has a purity greater than about 80% before recrystallization.
42. The process according to any of claims 1-41, characterized in that the recovered modafinil or the analogue thereof has a higher purity of approximately 85% before recrystallization.
43. The process according to any of claims 1-42, characterized in that the recovered modafinil or the analogue thereof has a purity greater than about 90% before recrystallization.
44. The process according to any of claims 1-43, characterized in that the recovered modafinil or the analogue thereof has a purity greater than about 95% before recrystallization.
45. The process according to any of claims 1-44, characterized in that the recovered modafinil or the analogue thereof has a purity greater than about 99% before recrystallization.
46. The process according to any of claims 1-45, characterized in that the recovered modafinil or the analogue thereof has a purity of about 99.5% before recrystallization.
47. The process according to any of claims 1-46, characterized in that the recovered modafinil or the analogue thereof has a purity greater than about 99.5% before recrystallisation.
48. The process according to any of claims 1-47, characterized in that the recovered modafinil or the analogue thereof is recrystallized by mixing modafinil or the analog thereof as a aliphatic solvent of low boiling point and a halo-organic solvent.
49. The process according to claim 48, characterized in that the halo-organic solvent is selected from the group consisting of dichloromethane, dichloroethane, chloroform and combinations thereof.
50. The process according to any of claims 48 or 49, characterized in that the halo-organic solvent is chloroform.
51. The process according to any of claims 48-50, characterized in that the low-boiling aliphatic solvent is selected from the group consisting of pentane, hexane, octane, heptane and combinations thereof.
52. The process according to any of claims 48-51, characterized in that the low-boiling aliphatic solvent is heptane.