KR20170109274A - N-Imidoyl sulfoximine derivatives and its preparation method - Google Patents

Abstract

The present invention relates to novel N-imidoyl sulfoximine derivatives capable of being used in various research fields by having important structural properties used as ligands and chiral adjuvants, and a preparation method thereof and, more specifically, to a method for preparing N-imidoyl sulfoximine derivatives having carbon-nitrogen coupling functional groups introduced in nitrogen atoms of sulfoximines by conducting reaction of alkyne derivatives, azide derivatives and N-sulfoximine derivatives in the presence of copper catalyst and N-imidoyl sulfoximine derivatives manufactured thereby.

Description

N-imidoyl sulfoximine derivatives and its preparation method,

The present invention relates to an N -imidoylsulfoximine derivative and a process for preparing the same. More particularly, the present invention relates to a process for producing a N -imidoylsulfoximine derivative by reacting an alkane derivative, an azide derivative and a N-sulfoximine derivative in the presence of a copper catalyst, N-imidoylsulfoximine derivative having a nitrogen-bonded functional group introduced thereinto, and to an N-imidoylsulfoximine derivative prepared thereby.

Since sulfoximine derivatives have important physiological activities and are used as ligands and chiral auxiliary agents, the development of new synthetic methods is very important. Harmata, M. Chemtracts 2003, 16, 660, Reggelin, M (2004), 33, 482. Harmata, M., Chemtracts 2003, 16, 660. A new synthetic method has been reported from starting materials that are easy to use in many groups (Okamura, H., Bolm, Myner, AC, Bolm, AC, < RTI ID = 0.0 > C. < / RTI > C. In Organic Sulfur Chemistry in Asymmetric Synthesis, Toru, T., Bolm, C., Eds .; Wiley-VCH: Weinheim, Germany, 2008, p 209 and references therein; 2004, 47, 6854, V. Bizet, R. K., Kensler, TW, Peleg, S .; Saha, U. Chuang, SS; Bernstein, G .; Korczak, V. Bizet, CMM Hendriks, C. Bolm, Chem. Soc Rev. 2015, 44, 3378.).

Conventional sulfoximine functionalization reaction may include various types of NH bonding such as N-silylation, N-halogenation, N-acylation, N-alkenylation, N-vinylation and N-arylation Many studies have been made on the formation of NP and NS bonds by the vaporization method and the NH bond of sulfoximine. There has been a need for a method for synthesizing a compound in which a new functional group is introduced into sulfoximine using starting materials that are easy to use in the prior art.

The present inventors are expected to have physiological activity through the N -imidoyl and N -oximoimidyl reactions of the previously reported sulfoximines and to synthesize novel N -imidoyl sulfoximine derivatives which can be used as ligands and chiral auxiliary agents I want to.

It is an object of the present invention to provide novel N -imidoyl sulfoximine derivatives.

The present invention also relates to a process for efficiently producing an N-imidoyl sulfoximine derivative having a carbon-nitrogen bond functional group introduced into the nitrogen atom of sulfoximine by reacting an alkane derivative, an azide derivative and a N-sulfoximine derivative in the presence of a copper catalyst There is another purpose in providing a method.

The present invention provides an N -imidoyl sulfoximine derivative represented by the following general formula (1).

[Chemical Formula 1]

[In the above formula (1)

이며; R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) _{heteroaryl, - (CH 2) n -CN} , - (CH 2) n - OH or

;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

R 'is (C1-C10) alkyl or (C6-C12) aryl;

Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

The present invention also provides a process for preparing an N -imidoyl sulfoximine derivative represented by the general formula (1), comprising reacting an alkane derivative represented by the following general formula (4a), an azide derivative represented by the general formula (5) To provide the N -imidoyl sulfoximine derivative of formula (1)

[Chemical Formula 1]

[Chemical Formula 4a]

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4a), (5) and (6)

R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) heteroaryl, - (CH _{2) n} -CN or - (CH _{2) n} - OH;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

The aryl of R ¹ and R ² may be further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo (C 1 -C 10) alkyl;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

The present invention also relates to a process for preparing an N -imidoyl sulfoximine derivative represented by the following formula (I) by reacting an alkane derivative of the formula (4b), an azide derivative of the formula (5) and an N-sulfoximine derivative of the formula to provide:

[Chemical Formula 1]

(4b)

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4b), (5) and (6)

이며;R ¹ is

;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

R 'is (C1-C10) alkyl or (C6-C12) aryl;

Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

The N -imidoyl sulfoximine derivative according to the present invention can be usefully used as an important raw material or an intermediate in the fields of natural products exhibiting physiological activity, chiral auxiliary agents, ligands used in asymmetric synthesis, medicines such as anticancer agents, have.

The method for preparing N -imidoyl sulfoximine derivatives according to the present invention comprises reacting an alkane derivative, an azide derivative and a N-sulfoximine derivative in the presence of a copper catalyst to introduce a carbon-nitrogen bond functional group into the nitrogen atom of sulfoximine N-imidoylsulfoximine derivative can be efficiently produced with a high yield and a simple experimental procedure.

Hereinafter, the present invention will be described in detail.

Here, unless otherwise defined in the technical terms and the scientific terms used, those having ordinary skill in the art to which the present invention belongs have the same meaning as commonly understood by those skilled in the art. Repeated descriptions of the same technical constitution and operation as those of the conventional art will be omitted.

The present invention provides an N -imidazolyl sulfoximine derivative represented by the following formula (1): < EMI ID =

[Chemical Formula 1]

[In the above formula (1)

이며; R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) _{heteroaryl, - (CH 2) n -CN} , - (CH 2) n - OH or

;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

R 'is (C1-C10) alkyl or (C6-C12) aryl;

Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

The term " alkyl " of the present invention means a monovalent straight or branched saturated hydrocarbon radical consisting solely of carbon and hydrogen atoms. Examples of such alkyl radicals include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, , Pentyl, hexyl, and the like.

&Quot; Aryl ", as used herein, refers to an organic radical derived from an aromatic hydrocarbon by the removal of one hydrogen, with a single or fused ring containing in each ring suitably 4 to 7, preferably 5 or 6 ring atoms And includes a form in which a plurality of aryls are connected by a single bond. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, fluorenyl, indenyl, and the like.

&Quot; Halo " or " halogen " as used in the present invention means a fluorine, chlorine, bromine or iodine atom.

The term " alkoxy " as used in the present invention means an -O-alkyl radical where 'alkyl' is as defined above. Examples of such alkoxy radicals include, but are not limited to, methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like.

&Quot; Heteroaryl " in the present invention means an aryl group having 1 to 4 hetero atoms selected from N, O and S as an aromatic ring skeletal atom and the remaining aromatic skeletal atom carbon, Monocyclic heteroaryl, and condensed polycyclic heteroaryl with one or more benzene rings. The heteroaryl in the present invention also includes a form in which one or more heteroaryl is connected to a single bond. Specific examples thereof include monocyclic heteroaryl such as furyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, isoxazolyl, oxazolyl, pyridyl and the like, benzofuranyl, dibenzofuranyl, Examples of the polycyclic heterocycle such as benzothiophenyl, benzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, quinolyl, isoquinolyl, Aryl, and the like.

In an N -imidoyl sulfoximine derivative according to an embodiment of the present invention, it may be represented by the following formula (2) or (3)

(2)

이고; n, R', Ar', R² 및 Ar은 상기 화학식 1에서의 정의와 동일하다.In Formula 2, R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) _{heteroaryl, - (CH 2) n -CN} , - ( CH ₂ ) _n -OH or

ego; n, R ', Ar', R ² and Ar are as defined in the above formula (1).

(3)

이고; n, R', Ar', R² 및 Ar은 상기 화학식 1에서의 정의와 동일하다. In Formula 3, R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) _{heteroaryl, - (CH 2) n -CN} , - ( CH ₂ ) _n -OH or

ego; n, R ', Ar', R ² and Ar are as defined in the above formula (1).

이며; R² 및 R'는 각각 독립적으로 (C1-C7)알킬, 페닐, 나프틸 또는 바이페닐이며; L은 -CH₂- 또는 -C(=O)-이고; Ar 및 Ar'는 각각 독립적으로 페닐, 나프틸 또는 바이페닐이고, 상기 Ar의 페닐, 나프틸 및 바이페닐은 (C1-C7)알킬, (C1-C7)알콕시 및 할로겐으로 이루어진 군으로부터 선택되는 하나 이상의 치환체로 더 치환될 수 있으며; n은 1 내지 3의 정수이고; 상기 R¹, R² 및 R'의 페닐, 나프틸 및 바이페닐은 (C1-C7)알킬, (C1-C7)알콕시, 할로겐, 니트로 및 할로(C1-C7)알킬로 이루어진 군으로부터 선택되는 하나 이상의 치환체로 더 치환될 수 있다.In the N -imidoylsulfoximine derivative according to one embodiment of the present invention, R ¹ is (C ¹ -C 7) alkyl, (C ¹ -C 7) alkoxycarbonyl, phenyl, naphthyl, biphenyl, thiophenyl, furyl, imidazolyl, thiazolyl, pyridyl, _{quinolyl, - (CH 2) n -CN} , - (CH 2) n -OH or

; R ² and R 'are each independently (C 1 -C 7) alkyl, phenyl, naphthyl or biphenyl; L is -CH ₂ - or -C (= O) - and; Ar and Ar 'are each independently phenyl, naphthyl or biphenyl, wherein the phenyl, naphthyl and biphenyl of Ar are optionally substituted with one or more substituents selected from the group consisting of (C1-C7) alkyl, Or more of the substituents; n is an integer from 1 to 3; Wherein phenyl, naphthyl and biphenyl of R ¹ , R ² and R 'are selected from the group consisting of (C 1 -C 7) alkyl, (C 1 -C 7) alkoxy, halogen, nitro and halo Or more of the above substituents.

The N -imidoylsulfoximine derivative according to an embodiment of the present invention may be selected from the following compounds, but is not limited thereto.

In addition, the present invention includes the N -imidoyl sulfoximine derivative represented by the above formula (1) and the preparation method thereof as a scope of right, and a method for preparing the N -imidoyl sulfoximine derivative according to the present invention will be described in detail do.

The present invention provides a process for preparing an N -imidoyl sulfoximine derivative represented by the following general formula (1) by reacting an alkane derivative represented by the following general formula (4a), an azide derivative represented by the following general formula (5) do:

[Chemical Formula 1]

[Chemical Formula 4a]

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4a), (5) and (6)

R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) heteroaryl, - (CH _{2) n} -CN or - (CH _{2) n} - OH;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

The aryl of R ¹ and R ² may be further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo (C 1 -C 10) alkyl;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

The present invention also relates to a process for preparing an N -imidoyl sulfoximine derivative represented by the following formula (I) by reacting an alkane derivative of the formula (4b), an azide derivative of the formula (5) and an N-sulfoximine derivative of the formula to provide:

[Chemical Formula 1]

(4b)

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4b), (5) and (6)

이며;R ¹ is

;

R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;

L is -CH ₂ - or -C (= O) - and;

Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

n is an integer from 1 to 5;

R 'is (C1-C10) alkyl or (C6-C12) aryl;

Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;

The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;

Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.

In one embodiment according to the present invention, N in the formula (1) - yimido one sulphoxide civil derivative N of the formula (2) and (3) - comprising a yimido one sulphoxide civil derivative, as shown in the following schemes 1 and 2 , An alkane derivative of the general formula (4a) or (4b), an azide derivative of the general formula (5) and an N-sulfoximine derivative of the general formula (6) to prepare an N -imidoyl sulfoximine derivative of the general formula N -oximidoyl sulfoximine derivative is prepared.

[Reaction Scheme 1]

In the above scheme ^1, R 1 is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) heteroaryl, - (CH _{2) n} -CN, or - ( CH ₂ ) _n -OH, and n, R ² and Ar are as defined in the above formula (1).

[Reaction Scheme 2]

In the above Reaction Scheme 2, R < ¹ &^gt; And n, R ', Ar', R ² and Ar are as defined in the above formula (1).

Copper (Cu) The catalyst according to one embodiment of the present invention, CuI (copper (I) iodide) , CuBr (copper (I) bromide), CuCl (copper (I) chloride), Cu 2 O (Copper (I) oxide ), CuTC (Copper (I) -thiophene-2-carboxylate), and CuOTf (Copper (I) triflate). Of these, CuI is preferably selected.

The amount of the copper (Cu) catalyst according to an embodiment of the present invention is 0.1 to 0.5 mole based on 1 mole of the N-sulfoximine derivative represented by the formula (6), and the copper (Cu) , The N -imidoyl sulfoximine derivative of the formula (1) can be prepared. If the concentration is out of the above range, the yield and economical efficiency may be lowered.

In addition, in one embodiment of the present invention, a base may be further included in addition to the copper catalyst. Examples of the base include pyridine, potassium carbonate, potassium phosphate tribasic, sodium acetate, cesium carbonate, diisopropylethylamine, Diazabicyclo [2.2.2] octane, 1,8-diazabicyclo [5.4.0] undec-7-ene (1,8-diazabicyclo [5.4.0] undec-7-ene, tributylamine, and trimethylamine. Of these, triethylamine is preferably selected. The amount of the base to be used may be 0.1 to 2 moles based on 1 mole of the N-sulfoximine derivative represented by the above formula (6). The alkane derivative of formula (4a) may be used in an amount of 1 to 3 moles per mole of the N-sulfoximine derivative of formula (6), and the alkane derivative of formula (4b) Is used in the range of 0.5 to 1.5 mol per 1 mol of the N-sulfoximine derivative. The objective compound can be produced with high yield within the above range.

The azide derivative of Formula 5 according to an embodiment of the present invention is preferably used in a range of 1 to 3 mol per 1 mol of the N-sulfoximine derivative of Formula 6. [ The objective compound can be produced with high yield within the above range.

In one embodiment of the present invention, the reaction can be carried out in an organic solvent, and the organic solvent is not limited so long as it can dissolve the reactant. The organic solvent is selected from the group consisting of acetonitrile, toluene, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, benzene, xylene, chlorobenzene, hexafluorobenzene, octa It is preferable to use tetrahydrofuran in consideration of the solubility of the reactants and the ease of removal of the reactants, and it is more preferable to use tetrahydrofuran.

N in the general formula (I) of the present invention - the reaction temperature for the production of yimido one sulphoxide civil derivative is a room temperature (25 ℃) to 60 ℃, preferably N of the formula (2) at 25 to 30 ℃ - producing a yimido one sulphoxide civil derivative And then heated to 40 to 60 캜, more preferably to 45 to 55 캜, and still more preferably to 50 캜 to prepare an N -oximidoyl sulfoximine derivative represented by general formula (3). The reaction time may vary depending on the kind of the reactant, the type of the solvent, and the amount of the solvent. After confirming that the starting material is completely consumed through TLC or the like, the reaction is completed. When the reaction is completed, the solvent may be distilled off under reduced pressure, and then the target product may be separated and purified through a conventional method such as column chromatography.

Hereinafter, the structure of the present invention will be described in more detail with reference to examples. However, the following examples are provided to aid understanding of the present invention, and the scope of the present invention is not limited thereto.

Preparation of - ((4-methylphenylsulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 1] N - (4- phenyl) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

To the test tube, CuI (3.8 mg, 0.02 mmol), S- methyl- S- phenylsulfoximine (31.0 mg, 0.20 mmol) and THF (tetrahydrofuran, 1.0 mL) were added and pheylacetylene (20.4 mg, 0.20 mmol) and 4-methylbenzenesulfonyl azide 47.3 mg, 0.24 mmol) and triethylamine (24.3 mg, 0.24 mmol). The reaction is then carried out at 25 ° C. After the completion of the reaction was confirmed by TLC, the solvent was removed and the resultant product was separated by column chromatography (EtOAc: CH ₂ Cl ₂ : Hexane = 1: 1: 2) to obtain the objective compound N- (4-methylphenylsulfonyl) phenyl yimido one - S, S - phenyl sulfonic poksiyi imide was obtained (73.4 mg, 86%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.64-7.59 (m, 1H), 7.56-7.54 (m, 2H) 7.46-7.17 (m, 11H), 4.20-4.16 (m, 2H), 3.16 (s, 3H), 2.40 (s, 3H)

Preparation of - ((4-methoxyphenylsulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 2] N - (4- methoxyphenyl) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

The procedure of Example 1 was repeated except for using 4-methoxybenzenesulfonyl azide (51.2 mg, 0.24 mmol) instead of 4-methylbenzenesulfonyl azide of Example 1 to obtain N - (4-methoxyphenylsulfonyl) Phenylimidoyl- S , S -methylphenylsulfoximide (72.9 mg, 82%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.64-7.29 (m, 12H), 6.85 (d, J = 7.9 Hz, 2H), 4.22-4.18 (m, 2H), 3.84 (s, 3H), 3.16 ( s, 3H)

Preparation of - ((4-chlorophenylsulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 3] N - (4- chlorophenyl) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

The procedure of Example 1 was repeated except for using 4-chlorobenzenesulfonyl azide (52.2 mg, 0.24 mmol) instead of 4-methylbenzenesulfonyl azide of Example 1 to obtain N- (4-methoxyphenylsulfonyl) Phenylimidoyl- S , S -methylphenylsulfoximide (77.0 mg, 86%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.64-7.60 (m, 1H), 7.56-7.29 (m, 13H), 4.21-4.14 (m, 2H), 3.16 (s, 3H)

Preparation of - ((4-trifluoromethylphenylsulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 4] N - (phenyl-sulfonyl 4-trifluoromethyl) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

The procedure of Example 1 was repeated except for using 4-trifluoromethylbenzenesulfonyl azide (60.3 mg, 0.24 mmol) instead of 4-methylbenzenesulfonyl azide of Example 1 to obtain N - (4-trifluoromethylphenylsulfonyl ) Phenylimidoyl- S , S -methylphenylsulfoximide (82.3 mg, 86%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.65-7.53 (m, 7H), 7.43-7.28 (m, 7H), 4.22-4.13 (m, 2H), 3.16 (s, 3H)

Preparation of - ((4-nitrophenylsulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 5] N - (phenylsulfonyl 4-nitro) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

(4-nitrobenzenesulfonyl azide) (54.8 mg, 0.24 mmol) was used instead of 4-methylbenzenesulfonyl azide of Example 1 to obtain the title compound N - (4-nitrophenylsulfonyl) Phenylimidoyl- S , S -methylphenylsulfoximide (60.3 mg, 66%).

¹ H NMR (400 MHz, CD ₂ Cl ₂ ) ? 8.16 (d, J = 8.7 Hz, 2H), 7.72-7.56 3.18 (s, 3 H)

Example 6 Preparation of N - (methanesulfonyl) phenylimidoyl- S , S -methylphenylsulfoximide ( N - (methanesulfonyl) phenethylimidoyl- S, S- methylphenylsulfoximide)

Except that methanesulfonyl azide (29.1 mg, 0.24 mmol) was used in place of 4-methylbenzenesulfonyl azide of Example 1 to obtain the target compound N- (methanesulfonyl) phenylimidoyl- S , S -methylphenyl sulfoximide (57.0 mg, 81%) was obtained.

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.68 (t, J = 14.8 Hz, 3H), 7.58-7.54 (m, 2H), 7.37-7.27 (m, 5H), 4.13-4.04 (m, 2H), 3.24 (s, 3H), 2.62 (brs, 3H)

Preparation of - ((isopropanesulfonyl) phenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 7] N - (iso-propane-sulfonyl) phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

The procedure of Example 1 was repeated except for using isopropanesulfonyl azide (35.8 mg, 0.24 mmol) instead of 4-methylbenzenesulfonyl azide of Example 1 to obtain N - (isopropanesulfonyl) phenylimidoyl- S , S -methylphenyl sulfoximide (60.0 mg, 79%).

¹ H 2H NMR (400 MHz, CD ₂ Cl ₂ ) ? 7.69-7.65 (m, 3H), 7.57-7.53 (m, 2H), 7.44-7.42 (m, 1H), 4.23-4.05 (m, 2H), 3.17 (s, 3H), 2.81-2.75 (m, 1H), 1.05 (dd, J = 26.8, 6.6 Hz,

Preparation of - ((4-Methylphenylsulfonyl) -3 -methylphenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 8] N - (4- methylphenyl sulfonyl) -3-phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

Except that 1-ethynyl-3-methylbenzene (23.2 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -3 - methylphenylimidoyl- S , S -methylphenylsulfoximide (70.5 mg, 80%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.62 (t, J = 7.4 Hz, 1H), 7.58-7.56 (m, 2H), 7.47-7.43 (m, 4H), 7.19-7.10 (m, 6H), (M, 2H), 3.17 (s, 3H), 2.41 (s, 3H), 2.32

Preparation of - ((4-Methylphenylsulfonyl) -4 -methylphenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 9] N - (4- methylphenyl sulfonyl) -4-phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

Except that 1-ethynyl-4-methylbenzene (23.2 mg, 0.20 mmol) was used in place of pheylacetylene in Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -4 - methylphenylimidoyl- S , S -methylphenylsulfoximide (72.9 mg, 83%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.64-7.60 (m, 1H), 7.58-7.56 (m, 2H), 7.46-7.42 (m, 4H), 7.25-7.18 (m, 6H), 4.16-4.13 (m, 2H), 3.16 (s, 3H), 2.41 (s, 3H), 2.35 (brs,

[Example 10] N - (4- methylphenyl sulfonyl) -2-methoxyphenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-Methylphenylsulfonyl) -2-methoxyphenethylimidoyl- S, S -methylphenylsulfoximide) Manufacturing

Except that 1-ethynyl-2-methoxybenzene (26.4 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -2 -Methoxyphenylimidoyl- S , S -methylphenylsulfoximide (75.1 mg, 80%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.66-7.46 (m, 7H), 7.28-7.13 (m, 4H), 6.90-6.89 (m, 2H), 4.16 (brs, 2H), 3.73 (s, 3H ), 3.16 (s, 3 H), 2.41 (s, 3 H)

[Example 11] N - (4- methylphenyl sulfonyl) -3-methoxy-phenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -3-methoxyphenethylimidoyl- S, S -methylphenylsulfoximide) Manufacturing

Except that 1-ethynyl-3-methoxybenzene (26.4 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -3 -Methoxyphenylimidoyl- S , S -methylphenylsulfoximide (82.4 mg, 90%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.62 (t, J = 7.4 Hz, 1H), 7.58-7.56 (m, 2H), 7.47-7.43 (m, 4H), 7.31-7.18 (m, 3H), (S, 3H), 2.40 (s, 3H), 3.94 (s, 3H)

[Example 12] N - (4- methylphenyl sulfonyl) -4-methoxy-phenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -4-methoxyphenethylimidoyl- S, S -methylphenylsulfoximide) Manufacturing

Except that 1-ethynyl-4-methoxybenzene (26.4 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -4 -Methoxyphenylimidoyl- S , S -methylphenylsulfoximide (79.7 mg, 87%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.62 (t, J = 7.4 Hz, 1H), 7.57-7.55 (m, 2H), 7.46-7.17 (m, 8H), 6.87 (brs, 2H), 4.14- (M, 2H), 3.79 (s, 3H), 3.16 (s, 3H), 2.40

[Example 13] N - (4- methylphenyl sulfonyl) -2-bromophenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -2-bromophenethylimidoyl- S, S -methylphenylsulfoximide) Manufacturing

Except that 1-bromo-2-ethynylbenzene (36.2 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -2 -bromophenyl yimido one-S, S-phenyl sulfonic poksiyi imide was obtained (91.6 mg, 91%).

¹ H 2H NMR (400 MHz, CD ₂ Cl ₂ ) ? 7.66-7.57 (m, 6H), 7.49-7.45 (m, 2H), 7.27-7.14 , ≪ / RTI > 3H), 2.41 (s, 3H)

[Example 14] N - (4- methylphenyl sulfonyl) -4-bromophenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -4-bromophenethylimidoyl- S, S -methylphenylsulfoximide) Manufacturing

Except that 1-bromo-4-ethynylbenzene (36.2 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -4 - bromophenylimidoyl- S , S -methylphenylsulfoximide (77.8 mg, 77%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.65-7.61 (m, 1H), 7.57-7.55 (m, 2H), 7.48-7.17 (m, 10H), 4.17-4.12 (m, 2H), 3.17 (s , ≪ / RTI > 3H), 2.40 (s, 3H)

[Example 15] N - (4- methylphenyl sulfonyl) -4-trifluoromethyl-phenyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -4-trifluoromethylphenethylimidoyl- S, S -methylphenylsulfoximide )

The reaction was carried out in the same manner as in Example 1 except that 1-ethynyl-4- (trifluoromethyl) benzene (34.0 mg, 0.20 mmol) was used instead of the pheylacetylene of Example 1 to obtain the objective compound N- (4-methylphenylsulfonyl ) -4-trifluorophenylimidoyl- S , S -methylphenyl sulfoximide (81.4 mg, 82%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.64-7.43 (m, 11H), 7.19-7.18 (m, 2H), 4.28 (brs, 2H), 3.19 (s, 3H), 2.40 (s, 3H)

[Example 16] N - (4- methylphenyl sulfonyl) thiophene-3-carbonyl-ethyl shown one-S, S-phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -thiophen-3-ylethylimidoyl- S, S- methylphenylsulfoximide)

Except that 3-ethynylthiophene (21.6 mg, 0.20 mmol) was used instead of pheylacetylene in Example 1 to obtain the target compound N- (4-methylphenylsulfonyl) -thiophene-3- S , S -methylphenylsulfoximide (63.0 mg, 73%) was obtained.

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.62 (t, J = 7.4 Hz, 1H), 7.56 (d, J = 7.6 Hz, 2H), 7.47-7.16 (m, 9H), 4.24-4.15 (m, 2H), 3.19 (s, 3H), 2.40 (s, 3H)

Preparation of - ((4-methylphenylsulfonyl) -hexylimidoyl- S, S -methylphenylsulfoximide N) [ Example 17] N - (4- methylphenyl sulfonyl) hexyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

Except that 1-hexyne (16.4 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain the title compound N - (4-methylphenylsulfonyl) -hexylimido- S , And S -methylphenyl sulfoximide (62.5 mg, 77%).

¹ H 2H NMR (400 MHz, CD ₂ Cl ₂ ) ? 7.78-7.76 (m, 2H), 7.68-7.65 (m, 1H), 7.55-7.51 (M, 2H), 3.25 (s, 3H), 2.79 (brs, 2H), 2.39 (s, 3H), 1.71 (brs, 2H)

[Example 18] N - (4- phenyl-sulfonyl) -3,3-dimethyl-butyl yimido one - S, S - phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -3,3-dimethylbutylimidoyl- S, S- methylphenylsulfoximide)

The reaction was carried out in the same manner as in Example 1 except that 3,3-dimethylbut-1-yne (16.4 mg, 0.20 mmol) was used instead of the pheylacetylene of Example 1 to obtain N- (4-methylphenylsulfonyl) -3,3-dimethylbutylimidoyl- S , S -methylphenylsulfoximide (72.1 mg, 89%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.79 (d, J = 7.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.45 (brs 2H), 7.17 (d, J = 7.7 Hz, 2H), 3.23 (s, 3H), 2.79 (d, J =

Preparation of - ((4-methylphenylsulfonyl) -hexanenitrileimidoyl- S, S -methylphenylsulfoximide N) [ Example 19] N - (4- methylphenyl sulfonyl) hexahydro nitrile yimido days - - S, S-phenyl sulfonic poksiyi Mead

The procedure of Example 1 was repeated except for using 5-hexynenitrile (18.6 mg, 0.20 mmol) instead of pheylacetylene in Example 1 to obtain N - (4-methylphenylsulfonyl) -hexanonylimidosilane -S , S -methylphenylsulfoximide (61.2 mg, 73%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.78 (m, 2H), 7.67 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.37 (brs, 2H), 7.17 (d, J = 6.7 Hz, 2H), 3.27 (s, 3H), 2.87 (s, 2H), 2.39 (s, 5H), 1.80 (d, J = 66.4 Hz, 4H)

[Example 20] Ethyl N - (4- methylphenyl sulfonyl) phenyl-4-yl yimido -1- (S, S - phenyl sulfonic Foxy already pyridyl) methyl yimido yl acetate (ethyl N - (4-methylphenylsulfonyl ) -1 - (S, S-methylphenylsulfoximidyl) methylimidoylacetate)

Except that ethyl propiolate (19.6 mg, 0.20 mmol) was used in place of pheylacetylene of Example 1 to obtain ethyl N - (4-methylphenylsulfonyl) -4-methylphenylimido -1- ( S , S -methylphenylsulfoxyimidyl) methylimidoyl acetate (72.9 mg, 83%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.85 (d, J = 7.8 Hz, 2H), 7.62 (t, J = 7.1 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.34 (d , J = 6.6 Hz, 2H) , 7.12 (d, J = 7.2 Hz, 2H), 4.17 (d, J = 6.9 Hz, 2H), 3.89 (dd, J = 107.0, 16.2Hz, 2H), 3.25 (s , 3H), 2.38 (s, 3H), 1.26 (t, J = 6.9 Hz, 3H)

Example 21 3-hydroxy-height N - (4- methylphenyl sulfonyl) -propyl yimido one-S, S-phenyl sulfonic poksiyi mid (3-hydroxy N - (4 -methylphenylsulfonyl) -propylimidoyl- S, S -methylphenylsulfoximide )

The reaction was carried out in the same manner as in Example 1 except that propargyl alcohol (11.2 mg, 0.20 mmol) was used instead of the pheylacetylene of Example 1 to obtain the objective compound, 3-hydroxyphenyl N - (4-methylphenylsulfonyl) S - S , S -methylphenylsulfoximide (63.3 mg, 83%) was obtained.

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.80 (d, J = 7.8 Hz, 2H), 7.67 (t, J = 7.3 Hz, 1H), 7.54 (t, J = 7.6 Hz, 2H), 7.35 (s 2H), 7.17 (s, 2H), 3.95 (s, 2H), 3.28 (s, 3H)

[Example 22] 6- (N - (4- methylphenyl sulfonyl) -1- (S, S-phenyl isoquinoline sulfonic yimido one already pyridyl) methyl) - N - (4- methylphenyl sulfonyl) hexyl yimido days Preparation of ((4-methylphenylsulfonyl) -hexylimidoyl- S , S -methylphenylsulfoximide 6- (N - (4-methylphenylsulfonyl) -1- (S, S -methylphenylsulfoximidyl) methylimidoyl) - - N) - S, S -phenyl sulfonic poksiyi Mead

Heptadiyne (18.4 mg, 0.20 mmol) was added to the test tube, and CuI (7.6 mg, 0.04 mmol), S- methyl- S- phenylsulfoximine (62.0 mg, 0.40 mmol) and THF (tetrahydrofuran, -methylbenzenesulfonyl azide (91.4 mg, 0.48 mmol) and triethylamine (48.6 mg, 0.48 mmol). The reaction is then carried out at 25 ° C. After the completion of the reaction was confirmed by TLC, the solvent was removed and the resultant was separated by column chromatography (EtOAc: CH ₂ Cl ₂ : Hexane = 1: 1: 2) to obtain the desired compound 6- ( N- sulfonyl) -1- (S, S-phenyl isoquinoline sulfonic already pyridyl) methyl yimido yl) - N - (4- methylphenyl sulfonyl) hexyl yimido one-S, S-phenyl sulfonic poksiyi imide (71.4 mg, 48%) .

¹ H NMR (400 MHz, CD ₂ Cl ₂ ) ? 7.79 (d, J = 7.8 Hz, 4H), 7.67-7.64 (m, 2H), 7.56-7.51 (m, 4H), 7.38 d, J = 6.6 Hz, 4H ), 3.26 (s, 6H), 2.83 (s, 4H), 2.39 (s, 6H), 1.77 (s, 4H), 1.44 (s, 2H)

[Example 23] N - (4- phenyl) phenyl yimido one - S, S - methyl-4-phenyl sulfonic poksiyi imide (N - (4-Methylphenylsulfonyl) phenethylimidoyl- S, S -methyl-4-methylphenylsulfoximide) Manufacturing

Example 1 of S -methyl- S -phenylsulfoximine place of the S -, except for using (4-methyl) phenyl- S -methylsulfoximine (33.8 mg, 0.20 mmol) was reacted in the same manner as in Example 1, the aimed compound To obtain N- (4-methylphenylsulfonyl) phenylimidoyl- S , S -methyl-4-methylphenylsulfoximide (79.5 mg, 90%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.43 (d, J = 8.2 Hz, 4H), 7.35-7.18 (m, 9H), 4.16 (brs, 2H), 3.14 (s, 3H), 2.42 (s, 3H), 2.41 (s, 3H)

[Example 24] N - (4- phenyl) phenyl yimido one - S, S - methyl-4-methoxy-phenylsulfonyl poksiyi imide (N - (4-methylphenylsulfonyl) phenethylimidoyl- S, S -methyl-4- methoxyphenylsulfoximide)

Example 1 of S -methyl- S -phenylsulfoximine place of the S -, except for using (4-methoxy) phenyl- S -methylsulfoximine (37.0 mg, 0.20 mmol) was reacted in the same manner as in Example 1, the aimed compound To obtain N- (4-methylphenylsulfonyl) phenylimidoyl- S , S -methyl-4-methoxyphenylsulfoximide (77.5 mg, 85%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.49-7.19 (m, 11H), 6.88 (d, J = 8.9 Hz, 2H), 4.21-4.18 (m, 2H), 3.85 (s, 3H), 3.15 ( s, 3H), 2.41 (m, 3H)

[Example 25] N - (4- phenyl) phenyl yimido one - S, S - methyl-3,5-dimethyl-phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) phenethylimidoyl- S, S -methyl-3 , 5-dimethylphenylsulfoximide)

Example 1 S in place of S -methyl- S -phenylsulfoximine - (3,5- dimethyl) phenyl- S -methylsulfoximine by the reaction in the same manner as in Example 1, except that the (36.7 mg, 0.20 mmol) object To obtain N - (4-methylphenylsulfonyl) phenylimidoyl- S , S -methyl-3,5-dimethylphenylsulfoximide (84.6 mg, 93%).

¹ H 2H NMR (400 MHz, CD ₂ Cl ₂ ) ? 7.41-7.29 (m, 7H), 7.18-7.16 (m, 3H), 7.10 ), 2.41 (s, 3H), 2.26 (m, 6H)

[Example 26] N - (4- phenyl) phenyl yimido one - S, S - methyl-2-bromo-phenylsulfonyl poksiyi imide (N - (4-methylphenylsulfonyl) phenethylimidoyl- S, S -methyl-2- bromophenylsulfoximide)

Example 1 of S -methyl- S -phenylsulfoximine place of the S -, except for using (2-bromo) phenyl- S -methylsulfoximine (46.8 mg, 0.20 mmol) was reacted in the same manner as in Example 1, the aimed compound Phenylimidoyl- S , S -methyl-2-bromophenylsulfoximide (92.1 mg, 91%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.88 (dd, J = 7.9, 1.7 Hz, 1H), 7.61 (dd, J = 7.8, 1.2 Hz, 1H), 7.43 (d, J = 7.2 Hz, 2H) 3H), 7.31-7.23 (m, 7H), 7.14 (d, J = 8.0 Hz, 2H), 4.20 (dd, J =

[Example 27] N - (4- phenyl) phenyl yimido one - S, S - methyl-4-bromo-phenylsulfonyl poksiyi imide (N - (4-methylphenylsulfonyl) phenethylimidoyl- S, S -methyl-4- bromophenylsulfoximide)

Example 1 of S -methyl- S -phenylsulfoximine place of the S -, except for using (2-bromo) phenyl- S -methylsulfoximine (46.8 mg, 0.20 mmol) was reacted in the same manner as in Example 1, the aimed compound To obtain N- (4-methylphenylsulfonyl) phenylimidoyl- S , S -methyl-4-bromophenylsulfoximide (72.9 mg, 83%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.49-7.19 (m, 13H), 4.27-4.12 (m, 2H), 3.13 (s, 3H), 2.43 (s, 3H)

[Example 28] N - (4- methylphenyl sulfonyl) phenyl yimido one - S, S - methyl-2-naphthyl tilseol poksiyi imide (N - (4-methylphenylsulfonyl) phenethylimidoyl-S, S-methyl-2-naphthylsulfoximide) Manufacturing

Instead of S -methyl- S -phenylsulfoximine of Example 1 S - (2-naphthyl) - S -methylsulfoximine (41.1 mg, 0.20 mmol) and the N is the Example 1 was reacted in the same manner as the target compound, except for using - (4-methylphenylsulfonyl) methylphenylimidoyl- S , S -methyl-2-naphthylsulfoximide (83.1 mg, 87%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 8.11 (s, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 7.8 Hz 2H), 7.75-7.71 (m, 1H), 7.68-7.64 (m, 1H), 7.45-7.29 (m, 6H), 7.18 , 2H), 3.20 (s, 3H), 2.22 (s, 3H)

Preparation of - ((4-methylphenylsulfonyl) -oxophenethylimidoyl- S, S -methylphenylsulfoximide N) [ Example 29] N - (4- methylphenyl sulfonyl) -oxo phenyl yimido days - - S, S-phenyl sulfonic poksiyi Mead

To the test tube, CuI (3.8 mg, 0.02 mmol), S- methyl- S- phenylsulfoximine (31.0 mg, 0.20 mmol) and THF (tetrahydrofuran, 1.0 mL) were added and pheylacetylene (20.4 mg, 0.20 mmol) and 4-methylbenzenesulfonyl azide 45.7 mg, 0.24 mmol) and triethylamine (24.3 mg, 0.24 mmol). The reaction is then carried out at 25 ° C. After confirming that the reaction of the intermediate product is terminated using TLC, the mixture is reacted at 50 ° C for 12 hours. After confirming that the reaction was terminated by TLC, the solvent was removed and the product was separated by column chromatography (EtOAc: CH ₂ Cl ₂ : Hexane = 1: 1: 2) to obtain the target compound N - Sulfonyl) -oxophenylimidoyl- S , S -methylphenylsulfoximide (58.3 mg, 66%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.92 (d, J = 7.5 Hz, 2H), 7.85 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.3 Hz, 1H), 7.60 (t , J = 7.3 Hz, 1H) , 7.54 (t, J = 7.5 Hz, 2H), 7.48 (d, J = 7.6 Hz, 2H), 7.40 (d, J = 7.9 Hz, 2H), 7.15 (d, J = 7.2 Hz, 2H), 3.35 (s, 3H), 2.40 (s, 3H)

[Example 30] N - (4- methylphenyl sulfonyl) -oxo-4-methoxyphenyl yimido one-S, S-phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -oxo-4-methoxyphenethylimidoyl- S, S- methylphenylsulfoximide)

Except that 1-ethynyl-4-methoxybenzene (26.4 mg, 0.20 mmol) was used in place of pheylacetylene in Example 29 to obtain the objective compound N- (4-methylphenylsulfonyl) -4-methoxyphenylimidoyl- S , S -methylphenyl sulfoximide (52.6 mg, 57%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.88 (d, J = 8.9 Hz, 2H), 7.84 (d, J = 7.8 Hz, 2H), 7.60 (t, J = 7.0 Hz, 1H), 7.48 (t , J = 7.4 Hz, 2H) , 7.39 (d, J = 7.7 Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.89 (s, 3H ), 3.35 (s, 3 H), 2.40 (s, 3 H)

[Example 31] N - (4- methylphenyl sulfonyl) -oxo-4-bromophenyl yimido one-S, S-phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -oxo-4-bromophenethylimidoyl- S, S- methylphenylsulfoximide)

Except that 1-bromo-4-ethynylbenzene (36.2 mg, 0.20 mmol) was used in place of pheylacetylene of Example 29. The objective compound, N- (4-methylphenylsulfonyl) -4-bromophenylimidoyl- S , S -methylphenylsulfoximide (75.5 mg, 72%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.84 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.61 (t , J = 7.1 Hz, 1H) , 7.48 (t, J = 7.4 Hz, 2H), 7.38 (d, J = 7.6 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 3.36 (s, 3H ), 2.40 (s, 3H)

[Example 32] N - (4- methylphenyl sulfonyl) -oxo phenyl yimido one-S, S-methyl-4-bromo-phenylsulfonyl poksiyi imide (N - (4-methylphenylsulfonyl) -oxophenethylimidoyl- S, S -methyl -4-bromophenylsulfoximide)

Example 29 of S -methyl- S -phenylsulfoximine place of the S -, except for using (2-bromo) phenyl- S -methylsulfoximine (46.8 mg, 0.20 mmol) were reacted in the same manner as in Example 29 the aimed compound To obtain N - (4-methylphenylsulfonyl) -oxophenylimidoyl- S , S -methyl-4-bromophenylsulfoximide (59.9 mg, 58%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.93 (d, J = 7.4 Hz, 2H), 7.66 (d, J = 8.7 Hz, 3H), 7.58-7.52 (m, 4H), 7.37 (d, J = (D, J = 7.9 Hz, 2H), 3.31 (s, 3H), 2.45

[Example 33] N - (4- methylphenyl sulfonyl) -oxo-4-bromophenyl yimido one-S, S-methyl-4-phenyl sulfonic poksiyi imide (N - (4-methylphenylsulfonyl) -oxo-4- Preparation of bromophenethylimidoyl- S, S- methyl-4-methylphenylsulfoxyimide

Carried out in place of S -methyl- S -phenylsulfoximine of Example 29 S - (4-methyl) phenyl- S -methylsulfoximine 1-bromo-4-ethynylbenzene instead pheylacetylene of Example 29 using (33.8 mg, 0.20 mmol), and (36.2 mg, 0.20 mmol) in the same manner as in Example 29 to give the target compound N- (4-methylphenylsulfonyl) -oxo-4-bromophenylimidoyl- S , S -methyl -4-methylphenylsulfoximide (69.2 mg, 65%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.82 (d, J = 8.2 Hz, 2H), 7.73 (t, J = 8.0 Hz, 4H), 7.43 (d, J = 7.6 Hz, 2H), 7.30 (d 2H, J = 7.6 Hz, 2H), 7.20 (d, J = 7.5 Hz, 2H)

[Example 34] N - (4- methylphenyl sulfonyl) -oxo-4-methylphenyl yimido one-S, S-methyl-4-bromo-phenylsulfonyl poksiyi imide (N - (4-methylphenylsulfonyl) -oxo-4- methylphenethylimidoyl- S, S- methyl-4-bromophenylsulfoximide)

Carried out in place of S -methyl- S -phenylsulfoximine of Example 29 S - (2-bromo) phenyl- S -methylsulfoximine 1-ethynyl-4-methylbenzene in place of pheylacetylene of Example 29 using (46.8 mg, 0.20 mmol), and (23.2 mg, 0.20 mmol) to the reaction in the same manner as in example 29, except that the target compound N - (4- methylphenyl sulfonyl) -oxo-4-methylphenyl yimido one-S, S-methyl-4 - bromophenylsulfoximide (42.1 mg, 55%).

¹ H _{NMR (400 MHz, CD 2 Cl} 2) δ 7.82 (d, J = 7.6 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.52 (t, J = 8.1 Hz, 1H), 7.36 (d , J = 7.5 Hz, 4H) , 7.18 (d, J = 7.8 Hz, 2H), 3.30 (s, 3H), 2.45 (s, 6H)

Claims (11)

An N -imidoyl sulfoximine derivative represented by the following formula (1): < EMI ID =
[Chemical Formula 1]

In Formula 1,
R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) _{heteroaryl, - (CH 2) n -CN} , - (CH 2) n - OH or

;
R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;
L is -CH ₂ - or -C (= O) - and;
Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;
n is an integer from 1 to 5;
R 'is (C1-C10) alkyl or (C6-C12) aryl;
Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;
The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;
Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S. The method of claim 1, wherein
N -imidoyl sulfoximine derivatives selected from the following structures:

N, characterized in that for producing a yimido one sulphoxide derivative civil-to under the copper catalyst of the formula 4a alkyne derivative of formula 5 and N azide derivative of formula (1) reacting a N- sulfoxide civil derivative of formula (6) Lt; / RTI >
[Chemical Formula 1]

[Chemical Formula 4a]

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4a), (5) and (6)
R ¹ is (C1-C10) alkyl, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C3-C12) heteroaryl, - (CH _{2) n} -CN or - (CH _{2) n} - OH;
R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;
L is -CH ₂ - or -C (= O) - and;
Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;
n is an integer from 1 to 5;
The aryl of R ¹ and R ² may be further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo (C 1 -C 10) alkyl;
Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S. The method of claim 3,
Wherein the N -imidoyl sulfoximine derivative is represented by the following general formula (2) or (3).
(2)

(3)

In the general formulas (2) and (3), R ¹ , R ² and Ar are the same as defined in claim 3. The method of claim 3,
The copper catalyst is CuI (copper (I) iodide) , CuBr (copper (I) bromide), CuCl (copper (I) chloride), Cu 2 O (Copper (I) oxide), CuTC (Copper (I) -thiophene -2-carboxylate and CuOTf (Copper (I) triflate). The method of claim 3,
≪ / RTI > further comprising a base. The method according to claim 6,
The base is selected from the group consisting of pyridine, potassium carbonate, potassium phosphate tribase, sodium acetate, cesium carbonate, diisopropylethylamine, 1,4-diazabicyclic [2.2.2] octane, 1,8-diazabicyclic [5.4. 0] undec-7-ene, tributylamine and triethylamine. The method of claim 3,
The copper catalyst is used in an amount of 0.1 to 0.5 mole based on 1 mole of the N-sulfoximine derivative of Formula 6, the alkane derivative of Formula 4a is used in an amount of 1 to 3 moles per mole of the N-sulfoximine derivative of Formula 6, 5 is used in an amount of 1 to 3 mol per 1 mol of the N-sulfoximine derivative of the above formula (6). 8. The method of claim 7,
Wherein the base is used in the range of 0.1 to 2 mol per 1 mol of the N-sulfoximine derivative of the formula (6). The method of claim 3,
The reaction may be carried out in a solvent such as acetonitrile, toluene, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, benzene, xylene, chlorobenzene, hexafluorobenzene, octafluorotoluene, tetrabutyl alcohol, ≪ / RTI > and ethanol in one or more organic solvents. N, characterized in that for producing a yimido one sulphoxide derivative civil-to under the copper catalyst of the formula 4b alkyne derivative of formula 5 and N azide derivative of formula (1) reacting a N- sulfoxide civil derivative of formula (6) Lt; / RTI >
[Chemical Formula 1]

(4b)

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas (1), (4b), (5) and (6)
R ¹ is

;
R ² is (C 1 -C 10) alkyl or (C 6 -C 12) aryl;
L is -CH ₂ - or -C (= O) - and;
Ar is (C6-C12) aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;
n is an integer from 1 to 5;
R 'is (C1-C10) alkyl or (C6-C12) aryl;
Ar 'is (C6-C12) aryl which is unsubstituted or substituted by one or more substituents selected from the group consisting of (C1-C10) alkyl, (C1-C10) alkoxy and halogen;
The aryl of R ¹ , R ² and R 'is further substituted with one or more substituents selected from the group consisting of (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, halogen, nitro and halo Can be;
Wherein said heteroaryl comprises 1 to 4 heteroatoms selected from N, O and S.