KR101446708B1 - Optically active ethylenediamine derivatives and prepartion method thereof - Google Patents

Abstract

The present invention relates to an optically active ethylenediamine derivative derived from an amino acid and a method for preparing the same, and more particularly, to an optically active ethylenediamine derivative derived from an optically active ethylenediamine derivative, which is required to develop a useful use in asymmetric synthesis of an asymmetric catalyst, Can be easily produced in a high yield through a simple process without a protecting group from an amino acid having an activity and can be produced under mild and economical reaction conditions than conventional reaction conditions. Therefore, asymmetric catalytic ligands, organic catalysts . ≪ / RTI >

Description

TECHNICAL FIELD The present invention relates to optically active ethylenediamine derivatives and prepartion method thereof,

The present invention relates to an optically active ethylenediamine derivative derived from an amino acid and a process for producing the same.

Amino acid-derived 2-aminoethanol derivatives which are substituted at the α-position derived from amino acids are frequently found in chliral auxiliaries, ligands of asymmetric catalysts, organic catalysts and the like. Examples of the skeleton of the double-substituted 2-aminoethanol at the alpha position include oxazolidinone auxiliaries (non-patent documents 1-3) used as chiral auxiliaries, bisoxazoline ligands used as ligands of asymmetric catalysts Patent Document 4), oxazaborolidine used as an organic catalyst (non-patent document 5), α, α-diarylprolinol (non-patent reference 6-8), N- ).

Representative skeletons of the 2-aminoethanol double-substituted at the? -Position are as follows.

In addition to the typical skeletons described above, various skeletons of substituted 2-aminoethanol have been widely used as organic catalysts.

Currently, 2-aminoethanol derivatives that are dually substituted at the a-position are widely used in asymmetric catalysts, organic catalysts, and asymmetric synthesis reactions. Ethylenediamines are generally used as chelating ligands for coordination compounds. EDTA (ethylenediaminetetraacetic acid), which is the most widely used EDTA derivative, is a derivative of ethylenediamine and is widely used as a ligand for chelate formation in analytical chemistry because it forms a water-soluble chelate with almost all metal ions. The EDTA is usually prepared via Strecker synthesis from cyanide and formaldehyde. Hydroxyethylethylenediamine is one of the most commonly used chelating agents and a salen ligand produced by the condensation reaction of salicylaldehyde and ethylenediamine is widely used for research.

Unlike the 2-aminoethanol derivatives which are double-substituted at the? -Position, ethylenediamine derivatives derived from amino acids are rarely reported. Only the ligand of the asymmetric catalyst and the ethylenediamine derivative derived from valine are used as the organic catalyst. The structure of the catalyst used in the following asymmetric hydrogenation reaction (non-patent document 12) and Henry reaction (non-patent document 13) is illustrated.

The reaction using sodium trifluoroacetic acid (TFA) / sodium azide as the following general synthesis method of ethylenediamine from amino alcohol derived from valine is known (Non-Patent Document 14). This reaction is characterized in that ethylenediamine is synthesized from an amino alcohol in which the amino group is protected with a -CBz group.

As another method, a method of synthesizing ethylenediamine by adding an alkylating agent (Grignard regent) from N-diphenylphosphinoylketimine derived from amino acid through several steps has been reported as follows (Non-Patent Document 15). In the following reaction formula, AA represents a group originally derived from an amino acid.

As another method, the Mitsunobu method using diethyl azodicarboxylate (DEAD) / triphenylphosphine (Ph ₃ P) / triazole hydrohalic acid (HN ₃ ) from racemic amino alcohol is known as follows (Misunobu reaction , Non-Patent Document 16).

However, the above reaction is problematic in that it is very difficult to apply to mass production because of the troublesome separation and removal of reaction by-products.

Therefore, in order to develop useful applications for the asymmetric synthesis of ethylenediamine derived from an amino acid such as a ligand of an asymmetric catalyst, an organic catalyst, etc., research for easily preparing variously substituted ethylenediamine derivatives from amino acids is required.

Accordingly, the present inventors have studied a process for producing ethylenediamine derivatives which can relatively improve the overall production yield while maintaining mild reaction conditions from amino acids, while reacting aminoalcohol and sodium azide in the presence of sulfuric acid It was confirmed that an azide derivative could be produced in an excellent yield, and an ethylenediamine derivative was synthesized therefrom to complete the present invention.

US 2009/013716 A1

Bull, S. G., et al., Svnlett 1998, 519 Beaumont, S., et al., J. Am. Chem. Soc. 2010, 132, 1482 Nunnery, J. K., et al., Tetrahedron Lett. 2011, 52, 2929 Hong, S., et al., J. Am. Chem. Soc. 2003, 125, 14768 Corey, E. J., et al., Angew. Chem. Int. Ed. 1998, 37, 1986 Franzn, J., et al., J. Am. Chem. Soc. 2005, 127, 18296 Ibrahim, I., et al., Angew. Chem. Int. Ed. 2007, 46, 4507 Enders, D., et al., Science 2006, 441, 861 Concelln, C., et al., Adv. Synth. Catal. 2009, 351, 3001 Liu, F., et al., Angew. Chem. Int. Ed. 2011, 50, 12626 Campbell, C. D., et al., Tetrahedron: Asymmetry 2011, 22 T. Kjkuma., Et al., J. Am. Chem. Soc. 2000, 122, 6510 D. Uraguchi., Et. al., J. Am. Chem. Soc. 2007, 129, 12392 J. Wey., Et al., Tetrahedron Lett. 1993, 34, 1905 Kohmura, et. al., J. Org. Chem., 2004, 69, 6329 H. Brunner., Et. al., Chem. Ber., 1990, 123, 1029

It is an object of the present invention to provide an ethylenediamine derivative having optical activity.

It is another object of the present invention to provide a process for producing an ethylenediamine derivative having optical activity.

It is still another object of the present invention to provide an intermediate compound of an ethylenediamine derivative having optical activity.

In order to achieve the above object,

The present invention provides an ethylenediamine derivative represented by the following general formula (1).

The present invention also provides a process for producing an ethylenediamine derivative as shown in Reaction Scheme 1 below.

Further, the present invention provides an intermediate of an ethylenediamine derivative represented by the following formula (3).

According to the present invention, variously substituted ethylenediamine derivatives which are required to develop useful applications in the asymmetric synthesis of asymmetric catalyst ligands, organic catalysts and the like can be easily isolated from optically active amino acids by a simple process, And can be produced under mild and economical reaction conditions than conventional reaction conditions. Therefore, it can be usefully used as an asymmetric catalyst ligand and an organic catalyst useful in the asymmetric synthesis process.

The present invention provides an optically active ethylenediamine derivative represented by the following Formula 1:

Hereinafter, the present invention will be described in detail.

In the ethylenediamine derivative of the formula (1) according to the present invention, the substituents R ₁ , R ₂ , R ₃ and Ar are defined as follows.

In Formula 1,

R < ₁ > is hydrogen; R ₂ is hydrogen or an amino group protecting group; Or R ₁ and R ₂ together with the nitrogen atom to which they are attached may form a 5- to 6-membered heterocycle; R ₃ is hydrogen; C ₁ -C ₄ linear or branched alkylthiol group substituted with an unsubstituted or hydroxyl group, a thiol group, an amino group, an aminocarbonyl group, a carboxyl group, guanidinyl (NH ₂ C (═NH) NH-), unsubstituted or substituted with a hydroxy group C ₁ to C ₄ linear or branched alkyl substituted with any substituent selected from the group consisting of C ₅ to C ₆ aryl, 5 to 6 membered heterocycloaryl containing a nitrogen atom and 13-membered bicyclic heterocycloaryl group in 8 ego; Or R ₂ and R ₃ may form a ring together to form a 5- to 6-membered heterocycle containing a nitrogen atom; Ar is unsubstituted or C ₁ to C ₄ straight or branched chain alkyl, C ₁ to C ₄ alkoxy and C ₁ to C ₄ C ₁ -C ₆ aryl substituted with one or more substituents selected from the group consisting of halogen, haloalkyl, or C ₈ to C ₁₃ double ring aryl.

Preferably, in the ethylenediamine derivative of Formula 1 according to the present invention,

R < ₁ > is hydrogen; R ₂ is hydrogen or methyl carbonyl group (-COCH _3), a trifluoromethyl-carbonyl (-COCF _3), phenylcarbonyl (-COPh), benzyloxycarbonyl (-Cbz), t- butyloxycarbonyl ( -Boc), p-toluenesulfonyl (-Ts), methanesulfonyl (-Ms); Or R < ₁ > and R < ₂ > together with the nitrogen atom to which they are attached may form pyrrolidinyl or piperidinyl as 5- to 6-membered heterocyclo; R ₃ is selected from the group consisting of hydrogen, methyl, isopropyl, isobutyl, sec-butyl, hydroxymethyl, 1-hydroxyethyl, mercaptomethyl, methylmercaptoethyl, imidazo- Hydroxybenzyl and indol-3-ylmethyl, and the 5- to 6-membered heterocycle formed by R ₂ and R ₃ may form pyrrolidinyl or piperidinyl; Ar is selected from 4-methylphenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 3,5-dimethylphenyl, 3,5-dimethoxyphenyl, 3,5-dififluoromethylphenyl and 2-naphthyl .

More preferably, in the ethylenediamine derivative of Formula 1 according to the present invention,

Wherein R < ₁ > is hydrogen; R ₂ is selected from the group consisting of hydrogen or a group consisting of trifluoromethylcarbonyl (-COCF ₃ ), benzyloxycarbonyl (-Cbz), t-butyloxycarbonyl (-Boc), p-toluenesulfonyl Any one amino group protecting group selected; Or R < _{1 &} And R < ₂ > together with the nitrogen atom to which they are attached are piperidinyl; R ₃ is any one selected from the group consisting of methyl, isopropyl, phenyl and benzyl; Or R < ₂ > and R < ₃ > together form a ring to be a pyrrolidinyl containing a nitrogen atom; Ar is any one selected from phenyl, 4-methoxyphenyl, 3,5-ditrifluoromethylphenyl and 2-naphthyl.

Most preferably, the ethylenediamine derivative of Formula 1 according to the present invention is any one selected from the group consisting of the following compounds.

1) (2S) - {2- (N-tosyl) amino} -1,1-diphenylpropylamine;

2) (2S) - {2- (N-tosyl) amino} -3-methyl-1,1-diphenylbutylamine;

3) (2S) - {2- (N-tosyl) amino} -1,1-bis (4-methoxyphenyl) -3-methylbutylamine;

4) (2S) - {2- (N-Trifluoroacetyl) amino} -1,1-bis (4-methoxyphenyl) -3-methylbutylamine;

5) (2S) - {2- (N-tosyl) amino} -1,1,2-triphenylethylamine;

6) (2S) -2N-carbobenzyloxy-1,1,3-triphenyl-1,2-propanediamine;

7) (1S) -1 - {(N-tosyl) -2-pyrrolidinyl} -1,1 diphenylmethylamine;

8) (1S) -1- (N-tosyl) -2-pyrrolidinyl-1,1-di (2-naphthyl) methylamine;

9) (S) -1,1-diphenylpropane-1,2-diamine;

10) (2S) -1,1-diphenyl-3-methyl-1,2-butanediamine;

11) (2S) -1,1,2-triphenyl-1,2-ethanediamine;

12) (2S) -1,1,3-triphenyl-1,2-propanediamine;

13) (2S) 1,1,2-Triphenyl-2- (1-piperidinyl) ethylamine; And

14) (1S) -1,1-Bis- (3,5-ditrifluoromethylphenyl) -1- (2-pyrrolidinyl) methylamine.

The present invention also provides a process for preparing the ethylenediamine derivative compound of Formula 1.

As shown in the following Reaction Scheme 1,

Performing an azidation reaction with sodium azide at a temperature of 0 ° C to room temperature in the presence of sulfuric acid (step 1); And

And reducing the compound (3) obtained in the above step 1 with Pd / C or LiAlH ₄ (step 2).

<Reaction Scheme 1>

Hereinafter, the above manufacturing method will be described in more detail by stages.

First, step 1 according to the present invention is a step of performing an azide reaction of the aminoethanol compound (2) as a starting material to introduce an azide group (-N ₃ ) instead of a hydroxyl group of the amino alcohol.

In step 1, the reaction is carried out in a solvent such as dichloromethane, chloroform, tetrahydrofuran (THF), toluene, N, N-dimethylsulfoxide, N, N-dimethylformamide, acetic acid, trifluoroacetic acid (TFA) , Trifluoromethanesulfonic acid (TfOH), and the like. In addition, in the step 1, it is preferable to control the reaction temperature in the range of 0 ° C to room temperature to facilitate the azidation reaction. If the reaction temperature is lower than 0 ° C, the reaction rate may be lowered. If the reaction temperature is higher than room temperature, the effect on the reaction rate is insignificant.

Furthermore, it is preferable that the step 1 is further carried out at a reaction time of 5 to 15 minutes. If the reaction time is less than 5 minutes, the reaction is not completely terminated and the yield of the compound (3) is lowered. When the reaction time exceeds 15 minutes, the product is decomposed and by-products are formed.

The step 1 according to the present invention may be carried out in the presence of sodium azide (NaN ₃ ) in the presence of sulfuric acid to azadify the hydroxy group of the starting aminoethanol compound (2).

The azidation reaction of Step 1 is much simpler and more economical than the known method, and has an advantage of facilitating the reaction. In particular, an azide compound can be obtained without using an amino alcohol as a starting material and without protecting the amino group with a protecting group. However, the production method of the present invention does not exclude that an azide compound is obtained from an amino alcohol whose amino group is protected with a protecting group.

Next, step 2 according to the present invention is a step of reducing the azidated reaction product (3) in step 1 to obtain an ethylenediamine derivative.

In step 2, the reaction may be carried out in an organic solvent such as, for example, methanol, ethanol, ethyl acetate, tetrahydrofuran (THF), or a mixed solvent thereof. Step 1 may be carried out using LiAlH ₄ or Pd / C in the presence of hydrogen to reduce the azide group of the amino azide compound represented by the formula (3).

Step 2 is a general method for producing an amine by reducing an azide group, which is advantageous in that the production process is simple and the production yield thereof is good and mass production is easy. As in step 1 above, the target compound (1) can be obtained without protecting the amino group of the amino group of formula (3) with a protecting group. However, the production method of the present invention does not exclude that the amino group is free from ethylenediamine (1) from the amino azide protected with a protecting group.

Further, the present invention provides a compound represented by the following general formula (3).

(Wherein R ₁ , R ₂ , R _3, and Ar are the same as in Formula 1).

The compound of formula (3) according to the present invention is an intermediate for preparing the ethylenediamine derivative of formula (1) to be achieved by the present invention.

The compound of Formula 3 according to the present invention is any one selected from the group consisting of the following compounds.

1) (S) -N-tosyl-1-methyl-2,2-diphenyl-2-azidethylamine;

2) (S) -N-tosyl-1-isopropyl-2,2-diphenyl-2-azidoethylamine;

3) (S) -N-tosyl-1-isopropyl-2,2-bis (4-methoxyphenyl) -2-azidethylamine;

4) (S) -N-Trifluoroacetyl-1-isopropyl-2,2-bis (4-methoxyphenyl) -2-azidethylamine;

5) (S) -N-tosyl-l, 2,2-triphenyl-2-azidethylamine;

6) (S) -N-carbobenzyloxy-1-benzyl-2,2-diphenyl-2-azidethy lamine;

7) Dithenyl [(2S) -N-tosyl-2-pyrrolidinyl] azidomethane;

8) di (2-naphthyl) [(2S) -N-tosyl-2-pyrrolidinyl] azidomethane;

9) (S) -l-methyl-2,2-diphenyl-2-azidethylamine;

10) (S) -l-Isopropyl-2,2-diphenyl-2-azidethylamine;

11) (S) -1, 2, 2-triphenyl-2-azidethylamine;

12) (S) -l-Benzyl-2,2-diphenyl-2-azidethy lamine;

13) (2S) -1- (2-azido-1,2,2-triphenylethyl) piperidine; And

14) (S) -2- (Azido-bis (3,5-bis (trifluoromethyl) phenyl) methyl) pyrrolidine.

The intermediate compound of Formula 1 according to the present invention can be usefully used in the asymmetric synthesis of asymmetric catalyst ligands and organic catalysts.

Hereinafter, the present invention will be described more specifically by way of examples.

The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

Preparation of starting material:

The compound of the following formula (2) used as a starting material in the present invention may be any of those in which the amino group is not protected or protected. The aminoalcohol of Formula 2 can be easily obtained by subjecting a compound having a structure represented by Formula 5 below to alkylation using a conventional alkylating agent.

In the above formula, R ₃ is as defined in formula (1) of the present invention, and R is preferably a lower alkyl group.

Aminoalcohol as a starting material of the present invention can be obtained through the above alkylation reaction, and aminoalcohol in which an amino group of an amino alcohol is introduced with an ordinary amino group protecting group can also be used as a starting material.

Hereinafter, embodiments of the present invention will be described in detail.

EXAMPLE 1 Preparation of (2S) - {2- (N-tosyl) amino} -3-methyl-1,1-diphenylpropylamine (1a)

Step 1: Preparation of (S) -N-tosyl-1-methyl-2,2-diphenyl-

Sodium azide (118 mg, 1.82 mmol) and toluene (7 ml) were added to a round bottom flask. To the mixture was slowly added concentrated sulfuric acid (0.1 ml, 98%, d = 1.84) and stirred at room temperature for 15 minutes. (S) -N-tosyl-2-amino-1,1-diphenyl-1-propanol (100 mg, 0.26 mmol) dissolved in toluene (5 ml) was added and vigorously stirred for 15 minutes. % aq. Sodium bicarbonate (10 ml) was added to complete the reaction. The aqueous layer is extracted with ethyl acetate (2 X 15 ml), the combined organic layers are dried over sodium sulfate and the solvent is removed. The residue was purified by column chromatography (SiO ₂ , n-hexane / ethyl acetate = 9/1) to give the desired compound (87.7 mg, 83%) pure.

mp. 137 - 138 캜;

IR (neat): 2103 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 8.73 (s, 1H), 7.52 (d, 2H, J = 8.1 Hz, Ar-H)), 7.33-7.12 (m, 12H, Ar-H), 3.28 (m, 1H, -CH), 2.41 (s , 3H, Ar-CH 3), 0.80 (d, 3H, J = 6.6 Hz, -CH 3) ppm;

¹³ C NMR (CDCl ₃ ): δ 178.75, 144.42, 138.33, 134.84, 130.45, 129.77, 128.37, 127.72, 127.59, 63.04, 29.51, 21.74, 18.38 ppm;

optical rotation: -12.57 ° (c = 0.565, CDCl 3).

Step 2: Preparation of (2S) - {2- (N-tosyl) amino} -3-methyl-1,1 diphenylpropylamine (1a)

(86 mg, 0.21 mmol) obtained in the above step 1 was dissolved in ethanol / ethyl acetate (8 mL, v / v = 1/1), and 10% Pd / C (18 mg) was added thereto. The mixture solution was hung with a balloon filled with hydrogen and hydrogenated for 1 hour. The thin film chromatograph (TLC) confirmed that the starting material was completely consumed. The catalyst was removed using Celite and the solution was concentrated under reduced pressure. Column chromatograph the residue (SiO _2, methanol / ethyl acetate = 1/30) to obtain the title compound pure (60 mg, 75%).

mp. 145 - 145.5 캜;

IR: 3321, 3129 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 7.52 (d, 2H, J = 8.4 Hz, Ar-H), 7.33-7.12 (m, 12H, Ar-H), 4.89 (d, 1H, J = 9 Hz), 4.29-4.25 (m, 1H), 2.39 (s, 3H, Ar-CH 3), 1.78 (brs, 2H, -NH 2), 1.09 (d, 3H, J = 6 Hz) ppm;

¹³ C NMR: δ 145.08, 144.96, 142.84, 137.91, 129.50, 128.22, 128.15, 126.86, 126.83, 126.68, 126.49, 64.20, 55.59, 21.46, 17.93 ppm;

MS (m / z): 381.98, 364, 303.1, 198, 182 (100%), 104, 90.9, 77;

Optical rotation: at 19.1 ℃, -42.96 ° (c = 0.540, CHCl 3).

Example 2 Preparation of (2S) - {2- (N-tosyl) amino} -3-methyl-1,1-diphenylbutylamine (1b)

Step 1: Preparation of ( S ) -N -tosyl-1-isopropyl-2,2-diphenyl-2-azidoethylamine (3b)

(S) -N- tosyl-2-amino-1,1-diphenyl-1-propanol instead of (S) - a tosyl-2-amino-3-methyl-1,1-diphenyl-1-butanol - N (172 mg, 79%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

mp. 157 - 158 캜;

IR (neat): 2103, 3187 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 7.58 (d, 2H, J = 1.8 Hz, Ar-H), 7.35-7.25 (m, 10H, Ar-H), 7.18 (d, 2H, J = 7.8, Ar- H), 4.48 (d, 1H , J = 15 Hz), 4.30 (d, 1H, J = 9 Hz), 2.38 (s, 3H), 2.08-2.03 (m, 1H), 1.06 (d, 3H, J = 6 Hz), 0.42 (d, 3H, J = 6 Hz) ppm;

¹³ C NMR: δ 143.02, 139.99, 139.19, 139.03, 129.42, 128.61, 128.58, 128.30, 128.15, 127.86, 126.98, 63.44, 31.06, 28.76, 23.07, 21.60, 16.92 ppm;

Optical rotation: at 20.7 ℃, + 8.68 ° (c = 0.535, CHCl 3).

Step 2; (2S) - {2- (N-tosyl) amino} -3-methyl-1,1-diphenylbutylamine (1b)

( S ) -N -tosyl-1-isopropyl-2,2-diphenyl-2-azidoethylamine obtained in the above step 1 was reacted with (S) (127 mg, 74%) was obtained by carrying out the same procedure as in the step 2 of Example 1, except that ethylamine was used instead of 2-

mp. 105 - 106 캜;

IR (neat): 3323, 3129 cm &lt; ^{-1 &} gt ;;

^{1 H NMR (300 MHz, CDCl} 3): δ 7.46 (d, 2H, J = 8.1 Hz, Ar-H), 7.39-7.27 (m, 8H, Ar-H), 7.26-7.10 (m, 4H, Ar -H), 4.98 (d, 1H , J = 9 Hz), 4.19 (d, 1H, J = 9 Hz), 2.37 (s, 3H, Ar-CH 3), 1.95-1.93 (m, 1H), 1.82 _{(brs, 2H, -NH 2)} , 0.94 (d, 3H, J = 6.9 Hz, ali-H), 0.64 (d, 3H, J = 6.9 Hz, ali-H) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 146.00, 145.39, 142.39, 138.75, 129.29, 128.20, 128.07, 126.88, 126.81, 126.72, 126.58, 126.51, 115.74, 66.28, 64.36, 29.02, 23.40, 21.40, 17.86 ppm ;

Optical rotation: at 21.8 ℃, + 72.38 ° (c = 0.630, CHCl 3);

HRMS: Calcd. for C ₂₄ H ₂₈ N ₂ O ₂ S 408.1871 and found 408.1865.

Preparation of {2-amino (N tosyl -)} -1,1- bis (4-methoxyphenyl) -3-methyl-butylamine (1c) <Example 3> (2 S)

Step 1: Preparation of ( S ) -N -tosyl-1-isopropyl-2,2-bis (4-methoxyphenyl)

Instead of ( S ) -N -tosyl-2-amino-3-methyl-1,1-bis (4-methoxyphenyl) ) -L-butanol was used in place of 2-chloro-2-fluorobenzaldehyde in step 1 of Example 1 to obtain the desired compound (87 mg, 70%).

mp. 169 - 170 캜;

IR (neat): 3307, 2961 , 2105 (-N 3) cm -1;

_{^{1 H NMR (CDCl 3, 300MHz}} ): δ 7.61 (d, 2H, J = 8.1 Hz, Ar-H), 7.29-7.14 (m, 6H, Ar-H), 6.84-6.79 (m, 4H, Ar- H), 4.29 (q, 2H , J = 12 Hz), 3.80 (s, 3H), 3.79 (s, 3H, Ar-CH 3), 2.39 (s, 3H, Ar-CH 3), 2.06-2.01 ( m, 1 H), 1.05 (d, 3H, J = 6.9 Hz), 0.39 (d, 3H, J = 6.9 Hz) ppm;

¹³ C NMR (CDCl _{3 ,} 75 MHz): δ 159.20, 159.06, 142.77, 138.99, 131.89, 130.98, 129.49, 129.20, 128.99, 126.79, 113.60, 75.98, 63.46, 55.24, 55.18, 28.53, 22.92, 21.44, 16.90 ppm;

Optical rotation: at 25.3 ℃, -8.22 ° (c = 0.515, CHCl 3).

Step 2: (2 S) - Preparation of {2-amino (N tosyl)} -1,1- bis (4-methoxyphenyl) -3-methyl-butylamine (1c)

( S ) -N -tosyl-2-amino-3-methyl-1,1-bis (4-methoxyphenyl) The target compound (63 mg, 74%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using 2,2-diphenyl-2-azidopropylamine instead of 2,2-diphenyl-2-

White solid, mp. 173 - 174 캜;

^{1 H NMR (300 MHz, CDCl} 3): δ 7.45 (d, 2H, J = 8.4 Hz, Ar-H), 7.27 (d, 2H, J = 6.3 Hz, Ar-H), 7.13-7.09 (m, 4H, Ar-H), 6.85 (d, 2H, J = 8.4 Hz, Ar-H), 6.59 (d, 2H, J = 8.4 Hz, Ar-H), 4.98 (d, 1H, J = 9.2 Hz) , 4.07 (d, 1H, J = 9.2 Hz), 3.79 (s, 3H, Ar-OMe), 3.773 (s, 3H, Ar-OMe), 2.37 (s, 3H, Ar-CH 3), 1.99-1.96 (m, 1H), 1.68 ( brs, 2H, -NH 2), 0.97 (d, 3H, J = 6.9 Hz), 0.67 (d, 3H, J = 6.9 Hz) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 158.29, 142.26, 138.82, 138, 137.60, 129.8, 129.16, 128.67, 128.14, 128.08, 127.84, 127.64, 127.58, 127.09, 126.96, 126.68, 113.47, 113.19, 65.54, 64.63, 55.19, 49.78, 29.02, 23.38, 21.53 ppm;

Optical rotation: at 20 ° C, +93.13 ° (c = 0.51, CHCl ₃ );

HRMS: Calcd. for C ₂₆ H ₃₂ N ₂ O ₄ S 468.2083 and found 468.2081.

EXAMPLE 4 Preparation of ( 2S ) - {2- ( N -trifluoroacetyl) amino} -1,1-bis (4-methoxyphenyl) -3-methylbutylamine

Step 1: Preparation of ( S ) -N -trifluoroacetyl-l-isopropyl-2,2-bis (4-methoxyphenyl)

Instead of ( S ) -N -trifluoroacetyl-2-amino-3-methyl-1,1-bis (4- (72 mg, 41%) was obtained by carrying out the same procedure as in the step 1 of Example 1, except that the title compound was obtained.

IR (Neat): 2103 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 7.28-7.24 (m, 4H), 6.93-6.85 (m, 4H), 6.37 (d, 1H, J = 10.5 Hz), 4.93 (d, 1H, J = 10.5 Hz) , 3.78 (s, 3H), 3.76 (s, 3H), 2.10-2.05 (m, 1H), 1.27-1.21 (m, 1H), 1.09 (d, 3H, J = 6.9 Hz), 0.62 (d, 3H , J = 6.9Hz) ppm;

¹³ C NMR (CDCl ₃ ): δ 159.27, 159.20, 159.14, 159.12, 159.10, 159.08, 158.48, 156.90 (qt), 129.74, 128.56, 128.36, 113.91, 113.79, 113.75, 113.33, 75.18, 60.15, 58.27, 54.98 2C), 28.59, 22.77, 16.33 ppm;

Optical rotation: at 20 ℃, -76.04 ° (c = 0.587, CHCl 3).

Step 2: (2 S) - Preparation of {(trifluoroacetyl N) 2-amino} -1,1-bis (4-methoxyphenyl) -3-methyl-butyl amine (1d)

( S ) -N -Trifluoroacetyl-1-isopropyl-2,2-bis (4-methoxyphenyl) -Methyl-2,2-diphenyl-2-azidethyridine The title compound (57 mg, 54%) was obtained in the same manner as in Step 2 of Example 1 except for using in place of ethylamine.

IR (neat): 3105 cm &lt; ^{-1 &} gt ;;

^{1 H NMR (300 MHz, CDCl} 3): δ 7.32-7.27 (m, 2H), 7.17 (dd, 2H, J = 4.5, 8.4 Hz), 6.89 (dd, 2H, J = 4.5, 8.4 Hz), 6.78 -6.73 (m, 2H), 4.72 (dd, 1H, J = 2.1, 9.0 Hz), 3.78 (s, 3H), 3.72 (s, 3H), 1.97 (brs, 2H), 1.27-1.23 (m, 1H ), 0.96 (d, 3H, J = 6.9 Hz), 0.81 (d, 3H, J = 6.9 Hz) ppm.

Preparation of {amino (tosyl N)} -1,1,2- triphenyl amine (1e) <Example 5> (2 S) -2

Step 1: Preparation of ( S ) -N -tosyl-1,2,2-triphenyl-2-azidoethylamine (3e)

Except that ( S ) -N -tosyl-2-amino-1,1,2-triphenylethanol was used in place of ( S ) -N -tosyl- (245 mg, 63%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

mp. 193 - 194 캜;

IR (Neat): 2101 (-N 3), 3287 cm -1;

_{^{1 H NMR (CDCl 3):}} δ 7.39-7.31 (m, 5H, Ar-H), 7.22-7.13 (m, 8 H, Ar-H), 6.95 (t, 1H, J = 7.5 Hz), 6.86- 6.76 (m, 3H, Ar- H), 6.46 (d, 2H, J = 7.35 Hz, Ar-H), 5.44 (d, 1H, J = 9.6 Hz), 5.03 (d, 1H, J = 9.6 Hz) , 2.23 (s, 3H, Ar -CH 3) ppm;

¹³ C NMR (CDCl _{3 ,} 75 MHz):? 142.78, 139.89, 138.78, 137.01, 135.07, 128.86, 128.83, 128.39, 128.30, 128.08, 127.95, 127.10, 127.00, 126.93, 75.51, 62.28, 21.29 ppm;

( M / z ): 468 (0.01%), 426 (0.99%, expulsion of N ₃ ), 260 (100%), 180 (76.70%), 154 (84.62% 46.73%);

Optical rotation: at 27.2 ° C, -25.74 ° (c = 0.545, CHCl ₃ ).

Step 2: (2 S) -2 - Preparation of {(N tosyl) amino} -1,1,2- triphenyl amine (1e)

( S ) -N -tosyl-1,2,2-triphenyl-2-azidoethylamine obtained in the above step 1 was reacted with (S) -N-tosyl- (125 mg, 81%) was obtained by carrying out the same procedure as in the step 2 of Example 1, except that acetic acid was used in place of ethylamine.

mp. 212 - 213 캜;

IR (neat): 3103 (-NH 2) cm -1;

^{1 H NMR (300 MHz, CDCl} 3): δ 7.34 (d, 2H, J = 6.6 Hz, Ar-H), 7.31-7.23 (m, 6H, Ar-H), 7.10 (m, 3H, Ar-H ), 7.06-7.01 (m, 4H, Ar-H), 6.80 (t, 2H, J = 7.5 Hz, Ar-H), 6.54 (d, 2H, J = 7.5 Hz, Ar- , 1H, J = 7.6 Hz, -CH), 5.40 (d, 1H, J = 7.6 Hz), 2.27 (s, 3H, -CH 3), 1.94 (brs, 2H, -NH 2) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ):? 145.37,144.24,142.44,137.7,135.75,128.85,128.72,128.47,128.30,127.97,127.79,127.46,127.15,127.05,126.88,126.76,126.61,126.55,64.98,128. 62.85, 21.33 ppm;

Optical rotation: at 11.5 ℃, -13.92 ° (c = 0.51, CHCl 3);

HRMS: Calcd. for C ₂₇ H ₂₆ N ₂ O ₂ S 442.1715 and found 442.1738.

Preparation of the carbonate-benzyloxy -1,1,3- triphenyl-1,2-propanediamine (1f) - <Example 6> (2 S) -2 N

Step 1: Preparation of ( S ) -N -carbobenzyloxy-1-benzyl-2,2-diphenyl-2-azidecylamine (3f)

(S) -N-carbobenzyloxy-1,1-diphenyl-2-benzyl-2-aminoethanol was used instead of ( S ) -N -tosyl- (159 mg, 66%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

¹ H NMR (CDCl ₃ ):? 7.47-7.35 (m, 12H, Ar-H), 7.24-7.20 (m, 3H, Ar- 1H), 5.05 (m, 1H), 4.95-4.78 (m, 2H), 3.31 (dd, 1H, J = 14.1, 2.4 Hz), 2.20-2.16 (m,

¹³ C NMR: δ 155.85, 140.05, 139.77, 137.66, 136.53, 129.34, 128.64, 128.61, 128.55, 128.48, 128.21, 128.12, 126.68, 76.21, 66.78, 57.56, 38.65 ppm;

Optical rotation: at 10 ° C, -21.81 ° (c = 0.55, CHCl ₃ ).

Step 2: (2 S) -2 N - Preparation of the carbonate-benzyloxy -1,1,3- triphenyl-1,2-propanediamine (1f)

( S ) -N -carbobenzyloxy-1-benzyl-2,2-diphenyl-2-azidoethylamine (47 mg, 0.1 mmol) obtained in the above step 1 was dissolved in THF (5 ml) Reduction was carried out with LiAlH ₄ (3.8 mg, 0.1 mmol) to obtain the desired compound (25 mg, 58%).

IR (neat): 2104 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 7.50-6.94 (m, 20H), 5.18 (d 1H, J = 10.2 Hz), 4.93 (m, 1H), 4.90 (q, 2H, J = 12.3 Hz, 2.93 (dd , 1H, J = 13.8, 1.9 Hz), 2.44 (dd, 1H, J = 13.8, 10.4 Hz), 2.03 (brs, 2H) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 156.1, 146.5, 145.8, 138.6, 1636.9, 129.4, 128.6, 128.5, 128.4, 128.3, 127.9, 126.9, 126.6, 126.4, 66.3, 65.1, 58.3, 37.9 ppm.

Example 7 Preparation of ( 1S ) -1 - {( N -tosyl) -2-pyrrolidinyl} -1,1-diphenylmethylamine (1 g)

Step 1: Preparation of diphenyl [(2 S) - - N tosyl-2-pyrrolidinyl] Oh map methane (3g)

(S) -N- tosyl-2-amino-1,1-diphenyl-1-propanol instead of diphenyl and the embodiment except [(2 S) - tosyl-2-pyrrolidinyl - N] the use of methanol The target compound (205 mg, 69%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

mp. 99 - 100 캜;

IR (neat): 2103 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 7.69-7.67 (m, 2H, Ar-H), 7.39-7.26 (m, 8H), 5.21 (dd, 1H, J = 8.9, 3.2 Hz, ali-H)), 3.45-3.36 (m, 1H, ali- H), 2.44 (s, 3H, Ar-CH 3), 2.43-2.34 (m, 1H), 2.06-1.96 (m, 1H, ali-H), 1.95-1.82 (m, 1H, ali-H), 1.38-1.35 (m, 1H, ali-H), 1.34-1.29 (m, 1H, ali-H) ppm;

¹³ C NMR (CDCl ₃ ): δ 143.44, 140.37, 139.56, 137.12, 129.67, 129.26, 128.86, 128.43, 128.34, 128.15, 128.02, 127.53, 76.20, 65.78, 49.46, 29.08, 24.29, 21.70 ppm;

MS ( m / z ): 281.1 (0.77%), 251 (3.79%), 194.1 (8.48%), 180 (87.78%), 103.72 (26.54%), 72 (100%);

Optical rotation: at 12.2 ℃, -38.17 ° (c = 0.543, CHCl 3).

Step 2: (1 S) -1 - Preparation of {2-pyrrolidinyl profile (tosyl N)} -1,1- diphenylmethyl amine (1g)

Diphenyl obtained in Step 1 [(2 S) - N - tosyl-2-pyrrolidinyl] ah map methane (S) -N- methyl-1-tosyl-2,2-diphenyl-2-azido The target compound (138 mg, 83%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using in place of ethylamine.

White solid, mp. 150 - 150.5 DEG C

_{^{1 H NMR (CDCl 3, 300}} MHz): δ 7.75 (d, 2H, J = 8.4 Hz), 7.38-7.21 (m, 12H), 4.83-4.80 (m, 1H), 3.31-3.22 (m, 1H) 2H), 1.25-1.05 (m, IH), 0.63-0.54 (m, IH), 2.52-2.04 (m, ppm;

¹³ C NMR (CDCl ₃ ): δ 146.71, 144.32, 143.63, 135.44, 129.79 (2C), 128.67 (2C), 128.06 (4C), 127.62, 127.49, 126.98 (2C), 126.85 49.74, 28.90, 23.40, 21.54 ppm;

MS: 407.1 (1.08%), 390.1, 329.1, 224.1, 182 (100%), 154.9, 91, 77, 65;

Optical rotation: at 18.2 ° C, -90.10 ° (c = 0.495, CHCl ₃ ).

Preparation of (N tosyl) -2- program pyrrolidinyl-1,1-di (2-naphthyl) methylamine (1h) <Example 8> (1 S) -1-

Preparation of [2-pyrrolidinylmethyl tosylate (2 S) - - N] O map methane (3h) of di (2-naphthyl) Step 1

(S) -N- tosyl-2-amino-1,1-diphenyl-1-propanol instead of di (2-naphthyl) [(2 S) - N - tosyl-2-pyrrolidinyl] using methanol , The objective compound (78 mg, 59%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

mp. 159-160 DEG C;

IR (neat): 2104 cm & lt ^{; -1 &gt;;}

_{^{1 H NMR (CDCl 3):}} δ 7.98 (s, 1H), 7.97-7.74 (m, 7H), 7.69 (d, 2H, J = 8 Hz), 7.57-7.34 (m, 4H), 7.33-7.30 ( 2H), 2.48 (s, 3H), 2.42-2.05 (m, 2H), 7.20 (d, 2H, J = 8 Hz), 5.54-5.50 (m, , 1.24-1.17 (m, 1H), 1.15-0.92 (m, 1H) ppm;

¹³ C NMR (CDCl ₃ ):? 143.80, 142.96, 140.96, 135.18, 132.67, 132.61, 132.49,129.73,128.38,128.32,127.67,127.57 (2C), 127.52,127.41,127.46,127.1 (2C) , 126.25, 126.22, 126.11, 126.08, 125.99, 124.86, 80.20, 67.31, 49.94, 29.85, 24.14, 21.54 ppm;

MS: 532.66 (does not appear in the mass spectrum), 371.3, 334.2, 306.1, 280.1, 265.1, 224.1 (100%), 155, 127, 91, 77;

Optical rotation: at 20 ° C, -23.92 ° (c = 0.485, CHCl ₃ ).

Step 2: (1 S) -1- - Preparation of (N tosyl) -2-loop pyrrolidinyl-1,1-di (2-naphthyl) methylamine (1h)

D obtained in the above Step 1 (2-naphthyl) [(2 S) - N - tosyl-2-pyrrolidinyl] ah map methane (S) -N- tosyl-1-methyl-2,2-diphenyl (54 mg, 64%) was obtained by carrying out the same procedure as in the step 2 of Example 1, except that ethylamine was used instead of 2-

^{1 H NMR (300 MHz, CDCl} 3): δ 7.73 (d, 2H, J = 7.8 Hz), 7.32 (d, 2H, J = 7.8 Hz), 7.05-6.94 (m, 4H), 6.93-6.87 (m , 2H), 4.81-4.78 (m, 1H), 3.33-3.24 (m, 1H), 2.70-2.44 (m, 4H) , 1H) ppm;

Optical rotation: at 20 ° C, -69 ° (c = 0.685, CHCl ₃ ).

Example 9 Preparation of (S) -1,1-diphenylpropane-1,2-diamine (1i)

Step 1: Preparation of ( S ) -1-methyl-2,2-diphenyl-2-azidoethylamine (3i)

(S) in the example except -N- tosyl-2-amino-1,1-diphenyl-1-propanol instead of 2 S) the use of 1,1-diphenyl-2-amino-1-propanol 1, the target compound (192 mg, 78%) was obtained.

IR (neat): 2103 cm &lt; ^{-1 &} gt ;;

_{^{1 H NMR (CDCl 3):}} δ 8.73 (s, 1H), 7.52 (d, 2H, J = 8.1 Hz, Ar-H)), 7.33-7.27 (m, 5H, Ar-H), 7.21 (d, 2H, Ar-H, J = 8.1 Hz), 7.15-7.12 (m, 4H, Ar-H), 3.33-3.24 (m, 1H, -CH), 2.41 (s, 3H, -CH 3), 0.80 ( d, 3H, J = 6.6 Hz , -CH 3) ppm;

¹³ C NMR (CDCl ₃ ): δ 178.75, 144.42, 138.33, 134.84, 130.45, 129.77, 128.37, 127.72, 127.59, 63.04, 29.51, 21.74, 18.38 ppm;

Optical rotation: -12.57 ° (c = 0.565, CHCl 3).

Step 2: Preparation of (S) -1,1-diphenylpropane-1,2-diamine (1i)

( S ) -1-methyl-2,2-diphenyl-2-azidoethylamine obtained in the above step 1 was reacted with (S) -N-tosyl- (154 mg, 68%) was obtained by carrying out the same procedure as in the step 2 of Example 1, except that the compound was used instead of ethylamine.

^{1 H NMR (300 MHz, CDCl} 3): δ 7.46-7.42 (m, 3H), 7.33-7.20 (m, 7H), 4.12 (q, J = 6.3 Hz, 1H), 1.92 (brs, 2H), 1.09 (d, J = 6.2 Hz, 3 H) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 146.3, 145.1, 128.7, 128.4, 127.0, 26.9, 126.6, 64.3, 52.1, 22.1 ppm;

Optical rotation: 20.22 ° (c = 0.33, CHCl 3);

FAB-MS: 227 (M + 1).

Example 10 Preparation of ( 2S ) -1,1-diphenyl-3-methyl-1,2-butanediamine (1 j)

Step 1: Preparation of ( S ) -1-isopropyl-2,2-diphenyl-2-azidoethylamine (3j)

(S) and is carried out except for the use -N- tosyl-2-amino-1,1-diphenyl-1-propanol instead of (2 S) -1,1-diphenyl-2-amino-1-propanol The objective compound (372 mg, 74%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

_{^{1 H NMR (CDCl 3):}} δ 7.47-7.23 (m, 10H, Ar-H), 3.78 (s, 1H), 1.84-1.77 (m, 1H), 1.20 (brs, 2H, -NH 2), 1.01 (d, 3H, J = 6 Hz), 0.58 (d, 3H, J = 6 Hz) ppm;

¹³ C NMR (CDCl ₃ ): δ 141.59, 141.24, 128.66, 128.47, 128.02, 127.74, 127.52, 127.45, 76.96, 61.61, 27.93, 23.56, 15.75 ppm.

Step 2: Preparation of ( 2S ) -1,1-diphenyl-3-methyl-1,2-butanediamine (1j)

( S ) -1-isopropyl-2,2-diphenyl-2-azidoethylamine obtained in the above step 1 was reacted with (S) -N-tosyl- (310 mg, 83%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using in place of ethylamine.

_{^{1 H NMR (CDCl 3):}} δ 7.52-7.43 (m, 4H, Ar-H), 7.29-7.23 (m, 4H, Ar-H), 7.20-7.13 (m, 2H, Ar-H), 3.67 ( d, 1H, J = 0.5 Hz ), 1.92-1.81 (m, 1H), 1.57 (brs, 4H, 2 x NH 2), 0.98 (d, 3H, J = 6.7 Hz), 0.74 (d, 3H, J = 6.7 Hz) ppm;

¹³ C NMR (CDCl ₃ ): δ 147.96, 147.29, 128.40, 128.36, 128.23, 127.54, 127.50, 126.75, 126.33, 65.89, 60.84, 28.06, 24.12, 17.10 ppm.

Preparation of <Example 11> (2 S) -1,1,2- triphenyl-1, 2-ethane diamine (1k)

Step 1: Preparation of ( S ) -1,2,2-triphenyl-2-azidoethylamine (3k)

Except that ( S ) -2-amino-1,1,2-triphenylethanol was used in place of (S) -N-tosyl-2-amino- , The objective compound (417 mg, 78%) was obtained.

IR (neat): 2103 cm & lt ^{; -1 &gt;;}

^{1 H NMR (300 MHz, CDCl} 3): δ 7.44-7.32 (m, 5H, Ar-H), 7.18-7.06 (m, 8H, Ar-H), 6.95-6.91 (m, 2H, Ar-H) , 5.04 (s, 1H, CH ), 1.71 (brs, 2H, -NH 2) ppm;

¹³ C NMR (CDCl ₃ ): δ 141.19, 140.38, 139.75, 128.81, 128.69, 128.37, 127.99, 127.89, 127.67, 127.50, 127.46, 127.37, 76.53, 62.81 ppm;

MS: 315 (0.55%), 251 (5.67%), 180.1 (39.72%), 105.9 (100%), 77 (18.49%);

Optical rotation: at 28 ° C, -86.78 ° (c = 0.545, CHCl ₃ ).

Step 2: (2 S) -1,1,2- Preparation of triphenyl-1, 2-ethane diamine (1k)

( S ) -1,2,2-triphenyl-2-azidecylamine obtained in the above step 1 was reacted with (S) -N-tosyl-1-methyl-2,2- The objective compound (215 mg, 48%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using in place thereof.

¹ H NMR (300 MHz, CDCl ₃ ):? 7.70 (dd, 2H, J = 8.7,1.2 Hz, Ar-H), 7.38-7.33 , Ar-H), 5.10 ( s, 1H, CH), 1.84 (brs, 4H, 2 x NH 2) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ):? 144.0, 142.5 (d), 128.9, 128.7, 128.5, 128.2 (d), 127.6, 127.2, 126.9, 126.1, 61.0, 60.0 ppm;

FAB-MS: 289 (M + 1).

Preparation of <Example 12> (2 S) -1,1,3- triphenyl-1,2-propanediamine (1l)

Step 1: Preparation of ( S ) -1-benzyl-2,2-diphenyl-2-azidinediethylamine (3l)

Except that ( S ) -1,1-diphenyl-2-benzyl-2-aminoethanol was used in place of (S) -N-tosyl-2-amino- The target compound (137 mg, 75%) was obtained by carrying out the same procedure as in the step 1 of Example 1.

IR: 2104 cm ^-1 ;

¹ H NMR (300 MHz, CDCl ₃ ):? 7.38-7.35 (m, 2H, Ar-H), 7.28-7.02 (m, 13H, Ar-H), 3.98-3.94 , 1H, J = 15.5 Hz) , 2.04-1.96 (m, 1H), 1.13-1.08 (m, 1H), 1.06 (brs, 2H, -NH 2) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 140.91, 140.28, 139.77, 129.28, 128.66, 128.61, 128.55, 128.10, 127.86, 127.77, 127.65, 126.55, 76.43, 59.72, 39 ppm;

Optical rotation: at 12 ° C, -50.79 ° (c = 0.51, CHCl ₃ ).

Step 2: (2 S) -1,1,3- Preparation of triphenyl-1,2-propanediamine (1l)

( S ) -1-benzyl-2,2-diphenyl-2-azidoethylamine obtained in the above step 1 was reacted with (S) -N-tosyl- The objective compound (113 mg, 84%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using in place of ethylamine

¹ H NMR (300 MHz, CDCl ₃ ):? 7.63-7.57 (m, 5H, Ar-H), 7.37-7.29 (m, 6H, Ar- , 4.16-4.09 (m, 1H), 2.85 (dd, 1H, J = 12, 1.5 Hz), 2.34-2.27 (m, 1H), 1.65 (s, 4H, 2 x -NH 2) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ): δ 147.17, 146.35, 140.41, 129.22, 128.74, 128.53, 128.51, 126.58, 126.49, 64.23, 59.10, 38.20 ppm;

Optical rotation: at 12 ° C, -10.8 ° (c = 0.25, CHCl ₃ ).

Preparation of <Example 13> (2 S) -1,1,2- triphenyl-2- (1-piperidinyl) ethylamine (1m)

Step 1: Preparation of (2S) -1- (2-azido-1,2,2-triphenylethyl) piperidine (3m)

(2S) -1,1,2-triphenyl-2- (piperidin-1-yl) ethanol was used instead of (S) -N-tosyl- The procedure of Step 1 of Example 1 was followed except that it was used without purification.

Step 2: (2 S) -1,1,2- Preparation of triphenylsulfonium 2- (1-piperidinyl) ethylamine (1m)

(2S) -1- (2-azido-1,2,2-triphenylethyl) piperidine obtained in the above step 1 was reacted with (S) -N-tosyl- The target compound (94 mg, 72%) was obtained by carrying out the same procedure as in the step 2 of Example 1 except for using in place of 2-azidopropylamine.

^{1 H NMR (300 MHz, CDCl} 3): δ 7.57 (d, J = 7.9 Hz, 1H), 7.42 (d, J = 7.9 Hz, 2H), 7.29-7.21 (m, 6H), 7.16-7.08 (m 2H), 1.98-1.92 (m, 2H), 1.47 (m, 2H), 7.88 (dd, J = 2.8,4.4 Hz, 1H) 1.39 (m, 4H), 1.29-1.24 (m, 2H) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ):? 146.9, 147.0, 138.3, 131.1, 127.8, 127.6, 127.5, 127.4, 126.5, 126.1, 125.9, 65.3, 54.9, 27.1, 24.6 ppm;

Optical rotation: + 73.94 ° (c = 0.33, CHCl 3);

FAB-MS: 357 (M + 1).

Preparation of (3,5-di-trifluoromethylphenyl) -1- (2-pyrrolidinyl) methylamine (1n) - <Example 14> (1 S) -1,1- bis

Step 1: Preparation of (S) -2- (azabis- (3,5-bis (trifluoromethyl) phenyl) methyl) pyrrolidine (3n)

(S) -bis (3,5-bis (trifluoromethyl) phenyl) pyrrolidin-2-yl) propionic acid was used in place of (S) -N- The procedure of Step 1 of Example 1 was followed except that methanol was used and used without purification.

Step 2: (1 S) -1,1- bis - Preparation of (3,5-di-trifluoromethylphenyl) -1- (2-pyrrolidinyl) methylamine (1n)

(S) -2 - (azabic [3,5-bis (trifluoromethyl) phenyl) methyl) pyrrolidine obtained in the above Step 1 was reacted with (S) -N- -Diphenyl-2-acridine The title compound (53 mg, 81%) was obtained by carrying out the same procedure as in the step 2 of Example 1, except for using in place of ethylamine.

^{1 H NMR (300 MHz, CDCl} 3): δ 8.05 (s, 2H), 7.97 (s, 2H), 7.77 (s, 2H), 4.35 (t, J = 7.8 Hz, 1H), 3.08-3.03 (m , 2H), 1.81 (m, 2H), 1.72 (brs, 2H), 1.61-1.53 (s, 3H) ppm;

¹³ C NMR (75 MHz, CDCl ₃ ):? 146.6, 131.2, 126.2, 125.8, 125.5 (m), 64.4, 47.1, 26.9, 25.7 ppm;

FAB-MS: 525 (M + 1).

Claims (10)

As shown in Scheme 1 below,
Performing an azidation reaction with sodium azide at a temperature of 0 ° C to room temperature in the presence of sulfuric acid (step 1); And
And reducing the compound represented by the formula (3) obtained in the step (1) using LiAlH ₄ (step 2). The process for producing the ethylenediamine derivative represented by the formula

<Reaction Scheme 1>

(In each of the formulas (1), (2) and (3)
Wherein R ₁ and R ₂ together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocycle, wherein R ₃ is hydrogen; C ₁ -C ₄ linear or branched alkylthiol group substituted with an unsubstituted or hydroxyl group or thiol group, an amino group, an aminocarbonyl group, a carboxyl group, guanidinyl (NH ₂ C (═NH) NH-), unsubstituted or substituted with a hydroxy group C ₁ to C ₄ straight or branched chain alkyl substituted with any substituent selected from the group consisting of C ₅ to C ₆ aryl, 5 to 6-membered heterocycloaryl containing a nitrogen atom and 8 to 13-membered double-ring heterocycloaryl group, ego; or
Wherein R ₂ and R ₃ together form a ring to form a 5- to 6-membered heterocycle comprising a nitrogen atom, wherein R ₁ is hydrogen or p-toluenesulfonyl;
Ar is an unsubstituted or C ₁ to C ₄ linear / branched alkyl, C ₁ to C ₄ alkoxy and C ₁ to C ₄ haloalkyl alkyl substituted with 1 substituent at least one selected from the group consisting of C ₅ to C ₆ aryl, or C is a bicyclic aryl group of _{from 8} to ₁₃ C).
2. The method of claim 1, wherein the 5- to 6-membered heterocycle formed by R ₁ and R ₂ is pyrrolidinyl or piperidinyl.
The process for producing an ethylenediamine derivative according to claim 1, wherein the 5- to 6-membered heterocycle formed by R ₂ and R ₃ is pyrrolidinyl or piperidinyl.
The compound according to claim 1, wherein Ar is phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, 3,5-dimethylphenyl, 3,5-dimethoxyphenyl, Methylphenyl, and 2-naphthyl. 2. A process for producing an etalenediamine derivative according to claim 1,
2. The compound of claim 1, wherein the 5 to 6 membered heterocycle formed by R &lt; ₁ &gt; and R &lt; ₂ &gt; is piperidinyl;
Wherein the 5 to 6 membered heterocycle formed by R &lt; ₂ &gt; and R &lt; ₃ &gt; is pyrrolidinyl;
Wherein Ar is any one selected from the group consisting of phenyl, 4-methoxyphenyl, 3,5-ditrifluoromethylphenyl, and 2-naphthyl.
2. The method according to claim 1, wherein the derivative represented by the formula (1) is any one selected from the group consisting of the following compounds:
7) (1S) -1 - {(N-tosyl) -2-pyrrolidinyl} -1,1 diphenylmethylamine;
8) (1S) -1- (N-tosyl) -2-pyrrolidinyl-1,1-di (2-naphthyl) methylamine;
13) (1S) -1,1-Bis- (3,5-ditrifluoromethylphenyl) -1- (2-pyrrolidinyl) methylamine; And
14) (S) -1-Isopropyl-2,2-bis (4-methoxyphenyl) -2-azidoethylamine. delete delete delete delete