Novel vinamidinium salt and uv-a absorbent containing said novel vinamidinium salt

Abstract

Provided is a novel vinamidinium salt which is characterized by being represented by formula (1). (In formula (1), R1, R2, R5, R6 and R7 each independently represent a hydrogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms, or the like; R3 and R4 each independently represent a hydrogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms, or the like; Y is O, S, NR8, or CR8R9; R8 and R9 each independently represent a hydrogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms, or the like; R1 to R9 may be bonded to each other to form a cyclic structure; and X- represents an anion.)

Description

Novel vinamidinium salts and UV-A absorbers containing such novel vinamidinium salts

[0001] The present invention relates to novel vinamidinium salts and UV-A absorbers containing such novel vinamidinium salts.

[0002] The ultraviolet rays contained in sunlight are classified by wavelength into UV-A (320-400 nm), UV-B (280-320 nm), and UV-C (200-280 nm). Of these, UV-A and UV-B have an effect on living organisms, but UV-B has stronger energy than UV-A and is more likely to cause sunburn, so the majority of conventional commercially available sunscreens have primarily been UV-B absorbers and reflectors.

[0003] However, it has become clear that UV-A, which is not absorbed by the ozone layer and reaches the dermis, causes wrinkles and sagging skin, and therefore it is also important to protect the skin from UV-A.

[0004] Conventional UV-A absorbers are limited to a few benzene-based compounds that may cause side effects such as skin irritation. Non-benzene-based mycosporine-like amino acids have also been reported, but they are not sufficient due to factors such as weak absorption, a short wavelength absorption maximum, and the need for acidic conditions (see Non-Patent Document 1).

[0005] On the other hand, methylobamine, a natural organic compound derived from microorganisms, is a non-benzene-based hydrophilic low-molecular-weight compound that has been reported to have excellent UV-A absorption properties (see Patent Document 1). However, it is difficult to obtain as a natural trace component, and its properties are not fully understood, making it difficult to supply by chemical synthesis.

[0006] Vanessa Geraldes, Ernani Pinto, Mycosporine-Like Amino Acids (MAAs): Biology, Chemistry and Identification Features.2021

[0007] Patent No. 5751517

[0008] An object of the present invention is to provide novel vinamidinium salts that are useful as UV-A absorbers.

[0009] The present inventors have discovered that vinamidinium salts having a specific structure have excellent UV-A absorption properties, and have thus completed the present invention.

[0010] That is, the present invention is as follows: [1] A vinamidinium salt represented by the following formula (1): (In formula (1), R １ , R ２ , R ５ , R ６ and R ７ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R ３ and R ４ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, a hydroxy group, or a halogen atom; Y is O, S, NR ８ , C.R. ８ R ９ and R ８ and R ９ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R １ ~R ９ may be bonded to each other to form a cyclic structure; X － represents an anion.) [2] R ６ and R ７

[0023] The vinamidinium salt according to the above [1], wherein these, together with the nitrogen atom to which they are bonded, form a nitrogen-containing cyclic group. [3] The vinamidinium salt according to the above [2], wherein the nitrogen-containing cyclic group is at least one group selected from an azetidine group, a pyrrolidine group, a piperidine group, an azepane group, a morpholine group, a thiomorpholine group, a thiomorpholine dioxide group, and a piperazine group. [4] The vinamidinium salt according to any one of the above [1] to [3], represented by the following formula (1A): [5] In formula (1A), R １ represents an alkyl group having 1 to 4 carbon atoms, and R ２ represents a methyl group, and R ３ ~R ５ represents a hydrogen atom, and X － is PF ６ － The vinamidinium salt according to the above [4], which represents:

[0011] [6] A vinamidinium salt represented by the following formula (2): (In formula (2), R １ , R ２ and R ５ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R ３ and R ４ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, a hydroxy group, or a halogen atom; Y is O, S, NR ８ , C.R. ８ R ９ and R ８ and R ９each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R １ ~R ５ , R ８ and R ９ may be bonded to each other to form a cyclic structure; X － represents an anion.) [7] X － But PF ６ － , B.F. ４ － , halide ion, R Ａ CO ２ － (R Ａ represents an organic group having 1 to 20 carbon atoms, and R Ｂ SO ４ － (R Ｂ represents an organic group having 1 to 20 carbon atoms.) The vinamidinium salt according to any one of [1] to [6] above, wherein the anion is selected from the group consisting of

[0012] [8] A UV-A absorber comprising the vinamidinium salt according to any one of [1] to [6] above. [9] The UV-A absorber according to [8] above, characterized by being transparent.

[10] A skin external preparation comprising the vinamidinium salt according to any one of [1] to [6] above.

[11] A glass material comprising the vinamidinium salt according to any one of [1] to [6] above.

[12] A resin material comprising the vinamidinium salt according to any one of [1] to [6] above.

[0013] The novel vinamidinium salt of the present invention exhibits excellent UV-A absorbing effect.

[0014]

[0033] Figure 1 shows a UV absorption spectrum of the vinamidinium salt (3a) of the present invention.

[0034] Figure 2 shows a UV absorption spectrum of the vinamidinium salt (3b) of the present invention.

[0035] Figure 3 shows a UV absorption spectrum of the vinamidinium salt (3c) of the present invention.

[0036] Figure 4 shows a UV absorption spectrum of the vinamidinium salt (3d) of the present invention.

[0037] Figure 5 shows a UV absorption spectrum of the vinamidinium salt (3e) of the present invention.

[0038] Figure 6 shows a UV absorption spectrum of the vinamidinium salt (3f) of the present invention.

[0039] Figure 7 shows a UV absorption spectrum of the vinamidinium salt (3g) of the present invention.

[0039] Figure 8 shows a UV absorption spectrum of the vinamidinium salt (3h) of the present invention.

[0039] Figure 9 shows a UV absorption spectrum of the vinamidinium salt (3i) of the present invention.

[0039] Figure 10 shows a UV absorption spectrum of the vinamidinium salt (3j) of the present invention.

[0039] Figure 11 shows a UV absorption spectrum of the vinamidinium salt (3k) of the present invention.

[0039] Figure 12 shows a UV absorption spectrum of the vinamidinium salt (3l) of the present invention.

[0039] Figure 13 shows a UV absorption spectrum of the vinamidinium salt (3m) of the present invention. 1 shows a UV absorption spectrum of the vinamidinium salt (3n) of the present invention. 2 shows a UV absorption spectrum of the vinamidinium salt (3o) of the present invention. 3 shows a UV absorption spectrum of the vinamidinium salt (7a) of the present invention. 4 shows a UV absorption spectrum of the vinamidinium salt (11a) of the present invention.

[0015] The vinamidinium salt of the present invention is characterized by being represented by the following formula (1):

[0016]

[0017] In formula (1), R １ , R ２ , R ５ , R ６ and R ７ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group.

[0018] Examples of the substituent include an alkoxy group having 1 to 4 carbon atoms, a halogen atom, and a hydroxyl group. In addition to the above substituents, examples of the substituent on the aromatic ring of the aryl group or aralkyl group include an alkyl group having 1 to 4 carbon atoms. A suitable example of the alkyl group having a substituent is a perfluoroalkyl group.

[0019] R １ As the alkyl group, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or an alkynyl group having 1 to 4 carbon atoms is preferred, with an alkyl group having 1 to 4 carbon atoms being more preferred. Examples of the alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, a propyl group, a butyl group, and an isopropyl group. Examples of the aryl group having 6 to 14 carbon atoms include a phenyl group and a naphthyl group. Examples of the aralkyl group having 7 to 20 carbon atoms include a benzyl group.

[0020] The alkyl group, alkenyl group, and alkynyl group may be linear, branched, or cyclic (cycloalkyl). Examples of the alkenyl group include a vinyl group and an allyl group. Examples of the alkynyl group include an ethynyl group and a propargyl group.

[0021] R ２ As the alkyl group, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or an alkynyl group having 1 to 4 carbon atoms is preferred, an alkyl group having 1 to 4 carbon atoms is more preferred, and a methyl group is particularly preferred.

[0022] R ３ and R ４ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, a hydroxy group, or a halogen atom.

[0023] R ３ and R ４is preferably a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or an alkynyl group having 1 to 4 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and particularly preferably a hydrogen atom.

[0024] R ５ is preferably a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or an alkynyl group having 1 to 4 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and particularly preferably a hydrogen atom.

[0025] R ６ and R ７ As the alkyl group, a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a cyclic structure as described below is preferred.

[0026] R １ ~R ９ may be bonded to each other to form a cyclic structure, R １ ~R ４ and R ２ and R ５ are linked to each other to form a ring, or R ５ ~R ７ are linked to each other to form a ring, or R ６ and R ７ are linked to each other to form a ring.

[0027] R １ ~R ４ In an embodiment in which any of R ３ and R ４ are preferably linked to each other to form a ring. ６ and R ７ are preferably linked to each other to form a ring, and specifically, they preferably form a nitrogen-containing cyclic group together with the nitrogen atom to which they are bonded.

[0028] Examples of the nitrogen-containing cyclic group include an azetidine group, a pyrrolidine group, a piperidine group, an azepane group (perhydroazepine group), a morpholine group, a thiomorpholine group, a thiomorpholine dioxide group, and a piperazine group.

[0029] Specifically, R ６ and R ７ Examples of the nitrogen-containing cyclic group formed by combining the nitrogen atom to which the nitrogen atom is bonded include the following.

[0030]

[0031] Y is O, S, NR ８ , C.R. ８ R ９ and R ８ and R ９ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group. Y is preferably O (oxygen atom) or S (sulfur atom), and more preferably O (oxygen atom).

[0032] X － represents an anion. － The anion of ６ － , B.F. ４ － , halide ion, R Ａ CO ２ － , R Ｂ SO ４ － etc. Ａ and R Ｂ represents an organic group having 1 to 20 carbon atoms, for example, an alkyl group having 1 to 20 carbon atoms, and an alkyl group having 1 to 4 carbon atoms is preferred. ６ － is particularly preferred.

[0033] Of the vinamidinium salts represented by formula (1) of the present invention, vinamidinium salts represented by the following formula (1A) are preferred: ６ and R ７However, a structure in which the aryl group forms a morpholine group together with the nitrogen atom to which it is bonded is preferred.

[0034]

[0035] In addition, in the vinamidinium salt represented by formula (1A), R １ represents an alkyl group having 1 to 4 carbon atoms, and R ２ represents a methyl group, and R ３ ~R ５ represents a hydrogen atom, and X － is PF ６ － Particularly preferred are vinamidinium salts which represent:

[0036] In addition, in the vinamidinium salt represented by formula (1A), R １ represents an alkyl group having 1 to 4 carbon atoms, and R ２ represents a methyl group, and R ３ and R ４ are bonded to each other in a cyclic structure, and R ５ represents a hydrogen atom, and X － is PF ６ － Particularly preferred are vinamidinium salts which represent:

[0037] Of the vinamidinium salts represented by formula (1) of the present invention, vinamidinium salts represented by the following formula (1B) are preferred: ６ and R ７ However, a structure in which the aryl group forms a morpholine group together with the nitrogen atom to which it is bonded is preferred.

[0038]

[0039] In the vinamidinium salt represented by formula (1B), R １ represents an alkyl group having 1 to 4 carbon atoms, and R ２ represents a methyl group, and R ３ ~R ５ represents a hydrogen atom, and X － is PF ６ － Particularly preferred are vinamidinium salts which represent:

[0040] Another vinamidinium salt of the present invention is characterized by being represented by the following formula (2):

[0041]

[0042] R in formula (2) １ ~R ５ The details of are the same as those explained in the above formula (1).

[0043] As the vinamidinium salt represented by formula (2), a vinamidinium salt represented by the following formula (2A) is particularly preferred. That is, in formula (2), Y is represented by O, and R ２ is represented by a methyl group, and R ３ ~R ５ is particularly preferably represented by a hydrogen atom.

[0044]

[0045] The vinamidinium salts of the present invention represented by formulas (1) and (2) absorb light in the UV-A region (320 to 400 nm). ｍａｘ ) at 320 to 400 nm.

[0046] The vinamidinium salt of the present invention has a molar absorption coefficient (ε) in the UV-A wavelength region of 20,000 M. －１ cm －１ More than 35,000M is preferable. －１ cm －１ More preferably, 40,000M or more －１ cm －１ The above is more preferred.

[0047] The vinamidinium salt of the present invention has superior absorption properties compared to conventional compounds that exhibit UV-A absorption properties. Specifically, the vinamidinium salt of the present invention has a maximum absorption wavelength that is longer than that of conventional compounds that exhibit UV-A absorption properties, allowing it to cover a wide range of the UV-A region. It also has a high molar extinction coefficient. Furthermore, it is not pH-dependent and can absorb UV-A while maintaining a stable ionic state.

[0048] Furthermore, it is particularly preferred that the vinamidinium salt of the present invention does not absorb wavelengths of visible light, i.e., it is particularly preferred that the vinamidinium salt of the present invention is transparent.

[0049] The vinamidinium salt of the present invention absorbs light with wavelengths in the UV-A region as described above, and is therefore useful as a UV-A absorber. Utilizing this UV-A absorbing function, the salt can be incorporated into external skin preparations, glass materials, resin materials, and the like.

[0050] Specifically, the vinamidinium salt of the present invention is useful for applications such as external skin preparations as cosmetics, pharmaceuticals, and quasi-drugs, glass and resin materials as building materials and vehicle materials, general glass and plastic products, etc. In particular, when the vinamidinium salt of the present invention is non-benzene-based, it is useful as an external skin preparation because it is hypoallergenic to the skin.

[0051] Next, an example of a method for producing the vinamidinium salt of the present invention will be described. ２ is a methyl group, R ３ ~R ５ is a hydrogen atom, X － is PF ６ － In addition, when Y is a sulfur atom or the like, or when R ３ ~R ５ The case where the compound forms a cyclic structure can also be produced in the same manner.

[0052] As a starting material for producing the vinamidinium salt of the present invention, the morpholinone shown below can be used.

[0053]

[0054] First, an alkyl group is introduced into the nitrogen of morpholinone, which is a starting material, to obtain the following N-alkylmorpholinone 1. １ The details of are the same as those explained in the above formula (1).

[0055]

[0056] Subsequently, the N-alkylmorpholinone 1 is treated with methyllithium to obtain the cyclic enamine 2 shown below, in which the carbonyl group is methylated.

[0057]

[0058] (In the case of the compound of formula (1)) Next, the cyclic enamine 2 is reacted with a Vilsmeier-type reagent prepared from N-formylamide and phosphorus oxychloride, followed by the addition of an aqueous solution of sodium hexafluorophosphate to convert it into a hexafluorophosphate salt, thereby obtaining the vinamidinium salt 3 of formula (1) of the present invention.

[0059]

[0060] Specific examples of N-formylamides in the above reaction include N,N-dimethylformamide, N,N-diethylformamide, N,N-diisopropylformamide, azetidine-1-carbaldehyde, pyrrolidine-1-carbaldehyde, piperidine-1-carbaldehyde, azepane-1-carbaldehyde, N,N-diphenylformamide, morpholine-4-carbaldehyde, thiomorpholine-4-carbaldehyde, and thiomorpholine-4-carbaldehyde 1,1-dioxide, as shown below.

[0061]

[0062] (Compound of Formula (2)) The vinamidinium salt of the present invention represented by formula (2) uses the following piperazine-1,4-dicarbaldehyde as the N-formylamide for the cyclic enamine 2.

[0063]

[0064] Subsequently, an aqueous solution of sodium hexafluorophosphate is added to convert it into a hexafluorophosphate salt, thereby obtaining the vinamidinium salt 3 of the present invention represented by formula (2).

[0065]

[0066] Specific examples of the vinamidinium salt of the present invention are shown below. For example, in the vinamidinium salt of the present invention represented by formula (1) (where Y is an oxygen atom, but can be replaced with a sulfur atom or the like), R ６ and R ７ Examples of vinamidinium salts in which the alkyl group is an alkyl group or an aryl group include the following compounds.

[0067]

[0068] For example, in the vinamidinium salt of the present invention represented by formula (1) (Y is an oxygen atom, but it can be replaced with a sulfur atom or the like), R ６ and R ７ However, examples of vinamidinium salts that form a nitrogen-containing cyclic group together with the nitrogen atom to which they are bonded include the following compounds.

[0069]

[0070] For example, in the vinamidinium salt of the present invention represented by formula (1) (Y is an oxygen atom, but it can be replaced with a sulfur atom or the like), R １ Examples of vinamidinium salts having an aralkyl group include the following compounds:

[0071]

[0072] For example, in the vinamidinium salt of the present invention represented by formula (1) (Y is an oxygen atom, but it can be replaced with a sulfur atom or the like), R ６ and R ７ However, examples of vinamidinium salts of each hydrogen atom include the following compounds.

[0073]

[0074] The vinamidinium salt 3o can be obtained, for example, by subjecting the vinamidinium salt 3a to amine exchange.

[0075] Furthermore, examples of the vinamidinium salt of the present invention represented by formula (2) (the case where Y is an oxygen atom is exemplified, but it can be replaced with a sulfur atom or the like) include the following compounds:

[0076]

[0077] Specific examples of the present invention will be described below, but the scope of the present invention is not limited to these examples.

[0078] <Outline of the Method for Producing a Vinamidinium Salt of the Present Invention> As shown in the reaction scheme below, first, N-alkylmorpholinone 1 is synthesized by alkylation of morpholinone, and then N-alkylmorpholinone 1 is treated with methyllithium to form cyclic enamine 2. Furthermore, cyclic enamine 2 is reacted with a Vilsmeier-type reagent prepared from N-formylamide and phosphorus oxychloride, followed by conversion to a hexafluorophosphate salt to synthesize vinamidinium salt 3 of the present invention.

[0079]

[0080] [Example 1] <Production of vinamidinium salt 3a of the present invention>

[0081]

[0082] (Synthesis of Compound 1) Under an argon atmosphere, morpholin-3-one (14.9 g, 148 mmol) was dissolved in distilled and dried N,N-dimethylformamide (150 mL). The resulting solution was cooled to 0°C, and sodium hydride (60% in mineral oil, 7.00 g, 175 mmol) was added. 1-Bromobutane (16.5 mL, 153 mmol) was slowly added dropwise to this suspension, and the reaction mixture was warmed to room temperature and stirred for 6 hours. After quenching the reaction by adding water, the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The resulting crude product was purified by vacuum distillation (0.7 torr, 108°C) to obtain 19.5 g (84%) of Compound 1 (4-butylmorpholin-3-one) as a colorless, transparent oil.

[0083]

[0084] １ HNMR (400MHz, CDCl ３ ) δ4.16 (s, 2H), 3.88 (dd, J=5.5, 4.6Hz, 2H), 3.41 (t, J=7.3Hz, 2H), 3.36 (appare ntt, J = 5.1Hz, 2H), 1.59-1.52 (m, 2H), 1.39-1.32 (m, 2H), 0.94 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ166.5, 68.1, 63.9, 46.1, 46.0, 28.9, 20.0, 13.8; IR (NaCl): 2958, 1639 cm －１ ; MS (EI) m / z (%) 157 (M ＋ , 28), 86 (100); HRMS (EI) calcdforC ８ H １５ NO ２ :157.1103,found:157.1101.

[0085] (Synthesis of Compound 2) Under an argon atmosphere, compound 1 (3.67 g, 23.4 mmol) was dissolved in dehydrated diethyl ether (87 mL). This solution was cooled to −18°C, and then methyllithium (1.14 M diethyl ether solution, 27.0 mL, 30.8 mmol) was slowly added dropwise. The reaction mixture was stirred at −18°C for 2.5 hours, and then ice was added to quench the reaction. After warming to room temperature, the mixture was extracted three times with diethyl ether. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by distillation under reduced pressure (10 torr, 80°C) to obtain 2.73 g (76%) of compound 2 (4-butyl-5-methyl-3,4-dihydro-2H-1,4-oxazine) as a colorless, transparent oil.

[0086]

[0087] １ HNMR (400MHz, CDCl ３) δ5.74 (s, 1H), 3.89 (t, J = 4.8Hz, 2H), 3.07 (t, J = 4.8Hz, 2H), 2.78 (dd, J=7.6, 7.6Hz, 2H), 1.64 (s, 3H), 1.48-1.38 (m, 2H), 1.36-1.26 (m, 2H),; １３ CNMR (100MHz, CDCl ３ ) δ123.5, 121.9, 63.0, 50.8, 47.5, 29.4, 20.2, 15.7, 14.0; IR (NaCl): 2958, 1607 cm －１ :MS (EI) m / z (%) 310 (2M ＋ , 65), 211 (100), 155 (M ＋ , 67), 112 (60); HRMS (EI) calcdforC ９ H １７ NO:155.1310,found:155.1309.

[0088] (Synthesis of Compound 3a) Under an argon atmosphere, N,N-dimethylformamide (350 μL, 4.74 mmol) was added to a flask and cooled to 0°C, followed by the slow dropwise addition of phosphorus oxychloride (90.0 μL, 0.968 mmol). The resulting solution was warmed to room temperature, followed by the dropwise addition of a solution of compound 2 (98.1 mg, 0.645 mmol) in dichloromethane (3.0 mL). The reaction mixture was warmed to 50°C and stirred for 5 hours, then cooled to room temperature, and an aqueous solution of sodium hexafluorophosphate (3.0 M, 0.86 mL, 2.6 mmol) was added. The reaction mixture was stirred for 20 minutes, followed by the addition of water and extraction three times with dichloromethane. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated using an evaporator. The remaining N,N-dimethylformamide was then distilled off using a Kugelrohr distillation apparatus, and the residue was purified by alumina column chromatography (CHCl ３ / hexane = 1:1 to 3:1) to obtain 140 mg (61%) of Compound 3a (vinamidinium salt 3a of the present invention) as an orange oil.

[0089]

[0090] １ HNMR (400MHz, CDCl３ ) δ7.22 (s, 1H), 4.07 (t, J=4.6Hz, 2H), 3.60 (t, J=4.3Hz, 2H), 3.51 (t, J=8.0Hz, 2H), 3.41 (s, 3H), 3.31 (s, 3H), 2.30 (s, 3H), 1.66-1.62 (m, 2H), 1.39-1.30 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (151MHz, CDCl ３ ) δ156.0, 145.0, 125.1, 61.7, 53.4, 48.8, 48.5, 40.2, 29.6, 19.7, 14.1, 13.5; IR (KBr): 2962, 1641 cm －１ ; MS (FAB+) m / z (%) 211 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+, [M-PF ６ ] ＋ )calcdforC １２ H ２３ N ２ O:211.1810,found:211.1809.

[0091] The UV absorption spectrum (λ) of the vinamidinium salt 3a of the present invention prepared as above was ｍａｘ :361nm, ε:42229M －１ cm －１ ) is shown in Figure 1.

[0092] [Example 2] <Production of vinamidinium salt 3b of the present invention>

[0093]

[0094] In the same manner as in Example 1, compound 3b (vinamidinium salt 3b of the present invention) was synthesized from compound 2 (101 mg, 0.651 mmol) and N,N-diethylformamide (520 μL, 4.68 mmol), and purified by alumina column chromatography (CHCl ３ The crude product was purified using a 1:2 to 1:1 mixture of hexane and 1:2 hexane. The yield was 147 mg (59%) of an orange oil.

[0095]

[0096] １HNMR (400MHz, CDCl ３ ) δ7.18 (s, 1H), 4.08 (t, J = 4.6Hz, 2H), 3.73 (q, J = 7.2Hz, 2H), 3.63 (t, J = 4.3Hz, 2H), 3.54-3.48 (m, 4H), 2.31 (s, 3H), 1.66-1.62 (m, 2H), 1.39-1.36 (m, 2H), 1.32 (t, J = 7.1Hz, 4H), 1.25 (t, J = 7.1Hz, 3H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ156.2, 143.4, 124.9, 61.8, 53.9, 53.5, 48.9, 45.4, 29.7, 19.8, 14.7, 14.5, 14.3, 13.6; IR (KBr): 2962, 1628 cm －１ ; MS (FAB) m / z (%) 239 ([M-PF ６ ] ＋ , 100); HRMS (FAB) calcdforC １４ H ２７ N ２ O[M-PF ６ ] ＋ :239.2123,found:239.2125.

[0097] The UV absorption spectrum (λ) of the vinamidinium salt 3b of the present invention prepared as above was ｍａｘ :363nm, ε:48009M －１ cm －１ ) is shown in Figure 2.

[0098] [Example 3] <Production of vinamidinium salt 3c of the present invention>

[0099]

[0100] In the same manner as in Example 1, compound 3c (vinamidinium salt 3c of the present invention) was synthesized from compound 2 (101 mg, 0.651 mmol) and N,N-diisopropylformamide (700 μL, 4.82 mmol), and purified by alumina column chromatography (CHCl ３ The crude product was purified using a 1:10 to 1:1 mixture of hexane and hexane. The yield was 202 mg (76%) of an orange oil.

[0101]

[0102] １ HNMR (600MHz, CDCl ３ ) δ7.00 (s, 1H), 5.18 (brs, 1H), 4.10 (q, J = 4.5Hz, 2H), 3.78-3.74 (m, 1H), 3.63 (t, J = 4.6Hz, 2H), 3.56-3.53 (m, 2H), 2. 31 (s, 3H), 1.66-1.61 (m, 2H), 1.38-1.34 (m, 2H), 1.32 (d, J = 6.9Hz, 6H), 1.25 (d, J = 6.6Hz, 6H), 0.95 (t, J = 7.4Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ156.2, 139.1, 125.2, 61.8, 53.7, 51.8, 49.4, 49.0, 29.6, 23.7, 20.5, 19.7, 14.6, 13.5; IR (KBr): 2968, 1622 cm －１ ; MS (FAB) m / z (%) 267 ([M-PF ６ ] ＋ , 100); HRMS (FAB) calcdforC １６ H ３１ N ２ O[M-PF ６ ] ＋ :267.2436,found:267.2439.

[0103] The UV absorption spectrum (λ) of the vinamidinium salt 3c of the present invention prepared as above was ｍａｘ :355nm, ε:40767M －１ cm －１ ) is shown in Figure 3.

[0104] [Example 4] <Production of vinamidinium salt 3d of the present invention>

[0105]

[0106] Azetidine hydrochloride (1.01 g, 10.7 mmol) in CH ２ Cl ２ To the suspension (42.0 mL), proton sponge (2.45 g, 11.4 mmol) was added. The resulting suspension was heated to 50°C, stirred for 1 hour, and then returned to room temperature. In a separate flask, N-formylsaccharin (2.38 g, 11.2 mmol) in CH２ Cl ２ A (250 mL) solution was prepared, and the amine solution prepared above was added to this. The resulting reaction solution was heated to 50°C and stirred for 23 hours. After returning to room temperature, the solvent was removed using an evaporator, and the mixture was further purified by vacuum distillation (4.0 torr, 90°C) using a Kugelrohr distillation apparatus to obtain 644 mg (71%) of azetidine-1-carbaldehyde as a colorless oil.

[0107]

[0108] １ HNMR (400MHz, CDCl ３ ) δ7.94 (s, 1H), 4.18 (t, J=7.7Hz, 2H), 4.05 (t, J=7.7Hz, 2H), 2.42-2.34 (m, 2H)

[0109] In the same manner as in Example 1, compound 3d (vinamidinium salt 3d of the present invention) was synthesized from compound 2 (104 mg, 0.671 mmol) and azetidine-1-carbaldehyde (408 mg, 4.80 mmol). The compound was purified by alumina column chromatography (CHCl ３ The product was purified in a 1:1 mixture of hexane and hexane. The yield was 145 mg (61%) of a black oil.

[0110]

[0111] １ HNMR (600MHz, CDCl ３ ) δ7.29 (s, 1H), 4.65 (t, J = 7.9Hz, 2H), 4.50 (t, J = 8.0Hz, 2H), 4.02 (t, J = 4.6Hz, 2H), 3.54 (t, J = 4.6Hz, 2H), 3.46 (t, J = 7.7Hz, 2H), 2.49-2.43 (m, 2H), 2.22 (s, 3H), 1.64-1.59 (m, 2H), 1.39-1.32 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ153.5, 143.4, 125.8, 61.9, 56.8, 56.3, 52.9, 48.6, 29.8, 19.8, 17.2, 13.8, 13.6; IR (KBr): 2957, 1634 cm －１; MS (FAB) m / z (%) 223 ([M-PF ６ ] ＋ , 100); HRMS (FAB) calcdforC １３ H ２３ N ２ O[M-PF ６ ] ＋ :223.1810,found:223.1810.

[0112] The UV absorption spectrum (λ) of the vinamidinium salt 3d of the present invention prepared above was ｍａｘ :367nm, ε:41949M －１ cm －１ ) is shown in Figure 4.

[0113] [Example 5] <Production of vinamidinium salt 3e of the present invention>

[0114]

[0115] In the same manner as in Example 1, compound 3e (vinamidinium salt 3e of the present invention) was synthesized from compound 2 (101 mg, 0.652 mmol) and pyrrolidine-1-carbaldehyde (460 μL, 4.83 mmol). The compound was purified by alumina column chromatography (CHCl ３ The product was purified using a solvent mixture of hexane (1:2 to 2:1) and hexane (1:2 to 2:1). The yield was 150 mg (61%) of orange crystals.

[0116]

[0117] １ HNMR (600MHz, CDCl ３ ) δ7.48 (s, 1H), 4.05 (t, J = 4.6Hz, 2H), 3.91 (t, J = 6.9Hz, 2H), 3.78 (t, J = 6.6Hz, 2H), 3.59 (t, J = 4.6Hz, 2H), 3.50 (t, J = 7.8 Hz, 2H), 2.29 (s, 3H), 2.04-1.97 (m, 2H), 1.95-1.88 (m, 2H), 1.65-1.59 (m, 2H), 1.40-1.31 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３) δ155.1, 142.4, 125.4, 61.8, 55.8, 53.1, 50.4, 48.8, 29.7, 25.8, 23.9, 19.7, 14.0, 13.5; IR (KBr): 2960, 1628 cm －１ ; MS (FAB+) m / z (%) 237 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB) calcdforC １４ H ２５ N ２ O[M-PF ６ ] ＋ :237.1967, found:237.1968.

[0118] The UV absorption spectrum (λ) of the vinamidinium salt 3e of the present invention prepared as above was ｍａｘ :368nm, ε:35944M －１ cm －１ ) is shown in Figure 5.

[0119] [Example 6] <Production of vinamidinium salt 3f of the present invention>

[0120]

[0121] In the same manner as in Example 1, compound 3f (vinamidinium salt 3f of the present invention) was synthesized from compound 2 (101 mg, 0.652 mmol) and piperidine-1-carbaldehyde (520 μL, 4.69 mmol). The compound was purified by alumina column chromatography (CHCl ３ The crude product was purified using a 1:2 to 1:1 mixture of hexane and 1:2 hexane. The yield was 182 mg (71%) of an orange oil.

[0122]

[0123] １ HNMR (400MHz, CDCl ３ ) δ7.17 (s, 1H), 4.08 (t, J = 4.6Hz, 2H), 4.03 (brs, 2H), 3.62-3.57 (m, 4H), 3.51 (t, J = 7.8Hz, 2H), 2.30 (s, 3H), 1.79 (brs, 2H), 1.70 (brs, 4H), 1.65-1.60 (m, 2H), 1.41-1.32 (m, 2H), 0.96 (t, J = 7.3Hz, 3H);１３ CNMR (150MHz, CDCl ３ ) δ155.8, 142.8, 124.5, 61.8, 58.7, 53.4, 49.5, 48.8, 29.7, 27.0, 26.3, 23.6, 19.7, 14.2, 13.6; IR (KBr): 2936, 1630cm －１ ; MS (FAB+) m / z (%) 251 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+) calcdforC １５ H ２７ N ２ O[M-PF ６ ] ＋ :251.2123,found:251.2120.

[0124] The UV absorption spectrum (λ) of the vinamidinium salt 3f of the present invention prepared above was ｍａｘ :362nm, ε:43353M －１ cm －１ ) is shown in Figure 6.

[0125] [Example 7] <Production of 3 g of vinamidinium salt of the present invention>

[0126]

[0127] Azepane (1.10 mL, 9.78 mmol) was added dropwise to a suspension of N-formylsaccharin (2.13 g, 10.1 mmol) and THF (10.0 mL) at room temperature. After stirring for 1 hour, the mixture was diluted with dichloromethane, and saturated aqueous sodium bicarbonate was added. The mixture was extracted three times with dichloromethane, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated using an evaporator. The resulting crude product was purified by distillation under reduced pressure (2.5 torr, 120°C) to yield 658 mg (51%) of azepane-1-carbaldehyde as a colorless oil.

[0128]

[0129] １ HNMR (400MHz, CDCl ３) δ8.08 (s, 1H), 3.46 (t, J=5.9Hz, 2H), 3.38 (t, J=5.9Hz, 2H), 1.76-1.72 (m, 4H), 1.60-1.56 (m, 4H)

[0130] In the same manner as in Example 1, compound 3g (3g of the vinamidinium salt of the present invention) was synthesized from compound 2 (102mg, 0.658mmol) and azepan-1-carbaldehyde (629mg, 4.95mmol). The compound was purified by alumina column chromatography (CHCl ３ The product was purified using a solvent mixture containing 1,000 ml of hexane (hexane = 1:5). The yield was 133 mg (71%) of a black oil.

[0131]

[0132] １ HNMR (400MHz, CDCl ３ ) δ7.20 (s, 1H), 4.06 (t, J = 4.6Hz, 2H), 3.86 (t, J = 5.9Hz, 2H), 3.65 (t, J = 6.4Hz, 2H), 3.61 (d, J = 4.6Hz, 2H), 3.52 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 1.84 (m, 2H), 1.77 (m, 2H), 1.67-1.61 (m, 6H), 1.42-1.32 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ156.3, 144.6, 125.1, 61.9, 60.6, 53.6, 51.3, 49.0, 29.8, 29.0, 28.4, 26.8, 25.3, 19.8, 14.4, 13.6; IR (KBr): 2959, 1624 cm －１ ; MS (FAB+) m / z (%) 265 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+) calcdforC １６ H ２９ N ２ O[M-PF ６ ] ＋ :265.2280,found:265.2279.

[0133] The UV absorption spectrum (λ) of 3 g of the vinamidinium salt of the present invention produced as described above wasｍａｘ :364nm, ε:24508M －１ cm －１ ) is shown in Figure 7.

[0134] [Example 8] <Preparation of vinamidinium salt 3h of the present invention>

[0135]

[0136] N,N-Diphenylformamide (191 mg, 0.970 mmol) was dissolved in dichloromethane (360 μL) and cooled to 0°C. To this solution, phosphorus oxychloride (90.0 μL, 0.968 mmol) was slowly added dropwise. Compound 3h (vinamidinium salt 3h of the present invention) was then synthesized from compound 2 (100 mg, 0.645 mmol) in the same manner as in Example 1. Using alumina column chromatography (CHCl ３ The product was purified with MeOH / hexane (1:5) and then recrystallized (MeOH / hexane). The yield was 31 mg (10%) of pale yellow prisms.

[0137]

[0138] １ HNMR (400MHz, CDCl ３ ) δ7.42-7.37 (m, 5H), 7.31 (t, J = 7.3Hz, 2H), 7.14 (d, J = 7.8Hz, 4H), 3.75 (t, J = 4.8Hz, 2H), 3.70 (t, J = 7.8 Hz, 2H), 3.62 (t, J = 4.6Hz, 2H), 2.49 (s, 3H), 1.75-1.67 (m, 2H), 1.45-1.35 (m, 2H), 0.99 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ161.7, 136.3, 129.4, 129.3, 127.3, 124.7, 60.2, 55.1, 49.6, 29.3, 19.9, 15.0, 13.6; IR (KBr): 2963, 1620, 1573 cm －１ ; MS (FAB+) m / z (%) 335 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+) calcdforC ２２ H２７ N ２ O[M-PF ６ ] ＋ :335.2123,found:335.2124.

[0139] The UV absorption spectrum (λ) of the vinamidinium salt 3h of the present invention prepared as above was ｍａｘ :401nm, ε:45942M －１ cm －１ ) is shown in Figure 8.

[0140] [Example 9] <Preparation of vinamidinium salt 3i of the present invention>

[0141]

[0142] Compound 3i (vinamidinium salt 3i of the present invention) was synthesized from compound 2 (300 mg, 1.94 mmol) and morpholine-4-carbaldehyde (1.44 mL, 14.3 mmol) in the same manner as in Example 1. The compound was purified by alumina column chromatography (AcOEt / hexane = 1:20 to 1:1) and recrystallization (isopropanol). The yield was 324 mg (42%) of colorless crystals (mp. 91.2-92.2°C).

[0143]

[0144] １ HNMR (600MHz, CDCl ３ ) δ7.24 (s, 1H), 4.13 (brs, 2H), 4.09 (t, J = 4.7Hz, 2H), 3.85 (brs, 2H), 3.77 (brs, 2H), 3.66 (brs, 2H), 3.61 (t, J = 4.6Hz, 2H), 3.53 (t, J = 7.8Hz, 2H), 2.34 (s, 3H), 1.66-1.62 (m, 2H), 1.40-1.34 (m, 2H), 0.97 (t, J = 7.4Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ157.1, 142.3, 124.8, 67.0, 66.4, 61.6, 56.2, 53.6, 49.1, 48.8, 29.5, 19.6, 14.1, 13.4; IR (KBr): 2936, 1643, 1558 cm －１ ; MS (FAB+) m / z (%) 253 ([M-PF６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+) calcdforC １４ H ２５ N ２ O ２ [M-PF ６ ] ＋ :253.1916,found:253.1913.

[0145] The UV absorption spectrum (λ) of the vinamidinium salt 3i of the present invention prepared as above was ｍａｘ :363nm, ε:56073M －１ cm －１ ) is shown in Figure 9.

[0146] [Example 10] <Preparation of vinamidinium salt 3j of the present invention>

[0147]

[0148] Thiomorpholine-4-carbaldehyde was synthesized from thiomorpholine (1.46 mL, 14.6 mmol) in the same manner as in Example 7 and purified by reduced pressure distillation (1.5 torr, 150°C). The yield was 658 mg (51%) and it was a colorless oil.

[0149]

[0150] １ HNMR (400MHz, CDCl ３ ) δ8.03 (s, 1H), 3.82-3.79 (m, 2H), 3.65-3.62 (m, 2H), 2.66-2.59 (m, 4H); １３ CNMR (101MHz, CDCl ３ ) δ160.9, 48.1, 42.1, 28.1, 26.8; IR (KBr): 2916, 1667 cm －１ ; MS (EI+) m / z (%) 131 (M+, 100), 103 (14); HRMS (EI) calcdforC ５ H ９ NOS:131.04005,found:131.0402.

[0151] Thiomorpholine-4-carbaldehyde (627 mg, 4.79 mmol) was cooled to 10°C, and then phosphorus oxychloride (90.0 μL, 0.968 mmol) was slowly added dropwise. Compound 3j (vinamidinium salt 3j of the present invention) was then synthesized from compound 2 (100 mg, 0.645 mmol) in the same manner as in Example 1. The product was purified by alumina column chromatography (AcOEt / hexane = 1:20 to 1:1) and recrystallization (isopropanol). The yield was 324 mg (42%) of a black solid.

[0152]

[0153] １ HNMR (400MHz, CDCl ３ ) δ7.19 (s, 1H), 4.30 (brs, 2H), 4.10 (t, J = 4.6Hz, 2H), 3.87 (brs, 2H), 3.63 (t, J = 4.6Hz, 2H), 3.54 (t, J = 7.8Hz, 2H), 2.85 (brs, 2H), 2.75 (brs, 2H), 2.34 (s, 3H), 1.67-1.61 (m, 2H), 1.42-1.33 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ157.9, 142.6, 125.0, 61.8, 59.5, 53.9, 51.4, 49.0, 29.6, 28.6, 28.1, 19.8, 14.5, 13.6; IR (KBr): 2959, 1636, 1566 cm －１ ; MS (FAB+) m / z (%) 269 ([M-PF ６ ] ＋ , 100); MS (ESI-) m / z144.9; HRMS (FAB+) calcdforC １４ H ２５ N ２ OS [M-PF ６ ] ＋ :269.1688,found:269.1687.

[0154] The UV absorption spectrum (λ) of the vinamidinium salt 3j of the present invention prepared above was ｍａｘ :363nm, ε:41098M －１ cm －１ ) is shown in FIG.

[0155] Example 11 Thiomorpholine-4-carbaldehyde 1,1-dioxide was synthesized from thiomorpholine-1,1-dioxide (1.46 g, 10.8 mmol) in the same manner as in Example 7, and the obtained product was purified by silica gel column chromatography (CH ２ Cl ２ The product was purified with HCl / MeOH (20:1) in a 20:1 ratio. The yield was 908 mg (50%) as colorless prisms.

[0156]

[0157] １ HNMR (400MHz, CDCl ３ ) δ8.11 (s, 1H), 4.05 (t, J=5.5Hz, 2H), 3.89 (t, J=5.5Hz, 2H), 3.10-3.04 (m, 4H); １３ CNMR (100MHz, CDCl ３ ) δ160.8, 52.3, 51.4, 43.8, 37.7; IR (KBr): 2937, 1665 cm －１ MS (EI+) m / z (%) 163 (M+, 32), 99 (100); MS (ESI-) m / z 144.9; HRMS (EI+) calcdforC ５ H ９ NO ３ S:163.0298,found:163.0301.

[0158] Thiomorpholine-4-carbaldehyde 1,1-dioxide (158 mg, 0.969 mmol) was dissolved in acetonitrile (360 μL) and cooled to 20°C. To this solution, phosphorus oxychloride (90.0 μL, 0.968 mmol) was slowly added dropwise. The resulting solution was warmed to room temperature, and then a solution of compound 2 (100 mg, 0.645 mmol) in acetonitrile (0.30 mL) was added dropwise. Thereafter, reprecipitation (MeOH / CHCl 3 ) was carried out in the same manner as in Example 1. ３ Compound 3k (vinamidinium salt 3k of the present invention) was synthesized by purification using the method described above. The yield was 17.9 mg (6%) and the compound was in the form of yellow prisms.

[0159]

[0160] １ HNMR (600MHz, DMSO-d ６ , 100℃) δ7.44 (s, 1H), 4.19 (brs, 4H), 4.08 (t, J = 4.8Hz, 2H), 3.71 (t, J = 4.5Hz, 2H), 3.63 (t, J = 7.6Hz, 2H), 3.3 3 (brs, 4H), 2.37 (s, 3H), 1.68-1.63 (m, 2H), 1.39-1.33 (m, 2H), 0.94 (t, J = 7.2Hz, 3H); 13CNMR (150MHz, DMSO-d ６ , 100℃) δ159.7, 141.9, 125.2, 61.4, 53.1, 51.5, 49.6, 48.4, 28.4, 18.7, 13.9, 12.8; IR (KBr): 2961, 1636, 1562 cm －１ ; MS (FAB+) m / z (%) 301 ([M-PF ６ ] ＋ , 100);HRMS(FAB+)calcdforC １４ H ２５ N ２ O ３ S[M-PF ６ ] ＋ :301.1586,found:301.1586.

[0161] The UV absorption spectrum (λ) of the vinamidinium salt 3k of the present invention prepared as above ｍａｘ :364nm, ε:41282M －１ cm －１ ) is shown in FIG.

[0162] [Example 12] <Preparation of vinamidinium salt 3l of the present invention>

[0163]

[0164] In the same manner as in Example 1, compound 3l (vinamidinium salt 3l of the present invention (EZ isomer mixture, 2.3:1)) was synthesized from compound 2 (149 mg, 0.961 mmol) and piperazine-1,4-dicarbaldehyde (45.9 mg, 0.323 mmol) and purified by recrystallization (methanol). The yield was 79.9 mg (35%) of yellow-green crystals.

[0165]

[0166] １ HNMR (400MHz, DMSO-d ６ ) δ7.53 (s, 1.4H), 7.52 (s, 0.6H), 4.07-4.35 (brs, 3H), 4.04 (t, J = 4.1Hz, 4H), 4.02-3.69 (br, 6H), 3.68 (t, J = 4.1Hz, 4H) ), 3.59 (t, J = 7.5Hz, 4H), 2.35 (s, 4.2H), 2.34 (s, 1.8H) 1.63-1.58 (m, 4H), 1.32 (q, J = 7.5Hz, 4H), 0.93 (t, J = 7.3Hz, 6H); １３ CNMR (150MHz, DMSO-d ６ ) δ158.1, 142.1, 124.4, 61.7, 54.7, 53.1, 48.5, 48.0, 28.9, 19.3, 14.1, 13.6; IR (KBr): 2959, 1692, 1635, 1570 cm －１ ; MS (FAB+) m / z (%) 563 ([M-PF ６ ] ＋ , 100); HRMS (FAB+) calculated for C ２４ H ４２ F ６ N ４ O ２ P[M-PF ６ ] ＋ :563.2950,found:563.2946.

[0167] The UV absorption spectrum (λ) of the vinamidinium salt 31 of the present invention prepared above was ｍａｘ :368nm, ε:53549M －１ cm －１ ) is shown in FIG.

[0168] [Example 13] <Production of vinamidinium salt 3m of the present invention>

[0169]

[0170] POCl was added to DMF (0.300 mL, 3.88 mmol) cooled to 0°C. ３ (75.0 μL, 0.804 mmol) was added, and the temperature was raised to room temperature. ２ Cl ２(0.110 mL) solution was added, and then the temperature was raised to 50° C. After stirring for 5 hours, the temperature was returned to room temperature and 5M NaPF ６ An aqueous solution (160 μL, 0.800 mmol) was added and stirred. ２ Cl ２ The organic layer was washed with water and ４ The resulting crude product was dried on an alumina column (CHCl ３ / MeOH=40:1) to obtain 149 mg (74%) of the target compound as red crystals.

[0171]

[0172] １ HNMR (400MHz, CDCl ３ ) δ7.37 (t, J=7.3Hz, 2H), 7.30 (t, J=7.5Hz, 1H), 7.27 (s, 1H), 7.15 (d, J=7.3Hz, 2H), 4.72 (s , 2H), 4.04 (t, J=4.6Hz, 2H), 3.54 (t, J=4.6Hz, 2H), 3.41 (s, 3H), 3.29 (s, 3H), 2.30 (s, 3H).

[0173] The UV absorption spectrum (λ) of the vinamidinium salt 3m of the present invention prepared as above was ｍａｘ :363nm, ε:39005M －１ cm －１ ) is shown in FIG.

[0174] [Example 14] <Production of vinamidinium salt 3n of the present invention>

[0175]

[0176] N-Formylmorpholine (0.390 mL, 3.87 mmol) cooled to 18°C ​​was added to POCl ３ (75.0 μL, 0.804 mmol) was added, and the temperature was raised to room temperature. ２ Cl ２ (0.110 mL) solution was added, and then the temperature was raised to 50° C. After stirring for 5 hours, the temperature was returned to room temperature and 5M NaPF ６ An aqueous solution (160 μL, 0.800 mmol) was added and stirred. ２Cl ２ The organic layer was washed with water and ４ The resulting oily crude product was dried in CHCl ３ The target product was precipitated by adding the above solution. The crystals were isolated to obtain 163 mg (72%) of the target product as pale yellow prisms.

[0177]

[0178] １ HNMR (400MHz, DMSO-d ６ ) δ7.65 (s, 1H), 7.43 (dd, J = 8.0, 6.6Hz, 2H), 7.37 (d, J = 7.3Hz, 1H), 7.28 (d, J = 6.9Hz, 2H), 4.89 (s, 2H) ), 4.11 (s, 2H), 4.08 (t, J = 4.6Hz, 2H), 3.74 (s, 2H), 3.70 (s, 4H), 3.62 (t, J = 4.6Hz, 2H), 2.36 (s, 3H). MS (ESI+) m / z287.1 (M-PF ６ ); (ESI-) m / z144.9.

[0179] The UV absorption spectrum (λ) of the vinamidinium salt 3n of the present invention prepared as above was ｍａｘ :364nm, ε:43579M －１ cm －１ ) is shown in FIG.

[0180] [Example 15] <Production of vinamidinium salt 3o of the present invention>

[0181]

[0182] Vinamidinium salt 3a (10.2 mg, 0.0285 mmol) was dissolved in ammonia methanol solution (7 M, 400 μL, 2.80 mmol) and stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure using an evaporator, and the resulting crude product was extracted with MeOH / CHCl ３ The resulting mixture was recrystallized from the above solution to obtain 9.1 mg (99%) of the target product (vinamidinium salt 30 of the present invention) as a colorless transparent prism.

[0183]

[0184] mp: >124°C (decomp); １HNMR (400MHz, CD ３ OD) δ7.88 (s, 1H), 4.11 (t, J = 4.3Hz, 2H), 3.55-3.48 (m, 4H), 2.23 (s, 3H), 1.72-1.64 (m, 2H), 1.41-1.31 (m, 2H), 0.98 (t, J = 7.3Hz, 3H); １３ C-NMR (150MHz, CD ３ OD) δ161.8, 143.1, 126.1, 63.8, 57.8, 47.0, 31.0, 20.6, 14.9, 13.9; IR (KBr): 2962, 1612 cm －１ ; MS (EI) m / z (%) 183 ([M-PF ６ ] ＋ , 100); HRMS (EI) calculated for C １０ H １９ N ２ O[M-PF ６ ] ＋ :183.1497,found:183.1497.

[0185] The UV absorption spectrum of the vinamidinium salt 3o of the present invention prepared above (solvent: MeOH, λ ｍａｘ :344nm, ε:39667M －１ cm －１ ) is shown in FIG.

[0186] [Example 16] <Production of vinamidinium salt 7a of the present invention>

[0187]

[0188] <Outline of Production Method> As shown in the reaction formula below, first, compound 5 having an N-alkylmorpholinone structure is synthesized by alkylation reaction of compound 4 having a morpholinone structure, and then compound 5 is treated with methyllithium to produce compound 6 having a cyclic enamine structure. Furthermore, compound 6 is reacted with a Vilsmeier-type reagent prepared from N-formylamide and phosphorus oxychloride, and then converted to a hexafluorophosphate salt to synthesize the vinamidinium salt 7a of the present invention.

[0189]

[0190] <Specific Manufacturing Method> (Synthesis of Compound 5) Compound 4 (503 mg, 3.24 mmol), prepared according to the literature (S. Dugar, A. Sharma, B. Kuila, D. Mahajan, S. Dwivedi, V. Tripathi, Synthesis, 2015, 47, 712.), was dissolved in distilled and dried N,N-dimethylformamide (6.30 mL). The resulting solution was cooled to 18°C, and sodium hydride (60% in mineral oil, 221 mg, 5.53 mmol) was added. 1-Bromobutane (560 μL, 5.19 mmol) was slowly added dropwise to this suspension, and the reaction mixture was warmed to room temperature and stirred for 18 hours. Water was added to the reaction solution to quench the reaction, and the mixture was extracted three times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The obtained crude product was purified by silica gel column chromatography (AcOEt / hexane=1:5) and reduced pressure distillation (0.14 torr, 180°C) to obtain 587 mg (86%) of compound 5 (4-butylhexahydro-2H-benzo[b][1,4]oxazin-3(4H)-one) as a colorless transparent oil.

[0191]

[0192] １ HNMR (400MHz, CDCl ３ ) δ4.29 (d, J=16.4Hz, 1H), 4.21 (d, J=16.4Hz, 1H), 3.78 (ddd, J=15.1, 8.6, 5.2Hz, 1H), 3.31-3.27 (m, 1H), 3.19-3.11 (m, 2H), 2.20- 2.17 (m, 1H), 2.04-2.01 (m, 1H), 1.84-1.81 (m, 2H), 1.58-1.54 (m, 1H), 1.44-1.27 (m, 6H), 1.21-1.16 (m, 1H), 0.93 (t, J = 7.3Hz, 3H); １３ C-NMR (151MHz, CDCl ３ ) δ167.3, 78.1, 68.3, 58.8, 40.4, 30.6, 29.7, 28.5, 23.9, 23.7, 20.0, 13.7. IR (KBr): 2939, 1651cm －１ .

[0193] (Synthesis of Compound 6) Under an argon atmosphere, compound 5 (302 mg, 1.43 mmol) was dissolved in anhydrous diethyl ether (5.20 mL). This solution was cooled to −18°C, and then methyllithium (1.07 M diethyl ether solution, 1.70 mL, 1.82 mmol) was slowly added dropwise. The reaction mixture was stirred at −18°C for 8 hours, and then ice was added to quench the reaction. After warming to room temperature, the mixture was extracted three times with diethyl ether. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by distillation under reduced pressure (1.6 torr, 100°C) to obtain 159 mg (54%) of compound 6 (4-butyl-3-methyl-4a,5,6,7,8,8a-hexahydro-4H-benzo[b][1,4]oxazine) as a pale orange oil.

[0194]

[0195] １ HNMR (400MHz, CDCl ３ ) δ5.70 (d, J = 1.4Hz, 1H), 3.53-3.48 (m, 1H), 2.97-2.92 (m, 2H), 2.79-2.73 (m, 1H), 2.22-2.19 (m, 1H), 2.04-1.97 (m, 1H), 1.78-1.75 (m, 2H), 1.65 (d, J = 0.9Hz, 3H), 1.51-1.45 (m, 1H), 1.32-1.18 (m, 6H), 1.11-1.07 (m, 1H), 0.92 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ122.8, 122.7, 76.9, 57.8, 44.3, 31.2, 28.2, 27.6, 24.4, 24.0, 20.3, 15.5, 14.0; IR (KBr): 2934, 1667 cm －１ .

[0196] (Synthesis of Compound 7a) Under an argon atmosphere, N-formylmorpholine (350 μL, 3.47 mmol) was added to a flask and cooled to 13°C, followed by the slow dropwise addition of phosphorus oxychloride (68.0 μL, 0.729 mmol). The resulting solution was warmed to room temperature, followed by the dropwise addition of a solution of compound 6 (101 mg, 0.483 mmol) in dichloromethane (200 μL). The reaction mixture was warmed to 50°C and stirred for 4 hours, then cooled to room temperature, and an aqueous solution of sodium hexafluorophosphate (3.0 M, 650 μL, 1.95 mmol) was added. The reaction solution was stirred for 30 minutes, followed by the addition of water and extraction three times with dichloromethane. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated using an evaporator. Furthermore, the remaining N-formylmorpholine was distilled off using a Kugelrohr distillation apparatus, and the residue was recrystallized from ethanol to obtain 124 mg (57%) of Compound 7a as brown prisms.

[0197]

[0198] １ HNMR (400MHz, CDCl ３ ) δ7.35 (s, 1H), 4.22-4.07 (m, 2H), 3.87-3.83 (m, 2H), 3.80-3.74 (m, 2H), 3.71-3.66 (m, 2H), 3.63-3.40 (m, 3H), 3.29-3.2 4 (m, 1H), 2.36 (s, 3H), 2.35-2.28 (m, 1H), 2.17-2.10 (m, 1H), 1.95-1.86 (m, 2H), 1.56-1.30 (m, 8H), 0.97 (t, J = 7.3Hz, 3H); １３ C-NMR (100MHz, CDCl ３ ) δ158.1, 143.2, 125.6, 75.7, 67.1, 66.4, 60.5, 56.4, 49.2, 46.9, 30.7, 30.5, 27.5, 24.1, 23.1, 19.7, 15.0, 13.5; IR (KBr): 2947, 1624 cm －１ ; MS (EI) m / z (%) 307 ([M-PF ６ ] ＋ , 100); HRMS (EI) calculated for C １８ H ３１ N２ O ２ [M-PF ６ ] ＋ :307.2386,found:307.2386.

[0199] The UV absorption spectrum of the vinamidinium salt 7a of the present invention prepared above (solvent: CHCl ３ , λ ｍａｘ :368nm, ε:38672M －１ cm －１ ) is shown in FIG.

[0200] [Example 17] <Production of vinamidinium salt 11a of the present invention>

[0201]

[0202] <Outline of Production Method> As shown in the reaction scheme below, first, N-alkylthiomorpholinone 9 is synthesized by alkylation of thiomorpholinone 8, and then N-alkylthiomorpholinone 9 is treated with methyllithium to form cyclic enamine 10. Furthermore, cyclic enamine 10 is reacted with a Vilsmeier-type reagent prepared from N-formylamide and phosphorus oxychloride, followed by conversion to a hexafluorophosphate salt to synthesize the vinamidinium salt 11a of the present invention.

[0203]

[0204] <Specific Production Method> (Synthesis of Compound 9) Compound 8 (2.39 g, 20.4 mmol), prepared with reference to a literature reference (H. Ishibashi, M. Uegaki, M. Sakai, Y. Takeda, Tetrahedron, 2001, 57, 2115), was dissolved in distilled and dried N,N-dimethylformamide (21.0 mL) under an argon atmosphere. The resulting solution was cooled to 0°C, and sodium hydride (60% in mineral oil, 1.31 g, 32.8 mmol) was added. 1-Bromobutane (3.20 mL, 29.7 mmol) was slowly added dropwise to this suspension, and the reaction mixture was warmed to room temperature and stirred for 14 hours. Water was added to the reaction mixture to quench the reaction, and the mixture was extracted three times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The resulting crude product was purified by silica gel column chromatography (AcOEt / hexane=1:5) and vacuum distillation (0.7 torr, 134° C.) to obtain 2.75 g (78%) of Compound 9 as a colorless, transparent oil.

[0205]

[0206] １ HNMR (400MHz, CDCl ３ ) δ3.60 (t, J=5.7Hz, 2H), 3.41 (t, J=7.5Hz, 2H), 3.30 (s, 2H), 2.86 (t, J= 5.7Hz, 2H), 1.59-1.50 (m, 2H), 1.33-1.29 (m, 2H), 0.94 (t, J = 7.3Hz, 3H); １３ CNMR (150MHz, CDCl ３ ) δ166.1, 48.9, 47.6, 30.1, 29.6, 26.4, 19.9, 13.7; IR (KBr): 1636cm －１ ;

[0207] (Synthesis of Compound 10) Under an argon atmosphere, Compound 9 (1.00 g, 5.78 mmol) was dissolved in dehydrated tetrahydrofuran (8.80 mL), and LaCl ３2LiCl (0.6 M tetrahydrofuran solution, 12.5 mL, 7.50 mmol) was added at room temperature. After cooling the solution to -18°C, methylmagnesium bromide (0.78 M tetrahydrofuran solution, 9.50 mL, 7.41 mmol) was slowly added dropwise. The reaction mixture was stirred at -18°C for 2 hours, and then cooled with ice and saturated NH ４ The reaction was quenched by adding aqueous Cl solution. After warming to room temperature, the mixture was extracted three times with diethyl ether. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by distillation under reduced pressure (2.0 torr, 150°C) to obtain 743 mg (76%) of compound 10 as a colorless, transparent oil.

[0208]

[0209] １ HNMR (400MHz, CDCl ３ ) δ4.46 (s, 1H), 3.46-3.43 (m, 2H), 2.93 (t, J=7.5Hz, 2H), 2.84-2.82 (m, 2H) , 1.86 (s, 3H), 1.48-1.40 (m, 2H), 1.33-1.26 (m, 2H), 0.92 (t, J = 7.3Hz, 3H); １３ C-NMR (101MHz, CDCl ３ ) δ137.1, 83.7, 51.4, 49.5, 30.6, 24.0, 21.8, 20.1, 14.0; IR (KBr): 2957, 1601 cm －１ .

[0210] (Synthesis of Compound 11a) Under an argon atmosphere, N-formylmorpholine (480 μL, 4.76 mmol) was added to a flask and cooled to 13°C, followed by the slow dropwise addition of phosphorus oxychloride (90.0 μL, 0.965 mmol). The resulting solution was slowly warmed to room temperature, followed by the dropwise addition of a solution of compound 10 (109 mg, 0.645 mmol) in dichloromethane (240 μL). The reaction mixture was heated to 50°C and stirred for 3 hours, then cooled to room temperature, and an aqueous solution of sodium hexafluorophosphate (3.0 M, 860 μL, 2.58 mmol) was added. The reaction mixture was stirred for 15 minutes, followed by the addition of water, followed by extraction three times with dichloromethane. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated using an evaporator. The remaining N-formylmorpholine was then removed using a Kugelrohr distillation apparatus, and the resulting crude product was purified by silica gel column chromatography (CHCl ３ toCHCl ３ Purification by washing with EtOH (30:1) and EtOH gave 155 mg (58%) of compound 11a as a red oil.

[0211]

[0212] １ HNMR (400MHz, CDCl ３ ) δ7.85 (s, 1H), 3.96-3.89 (m, 6H), 3.83 (t, J = 4.8Hz, 4H), 3.59 (t, J = 8.0Hz, 2H), 2.95 (t, J = 4.9Hz, 2H), 2.51 (s, 3H), 1.72-1.64 (m, 2H), 1.43-1.34 (m, 2H), 0.97 (t, J = 7.3Hz, 3H); １３ C-NMR (101MHz, CDCl ３ ) δ167.5, 155.2, 92.0, 66.8, 56.1, 53.2 (2C), 29.7, 23.8, 19.8, 18.3, 13.6; IR (KBr): 2964, 1607, 1549 cm －１ ; MS (EI) m / z (%) 269 ([M-PF ６ ] ＋ , 100); HRMS (EI) calculated for C １４ H ２５ N２ OS [M-PF ６ ] ＋ :269.1689,found:269.1687.

[0213] The UV absorption spectrum of the vinamidinium salt 11a of the present invention prepared above (solvent: CHCl ３ , λ ｍａｘ :377nm, ε:24524M －１ cm －１ ) is shown in FIG.

[0214] The novel vinamidinium salt of the present invention can be used as a UV-A absorber (ultraviolet protection agent) in the fields of cosmetics, industrial products, etc., and is therefore industrially useful.

Claims

1. A vinamidinium salt represented by the following formula (1): (In formula (1), R １ , R ２ , R ５ , R ６ and R ７ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R ３ and R ４ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, a hydroxyl group, or a halogen atom; Y is O, S, NR ８ , C.R. ８ R ９ and R ８ and R ９ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R １ ~R ９ may be bonded to each other to form a cyclic structure; X － represents an anion.) 2. R ６ and R ７ 2. The vinamidinium salt according to claim 1, characterized in that these, together with the nitrogen atom to which they are bonded, form a nitrogen-containing cyclic group.

3. The vinamidinium salt according to claim 2, wherein the nitrogen-containing cyclic group is at least one group selected from the group consisting of azetidine, pyrrolidine, piperidine, azepane, morpholine, thiomorpholine, thiomorpholine dioxide and piperazine.

4. The vinamidinium salt according to claim 1, which is represented by the following formula (1A):

5. In formula (1A), R １ represents an alkyl group having 1 to 4 carbon atoms; R ２ represents a methyl group, R ３ ~R ５ represents a hydrogen atom, and X － PF ６ － 5. The vinamidinium salt according to claim 4, characterized in that it represents 6. A vinamidinium salt represented by the following formula (2): (In formula (2), R １ , R ２ and R ５ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R ３ and R ４ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, a hydroxyl group, or a halogen atom; Y is O, S, NR ８ , C.R. ８ R ９ and R ８ and R ９ each independently represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an alkenyl group having 1 to 10 carbon atoms which may have a substituent, an alkynyl group having 1 to 10 carbon atoms which may have a substituent, an alkoxy group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 14 carbon atoms which may have a substituent, an aralkyl group having 7 to 20 carbon atoms which may have a substituent, or a hydroxy group; R １ ~R ５ , R ８ and R ９ may be bonded to each other to form a cyclic structure; X － represents an anion.) 7. X － But, P.F. ６ － , B.F. ４ － , halide ion, R Ａ CO ２ － (R Ａ represents an organic group having 1 to 20 carbon atoms; and R Ｂ SO ４ － (R Ｂ 7. The vinamidinium salt according to claim 1, wherein the anion is selected from the group consisting of:

8. A UV-A absorbent comprising the vinamidinium salt according to claim 1 or 6.

9. The UV-A absorbent according to claim 8, characterized in that it has transparency.

10. A skin preparation for external use, comprising the vinamidinium salt according to claim 1 or 6.

11. A glass material comprising the vinamidinium salt according to claim 1 or 6.

12. A resin material comprising the vinamidinium salt according to claim 1 or 6.

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