KR20200073499A - Novel 3,3-difluoroallylamine derivatives or its salt and pharmaceutical compositions comprising the same - Google Patents

Abstract

The present invention provides a 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof, a method for manufacturing the same, a pharmaceutical composition containing the same, and a use thereof. The 3,3-difluoroallylamine derivative or the pharmaceutically acceptable salt thereof has selective inhibitory activity on VAP-1, thereby being able to be usefully applied for treating and preventing, for example, non-alcoholic steatohepatitis (NASH).

Description

Novel 3,3-difluoroallylamine derivatives or its salts and pharmaceutical compositions comprising the same}

The present invention relates to a 3,3-difluoroallylamine derivative having a selective inhibitory activity against vascular adhesion protein-1 or a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition comprising the same, and a use thereof.

Vascular adhesion protein-1 (abbreviated as VAP-1) is a semicarbazide-sensitive amine oxidase (SSAO) abundantly present in human plasma. The VAP-1 gene is an in vitro enzyme (ectoenzyme) comprising a short cytoplasmic tail, a single transmembrane domain, and a large and high glycosylated extracellular domain containing an active center. In addition, VAP-1 has a soluble form (soluble VAP-1, sVAP-1) present in serum as well as a membrane-bound form present in vascular endothelium. This form has been demonstrated to be a truncated product of membrane bound VAP-1 and appears to have properties similar to the tissue-bound form. It has been reported that VAP-1 is stored in granules in endothelial cells and then increases in expression and expression in inflammatory tissues due to increased migration and expression to the cell membrane through stimulation of inflammatory responses.

Substrates for VAP-1 include methylamine and aminoacetone produced in any part of the body, as well as some xenobiotic amines such as tyramine and benzylamine. .

VAP-1 has two physiological functions, the first is the amine oxidase activity described above, and the second is cell adhesion activity. These two activities of VAP-1 have been shown to play an important role in the leakage of infectious cells by acting as an adhesion protein for leukocytes at the site of inflammation [Trends Immunol. (2001) 22: 211]. Transgenic mice deficient in VAP-1 are healthy, grow normally, have fertility and are normal in phenotype, but show a significant reduction in the inflammatory response caused by various inflammatory stimuli [Immunity. (2005) 22: 105].

In addition, in a number of animal models of human disease by using antibodies or small molecules (e.g. carrageenan induced foot inflammation, oxazolone induced colitis, lipopolysaccharide induced lung inflammation, collagen induced arthritis, endotoxin induced uveitis) The inhibitory effect of VAP-1 activity on white blood cells prevents clouding, adhesion and leakage, and reduces the severity of the disease by reducing the levels of inflammatory cytokines and chemokines [Eur J Immunol. (2005) 35: 3119; J Pharmacol Exp Ther. (2005) 315: 553; Annu Rep Med Chem. (2007) 42: 229; FASEB J. (2008) 22: 1094]. Inflammation is the first response of the immune system to infection or irritation, and the movement of white blood cells from circulation into tissues is essential for this process. White blood cells are first attached to the endothelium by binding to an attachment protein to begin the process of passing through the walls of blood vessels. VAP-1 is abundantly expressed in endothelial venules (HEV), such as high vascular endothelial cells of lymphoid organs, and hepatic sinusoidal endothelial cells (HSEC), smooth muscle cells and Expressed in adipocytes VAP-1 expression on the cell surface of endothelial cells is tightly regulated and increased during inflammation VAP-1 activates NF-κB in the presence of a substrate, and NF-κB attaches differently in vitro It is activated in HSEC with up-regulation of the molecules E-selectin and chemokine IL-8, suggesting that VAP-1 may be a key factor in the regulation of the inflammatory response. It can be seen that it is an effective anti-inflammatory drug in a wide range of human diseases.

Nonalcoholic fatty liver disease (NAFLD) is a disease that encompasses histologically simple steatosis, nonalcoholic hepatosteatosis (NASH) and cirrhosis of the liver. Among these, NASH, unlike simple steatosis (non-alcoholic fatty liver, NAFL), potentially progresses to cirrhosis and hepatocellular carcinoma. NASH, along with insulin resistance, is known to play an important role in the progression of the disease, oxidative stress, inflammatory cascade, and fibrosis. An increase in the concentration of sVAP-1 was observed in NAFLD patients, and carbon tetrachloride-induced liver fibrosis was decreased in VAP-1 knock-out (K/O) mice compared to wild-type animals. It has been confirmed through histological changes that hepatic fibrosis is improved by VAP-1 inhibition by [J Clin Invest (2015) 125: 501], and VAP-1 is correlated with NASH in clinical and disease animal models. This was confirmed. VAP-1 inhibitory activity in a carbon tetrachloride-induced animal model appears to be due to a decrease in leukocyte infiltration such as T cells, B cells, NKT cells, and NK cells that occur during hepatic fibrosis. Has the potential to cure sex diseases.

Therefore, substances that inhibit VAP-1 may be usefully applied to prevention and treatment of various inflammatory diseases and fibrotic diseases.

The present inventors have found that certain triazolone derivatives having a 3,3-difluoroallylamine group or pharmaceutically acceptable salts thereof have selective inhibitory activity against VAP-1. Therefore, the 3,3-difluoroallylamine derivative or a salt thereof can be usefully used for the treatment and prevention of various diseases mediated by VAP-1, for example, nonalcoholic hepatosteatosis (NASH). have.

Accordingly, an object of the present invention is to provide a 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof, a method for preparing the same, a pharmaceutical composition comprising the same, and uses thereof.

According to one aspect of the present invention, a 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof is provided.

According to another aspect of the present invention, a method for preparing the 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof is provided.

According to another aspect of the present invention, there is provided a pharmaceutical composition comprising the 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a treatment method comprising administering the 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof.

According to another aspect of the present invention, there is provided the use of the 3,3-difluoroallylamine derivative or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the selective inhibition of vascular adhesion protein-1 do.

It has been found by the present invention that certain triazolone derivatives having a 3,3-difluoroallylamine group or pharmaceutically acceptable salts thereof have selective inhibitory activity against VAP-1. Therefore, the compound according to the present invention or a pharmaceutically acceptable salt thereof can be usefully applied to the treatment and prevention of various diseases mediated by VAP-1, for example, non-alcoholic steatohepatitis (NASH).

In the present specification, the term'alkyl' refers to an aliphatic hydrocarbon radical, and includes both linear or branched hydrocarbon radicals. For example, C _1-6 alkyl is an aliphatic hydrocarbon having 1 to 6 carbon atoms, methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert- Butyl, neopentyl, isopentyl, and the like.

Further, the term'hydroxy' is defined as -OH, and the term'alkoxy' means a radical in which the hydrogen atom of the hydroxy group is substituted with alkyl, unless otherwise defined. For example, C _1-6 alkoxy is methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, isopentyloxy Includes all.

In addition, the term'halogen' means fluorine, bromine, chlorine and iodine.

Also, the term'amino' is defined as -NH ₂ and the term "alkylamino" means amino substituted with mono- or di-alkyl. For example, C _1-6 alkylamino includes amino substituted with mono- or di-C _1-6 alkyl.

In addition, the term'alkylthio' is defined as -SR (wherein R is alkyl), and the term'cyano' is defined as -CN.

The present invention provides a compound having a selective inhibitory activity against VAP-1, or a salt thereof, that is, a compound represented by Formula 1 below:

<Formula 1>

Where,

n is 0, 1 or 2,

A is an aryl or heteroaryl group selected from the group consisting of phenyl, pyridine, pyrazine, and thiophene,

The aryl or heteroaryl group is optionally substituted with 1 or 2 substituents selected from the group consisting of C _1-3 alkyl, halogen, benzyloxy, -R, -CH=CH-R, and -C≡CR,

R is benzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole, indazole, 1,3-dihydroindole- 2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one, 3,4-dihydro-1,4-benzoxazine, 2 ,3-Dihydro-1,4-benzoxazine photo, 1,4-benzoxazine-3-one, 1,4-dihydro-3,1-benzoxazine-2-one, 5,6,7,8- Tetrahydronaphthyridine, triazolo[1,5-a]pyridine, 2,3-dihydro-pyrido[2,3-b][1,4]oxazine, 3,4-dihydro-pyrido [3,2-b][1,4]oxazin, pyrido[2,3-b][1,4]oxazin-2-one, and pyrido[3,2-b][1,4 ] Is a cyclic ring selected from the group consisting of oxazin-3-one,

The cyclic ring is halogen, C _1-6 alkyl, trifluoromethyl, C _1-6 alkoxy, amino, mono- or di-C _1-6 alkylamino, C _1-6 alkoxy-C _1-6 alkylamino, C _1-6 alkylcarbonylamino, mono-C _1-6 alkylaminocarbonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkylsulfonyl, C _1-6 alkylcarbonyl, It is optionally substituted with 1 to 3 substituents selected from the group consisting of morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl, and pyrazolyl.

As used herein, "having a selective inhibitory activity against VAP-1" refers to various amine oxidases including human VAP-1, such as MAO-A (monoamine oxidase-A), MAO-B (monoamine oxidase-B) ), means that the inhibitory activity against human VAP-1 among DAO (diamine oxidase) is significantly high. In one embodiment, the term the "inhibitory activity against high-VAP-1 significantly" is in vitro enzyme assay (in vitro enzyme assay) the IC ₅₀ for the VAP-1 obtained in the test, IC ₅₀ of the MAO-A It means that it is at least 3000 times lower than that, at least 100 times lower than IC ₅₀ of MAO-B, and at least 100 times lower than IC ₅₀ of DAO.

In the compound of formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, preferably n may be 0 or 1.

Further, in the compound of Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, preferably A may be phenyl, pyridine or thiophene.

In addition, in the compound of Formula 1 according to the present invention, or a pharmaceutically acceptable salt thereof, preferably, the aryl or heteroaryl group is selected from the group consisting of C _1-3 alkyl, halogen, and -R, or two or two. It may be substituted with a substituent. Preferably, R may be a cyclic ring selected from the group consisting of benzene, pyridine, pyridin-2-one, pyrazole and 3,4-dihydroquinolin-2-one. More preferably, the cyclic ring may be substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl.

In one embodiment of the invention, n is 0; A is phenyl; The phenyl is substituted with 1 or 2 substituents selected from the group consisting of halogen and -R; R is a cyclic ring selected from the group consisting of benzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole; The cyclic ring is provided with a compound substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl or a pharmaceutically acceptable salt thereof. do.

In another embodiment of the invention, n is 0; A is pyridine; The pyridine is substituted with 1 or 2 substituents selected from the group consisting of C 1-3 alkyl, halogen, and -R; R is a cyclic ring selected from the group consisting of benzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole; The cyclic ring is provided with a compound substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl or a pharmaceutically acceptable salt thereof. do.

In another embodiment of the invention, n is 0; A is thiophene; The thiophene is substituted with one or two cyclic rings selected from the group consisting of benzene, pyridine, pyridin-2-one, 3,4-dihydroquinolin-2-one and pyrazole; The cyclic ring is provided with a compound substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl or a pharmaceutically acceptable salt thereof. do.

For the compound of Formula 1 or a pharmaceutically acceptable salt thereof, the preferred compound may be a compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4-triazole-3 -On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazole-3 -On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2,4-tri Azole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4-triazole -3-one;

6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]phenyl]-8-methyl -3,4-dihydro-1 H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4-triazole-3 -On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole -3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro-phenyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl]-1, 2,4-triazole-3-one;

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-fluoro- Phenyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]-1,2, 4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole -3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro-phenyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl]-1, 2,4-triazole-3-one;

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-fluoro- Phenyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]-1,2, 4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazole- 3-on;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]-1,2, 4-triazole-3-one;

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazole- 3-on;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2, 4-triazole-3-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazole- 3-on;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2, 4-triazole-3-one;

6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-4-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4-triazole- 3-on;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]-1,2, 4-triazole-3-one;

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-pyridyl] -1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2-pyridyl]- 1,2,4-triazole-3-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-methyl-3 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-methyl-3 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl] -1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3-pyridyl]- 1,2,4-triazole-3-one;

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-methyl-2 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-methyl-2 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2, 4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyri Dill]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-pyridyl] -1,2,4-triazole-3-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-fluoro- 3-pyridyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-fluoro- 3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyridyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2,4-triazole -3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]-1,2, 4-triazole-3-one;

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]pyrazin-2-yl] -1-methyl-3,4-dihydro-1 H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1,2,4- Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-triazole-3- On;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2,4-tri Azole-3-one;

4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-tri Azole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;

3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl] -N,N -dimethyl-benzenesulfonamide;

4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl] -N -methyl-benzamide;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro- Allyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]- 1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1 H -pyrazol-3-yl)phenyl]-2-thienyl] Methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl] -1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thi Enyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thier Neil]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl] Methyl]-1,2,4-triazole-3-one;

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-methyl-pyridin-2-one;

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-1-ethyl-pyridin-2-one;

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-isopropyl-pyridin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro- 2H -pyridin-4-yl)-2 -Thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro- 2H -pyridin-4-yl)-2 -Thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]- 1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1 H -indazol-6-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazole[1,5-a]pyridin-7-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2-thienyl] Methyl]-1,2,4-triazole-3-one;

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-7-fluoro-indolin-2-one;

N -[6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]-1,3-benzothiazol-2-yl]acetamide;

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-3,4-dihydro- 2H -isoquinolin-1-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-3,4-dihydro-1 H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-8-methyl- 1H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-8-fluoro-3,4-dihydro-1 H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-8-fluoro-1 H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro- 2H- 1,4-benzoxazine-6 -Yl)-2-thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxa-7-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- in Im carbonyl] -4 H -1,4- benzoxazin-3-one;

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1,4-dihydro-3,1-benzoxazine-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1,4-dihydro-3,1-benzoxazine-2-one;

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-4-methyl-1,4-benzoxazin-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl] -1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]- 1,2,4-triazole-3-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-3- Thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-3- Thienyl]-1-methyl-3,4-dihydroquinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thi Enyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thier Neil]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl ]Methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl ]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]- 1,2,4-triazole-3-one;

7-[( E )-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- 1]methyl]-2-thienyl]vinyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2- Thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thier Neil]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2 H -1,4-benzoxazine-6- 1)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;

6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]ethynyl]-3,4-dihydro- 1H -quinolin-2-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2,3-b] [1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2 H -pyrido[3,2-b] [1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2,3-b] [1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;

7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]ethynyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one;

7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] ethynyl -2-Im carbonyl]] -4 H - pyrido [3,2-b] [1,4] oxazin-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl ]Methyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-1,2 ,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl]ethyl]- 1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl ]Ethyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl] Ethyl]-1,2,4-triazole-3-one;

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-thienyl]ethyl ]-1,2,4-triazole-3-one;

6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]ethyl]- 2-thienyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;

6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]ethyl]- 2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one; And

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]- 1,2,4-triazole-3-one.

In the compound of Formula 1 or a pharmaceutically acceptable salt thereof, the more preferable compound may be a compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazole-3-one; And

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazole-3-one.

The compound of formula 1 of the present invention may be in the form of a pharmaceutically acceptable salt. The salts are conventional acid addition salts, for example salts derived from inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, sulfamic acid, phosphoric acid or nitric acid and acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, citric acid, maleic acid, mal Salts derived from organic acids such as ronic acid, methanesulfonic acid, tartaric acid, malic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, 2-acetoxybenzoic acid, fumaric acid, p-toluenesulfonic acid, oxalic acid or trifluoroacetic acid. In addition, the salts include conventional metal salt forms, for example salts derived from metals such as lithium, sodium, potassium, magnesium, or calcium. The acid addition salt or metal salt may be prepared according to a conventional method.

The compound of formula 1 according to the present invention or a pharmaceutically acceptable salt thereof can be prepared by various methods. For example, a compound of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention may be prepared by reacting a compound of Formula 2 with a compound of Formula 3a or a compound of Formula 3b to obtain a compound of Formula 1a; And deprotecting the compound of Formula 1a.

<Formula 1>

<Formula 1a>

<Formula 2>

<Formula 3a>

Z-R'

<Formula 3b>

HC≡CR'

In Formulas 1, 1a, 2, 3a and 3b, Boc is an amine protecting group (eg, tert-butoxycarbonyl, 9-fluorenylmethyloxycarbonyl (FMOC), benzyloxycarbonyl (CBZ), Triphenylmethyl (trityl, etc.), A'is an aryl or heteroaryl group selected from the group consisting of phenyl, pyridine, pyrazine, and thiophene, and Z is boronic acid (B(OH) ₂ ) or boronic acid pinacol. Is an ester, R'is one or two groups selected from the group consisting of C _1-3 alkyl, halogen, benzyloxy, -R, -CH=CH-R, and -C≡CR, A and R are above Same as defined.

The reaction of the compound of Chemical Formula 2 with a commercially available compound of Chemical Formula 3a may be performed through a Suzuki reaction. The reaction may be performed using a palladium catalyst, wherein the palladium catalyst is palladium diacetate (Pd(OAc) ₂ ), tris(dibenzylideneacetone)dipalladium (Pd ₂ (dba) ₃ ), tetrakis( Triphenylphosphine)palladium (Pd(PPh ₃ ) ₄ ) or palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl ₂ (dppf) ₂ ) and the like. When the reaction is performed under a palladium catalyst, a ligand and a base may be added in addition to the palladium catalyst. The ligand is ( S )-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP), 1,1'-bis(diphenylphosphino)ferrocene (dppf) or (tri- O-tolyl) phosphine (P (O-Tol) ₃ ) and the like, the base is cesium carbonate (Cs ₂ CO ₃ ), sodium carbonate (Na ₂ CO ₃ ), potassium carbonate (K ₂ CO ₃ ), potassium fluoride (KF), cesium fluoride (CsF), sodium hydroxide (NaOH), potassium phosphonate (K ₃ PO _4), sodium tert-butoxide (tert -BuONa) or potassium tert-butoxide ( tert -BuOK). The reaction is 50°C to 150°C in a non-polar organic solvent such as benzene or toluene, or a polar organic solvent such as dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or N , N -dimethylformamide. It can be carried out at ℃, preferably at 80 ℃ to 110 ℃. Other reaction conditions, including reaction time, can be carried out according to known methods for Suzuki reactions (Barbara Czako and Laszlo Kurti, STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS , 2005). In addition, the reaction of the compound of Formula 2 with a commercially available compound of Formula 3b (ie, an ethane derivative) is bis(triphenylphosphine)palladium(II) dichloride, tetrakis(triphenylphosphine)palladium( 0) can be performed through a Sonogashira coupling reaction using palladium reagent and copper iodide. The coupling reaction may be performed at room temperature or warming, for example, at a temperature of 20°C to 60°C. In addition, in order to improve the reaction rate and the reaction yield, the coupling reaction may be performed in the presence of a base such as diisopropylamine and triethylamine and a ligand such as triphenylphosphine.

The deprotection reaction of the compound of Formula 1a may be performed according to a known method (for example, Theodora W. Greene and Peter GM Wuts, Protective groups in organic synthesis , 3rd Ed., 1999). For example, the amine protecting group may be removed at room temperature using an acid such as trifluoroacetic acid or hydrochloric acid gas in an organic solvent such as dichloromethane, dioxane, ethyl acetate.

The compound of Formula 2 may be prepared according to the method of Scheme 1 below.

<Scheme 1>

In Reaction Scheme 1, A', n and Boc are the same as defined above.

The compound of Formula 4 is commercially available. The compound of Formula 4 may be converted to a compound of Formula 5 through a nucleophilic acylsubstitution reaction. The nucleophilic acyl substitution reaction may be performed at 0° C. to room temperature using pyridine or triethylamine in a solvent such as ethyl acetate or tetrahydrofuran (Chunquan Sheng; Xiaoying Che; Wenya Wang; Shengzheng Wang; Yongbing Cao; Zhenyuan Miao; Jianzhong Yao; Wannian Zhang, European Journal of Medicinal Chemistry , 46 , 5276-5282, 2011).

The compound of Formula 5 may be converted to the compound of Formula 6 through hydrazine decomposition reaction. The hydrazine decomposition reaction may be performed according to a known method (for example, WO 2005/014583, etc.).

The compound of Formula 6 may be converted to the compound of Formula 8 through a cyclization reaction. The cyclization reaction may be performed at room temperature to 80° C. using formamidine acetate and acetic acid in N , N -dimethylformamide or 1-propanol (Chunquan Sheng; Xiaoying Che; Wenya Wang; Shengzheng Wang ; Yongbing Cao; Zhenyuan Miao; Jianzhong Yao; Wannian Zhang, European Journal of Medicinal Chemistry , 46 , 5276-5282, 2011).

Alternatively, the compound of Formula 4 may be converted to the compound of Formula 8 through a cyclization reaction with the compound of Formula 7. The cyclization reaction may be carried out at 50°C to 150°C using sodium methoxide or potassium hydroxide in a solvent such as methanol or N,N -dimethylformamide. The compound of Chemical Formula 7 may be prepared through the commercialization of ethyl carbazate commercially available. The formylation reaction is preferably an orthoester reaction, and may be performed using, for example, triethyl orthoformate or trimethyl orthoformate. The formylation reaction may be performed at 80°C to 150°C in a solvent such as methanol or N,N -dimethylformamide.

The reaction between the compound of Formula 8 and the compound of Formula 9 may be performed according to the Mitzunobu reaction. For example, the reaction can be performed using diethylazodicarboxylate (DEAD) or diisopropylazodicarboxylate (DIAD) in the presence of triphenylphosphine or tri n -butylphosphine. In addition, polar organic solvents such as dichloromethane, dioxane, tetrahydrofuran, and dimethylformamide may be used as the reaction solvent. The reaction temperature may be performed at 0°C to room temperature, but in some cases, it may be performed at a higher temperature. Other reaction conditions, including reaction time, can be performed according to known methods for Mitzunobu reactions (Barbara Czako and Laszlo Kurti, STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS , 2005).

The compound of Formula 9 may be prepared according to Scheme 2, for example.

<Reaction Scheme 2>

In Reaction Scheme 2, TBDMS is a tert-butyldimethylsilyl hydroxyl protecting group, and Boc is the same as defined above.

The compound of Formula 10 is commercially available and may be prepared according to a known method (for example, WO 2013/163675). The compound of Formula 10 may be converted to a compound of Formula 11 through a gem-difluoroolefination reaction. The gem-difluoroolefin reaction is difluoromethyl 2- in the presence of a base such as potassium tert-BuOK or lithium bis(trimethylsilyl)amide (LiHMDS). This can be done using fluorinated sulfones such as pyridyl sulfone. In addition, an organic solvent such as dimethylformamide or tetrahydrofuran may be used as the reaction solvent, and the reaction temperature may be performed at -40°C to 0°C (Yanchuan Zhao; Weizhou Huang; Lingui Zhu; Jinbo Hu, Organic Letters , 12 , 1444-1447, 2010).

The compound of Formula 11 may be converted to the compound of Formula 9 by performing a deprotection reaction of a hydroxyl protecting group (TBDMS). The deprotection reaction of the hydroxyl protecting group can be carried out according to a known method (Theodora W. Greene and Peter GM Wuts, Protective groups in organic synthesis , 3rd Ed., 1999). For example, the deprotection reaction of the hydroxyl protecting group (TBDMS) may be performed at room temperature in a solvent such as dichloromethane or tetrahydrofuran, using an organic salt such as tetrabutylammonium fluoride (TBAF). .

The 3,3-difluoroallylamine derivative according to the present invention, that is, the compound of Formula 1 or a pharmaceutically acceptable salt thereof has a selective inhibitory activity against VAP-1, thereby preventing VAP-1-mediated diseases. It can be usefully applied for prevention or treatment. Preferably, the compound of Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof may be usefully applied to the prevention or treatment of non-alcoholic steatohepatitis (NASH).

Accordingly, the present invention includes a pharmaceutical composition that selectively inhibits vascular adhesion protein-1 (VAP-1), comprising a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. do. In one embodiment, the present invention provides a pharmaceutical composition for the prevention or treatment of non-alcoholic steatohepatitis (NASH) comprising an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. to provide.

The pharmaceutical composition of the present invention may include pharmaceutically acceptable carriers such as excipients, disintegrants, sweeteners, lubricants or flavoring agents, which are commonly used, and tablets, capsules, powders, granules and suspensions according to conventional methods. Oral preparations such as agents, emulsions or syrups; Alternatively, it may be formulated as a preparation for parenteral administration, such as a liquid for external use, a suspension for external use, an emulsion for external use, a gel (such as an ointment), an inhalant, a spray, or an injection. The formulations can be formulated in a variety of forms, such as single dosage forms or multiple dosage forms.

The pharmaceutical composition of the present invention may include excipients such as lactose and corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, stabilizers, and isotonic agents. If desired, sweetening and/or flavoring agents may be added.

Compositions of the present invention may be administered orally or parenterally, including inhalation, intravenous, intraperitoneal, subcutaneous, rectal and topical administration. Therefore, the composition of the present invention can be formulated in various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of tablets for oral use, carriers such as lactose and corn starch, and lubricants such as magnesium stearate may be usually added. For capsules for oral administration, lactose and/or dried corn starch can be used as a diluent. If oral aqueous suspensions are required, the active ingredient can be combined with emulsifiers and/or suspending agents. If desired, certain sweetening and/or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, sterile solutions of the active ingredient are usually prepared and the pH of the solution should be appropriately adjusted and buffered. For intravenous administration, the total concentration of solute should be adjusted to impart isotonicity to the formulation. The composition according to the invention may be in the form of an aqueous solution comprising a pharmaceutically acceptable carrier, such as saline with a pH of 7.4. The solution may be introduced into the intramuscular blood flow of the patient by local bolus injection.

The 3,3-difluoroallylamine derivative, that is, the compound of Formula 1 or a pharmaceutically acceptable salt thereof may be administered to the patient in an effective amount of about 0.001 mg/kg to about 100 mg/kg per day. Of course, the dose can be changed according to the patient's age, weight, susceptibility, symptoms or drug efficacy.

The present invention also selectively inhibits vascular adhesion protein-1 (VAP-1) in mammals, comprising administering to a mammal a therapeutically effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof. How to do. In one embodiment, the present invention provides a method of treating non-alcoholic steatohepatitis (NASH), comprising administering to a mammal a therapeutically effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof. do.

The present invention also provides the use of a compound of Formula 1 or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament that selectively inhibits vascular adhesion protein-1 (VAP-1) in a mammal. In one embodiment, the present invention provides the use of a compound of Formula 1 or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the prevention or treatment of non-alcoholic steatohepatitis (NASH).

Hereinafter, the present invention will be described in more detail through examples and test examples. However, these Examples and Test Examples illustrate the present invention, and the present invention is not limited to them.

Analysis of the compounds prepared in the following examples was performed as follows: Nuclear Magnetic Resonance (NMR) spectral analysis was performed on a Bruker 400 MHz spectrometer and an Agilent 600 MHz spectrometer, and chemical shift (chemical). shift) was analyzed in ppm. In addition, the Agilent 1260 Infinity Series Liquid Chromatography/Mass Selective Detector (MSD) with electrostatic spray interface (MSD in ESI+ (ESI-MS (cation) using a single quadrupole) z value, and [M+H]+ peak) The molecular weight indicated was measured Column chromatography was performed on silica gel (Merck, 70-230 mesh) (WC Still, J. Org. Chem . , 43 , 2923, 1978) In addition, the abbreviations used in the following examples are as follows: Me for methyl, Et for ethyl, Ph for phenyl, BOC for tert-butyloxycarbonyl, and TBDMS for tert-butyldimethylsilyl. In addition, the starting materials of each example were synthesized according to literatures with known compounds or purchased from Sigma Aldrich.

Reference Example 1. Tert-butyl N -[3,3-difluoro-2-(hydroxymethyl)allyl]carbamate

Step 1: Tert-butyl N -[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoro-allyl]carbamate

Under nitrogen conditions, 2.4 g of tert-butyl N -[3-[tert-butyl(dimethyl)silyl]oxy-2-oxo-propyl]carbamate and 1.0 g of 2-(difluoromethylsulfonyl)pyridine N ,N -dimethylformamide was dissolved in 34.5 mL and cooled to -70 °C. To the reaction mixture, 10.4 mL of a tetrahydrofuran solution of 1.0 M lithium bis(trimethylsilyl)amide was slowly added dropwise, stirred at -70°C for 30 minutes, and then slowly heated to -10°C and stirred. To the reaction mixture, 20 mL of an aqueous ammonium chloride solution was added, followed by adding 20 mL of a 3 N aqueous hydrogen chloride solution, followed by extraction three times with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 20/1) to prepare 446.0 mg (yield: 25.5%) of the title compound as a yellow liquid.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 4.98(s, 1H), 4.20(s, 2H), 3.83(s, 2H), 1.42(s, 9H), 0.89(s, 9H), 0.07(s , 6H)

Step 2: Tert-butyl N- [3,3-difluoro-2-(hydroxymethyl)allyl]carbamate

426 mg of tert-butyl N -[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoro-allyl]carbamate was dissolved in 2.0 mL of tetrahydrofuran, and then 1.0 M tetra After adding 1.5 mL of a tetrahydrofuran solution of butylammonium fluoride (TBAF), the mixture was stirred at room temperature for 2 hours. Ethyl acetate and water were added to the reaction mixture, and the organic layer was separated. Ethyl acetate was added to the aqueous layer, and the organic layer was separated again. The combined organic layers were washed with aqueous ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 2/1) to prepare 285 mg (yield: 100%) of the title compound as a colorless liquid.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 4.91(s, 1H), 4.14(s, 2H), 3.86(d, 2H), 3.72(s, 1H), 1.45(s, 9H)

Reference Example 2. 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one

Step 1: ( E )-ethyl 2-(ethoxymethylene)hydrazinecarboxylate

30.0 g of ethyl carbazate was dissolved in 240.2 mL of triethyl orthoformate, followed by stirring at 110°C overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give 30.3 g (yield: 65.6%) of the title compound as a white solid.

¹ H-NMR (DMSO-d ₆ , 400 MHz) δ 10.09 (s, 1H), 7.94 (s, 1H), 4.03 (t, 4H), 1.24-1.16 (m, 6H)

Step 2: 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one

4.3 g of ( E )-ethyl 2-(ethoxymethylene)hydrazine carboxylate prepared in step 1 was dissolved in 90.0 mL of methanol, 3.0 g of 4-fluoroaniline was added, and the mixture was refluxed at 80° C. for 5 hours. After the reaction mixture was cooled to room temperature, 7.7 mL of a sodium methoxide solution (25% in methanol) was added and refluxed at 80°C overnight. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. Ethyl acetate was added to the obtained residue, washed with an aqueous ammonia chloride solution, and the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to prepare 948 mg (yield: 19.6%) of the title compound as a light gray solid.

MS (ESI) m/z= 180.1 (M + H) +

Reference Example 3. 4-(3-bromophenyl)-1 H -1,2,4-triazole-5-one

Step 1: Phenyl (3-bromophenyl) carbamate

1.0 g of 3-bromoaniline and 0.98 mL of pyridine were dissolved in 10.0 mL of ethyl acetate, and 0.77 mL of phenylchloroformic acid was slowly added at 0°C, followed by stirring at room temperature for 3 hours. Ethyl acetate was added, washed with 1N hydrochloric acid solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.4 g (yield: 80.0%) of the title compound as a yellow solid.

Step 2: N- (3-bromophenyl)hydrazinecarboxamide

1.4 g of phenyl (3-bromophenyl) carbamate prepared in step 1 and 480.0 mg of hydrazine hydrate were dissolved in 4.0 mL of tetrahydrofuran and 4.0 mL of ethanol, and stirred at room temperature overnight. After concentration of the reaction mixture, washing with ethyl acetate gave 890.0 mg (yield: 80.0 %) of the title compound as a white solid.

Step 3: 4-(3-Bromophenyl)-1 H -1,2,4-triazole-5-one

890.0 mg of N- (3-bromophenyl)hydrazinecarboxamide prepared in Step 2 and 1.6 g of formamidine acetate were dissolved in 8.9 mL of 1-propanol, stirred at room temperature for 30 minutes, and 1.3 mL of acetic acid was added to 80 Stir at 8° C. for 8 hours. After the reaction mixture was cooled to room temperature, distilled water was added and stirred overnight. The resulting crystals were filtered and dried to give 742.8 mg (yield: 80.2%) of the title compound as a white solid.

MS (ESI) m/z= 241.2 (M + H)+

Reference Example 4. 4-(3,4-difluorophenyl)-1 H -1,2,4-triazole-5-one

492.0 mg (yield: 32.2%) of the title compound was prepared in the same manner as in Reference Example 2, except that 1.0 g of 3,4-difluoroaniline was used instead of 4-fluoroaniline in Step 2 of Reference Example 2. Did.

¹ H-NMR (MeOD, 400 MHz) δ 8.16 (s, 1H), 7.73 (t, 1H), 7.47-7.42 (m, 2H)

Reference Example 5. 4-(4-bromo-3-fluorophenyl)-1 H -1,2,4-triazole-5-one

The title compound was 517.3 mg (yield: 38.1%) in the same manner as in Reference Example 3, except that 1.0 g of 4-bromo-3-fluoroaniline was used instead of 3-bromoaniline in Step 1 of Reference Example 3. Was prepared.

MS (ESI) m/z= 259.1 (M + H)+

Reference Example 6. 4-(4-bromo-2-fluorophenyl)-1 H -1,2,4-triazole-5-one

443.5 mg of the title compound in the same manner as in Reference Example 3, except that 1.0 g of 4-bromo-2-fluoroaniline was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 32.7%) Was prepared.

MS (ESI) m/z= 259.2 (M + H)+

Reference Example 7. 4-(4-bromo-2-methylphenyl)-1 H -1,2,4-triazole-5-one

450 mg (yield: 33.0%) of the title compound was prepared in the same manner as in Reference Example 3, except that 1.0 g of 4-bromo-2-methylaniline was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

MS (ESI) m/z= 255.1 (M + H)+

Reference Example 8. 4-(6-Bromo-3-pyridyl)-1 H -1,2,4-triazole-5-one

500.7 mg (yield: 35.9%) of the title compound was prepared in the same manner as in Reference Example 3, except that 1.0 g of 3-amino-6-bromopyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

MS (ESI) m/z= 242.1 (M + H)+

Reference Example 9. 4-(6-bromo-2-pyridyl)-1 H -1,2,4-triazole-5-one

6.0 g (yield: 86.1%) of the title compound was prepared in the same manner as in Reference Example 3, except that 5.0 g of 2-amino-6-bromopyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 9.79 (s, 1H), 8.44 (s, 1H), 8.33 (d, 1H), 7.71 (t, 1H), 7.43 (d, 1H)

Reference Example 10. 4-(4-Bromo-2-pyridyl)-1 H -1,2,4-triazole-5-one

902.2 mg (yield: 64.8%) of the title compound was prepared in the same manner as in Reference Example 3, except that 1.0 g of 2-amino-4-bromopyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

MS (ESI) m/z= 242.1 (M + H)+

Reference Example 11. 4-(2-bromo-4-pyridyl)-1 H -1,2,4-triazole-5-one

2.0 g (yield: 28.7%) of the title compound was obtained in the same manner as in Reference Example 3, except that 5.0 g of 4-amino-2-bromopyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

¹ H-NMR (DMSO-d ₆ , 600 MHz) δ 8.65 (s, 1H), 8.45 (d, 1H), 8.17 (s, 1H), 8.12 (d, 1H), 7.97 (dd, 1H)

Reference Example 12. 4-(5-Bromo-3-methyl-2-pyridyl)-1 H -1,2,4-triazole-5-one

1.9 g of the title compound in the same manner as in Reference Example 3, except that 2.0 g of 2-amino-5-bromo-3-methylpyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 69.6%).

¹ H-NMR (DMSO-d ₆ , 400 MHz) δ 8.55 (d, 1H), 8.21 (s, 1H), 8.13 (s, 1H), 2.27 (s, 3H)

Reference Example 13. 4-(6-Bromo-4-methyl-3-pyridyl)-1 H -1,2,4-triazole-5-one

4.5 g of the title compound in the same manner as in Reference Example 3, except that 5.0 g of 2-bromo-4-methyl-5-aminopyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 66.1%).

MS (ESI) m/z= 256.0 (M + H)+

Reference Example 14. 4-(6-Bromo-5-methyl-3-pyridyl)-1 H -1,2,4-triazole-5-one

362.1 mg of the title compound in the same manner as in Reference Example 3 except that 1.0 g of 5-amino-2-bromo-3-picoline was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 26.5%).

MS (ESI) m/z= 256.1 (M + H)+

Reference Example 15. 4-(5-Bromo-3-fluoro-2-pyridyl)-1 H -1,2,4-triazole-5-one

715.0 mg (yield) of the title compound in the same manner as in Reference Example 3, except that 1.0 g of 2-amino-5-bromo-3-fluoropyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. : 52.7 %).

MS (ESI) m/z= 260.2 (M + H)+

Reference Example 16. 4-(6-Bromo-3-methyl-2-pyridyl)-1 H -1,2,4-triazole-5-one

1.8 g of the title compound was obtained in the same manner as in Reference Example 3, except that 2.0 g of 2-amino-6-bromo-3-methylpyridine was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 65.9%).

MS (ESI) m/z= 256.1 (M + H)+

Reference Example 17. 4-(5-Bromopyrazin-2-yl)-1 H -1,2,4-triazole-5-one

4.3 g (yield: 61.9%) of the title compound was prepared in the same manner as in Reference Example 3, except that 5.0 g of 2-amino-5-bromopyrazine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. It was prepared.

MS (ESI) m/z= 243.2 (M + H)+

Reference Example 18. 4-[(4-benzyloxyphenyl)methyl]-1 H -1,2,4-triazole-5-one

570 mg of the title compound in the same manner as in Reference Example 3, except that 1.0 g of (4-(benzyloxy)phenyl)methanamine was used instead of 3-bromoaniline in Step 1 of Reference Example 3 (yield: 43.2%) ).

MS (ESI) m/z= 282.2 (M + H)+

Reference Example 19. 4-[(5-bromo-2-thienyl)methyl]-1 H -1,2,4-triazole-5-one

The title compound 742.8 as a white solid was prepared in the same manner as in Reference Example 2, except that 1.0 g of (5-bromothio-2-yl)methylamine was used instead of 4-fluoroaniline in Step 2 of Reference Example 2. mg (yield: 80.3%) was prepared.

¹ H-NMR (MeOD, 400MHz) δ 7.83(s, 1H), 7.01(s, 1H), 6.94(s, 1H), 5.04(s, 2H)

Reference Example 20. 4-[(4-bromo-2-thienyl)methyl]-1 H -1,2,4-triazole-5-one

3.9 g (yield) of the title compound in the same manner as in Reference Example 2, except that 5.0 g of (4-bromothiophen-2-yl)methylamine was used instead of 4-fluoroaniline in Step 2 of Reference Example 2 above. : 57.6 %).

¹ H-NMR (DMSO-d ₆ , 400 MHz) δ 11.74 (s, 1H), 7.97 (s, 1H), 7.61 (s, 1H), 7.10 (s, 1H), 4.92 (s, 2H)

Reference Example 21. 4-[(5-bromo-3-methyl-2-thienyl)methyl]-1 H -1,2,4-triazole-5-one

The title compound was prepared in the same manner as in Reference Example 3, except that 2.6 g of (5-bromo-3-methylthiophen-2-yl)methaneamine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. 1.4 g (Yield: 41.2 %) was prepared.

MS (ESI) m/z= 275.1 (M + H)+

Reference Example 22. 4-[2-(2-thienyl)ethyl]-1 H -1,2,4-triazole-5-one

569 mg of the title compound as a white solid (yield: 72.0%) was prepared in the same manner as in Reference Example 3, except that 1.0 g of 2-thiophenethylamine was used instead of 3-bromoaniline in Step 1 of Reference Example 3. Got.

MS (ESI) m/z= 196.2 (M + H)+

Reference Example 23. 4-[2-(5-bromo-2-thienyl)ethyl]-1 H -1,2,4-triazole-5-one

The title was the same as in Reference Example 2, except that 2.3 g of 2-(5-bromothiophen-2-yl)ethan-1-amine was used instead of 4-fluoroaniline in Step 2 of Reference Example 2. 2.1 g of compound (yield: 68.6 %) was prepared.

MS (ESI) m/z= 275.2 (M + H)+

Reference Example 24. Tert-butyl N -[3,3-difluoro-2-[[4-(4-fluorophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl ]Allyl]Carbamate

321 mg of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one prepared in Step 2 of Reference Example 2, tert-butyl N prepared in Step 2 of Reference Example 1 400 mg of -[3,3-difluoro-2-(hydroxymethyl)allyl]carbamate and 940 mg of triphenylphosphine were dissolved in 4.5 mL of tetrahydrofuran, stirred and cooled to 0°C. 706 uL of diisopropyl azodicarboxylate (DIAD) was slowly added dropwise to the reaction mixture and stirred at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 2/1) to give 222 mg (yield: 32.3%) of the title compound as an off-white liquid.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 7.68(s, 1H), 7.52(s, 2H), 7.19(t, 2H), 5.37(s, 1H), 4.54(s, 2H), 3.79(s , 2H), 1.41(s, 9H)

Reference Example 25. Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro Rho-Allyl] Carbamate

4-(3-Bromophenyl)-1 H- 1 prepared in Reference Example 3 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 30 mg (yield: 10.0%) of the title compound was prepared in the same manner as in Reference Example 24, except that 161 mg of 2,4-triazole-5-one was used.

MS (ESI) m/z=346.2 (M + H)+

Reference Example 26. Tert-butyl N -[2-[[4-(3,4-difluorophenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3 -Difluoro-allyl]carbamate

4-(3,4-difluorophenyl)-1 prepared in Reference Example 4 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 1.8 g (yield: 100%) of the title compound was prepared in the same manner as in Reference Example 24, except that 883 mg of H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 303.1 (M + H)+

Reference Example 27. Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]- 3,3-difluoro-allyl]carbamate

4-(4-bromo-3-fluorophenyl) prepared in Reference Example 5 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 19 mg (yield: 9.3%) of the title compound was prepared in the same manner as in Reference Example 24, except that 150 mg of -1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= (M + H)+

Reference Example 28. Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]- 3,3-difluoro-allyl]carbamate

4-(4-bromo-2-fluorophenyl) prepared in Reference Example 6 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 448 mg (yield: 8.3%) of the title compound was prepared in the same manner as in Reference Example 24, except that 3.0 g of -1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 364.2 (M + H)+

Reference Example 29. Tert-butyl N -[2-[[4-(4-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3 ,3-difluoro-allyl]carbamate

4-(4-Bromo-2-methylphenyl)-1 prepared in Reference Example 7 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 35 mg (yield: 24.2%) of the title compound was prepared in the same manner as in Reference Example 24, except that 80 mg of H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 360.1 (M + H)+

Reference Example 30. Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3, 3-difluoro-allyl]carbamate

4-(4-bromo-3-pyridyl) prepared in Reference Example 8 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24- 1.3 g (yield: 41.3%) of the title compound was prepared in the same manner as in Reference Example 24, except that 1.7 g of 1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 347.2 (M + H)+

Reference Example 31. Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3, 3-difluoro-allyl]carbamate

4-(4-bromo-2-pyridyl) prepared in Reference Example 9 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24- 1.8 g (yield: 100%) of the title compound was prepared in the same manner as in Reference Example 24, except that 972 mg of 1 H -1,2,4-triazole-5-one was used.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 8.42(s, 1H), 8.32(d, 1H), 7.70(t, 1H), 7.43(d, 1H), 4.53(s, 2H), 3.78(s , 2H), 1.40(s, 9H)

Reference Example 32. Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3, 3-difluoro-allyl]carbamate

4-(4-Bromo-2-pyridyl) prepared in Reference Example 10 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24- 499 mg (yield: 49.9%) of the title compound was prepared in the same manner as in Reference Example 24, except that 540 mg of 1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 347.2 (M + H)+

Reference Example 33. Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3, 3-difluoro-allyl]carbamate

4-(2-bromo-4-pyridyl) prepared in Reference Example 11 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24- 1.2 g (yield: 90.0%) of the title compound was prepared in the same manner as in Reference Example 24, except that 702 mg of 1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z=347.1 (M + H)+

Reference Example 34. Tert-butyl N- [2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl ]-3,3-difluoro-allyl]carbamate

4-(5-bromo-3-methyl-2- prepared in Reference Example 12 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 The title compound 1.8 g (yield: 97.0 %) was prepared by the same method as Reference Example 24, except that 1.0 g of pyridyl)-1 H -1,2,4-triazole-5-one was used.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 8.42(s, 1H), 7.87(s, 1H), 7.74(s, 1H), 5.36(s, 1H), 4.53(s, 2H), 3.78(s , 2H), 2.40(s, 3H), 1.42(s, 9H)

Reference Example 35. Tert-butyl N- [2-[[4-(6-bromo-4-methyl-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl ]-3,3-difluoro-allyl]carbamate

4-(6-Bromo-4-methyl-3-prepared in Reference Example 13 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 56 mg (yield: 34.4%) of the title compound was prepared in the same manner as in Reference Example 24, except that 89 mg of pyridyl)-1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 361.1 (M + H)+

Reference Example 36. Tert-butyl N- [2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl ]-3,3-difluoro-allyl]carbamate

4-(6-bromo-5-methyl-3- prepared in Reference Example 14 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 405 mg (yield: 39.3%) of the title compound was prepared in the same manner as in Reference Example 24, except that 571 mg of pyridyl)-1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 361.1 (M + H)+

Reference Example 37. Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl] Methyl]-3,3-difluoro-allyl]carbamate

4-(5-bromo-3-fluoro-2 prepared in Reference Example 15 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 -Pyridyl) -1 H -1,2,4-triazole-5-one 780 mg (yield: 33.5%) of the title compound was prepared by the same method as Reference Example 24, except that 1.3 g was used. .

MS (ESI) m/z= 365.2 (M + H)+

Reference Example 38. Tert-butyl N- [2-[[4-(6-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl ]-3,3-difluoro-allyl]carbamate

4-(6-bromo-3-methyl-2- prepared in Reference Example 16 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 521 mg (yield: 50.5 %) of the title compound was prepared in the same manner as in Reference Example 24, except that 571 mg of pyridyl)-1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 361.2 (M + H)+

Reference Example 39. Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3, 3-difluoro-allyl]carbamate

4-(5-Bromopyrazin-2-yl) prepared in Reference Example 17 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24- 110 mg (yield: 43.1%) of the title compound was prepared in the same manner as in Reference Example 24, except that 138 mg of 1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 348.1 (M + H)+

Reference Example 40. Tert-butyl N -[2-[[4-[(4-benzyloxyphenyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3 -Difluoro-allyl]carbamate

4-[(4-benzyloxyphenyl)methyl]-1 prepared in Reference Example 18 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 20 mg (yield: 4.6%) of the title compound was prepared in the same manner as in Reference Example 24, except that 126 mg of H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 387.1 (M + H)+

Reference Example 41. Tert-butyl N -[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl] -3,3-difluoro-allyl]carbamate

4-[(5-bromo-2-thienyl) prepared in Reference Example 19 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 )Methyl]-1 H -1,2,4-triazole-5-one, except that 2.0 g was used, 3.3 g (yield: 87.2 %) of the title compound was prepared in the same manner as in Reference Example 24 above.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 7.38(s, 1H), 6.95(s, 1H), 6.85(s, 1H), 5.40(s, 1H), 4.88(s, 2H), 4.47(s , 2H), 3.71(s, 2H), 1.44(s, 9H)

Reference Example 42. Tert-butyl N -[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl] -3,3-difluoro-allyl]carbamate

4-[(4-bromo-2-thienyl) prepared in Reference Example 20 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 )Methyl]-1 H -1,2,4-triazole-5-one 2.9 g (yield: 64.9%) of the title compound was prepared in the same manner as in Reference Example 24, except that 2.3 g was used.

¹ H-NMR (CDCl ₃ , 400 MHz) δ 7.41(s, 1H), 7.22(s, 1H), 7.02(s, 1H), 5.38(s, 1H), 4.93(s, 2H), 4.48(s , 2H), 3.72(s, 2H), 1.44(s, 9H)

Reference Example 43. Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazole-1- Work]methyl]-3,3-difluoro-allyl]carbamate

4-[(5-bromo-3-methyl-2) prepared in Reference Example 21 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 -Thienyl)methyl]-1 H -1,2,4-triazole-5-one 546 mg of the title compound (yield: 33.0%) in the same manner as in Reference Example 24, except that 946 mg was used. Was prepared.

MS (ESI) m/z= 380.2 (M + H)+

Reference Example 44. Tert-butyl N -[3,3-difluoro-2-[[5-oxo-4-[2-(2-thienyl)ethyl]-1,2,4-triazole- 1-day]methyl]allyl]carbamate

4-[2-(2-thienyl)ethyl prepared in Reference Example 22 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24] 44 mg (yield: 14.3%) of the title compound was prepared in the same manner as in Reference Example 24, except that 87 mg of -1 H -1,2,4-triazole-5-one was used.

MS (ESI) m/z= 387.2 (M + H)+

Reference Example 45. Tert-butyl N -[2-[[4-(5-bromo-2-thienyl)ethyl]-5-oxo-1,2,4-triazol-1-yl]methyl] -3,3-difluoro-allyl]carbamate

4-[2-(5-bromo-2-cy) prepared in Reference Example 23 instead of 4-(4-fluorophenyl)-1 H -1,2,4-triazole-5-one in Reference Example 24 Enyl)ethyl]-1 H -1,2,4-triazole-5-one, except that 2.0 g was used, 780 mg (yield: 22.3%) of the title compound was prepared in the same manner as in Reference Example 24 above. Did.

MS (ESI) m/z= 380.1 (M + H)+

Example 1. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazole-3-one

Tert-butyl N- [3,3-difluoro-2-[[4-(4-fluorophenyl)-5-oxo-1,2,4-triazole-1-yl) prepared in Reference Example 24 ]Methyl]allyl] 287 mg of carbamate was dissolved in 10.0 mL of dichloromethane, and 1.1 mL of trifluoroacetic acid was added, followed by stirring at room temperature for 2.5 hours. After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 262 mg of the title compound as a white solid (yield: 100%).

¹ H-NMR (MeOD, 400 MHz) δ 8.23 (s, 1H), 7.65 (s, 2H), 7.27 (t, 2H), 4.64 (s, 2H), 3.73 (s, 2H)

Example 2. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3- prepared in Reference Example 25 31 mg (yield: 40.1 %) of the title compound was prepared in the same manner as in Example 1, except that 96 mg of difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.30 (s, 1H), 7.95 (s, 1H), 7.65-7.56 (m, 2H), 7.44 (t, 1H), 4.63 (s, 2H), 3.72 ( s, 2H)

Example 3. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(3,4-difluorophenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3 prepared in Reference Example 26 143 mg (yield: 100%) of the title compound as a colorless liquid was prepared in the same manner as in Example 1, except that 189 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.29 (s, 1H), 7.74 (t, 3H), 7.48 (s, 1H), 7.42 (t, 1H), 4.65 (s, 2H), 3.75 (s, 2H)

Example 4. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazole- 3-on

Tert-butyl N- [2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl prepared in Reference Example 27 ]-3,3-Difluoro-allyl] Carbamate 56 mg (yield: 58.0%) of the title compound was prepared in the same manner as in Example 1, except that 123 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.34 (s, 1H), 7.79-7.69 (m, 2H), 7.47 (d, 2H), 4.63 (s, 2H), 3.72 (s, 2H)

Example 5. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazole- 3-on

Tert-butyl N- [2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl prepared in Reference Example 28 ]-3,3-difluoro-allyl]carbamate The title compound was 51 mg (yield: 57.7%) in the same manner as in Example 1, except that 113 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.11 (s, 1H), 7.65-7.53 (m, 3H), 4.64 (s, 2H), 3.73 (s, 2H)

Example 6. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazole-3 -On

Tert-butyl N- [2-[[4-(4-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazole-1-yl]methyl prepared in Reference Example 29] 27 mg (yield: 69.0 %) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of -3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.02(s, 1H), 7.58-7.55(m, 2H), 7.34(d, 2H), 4.64(s, 2H), 3.73(s, 2H), 2.20( s, 3H)

Example 7. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazole-3- On

Tert-butyl N- [2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl] prepared in Reference Example 30]- 34 mg (yield: 87.7%) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.73(s, 1H), 8.35(s, 1H), 8.06(d, 1H), 7.76(d, 1H), 5.49(s, 2H), 4.62(s, 2H), 3.54(s, 2H)

Example 8. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazole-3- On

Tert-butyl N- [2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl] prepared in Reference Example 31- 325 mg (yield: 98.4%) of the title compound was prepared in the same manner as in Example 1, except that 369 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.58 (s, 1H), 8.26 (d, 1H), 7.87 (t, 1H), 7.58 (d, 1H), 4.65 (s, 2H), 3.74 (s, 2H)

Example 9. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazole-3- On

Tert-butyl N- [2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl] prepared in Reference Example 32]- 38 mg (yield: 98.0%) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.62(s, 1H), 8.48(s, 1H), 8.32(d, 1H), 7.56(d, 1H), 4.66(s, 2H), 3.75(s, 2H)

Example 10. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazole-3- On

Tert-butyl N- [2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl prepared in Reference Example 33]- 34 mg (yield: 88.4 %) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.69 (s, 1H), 8.44 (d, 2H), 8.21 (s, 1H), 7.89 (d, 1H), 4.65 (s, 2H), 3.73 (s, 2H)

Example 11. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 34 ]Methyl]-3,3-difluoro-allyl]carbamate The title compound was prepared 260 mg (yield: 73.0%) in the same manner as in Example 1, except that 455 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.50 (s, 1H), 8.13 (s, 2H), 4.64 (s, 2H), 3.73 (s, 2H), 2.34 (s, 3H)

Example 12. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(6-bromo-4-methyl-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 35 ]Methyl]-3,3-difluoro-allyl]carbamate 50 mg (yield: 89.2%) of the title compound was prepared in the same manner as in Example 1, except that 50 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.31(s, 1H), 8.08(s, 1H), 7.72(s, 1H), 4.65(s, 2H), 3.74(s, 2H), 2.29(s, 3H)

Example 13. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 36 ]Methyl]-3,3-difluoro-allyl]carbamate 50 mg (yield: 56.0%) of the title compound was prepared in the same manner as in Example 1, except that 50 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.57 (s, 1H), 8.35 (s, 1H), 8.06 (d, 1H), 4.64 (s, 2H), 3.67 (s, 2H), 2.46 (s, 3H)

Example 14. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4- Triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazole-1- prepared in Reference Example 37 19 mg (yield: 48.3%) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of 1]methyl]-3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.54 (s, 1H), 8.24 (d, 1H), 8.20 (s, 1H), 4.65 (s, 2H), 3.74 (s, 2H)

Example 15. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(6-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 38 28 mg (yield: 71.3 %) of the title compound was prepared in the same manner as in Example 1, except that 50 mg of ]methyl]-3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.15 (s, 1H), 7.79 (d, 1H), 7.66 (d, 1H), 4.65 (s, 2H), 3.72 (s, 2H), 2.31 (s, 3H)

Example 16. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazole-3- On

Tert-butyl N- [2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazole-1-yl]methyl] prepared in Reference Example 39- 56 mg (yield: 65.6%) of the title compound was prepared in the same manner as in Example 1, except that 110 mg of 3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.31 (s, 1H), 8.67 (s, 1H), 8.58 (s, 1H), 4.65 (s, 2H), 3.73 (s, 2H)

Example 17. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole- 3-on

Step 1: Tert-butyl N -[3,3-difluoro-2-[[4-[3-(4-methylsulfonylphenyl)phenyl]-5-oxo-1,2,4-triazole- 1-day]methyl]allyl]carbamate

Tert-butyl N- [2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3- prepared in Reference Example 25 70 mg of difluoro-allyl]carbamate and 31 mg of 4-(methanesulfonyl)phenylboronic acid are dissolved in 1.0 mL of 1,4-dioxane, 785 uL of 1 M potassium carbonate and palladium di[1,1'-bis (Diphenylphosphino)ferrocene]dichloride (PdCl ₂ (dppf)) 6 mg was added and stirred at 90°C overnight. The reaction mixture was filtered through a pad of celite, and the residue obtained by concentration under reduced pressure was dissolved in ethyl acetate, washed with distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 1/1) to prepare 53 mg (yield: 64.8 %) of the title compound.

MS (ESI) m/z= 421.1 (M + H)+

Step 2: 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole-3 -On

Tert-butyl N- [3,3-difluoro-2-[[4-[3-(4-methylsulfonylphenyl)phenyl]-5-oxo-1,2,4-trie prepared in step 1 53 mg of azole-1-yl]methyl]allyl]carbamate was dissolved in 1.0 mL of dichloromethane, 0.1 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 40 mg (yield: 93.1%) of the title compound as a white solid.

¹ H-NMR (MeOD, 400 MHz) δ 8.36 (s, 1H), 8.07-7.95 (m, 4H), 7.76-7.66 (m, 4H), 4.66 (s, 2H), 3.50 (s, 2H), 2.22(s, 3H)

Example 18. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4- Triazole-3-one

Tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1 instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 17 -35 mg (yield: 35.6 %) of the title compound was prepared in the same manner as in Example 17, except that 61 mg of carboxylate was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.33 (s, 1H), 7.88 (s, 1H), 7.66-7.55 (m, 5H), 7.14 (d, 2H), 4.67 (s, 2H), 3.71 ( s, 2H), 3.49-3.46 (m, 4H), 3.40-3.37 (m, 4H)

Example 19. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1, 2,4-triazole-3-one

Same as Example 17, except that in step 1 of Example 17, 43 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronic acid. The title compound was prepared 36 mg (Yield: 44.8%).

¹ H-NMR (MeOD, 400 MHz) δ 9.05(s, 1H), 8.41(s, 1H), 8.36(d, 1H), 8.06(s, 1H), 7.94(d, 1H), 7.83-7.72( m, 3H), 4.68(s, 2H), 3.74(s, 2H)

Example 20. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2 ,4-triazole-3-one

The title compound was obtained in the same manner as in Example 17, except that 39 mg of 6-(dimethylamino)pyridine-3-boronic acid was used instead of 4-(methanesulfonyl)phenylboronic acid in Step 1 of Example 17. 38 mg (Yield: 49.7%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.37 (s, 1H), 8.28 (d, 2H), 7.93 (s, 1H), 7.70-7.65 (m, 3H), 7.26 (d, 1H), 4.68 ( s, 2H), 3.76 (s, 2H), 3.32 (s, 6H)

Example 21. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2, 4-triazole-3-one

2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2 instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 17 -62 mg (yield: 81.2%) of the title compound was prepared in the same manner as in Example 17, except that 39 mg of dioxaborolan was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.33 (s, 1H), 7.83 (s, 1H), 7.57-7.55 (m, 3H), 7.18 (s, 1H), 6.91 (s, 2H), 6.01 ( s, 2H), 4.66 (s, 2H), 3.67 (s, 2H)

Example 22. 6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]phenyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one

Using 45 mg of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 17 Except for the same method as in Example 17, 33 mg (yield: 40.0%) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.34 (s, 1H), 7.87 (s, 1H), 7.65 (t, 1H), 7.59-7.56 (m, 2H), 7.39 (s, 2H), 4.66 ( s, 2H), 3.64 (s, 2H), 3.02 (t, 2H), 2.60 (t, 2H)

Example 23. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4- Triazole-3-one

The title compound 35 was obtained in the same manner as in Example 17, except that in step 1 of Example 17, 1-ethylpyrazole-4-boronic acid pinacol ester mg was used instead of 4-(methanesulfonyl)phenylboronic acid. mg (yield: 48.4%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.32(s, 1H), 8.11(s, 1H), 7.91(s, 1H), 7.83(s, 1H), 7.62(d, 1H), 7.54-7.47( m, 2H), 4.67 (d, 2H), 4.23 (q, 2H), 3.75 (s, 2H), 1.50 (t, 3H)

Example 24. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2, 4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate The title compound 25 was obtained in the same manner as in Example 17, except that 50 mg of oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. mg (yield: 52.8%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.38 (s, 1H), 8.08 (d, 1H), 7.86 (d, 1H), 7.79-7.67 (m, 3H), 4.63 (s, 2H), 3.18 ( s, 3H)

Example 25. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1 ,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and tert-butyl instead of 4-(methanesulfonyl)phenylboronic acid 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate In the same manner as in Example 17, except that 54 mg was used. 21 mg (yield: 43.7%) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.36 (s, 1H), 7.67-7.53 (m, 5H), 7.14 (d, 2H), 4.66 (s, 2H), 3.71 (s, 2H), 3.51- 3.39 (m, 8H)

Example 26. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl] Phenyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(instead of 4-(methanesulfonyl)phenylboronic acid 33 mg (yield: 71.2%) of the title compound was prepared in the same manner as in Example 17, except that 38 mg of trifluoromethyl)pyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.94 (s, 1H), 8.40 (s, 1H), 8.28 (d, 1H), 7.95 (d, 1H), 7.85-7.72 (m, 3H), 4.64 ( s, 2H), 3.39 (s, 2H)

Example 27. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro- Phenyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-( instead of 4-(methanesulfonyl)phenylboronic acid 24 mg (yield: 55.0 %) of the title compound was prepared in the same manner as in Example 17, except that 35 mg of dimethylamino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.40(s, 1H), 8.19(s, 1H), 8.12(d, 1H), 7.78-7.64(m, 3H), 7.21(d, 1H), 4.67( s, 2H), 3.75 (s, 2H), 3.32 (s, 6H)

Example 28. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(instead of 4-(methanesulfonyl)phenylboronic acid In the same manner as in Example 17, except that 35 mg of 1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan was used. 31 mg (yield: 71.0 %) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.36 (s, 1H), 7.67-7.54 (m, 3H), 7.06 (s, 2H), 6.94 (d, 1H), 6.02 (s, 2H), 4.65 ( s, 2H), 3.66 (s, 2H)

Example 29. 6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Fluoro-phenyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 8-methyl instead of 4-(methanesulfonyl)phenylboronic acid 27 mg of the title compound (yield: 56.4 %) in the same manner as in Example 17, except that 40 mg of 2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. ).

¹ H-NMR (MeOD, 400 MHz) δ 8.36 (s, 1H), 7.67-7.54 (m, 3H), 7.26 (s, 2H), 4.67 (s, 2H), 3.75 (s, 2H), 3.00 ( t, 2H), 2.60 (t, 2H), 2.32 (s, 3H)

Example 30. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-3-fluoro-phenyl)-5- prepared in Reference Example 27 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 1-ethyl instead of 4-(methanesulfonyl)phenylboronic acid 28 mg (yield: 81.4%) of the title compound was prepared in the same manner as in Example 17, except that 31 mg of pyrazole-4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.33 (s, 1H), 8.13 (s, 1H), 7.95 (s, 1H), 7.83 (t, 1H), 7.64 (d, 1H), 7.51 (d, 1H), 4.64(s, 2H), 4.26(q, 2H), 3.62(s, 2H), 1.51(t, 3H)

Example 31. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2, 4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate The title compound 29 was obtained in the same manner as in Example 17, except that 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. mg (yield: 61.2%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.19 (s, 1H), 8.08 (d, 2H), 7.97 (d, 2H), 7.81-7.72 (m, 3H), 4.68 (s, 2H), 3.76 ( s, 2H), 3.18 (s, 3H)

Example 32. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1 ,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and tert-butyl instead of 4-(methanesulfonyl)phenylboronic acid 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate In the same manner as in Example 17, except that 54 mg was used. 22 mg (yield: 45.8%) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.14 (s, 1H), 7.64-7.60 (m, 5H), 7.14 (d, 2H), 4.67 (s, 2H), 3.73 (s, 2H), 3.50- 3.40(m, 8H)

Example 33. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl] Phenyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(instead of 4-(methanesulfonyl)phenylboronic acid The title compound 25 mg (yield: 53.9%) was prepared in the same manner as in Example 17, except that 38 mg of trifluoromethyl)pyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.19 (s, 1H), 8.08 (d, 2H), 7.97 (d, 2H), 7.81-7.72 (m, 3H), 4.68 (s, 2H), 3.76 ( s, 2H), 3.18 (s, 3H)

Example 34. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro- Phenyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-( instead of 4-(methanesulfonyl)phenylboronic acid 35 mg (yield: 80.1 %) of the title compound was prepared in the same manner as in Example 17, except that 35 mg of dimethylamino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.30-8.16 (m, 3H), 7.74-7.62 (m, 3H), 7.20 (d, 1H), 4.67 (s, 2H), 3.73 (s, 2H), 1.87(s, 6H)

Example 35. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(instead of 4-(methanesulfonyl)phenylboronic acid In the same manner as in Example 17, except that 35 mg of 1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan was used. 30 mg (yield: 68.7 %) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.13 (s, 1H), 7.64-7.53 (m, 3H), 7.18 (s, 2H), 6.94 (s, 1H), 6.02 (d, 2H), 4.67 ( s, 2H), 3.73 (s, 2H)

Example 36. 6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3 -Fluoro-phenyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 8-methyl instead of 4-(methanesulfonyl)phenylboronic acid 33 mg of the title compound (yield: 68.9 %) in the same manner as in Example 17, except that 40 mg of 2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. ).

¹ H-NMR (MeOD, 400 MHz) δ 9.06 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 7.95-7.76 (m, 4H), 4.65 (s, 2H), 3.49 ( s, 2H)

Example 37. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-fluoro-phenyl)-5- prepared in Reference Example 28 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 1-ethyl instead of 4-(methanesulfonyl)phenylboronic acid 21 mg (yield: 61.1 %) of the title compound was prepared in the same manner as in Example 17, except that 31 mg of pyrazole-4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.16 (s, 1H), 8.11 (s, 1H), 7.93 (s, 1H), 7.61-7.56 (m, 3H), 4.65 (s, 2H), 4.23 ( q, 2H), 3.63(s, 2H), 1.50(t, 3H)

Example 38. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4 -Triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 25 mg of the title compound in the same manner as in Example 17, except that 60 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Yield: 44.0%).

¹ H-NMR (MeOD, 400 MHz) δ 9.04 (s, 1H), 8.44 (s, 1H), 8.30 (d, 2H), 8.24 (d, 1H), 8.13 (d, 1H), 8.06 (d, 2H), 4.69(s, 2H), 3.77(s, 2H), 3.18(s, 3H)

Example 39. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate and tert-butyl 4- instead of 4-(methanesulfonyl)phenylboronic acid [4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate The title compound was prepared in the same manner as in Example 17, except that 52 mg was used. 32 mg (Yield: 55.9%) were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.37 (s, 1H), 8.12 (d, 1H), 8.00-7.95 (m, 3H), 7.14 (d, 2H) 4.67 (s, 2H), 3.73 (s , 2H), 3.53(t, 4H), 3.39(t, 4H)

Example 40. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used instead of 4-(methanesulfonyl)phenylboronic acid 2-(trifluoro 17 mg (yield: 29.8%) of the title compound was prepared in the same manner as in Example 17, except that 37 mg of chloromethylpyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.41 (s, 1H), 9.10 (s, 1H), 8.71 (d, 1H), 8.46 (s, 1H), 8.31 (d, 1H), 8.23 (d, 1H), 7.96(d, 1H), 4.69(s, 2H), 3.77(s, 2H)

Example 41. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl] -1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-(dimethyl) instead of 4-(methanesulfonyl)phenylboronic acid. 19 mg (yield: 37.3%) of the title compound was prepared in the same manner as in Example 17, except that 33 mg of amino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.00(s, 1H), 8.68(d, 1H), 8.65(s, 1H), 8.42(s, 1H), 8.23(d, 1H), 8.07(d, 1H), 7.35(d, 1H), 4.68(s, 2H), 3.36(s, 3H)

Example 42. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 60 mg was used, and 2-(1, instead of 4-(methanesulfonyl)phenylboronic acid 3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 33 mg of the title compound in the same manner as in Example 17, except that 33 mg was used. 26 mg (yield: 50.0 %) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.37 (s, 1H), 8.11 (d, 1H), 7.93 (d, 1H), 7.57 (d, 1H), 7.55 (s, 1H), 6.94 (d, 1H), 6.04(s, 2H), 4.67(s, 2H), 3.76(s, 2H)

Example 43. 6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 8-methyl-2 instead of 4-(methanesulfonyl)phenylboronic acid -17 mg (yield: 29.8%) of the title compound in the same manner as in Example 17, except that 39 mg of oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.89 (s, 1H), 8.38 (s, 1H), 8.11 (d, 1H), 7.94 (d, 1H), 7.71 (s, 2H), 4.68 (s, 2H), 3.77(s, 2H), 3.01(t, 2H), 2.60(t, 4H), 2.33(s, 3H)

Example 44. 6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, (1-methyl- 22 mg of the title compound in the same manner as in Example 17, except that 39 mg of 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used (yield: 39.6 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.90(s, 1H), 8.38(s, 1H), 8.11(d, 1H), 7.96-7.86(m, 3H), 7.17(d, 1H), 4.68( s, 2H), 3.34 (s, 3H), 2.96 (t, 2H), 2.64 (t, 2H)

Example 45. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-3-pyridyl)-5-oxo-prepared in Reference Example 30 instead of methyl]-3,3-difluoro-allyl]carbamate 60 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 1-ethylpyrazole instead of 4-(methanesulfonyl)phenylboronic acid 22 mg (yield: 45.4%) of the title compound was prepared in the same manner as in Example 17, except that 30 mg of -4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.35 (s, 1H), 8.26 (s, 1H), 8.07 (s, 2H), 7.80 (d, 1H) 4.67 (s, 2H), 4.27 (q, 2H) ), 3.75(s, 2H), 1.52(t, 3H)

Example 46. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4 -Triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 35 mg of the title compound in the same manner as in Example 17, except that 50 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Yield: 74.2 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.85(s, 1H), 8.37(d, 2H), 8.28(d, 1H), 8.07(t, 3H), 7.99(d, 1H), 4.68(s, 2H), 3.77(s, 2H), 3.18(s, 3H)

Example 47. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate and tert-butyl 4- instead of 4-(methanesulfonyl)phenylboronic acid [4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate The title compound was prepared in the same manner as in Example 17, except that 52 mg was used. 33 mg (Yield: 68.9%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.79 (s, 1H), 8.07 (d, 3H), 7.95 (t, 1H), 7.80 (d, 1H), 7.13 (d, 2H), 4.67 (s, 2H), 3.72(s, 2H), 3.53(s, 4H), 3.39(s, 4H)

Example 48. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used instead of 4-(methanesulfonyl)phenylboronic acid 2-(trifluoro 28 mg (yield: 60.6%) of the title compound was prepared in the same manner as in Example 17, except that 26 mg of chloromethylpyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.44 (s, 1H), 8.88 (s, 1H), 8.75 (d, 1H), 8.33 (d, 1H), 8.13 (t, 1H), 8.05 (d, 1H), 7.95(d, 1H), 4.69(s, 2H), 3.77(s, 2H)

Example 49. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl] -1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-(dimethyl) instead of 4-(methanesulfonyl)phenylboronic acid. 25 mg (yield: 57.6 %) of the title compound was prepared in the same manner as in Example 17, except that 33 mg of amino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.83 (s, 1H), 8.70 (s, 1H), 8.63 (d, 1H), 8.21 (d, 1H), 8.05 (t, 1H), 7.86 (d, 1H), 7.24(d, 1H), 4.68(s, 2H), 3.76(s, 2H), 3.34(s, 6H)

Example 50. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(1, instead of 4-(methanesulfonyl)phenylboronic acid 3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 22 mg of the title compound in the same manner as in Example 17, except that 22 mg was used. 36 mg (Yield: 83.0%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.76 (s, 1H), 8.07 (d, 1H), 7.93 (t, 1H), 7.73 (d, 1H), 7.61 (d, 2H), 6.90 (d, 1H), 6.02(s, 2H), 4.66(s, 2H), 3.75(s, 2H)

Example 51. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 8-methyl-2 instead of 4-(methanesulfonyl)phenylboronic acid 29 mg (yield: 60.7%) of the title compound in the same manner as in Example 17 above, except that 39 mg of oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.81 (s, 1H), 8.10 (d, 1H), 7.96 (t, 1H), 7.80 (s, 3H), 4.68 (s, 2H), 3.76 (s, 2H), 3.03(t, 2H), 2.61(t, 2H), 2.34(s, 3H)

Example 52. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, (1-methyl- 36 mg (yield: 75.4) of the title compound in the same manner as in Example 17, except that 39 mg of 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used. %).

¹ H-NMR (MeOD, 400 MHz) δ 8.82 (s, 1H), 8.12 (d, 1H), 8.01-7.96 (m, 3H), 7.83 (d, 1H), 7.18 (d, 1H), 4.68 ( s, 2H), 3.76 (s, 2H), 3.36 (s, 3H), 3.00 (t, 2H), 2.66 (t, 2H)

Example 53. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 31 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 1-ethylpyrazole instead of 4-(methanesulfonyl)phenylboronic acid 24 mg (yield: 59.3%) of the title compound was prepared in the same manner as in Example 17, except that 30 mg of -4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.81 (s, 1H), 8.32 (s, 1H), 8.09 (s, 1H), 8.02 (d, 1H), 7.89 (t, 1H), 7.58 (d, 1H), 4.66(s, 3H), 4.25(q, 2H), 3.75(s, 2H), 1.51(t, 3H)

Example 54. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4 -Triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 34 mg of the title compound in the same manner as in Example 17 above, except that 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Yield: 72.0 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.68 (s, 1H), 8.58 (d, 2H), 8.12 (d, 2H), 8.04 (d, 2H), 7.72 (s, 1H), 4.66 (s, 2H), 3.66(s, 2H), 3.20(s, 3H)

Example 55. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate and tert-butyl 4- instead of 4-(methanesulfonyl)phenylboronic acid [4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate The title compound was prepared in the same manner as in Example 17, except that 52 mg was used. 25 mg (yield: 52.2%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.65 (s, 1H), 8.47 (d, 2H), 7.76 (d, 2H), 7.62 (s, 1H), 7.16 (d, 2H), 4.67 (s, 2H), 3.67 (s, 2H), 3.51 (d, 4H), 3.36 (d, 4H)

Example 56. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used instead of 4-(methanesulfonyl)phenylboronic acid 2-(trifluoro 29 mg (yield: 62.8%) of the title compound was prepared in the same manner as in Example 17, except that 31 mg of chloromethylpyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.11(s, 1H), 8.68(s, 1H), 8.59(s, 2H), 8.42(d, 1H), 7.99(d, 1H), 7.75(d, 1H), 4.67(s, 2H), 3.63(s, 2H)

Example 57. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl] -1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-(dimethyl) instead of 4-(methanesulfonyl)phenylboronic acid. 30 mg (yield: 69.1%) of the title compound was prepared in the same manner as in Example 17, except that 28 mg of amino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.68 (s, 1H), 8.52 (s, 1H), 8.46 (d, 2H), 8.25 (d, 1H), 7.65 (s, 1H), 7.19 (d, 1H), 4.69(s, 2H), 3.76(s, 2H), 3.31(s, 3H)

Example 58. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(1, instead of 4-(methanesulfonyl)phenylboronic acid 3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 28 mg of the title compound in the same manner as in Example 17, except that 28 mg was used. 26 mg (yield: 59.9%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.63 (s, 1H), 8.42 (d, 2H), 7.56 (s, 1H), 7.32-7.28 (m, 2H), 6.97 (d, 1H), 6.06 ( s, 2H), 4.66 (s, 2H), 3.54 (s, 2H)

Example 59. 6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-4 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 8-methyl-2 instead of 4-(methanesulfonyl)phenylboronic acid -25 mg (yield: 52.3%) of the title compound in the same manner as in Example 17, except that 33 mg of oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.61(s, 1H), 8.44(d, 2H), 7.60(d, 1H), 7.50(d, 2H), 4.64(s, 2H), 3.36(s, 2H), 3.04 (d, 2H), 2.62 (d, 2H)

Example 60. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(4-bromo-2-pyridyl)-5-oxo-prepared in Reference Example 32 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 1-ethylpyrazole instead of 4-(methanesulfonyl)phenylboronic acid 24 mg (yield: 59.3%) of the title compound was prepared in the same manner as in Example 17, except that 26 mg of -4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.62(s, 1H), 8.37-8.29(m, 3H), 8.02(s, 1H), 7.53(s, 1H), 4.68(s, 2H), 4.26( q, 2H), 3.76 (s, 2H), 1.52 (t, 3H)

Example 61. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4 -Triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 45 mg of the title compound in the same manner as in Example 17, except that 100 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Yield: 47.7%).

¹ H-NMR (MeOD, 400 MHz) δ 8.78(s, 1H), 8.63(s, 1H), 8.41(s, 1H), 8.29(s, 1H), 8.07(d, 2H), 7.91(s, 1H), 4.68(s, 2H), 3.76(s, 2H), 3.18(s, 3H)

Example 62. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate and tert-butyl 4- instead of 4-(methanesulfonyl)phenylboronic acid [4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate The title compound was obtained in the same manner as in Example 17, except that 87 mg was used. 50 mg (Yield: 52.2%) were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.67 (d, 1H), 8.61 (s, 1H), 8.27 (s, 2H), 7.99 (d, 2H), 7.75 (d, 1H), 7.16 (d, 2H), 4.68(s, 2H), 3.75(s, 2H), 3.55(t, 4H), 3.40(t, 4H)

Example 63. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl] -1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 6-(dimethyl) instead of 4-(methanesulfonyl)phenylboronic acid. 40 mg (yield: 46.1%) of the title compound was prepared in the same manner as in Example 17, except that 56 mg of amino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.75 (d, 1H), 8.65 (d, 3H), 8.34 (s, 1H), 7.90 (d, 1H), 7.36 (d, 1H), 4.68 (s, 2H), 3.76(s, 2H), 3.37(s, 6H)

Example 64. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(1, instead of 4-(methanesulfonyl)phenylboronic acid. 3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 67 mg of the title compound in the same manner as in Example 17, except that 67 mg was used. 38 mg (Yield: 43.8%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.63 (d, 1H), 8.59 (s, 1H), 8.19 (s, 1H), 7.78 (d, 1H), 7.52 (d, 1H), 7.49 (s, 1H), 6.93(d, 1H), 4.67(s, 2H), 3.75(s, 2H)

Example 65. 6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 8-methyl-2 instead of 4-(methanesulfonyl)phenylboronic acid -Oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester 64 mg (yield: 44.0%) of the title compound in the same manner as in Example 17, except that 64 mg was used. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.66 (d, 1H), 8.64 (s, 1H), 8.27 (s, 1H), 7.82 (d, 1H), 7.71 (s, 2H), 3.03 (t, 2H), 2.61(t, 2H), 2.29(s, 3H)

Example 66. 6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, (1-methyl- 46 mg of the title compound in the same manner as in Example 17, except that 64 mg of 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used (yield: 48.2 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.76 (d, 1H), 8.74 (s, 1H), 8.52 (s, 1H), 8.13 (s, 1H), 7.95 (d, 1H), 7.90 (s, 1H), 7.32(d, 1H), 4.69(s, 2H), 3.76(s, 2H), 3.41(s, 3H), 3.05(t, 2H), 2.70(t, 2H)

Example 67. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(2-bromo-4-pyridyl)-5-oxo-prepared in Reference Example 33 instead of methyl]-3,3-difluoro-allyl]carbamate 100 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 1-ethylpyrazole instead of 4-(methanesulfonyl)phenylboronic acid 42 mg (yield: 51.9%) of the title compound was prepared in the same manner as in Example 17, except that 50 mg of -4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.60(s, 1H), 8.58(d, 1H), 8.28(s, 1H), 8.10(d, 2H), 7.76(d, 1H), 4.67(s, 2H), 4.26(q, 2H), 3.75(s, 2H), 1.52(t, 3H)

Example 68. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1 ,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- Title was the same as in Example 17, except that 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Compound 38 mg (yield: 80.1 %) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.74(s, 1H), 8.25(s, 1H), 8.21(s, 1H), 8.09(d, 2H), 7.99(d, 2H), 4.69(s, 2H), 3.77(s, 2H), 3.19(s, 3H), 2.45(s, 3H)

Example 69. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and turt was substituted for 4-(methanesulfonyl)phenylboronic acid -Butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate Same as Example 17, except that 51 mg was used 39 mg (yield: 81.0 %) of the title compound were prepared by the method.

¹ H-NMR (MeOD, 400 MHz) δ 8.63(s, 1H), 8.16(s, 1H), 8.11(s, 1H), 7.68(d, 2H), 7.17(d, 2H), 4.68(s, 2H), 3.73(s, 2H), 3.51(s, 4H), 3.40(s, 4H), 2.40(s, 3H)

Example 70. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]- 2-pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 2 instead of 4-(methanesulfonyl)phenylboronic acid -(Trifluoromethyl) pyridine-5-boronic acid pinacol ester was prepared in the same manner as in Example 17, except that 25 mg of the title compound 35 mg (yield: 75.3%).

¹ H-NMR (MeOD, 400 MHz) δ 9.09 (s, 1H), 8.80 (s, 1H), 8.41 (d, 1H), 8.32 (s, 1H), 8.22 (s, 1H), 7.98 (d, 1H), 4.69(s, 2H), 3.77(s, 2H), 2.47(s, 3H)

Example 71. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2 -Pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, 6 30 mg (yield: 68.6%) of the title compound was prepared in the same manner as in Example 17, except that 32 mg of -(dimethylamino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.68 (s, 1H), 8.35 (s, 1H), 8.24 (d, 1H), 8.18 (s, 2H), 7.21 (d, 1H), 4.68 (s, 2H), 3.76(s, 2H), 3.31(s, 6H), 2.43(s, 3H)

Example 72. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2- Pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 3 instead of 4-(methanesulfonyl)phenylboronic acid 32 mg (yield: 73.1 %) of the title compound was prepared in the same manner as in Example 17, except that 22 mg of 4-(methylenedioxy)phenyl boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.59 (s, 1H), 8.16 (s, 1H), 8.07 (s, 1H), 7.21 (s, 1H), 7.20 (d, 1H), 6.96 (d, 1H), 6.03(s, 2H), 4.68(s, 2H), 3.76(s, 2H), 2.40(s, 3H)

Example 73. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5 -Methyl-3-pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 8 instead of 4-(methanesulfonyl)phenylboronic acid -Methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester 40 mg of the title compound in the same manner as in Example 17, except that 37 mg (yield: 83.3%).

¹ H-NMR (MeOD, 400 MHz) δ 8.54(s, 1H), 8.16(s, 1H), 8.06(s, 1H), 7.36(d, 2H), 4.70(s, 2H), 3.78(s, 2H), 3.01(t, 2H), 2.59(t, 2H), 2.40(s, 3H), 2.29(s, 3H)

Example 74. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5 -Methyl-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid ( 42 mg of the title compound in the same manner as in Example 17, except that 37 mg of 1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used. (Yield: 87.5%).

¹ H-NMR (MeOD, 400 MHz) δ 8.65 (s, 1H), 8.16 (d, 2H), 7.64 (d, 1H), 7.60 (s, 1H), 7.25 (d, 1H), 4.69 (s, 2H), 3.77(s, 2H), 3.39(s, 3H), 3.01(t, 2H), 2.67(t, 2H), 2.42(s, 3H)

Example 75. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-methyl-2-pyridyl)- prepared in Reference Example 34 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid 1 32 mg (yield: 78.2%) of the title compound was prepared in the same manner as in Example 17, except that 29 mg of ethyl pyrazole-4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.63(s, 1H), 8.23(s, 1H), 8.15(s, 1H), 8.09(s, 1H), 7.99(s, 1H), 4.68(s, 2H), 4.25(q, 2H), 3.75(s, 2H), 2.36(s, 3H), 1.51(t, 3H)

Example 76. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1 ,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- Title was the same as in Example 17, except that 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. 25 mg (yield: 52.3%) of compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.87 (s, 1H), 8.43 (s, 1H), 8.15-8.08 (m, 3H), 7.81 (d, 2H), 4.69 (s, 2H), 3.77 ( s, 2H), 3.20 (s, 3H), 2.44 (s, 3H)

Example 77. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]- 3-pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 2 instead of 4-(methanesulfonyl)phenylboronic acid 17 mg (yield: 35.8%) of the title compound was prepared in the same manner as in Example 17, except that 30 mg of -(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.93 (s, 2H), 8.45 (s, 1H), 8.27 (s, 1H), 8.19 (s, 1H), 7.97 (s, 1H), 4.68 (s, 2H), 3.77(s, 2H), 2.49(s, 3H)

Example 78. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3 -Pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, 6 19 mg (yield: 44.0%) of the title compound was prepared in the same manner as in Example 17, except that 27 mg of -(dimethylamino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.83(s, 1H), 8.40(s, 1H), 8.23(s, 1H), 8.10(s, 1H), 8.02(s, 1H), 7.06(s, 1H), 4.68(s, 2H), 3.76(s, 2H), 3.26(s, 6H), 2.50(s, 3H)

Example 79. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3- Pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 2 instead of 4-(methanesulfonyl)phenylboronic acid -(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 27 mg, except that 27 mg was used. 26 mg (yield: 59.6%) of the title compound were prepared by the method.

¹ H-NMR (MeOD, 400 MHz) δ 8.76 (s, 1H), 8.39 (s, 1H), 8.07 (s, 1H), 7.01-6.96 (m, 3H), 6.04 (s, 2H), 4.67 ( s, 2H), 3.76 (s, 2H), 2.43 (s, 3H)

Example 80. 6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3 -Methyl-2-pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 8 instead of 4-(methanesulfonyl)phenylboronic acid -Methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester 17 mg of the title compound in the same manner as in Example 17, except that 32 mg (yield: 35.8%).

¹ H-NMR (MeOD, 400 MHz) δ 8.77(s, 1H), 8.40(s, 1H), 8.07(s, 1H), 7.23(s, 2H), 4.68(s, 2H), 3.77(s, 2H), 3.02(t, 2H), 2.62(t, 2H), 2.44(s, 3H), 2.34(s, 3H)

Example 81. 6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3 -Methyl-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(6-bromo-5-methyl-3-pyridyl)- prepared in Reference Example 36 instead of methyl]-3,3-difluoro-allyl]carbamate- 50 mg of 5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid ( 22 mg of the title compound in the same manner as in Example 17, except that 32 mg of 1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used. (Yield: 46.8%).

¹ H-NMR (MeOD, 400 MHz) δ 8.80(s, 1H), 8.41(s, 1H), 8.09(s, 1H), 7.46(d, 1H), 7.42(s, 1H), 7.25(d, 1H), 4.68(s, 2H), 3.77(s, 2H), 3.42(s, 3H), 3.01(t, 2H), 2.69(t, 2H), 2.45(s, 3H)

Example 82. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate In the same manner as in Example 17, except that 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. 23 mg (yield: 48.1 %) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.77(s, 1H), 8.31(s, 1H), 8.28(s, 1H), 8.11(d, 2H), 8.02(d, 2H), 4.69(s, 2H), 3.77(s, 2H), 3.19(s, 3H)

Example 83. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyri Dill]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid Example 17 and above, except that 42 mg of tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate was used. 18 mg (yield: 38.9%) of the title compound were prepared by the same method.

¹ H-NMR (MeOD, 400 MHz) δ 8.67 (s, 1H), 8.24 (s, 1H), 8.12 (d, 1H), 7.72 (d, 2H), 7.18 (d, 2H), 4.68 (s, 2H), 3.76(s, 2H), 3.54(t, 4H), 3.41(t, 4H)

Example 84. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl] -2-pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid 21 mg (yield: 44.4%) of the title compound was prepared in the same manner as in Example 17, except that 29 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.13(s, 1H), 8.83(s, 1H), 8.44(d, 2H), 8.29(s, 1H), 8.00(s, 1H), 4.69(s, 2H), 3.77(s, 2H)

Example 85. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2 -Pyridyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid Example 17 and above, except that 27 mg of 2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan was used. 32 mg (yield: 74.1 %) of the title compound were prepared in the same manner.

¹ H-NMR (MeOD, 400 MHz) δ 8.60(s, 1H), 8.22(s, 1H), 8.07(d, 1H), 7.24(s, 1H), 7.22(s, 1H), 6.96(d, 1H), 6.04(s, 2H), 4.68(s, 2H), 3.74(s, 2H)

Example 86. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5 -Fluoro-3-pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid 17 mg (yield) of the title compound in the same manner as in Example 17, except that 31 mg of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used. : 35.2 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.58 (s, 1H), 8.23 (s, 1H), 8.07 (d, 1H), 7.41 (s, 1H), 4.69 (s, 2H), 3.78 (s, 2H), 3.01(t, 2H), 2.59(t, 2H), 2.31(s, 3H)

Example 87. 6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5 -Fluoro-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) boronic acid pinacol ester 31 mg in the same manner as in Example 17, except that 31 mg was used. mg (yield: 38.9%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.68 (s, 1H), 8.25 (s, 1H), 8.17 (d, 1H), 7.68 (d, 1H), 7.64 (s, 1H), 7.27 (d, 1H), 4.68(s, 2H), 3.77(s, 2H), 3.39(s, 3H), 3.02(t, 2H), 2.66(t, 2H)

Example 88. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyri Dill]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromo-3-fluoro-2-pyridyl) prepared in Reference Example 37 instead of methyl]-3,3-difluoro-allyl]carbamate 50 mg of -5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid 18 mg (yield: 45.4%) of the title compound was prepared in the same manner as in Example 17, except that 37 mg of 1-ethylpyrazole-4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.65(s, 1H), 8.28(s, 1H), 8.21(s, 1H), 8.10(d, 1H), 8.03(s, 1H), 4.67(s, 2H), 4.26(q, 2H), 3.75(s, 2H), 1.50(t, 3H)

Example 89. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2, 4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 38 mg of the title compound in the same manner as in Example 17, except that 70 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. Yield: 57.3%).

¹ H-NMR (MeOD, 400 MHz) δ 9.53 (s, 1H), 9.04 (s, 1H), 8.63 (s, 1H), 8.30 (d, 2H), 8.03 (d, 2H), 4.69 (s, 2H), 3.78(s, 2H), 3.17(s, 3H)

Example 90. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl) prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and tert-butyl 4- instead of 4-(methanesulfonyl)phenylboronic acid [4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate The title compound was prepared in the same manner as in Example 17, except that 61 mg was used. 30 mg (Yield: 44.6%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 9.45 (s, 1H), 8.98 (s, 1H), 8.63 (s, 1H), 8.07 (d, 2H), 7.18 (d, 2H), 4.68 (s, 2H), 3.76(s, 2H), 3.56(t, 4H), 3.41(t, 4H)

Example 91. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl ]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 2-(trifluoro) instead of 4-(methanesulfonyl)phenylboronic acid 32 mg (yield: 49.3%) of the title compound was prepared in the same manner as in Example 17, except that 43 mg of chloromethyl)pyridine-5-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.64 (s, 1H), 9.43 (s, 1H), 9.20 (s, 1H), 8.75 (d, 1H), 8.68 (s, 2H), 7.98 (d, 1H), 4.69(s, 2H), 3.78(s, 2H)

Example 92. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl] -1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used and 6-(dimethyl) instead of 4-(methanesulfonyl)phenylboronic acid 29 mg (yield: 47.6%) of the title compound was prepared in the same manner as in Example 17, except that 39 mg of amino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.48 (s, 1H), 8.97 (s, 1H), 8.76 (s, 1H), 8.63 (s, 1H), 8.44 (d, 1H), 7.05 (d, 1H), 4.68(s, 2H), 3.76(s, 2H), 3.32(s, 6H)

Example 93. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]- 1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 2-(1, instead of 4-(methanesulfonyl)phenylboronic acid. 3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan 39 mg in the same manner as in Example 17, except that 39 mg was used. 35 mg (Yield: 57.4%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 9.44 (s, 1H), 8.91 (s, 1H), 8.61 (s, 1H), 7.64 (d, 1H), 7.60 (s, 1H), 6.96 (d, 1H), 6.05(s, 2H), 4.67(s, 2H), 3.69(s, 2H)

Example 94. 6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]pyrazine- 2-yl]-1-methyl-3,4-dihydro-1 H -quinolin-2-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and instead of 4-(methanesulfonyl)phenylboronic acid, (1-methyl- 2-Oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester 41 mg (yield: 61.1 in the same manner as in Example 17, except that 45 mg was used) %).

¹ H-NMR (MeOD, 400 MHz) δ 9.47 (s, 1H), 8.98 (s, 1H), 8.64 (s, 1H), 8.03 (d, 1H), 7.99 (s, 1H), 7.25 (d, 1H), 4.68(s, 2H), 3.77(s, 2H), 3.39(s, 3H), 3.03(t. 2H), 2.68(t, 2H)

Example 95. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1, 2,4-triazole-3-one

Tert-butyl N -[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazole-1-yl] prepared in Reference Example 25 in Step 1 of Example 17] Tert-butyl N -[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-prepared in Reference Example 39 instead of methyl]-3,3-difluoro-allyl]carbamate 70 mg of 1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 1-ethylpyrazole instead of 4-(methanesulfonyl)phenylboronic acid 39 mg (yield: 68.6 %) of the title compound was prepared in the same manner as in Example 17, except that 35 mg of -4-boronic acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 9.37 (s, 1H), 8.79 (s, 1H), 8.60 (s, 1H), 8.34 (s, 1H), 8.12 (s, 1H), 4.67 (s, 1H), 4.27(q, 2H), 3.92(s, 2H), 1.52(t, 3H)

Example 96. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-[(4-benzyloxyphenyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3 prepared in Reference Example 40 17 mg (yield: 8.5%) of a colorless liquid title compound was prepared in the same manner as in Example 1, except that 126 mg of 3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.88 (s, 1H), 7.41-7.36 (m, 4H), 7.29 (d, 3H), 6.99 (d, 2H), 5.08 (s, 2H), 4.79 ( s, 2H), 4.57 (s, 2H), 3.66 (s, 2H)

Example 97. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 41] 92 mg (yield: 100%) of the title compound was prepared in the same manner as in Example 1, except that 116 mg of methyl]-3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.96 (s, 1H), 6.98 (d, 2H), 5.00 (s, 2H), 4.58 (s, 2H), 3.67 (s, 2H)

Example 98. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-tri Azole-3-one

Tert-butyl N- [2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 42] 34 mg (yield: 76.0%) of the title compound was prepared in the same manner as in Example 1, except that 57 mg of methyl]-3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.40 (s, 1H), 7.12 (s, 1H), 5.04 (s, 2H), 4.57 (s, 2H), 3.66 (s, 2H)

Example 99. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2 ,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazole prepared in Reference Example 43- 16 mg (yield: 3.7%) of the title compound was prepared in the same manner as in Example 1, except that 546 mg of 1-yl]methyl]-3,3-difluoro-allyl]carbamate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.90(s, 1H), 6.90(s, 1H), 4.94(s, 2H), 4.57(s, 2H), 3.67(s, 2H), 2.27(s, 3H)

Example 100. 4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2 ,4-triazole-3-one

Step 1: Tert-butyl N- [2-[[4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-5-oxo-1,2,4-triazole-1- Work]methyl]-3,3-difluoro-allyl]carbamate

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 41] Dissolve 80 mg of methyl]-3,3-difluoro-allyl]carbamate and 28 mg of 4-acetylphenylboronic acid in 1.6 mL of 1,4-dioxane, 0.9 mL of 1 M potassium carbonate and palladium di[1,1 7 mg of'-bis(diphenylphosphino)ferrocene]dichloride (PdCl ₂ (dppf)) was added and stirred at 90°C overnight. The reaction mixture was filtered through a pad of celite, and the residue obtained by concentration under reduced pressure was dissolved in ethyl acetate, washed with distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 1/1) to prepare 47 mg (yield: 54.2 %) of the title compound.

MS (ESI) m/z= 405.2 (M + H)+

Step 2: 4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2, 4-triazole-3-one

Tert-butyl N- [2-[[4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-5-oxo-1,2,4-triazole prepared in Step 1- 47 mg of 1-yl]methyl]-3,3-difluoro-allyl]carbamate was dissolved in 1.0 mL of dichloromethane, 0.1 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 4 mg (yield: 12.0%) of the title compound as a white solid.

¹ H-NMR (MeOD, 400 MHz) δ 8.00(s, 1H), 7.99(d, 2H), 7.72(d, 2H), 7.43(s, 1H), 7.18(s, 1H), 5.09(s, 2H), 4.60(s, 2H), 3.69(s, 2H), 2.60(s, 3H)

Example 101. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one

42 mg of the title compound in the same manner as in Example 100, except that 26 mg of 4-(methanesulfonyl)phenylboronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 82.2%) ).

¹ H-NMR (MeOD, 400 MHz) δ 8.01(s, 1H), 7.94(d, 2H), 7.84(d, 2H), 7.48(s, 1H), 7.19(s, 1H), 5.10(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.14(s, 3H)

Example 102. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methylsulfonylphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one

8 mg of the title compound in the same manner as in Example 100, except that 34 mg of 3-(methanesulfonyl)phenylboronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 11.0%) ).

¹ H-NMR (MeOD, 400 MHz) δ 8.11(s, 1H), 8.00(s, 1H), 7.92-7.86(m, 2H), 7.64(t, 1H), 7.42(s, 1H), 7.17( s, 1H), 5.09(s, 2H), 4.60(s, 2H), 3.69(s, 2H), 3.17(s, 3H)

Example 103. 3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl ]-2-thienyl]- N,N -dimethyl-benzenesulfonamide

In the same manner as in Example 100, except that in step 1 of Example 100 , 54 mg of 3-( N,N -dimethylaminosulfonyl)phenylboronic acid pinacol ester was used instead of 4-acetylphenylboronic acid. 16 mg (yield: 17.6%) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.00(s, 1H), 7.92(s, 2H), 7.72-7.63(m, 2H), 7.42(s, 1H), 7.19(s, 1H), 5.10( s, 2H), 4.60 (s, 2H), 3.68 (s, 2H), 2.72 (s, 6H)

Example 104. 4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl ]-2-thienyl] -N -methyl-benzamide

22 mg of the title compound in the same manner as in Example 100, except that 36 mg of (4-(methylcarbamoyl)phenyl)boronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 29.4%).

¹ H-NMR (MeOD, 400 MHz) δ 8.00(s, 1H), 7.83(d, 2H), 7.69(d, 2H), 7.39(s, 1H), 7.16(s, 1H), 5.08(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 2.93(s, 3H)

Example 105. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl] Methyl]-1,2,4-triazole-3-one

22 mg of the title compound in the same manner as in Example 100, except that 23 mg of 3,4,5-trimethoxyphenylboronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 45.4%).

¹ H-NMR (MeOD, 400 MHz) δ 7.98(s, 1H), 7.24(s, 1H), 7.12(s, 1H), 6.85(s, 2H), 5.05(s, 2H), 4.59(s, 2H), 3.88(s, 6H), 3.78(s, 3H), 3.67(s, 2H)

Example 106. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

Tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate instead of 4-acetylphenylboronic acid in step 1 of Example 100 40 mg (yield: 81.8 %) of the title compound was prepared in the same manner as in Example 100, except that 50 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.52 (d, 2H), 7.15 (s, 1H), 7.09 (s, 1H), 7.03 (d, 2H), 5.04 (s, 2H), 4.59(s, 2H), 3.66(s, 2H), 3.45(s, 4H), 3.38(s, 4H)

Example 107. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

Tert-butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) instead of 4-acetylphenylboronic acid in step 1 of Example 100) 11 mg (yield: 18.2%) of the title compound was prepared in the same manner as in Example 100, except that 51 mg of piperazine-1-carboxylate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.33-7.29 (m, 2H), 7.22 (s, 1H), 7.18-7.13 (m, 2H), 6.99 (d, 1H), 5.06(s, 2H), 4.59(s, 2H), 3.64(s, 2H), 3.45(t, 4H), 3.38(t, 4H)

Example 108. 4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3- Difluoro-allyl]-1,2,4-triazole-3-one

In the same manner as in Example 100, except that 923 mg of 4-(4-acetyl-1-piperazinyl)phenylboronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100. 695 mg (yield: 66.0 %) of the title compound were prepared.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.49 (d, 2H), 7.14 (d, 1H), 7.09 (d, 1H), 7.00 (d, 2H), 5.03 (s, 2H), 4.59(s, 2H), 3.74(t, 2H), 3.71(t, 2H), 3.66(s, 2H), 3.26(t, 2H), 3.21(t, 2H), 2.16(s, 3H) )

Example 109. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl ]Methyl]-1,2,4-triazole-3-one

The title compound was obtained in the same manner as in Example 100, except that in step 1 of Example 100, 54 mg of 4-(morpholine-4-carbonyl)phenylboronic acid pinacol ester was used instead of 4-acetylphenylboronic acid. 23 mg (yield: 29.4%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.00(s, 1H), 7.71(d, 2H), 7.47(d, 2H), 7.38(s, 1H), 7.16(s, 1H), 5.08(s, 2H), 4.59(s, 2H), 3.75-3.50(m, 8H), 3.68(s, 2H)

Example 110. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1 H -pyrazol-3-yl)phenyl]-2- Cyenyl]methyl]-1,2,4-triazole-3-one

It was titled in the same manner as in Example 100, except that 32 mg of [3-(1 H -pyrazol-3-yl)phenyl]boronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100. Compound 6 mg (yield: 5.9%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.04 (s, 1H), 8.00 (s, 1H), 7.70 (s, 2H), 7.56 (d, 1H), 7.46 (t, 1H), 7.37 (s, 1H), 7.17(s, 1H), 6.73(s, 1H), 5.09(s, 2H), 4.60(s, 2H), 3.65(s, 2H)

Example 111. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-cy Enyl]methyl]-1,2,4-triazole-3-one

The title compound was obtained in the same manner as in Example 100, except that in step 1 of Example 100, 25 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid. 7 mg (Yield: 9.1%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.97 (s, 1H), 8.24 (d, 1H), 8.02 (s, 1H), 7.84 (d, 1H), 7.57 (s, 1H), 7.24 (s, 1H), 5.12(s, 2H), 4.59(s, 2H), 3.67(s, 2H)

Example 112. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thier Neil]methyl]-1,2,4-triazole-3-one

45 mg (yield) of the title compound in the same manner as in Example 100, except that 32 mg of 6-(dimethylamino)pyridine-3-boronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100. : 100%).

¹ H-NMR (MeOD, 400 MHz) δ 8.11(d, 2H), 7.99(s, 1H), 7.28(s, 1H), 7.17(s, 2H), 5.08(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.28(s, 6H)

Example 113. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

40 mg of 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine instead of 4-acetylphenylboronic acid in step 1 of Example 100 29 mg (yield: 41.2%) of the title compound was prepared in the same manner as in Example 100, except that was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.34 (s, 1H), 7.99 (s, 1H), 7.88 (d, 1H), 7.21 (s, 1H), 7.14 (s, 1H), 6.83 (d, 1H), 5.06(s, 2H), 4.59(s, 2H), 3.93(s, 3H), 3.68(s, 2H)

Example 114. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-cy Enyl]methyl]-1,2,4-triazole-3-one

Tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 instead of 4-acetylphenylboronic acid in step 1 of Example 100 -Pyridyl] piperazine-1-carboxylate 35 mg (yield: 72.7%) of the title compound was prepared in the same manner as in Example 100, except that 54 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.41(s, 1H), 7.98(s, 1H), 7.83(d, 1H), 7.15(d, 2H), 6.96(d, 1H), 5.06(s, 2H), 4.59(s, 2H), 3.85(s, 4H), 3.68(s, 2H), 3.32(s, 4H)

Example 115. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl] -2-thienyl]methyl]-1,2,4-triazole-3-one

3-fluoro- N,N -dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- in place of 4-acetylphenylboronic acid in step 1 of Example 100- 2-yl) 26 mg (yield: 35.3%) of the title compound was prepared by the same method as Example 100, except that 46 mg of pyridin-2-amine was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.13 (s, 1H), 7.98 (s, 1H), 7.54 (d, 1H), 7.17 (s, 1H), 7.11 (s, 1H), 5.05 (s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.11(s, 6H)

Example 116. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

The same as in Example 100, except that in step 1 of Example 100, 55 mg of 2-(tert-butoxycarbonylamino)pyrimidine-5-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid. By the method, 25 mg (yield: 41.2 %) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.47 (s, 2H), 7.98 (s, 1H), 7.15 (d, 2H), 5.06 (s, 2H), 4.59 (s, 2H), 3.66 (s, 2H)

Example 117. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl] Methyl]-1,2,4-triazole-3-one

21 mg of the title compound in the same manner as in Example 100, except that 29 mg of 2-ethoxypyrimidine-5-boronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 29.4 %).

¹ H-NMR (MeOD, 400 MHz) δ 8.76 (s, 2H), 8.00 (s, 1H), 7.33 (s, 1H), 7.19 (s, 1H), 5.09 (s, 2H), 4.59 (s, 2H), 4.48 (q, 2H), 3.68 (s, 2H), 1.42 (t, 3H)

Example 118. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]- 2-thienyl]methyl]-1,2,4-triazole-3-one

N- (2-methoxyethyl)-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine instead of 4-acetylphenylboronic acid in step 1 of Example 100 21 mg (yield: 43.6%) of the title compound was prepared in the same manner as in Example 100, except that 30 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.49 (s, 2H), 7.94 (s, 1H), 7.14 (d, 1H), 5.50 (s, 4H), 5.05 (s, 2H), 4.55 (s, 2H), 3.38-3.28 (m, 7H)

Example 119. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

48 mg (yield) of the title compound in the same manner as in Example 100, except that 62 mg of 1-ethylpyrazole-4-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100. : 51.6 %).

¹ H-NMR (MeOD, 400 MHz) δ 7.96 (s, 1H), 7.89 (s, 1H), 7.66 (s, 1H), 7.06 (s, 1H), 7.01 (s, 1H), 5.02 (s, 2H), 4.58(s, 2H), 4.18(q, 2H), 3.67(s, 2H), 1.47(t, 3H)

Example 120. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2- Cyenyl]methyl]-1,2,4-triazole-3-one

2-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) instead of 4-acetylphenylboronic acid in step 1 of Example 100 17 mg (yield: 24.9 %) of the title compound was prepared in the same manner as in Example 100, except that 42 mg of -1 H -imidazole was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.20 (S, 1H), 7.14 (d, 1H), 7.05 (s, 1H), 5.09 (s, 2H), 4.57 (s, 2H), 3.68(s, 2H), 3.65(s, 3H)

Example 121. 5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl ]-2-thienyl]-1-methyl-pyridin-2-one

1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1 H instead of 4-acetylphenylboronic acid in step 1 of Example 100 -The title compound 8 mg (yield: 11.8%) was prepared in the same manner as in Example 100, except that 40 mg of pyridin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 2H), 7.77 (d, 1H), 7.12 (d, 2H), 6.58 (d, 1H), 5.04 (s, 2H), 4.59 (s, 2H), 3.68(s, 2H), 3.60(s, 3H)

Example 122. 5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl ]-2-thienyl]-1-ethyl-pyridin-2-one

Example 100, except that 70 mg of 1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in step 1 of Example 100 46 mg (yield: 52.4 %) of the title compound was prepared in the same manner as.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 2H), 7.77 (d, 1H), 7.13 (d, 2H), 6.59 (d, 1H), 5.05 (s, 2H), 4.59 (s, 2H), 4.08 (q, 2H), 3.68 (s, 2H), 1.36 (t, 3H)

Example 123. 5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-1-isopropyl-pyridin-2-one

Example 1 except that 27 mg of 1-isopropyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in step 1 of Example 100. In the same manner as 100, 14 mg (yield: 33.3%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.86 (s, 1H), 7.74 (d, 1H), 7.15 (d, 2H), 6.60 (d, 1H), 5.20 (m, 1H), 5.06(s, 2H), 4.59(s, 2H), 3.67(s, 2H), 1.44(d, 6H)

Example 124. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro- 2H -pyridin-4- Sun)-2-thienyl]methyl]-1,2,4-triazole-3-one

1-methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine instead of 4-acetylphenylboronic acid in step 1 of Example 100 14 mg (yield: 27.3%) of the title compound was prepared in the same manner as in Example 100, except that 31 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.95 (s, 1H), 7.06 (s, 2H), 6.08 (s, 1H), 5.02 (s, 2H), 4.58 (s, 2H), 3.85 (s, 2H), 3.67(s, 2H), 3.59(s, 2H), 2.96(s, 3H), 2.86(s, 2H)

Example 125. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro- 2H -pyridin-4- Sun)-2-thienyl]methyl]-1,2,4-triazole-3-one

1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6- instead of 4-acetylphenylboronic acid in step 1 of Example 100 11 mg (yield: 18.2%) of the title compound was prepared in the same manner as in Example 100, except that 35 mg of dihydropyridin-1(2 H )-yl)ethanone was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.94 (s, 1H), 7.03 (s, 1H), 6.95 (d, 1H), 6.09 (s, 1H), 5.00 (s, 2H), 4.58 (s, 2H), 4.16(d, 2H), 3.75(d, 2H), 3.66(s, 2H), 2.56(d, 2H), 2.15(s, 3H)

Example 126. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl ]Methyl]-1,2,4-triazole-3-one

42 mg of the title compound in the same manner as in Example 100, except that 21 mg of 3,4-(methylenedioxy)phenyl boronic acid was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100 (yield: 90.9%).

¹ H-NMR (MeOD, 400 MHz) δ 7.96 (s, 1H), 7.11 (s, 1H), 7.06 (s, 3H), 6.81 (d, 1H), 5.97 (s, 2H), 5.02 (s, 2H), 4.58(s, 2H), 3.67(s, 2H)

Example 127. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1 H -indazol-6-yl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

27 mg (yield) of the title compound in the same manner as in Example 100, except that 34 mg of 1 H -indazole-6-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in Step 1 of Example 100. : 63.6%).

¹ H-NMR (MeOD, 400 MHz) δ 8.02 (d, 2H), 7.78 (d, 1H), 7.73 (s, 1H), 7.42 (d, 1H), 7.36 (s, 1H), 7.16 (s, 1H), 5.08(s, 2H), 4.60(s, 2H), 3.68(s, 2H)

Example 128. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazole[1,5-a]pyridine- 7-day)-2-thienyl]methyl]-1,2,4-triazole-3-one

7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-[1,2,4 instead of 4-acetylphenylboronic acid in step 1 of Example 100 ] Triazolo[1,5-a] 40 mg (yield: 90.9%) of the title compound was prepared in the same manner as in Example 100, except that 34 mg of pyridine was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.74 (d, 1H), 8.40 (s, 1H), 8.03 (s, 1H), 7.87 (s, 1H), 7.57 (s, 1H), 7.47 (d, 1H), 7.21(s, 1H), 5.12(s, 2H), 4.60(s, 2H), 3.69(s, 2H)

Example 129. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2- Cyenyl]methyl]-1,2,4-triazole-3-one

With the exception of using 26 mg of benzo[c][1,2,5]oxadiazole-5-boronic acid pinacol ester in step 1 of Example 100 instead of 4-acetylphenylboronic acid, Example 100 and In the same manner, 34 mg (yield: 72.7%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.02 (d, 2H), 7.94 (d, 1H), 7.86 (d, 1H), 7.57 (d, 1H), 7.21 (d, 1H), 5.12 (s, 2H), 4.60(s, 2H), 3.67(s, 2H)

Example 130. 5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl ]-2-thienyl]-7-fluoro-indolin-2-one

7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline instead of 4-acetylphenylboronic acid in step 1 of Example 100- 14 mg (yield: 27.3%) of the title compound was prepared in the same manner as in Example 100, except that 39 mg of 2-on was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.35 (s, 1H), 7.29 (d, 1H), 7.22 (s, 1H), 7.11 (s, 1H), 5.05 (s, 2H), 4.58(s, 2H), 3.65(d, 2H), 3.59(s, 2H)

Example 131. N- [6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- 1]methyl]-2-thienyl]-1,3-benzothiazol-2-yl]acetamide

N- (6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thi in place of 4-acetylphenylboronic acid in step 1 of Example 100 28 mg (yield: 54.5 %) of the title compound was prepared in the same manner as in Example 100, except that 44 mg of azole-2-yl)acetamide was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.07 (s, 1H), 8.00 (s, 1H), 7.71 (d, 1H), 7.64 (d, 1H), 7.30 (d, 1H), 7.14 (d, 1H), 5.07(s, 2H), 4.60(s, 2H), 3.68(s, 2H), 2.27(s, 3H)

Example 132. 7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-3,4-dihydro- 2H -isoquinolin-1-one

Except that 38 mg of (1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in step 1 of Example 100, In the same manner as in Example 100, 33 mg (yield: 63.6%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.14(s, 1H), 8.00(s, 1H), 7.74(d, 1H), 7.35(d, 1H), 7.34(s, 1H), 7.15(s, 1H), 5.08(s, 2H), 4.59(s, 2H), 3.65(s, 2H), 3.53(t, 2H), 3.01(t, 2H)

Example 133. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-3,4-dihydro-1 H -quinolin-2-one

6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinoline instead of 4-acetylphenylboronic acid in step 1 of Example 100 26 mg (yield: 54.5 %) of the title compound was prepared in the same manner as in Example 100, except that 38 mg of -2(1 H )-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.43 (s, 1H), 7.40 (d, 1H), 7.20 (d, 1H), 7.10 (d, 1H), 6.87 (d, 1H), 5.05(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 2.98(t, 2H), 2.58(t, 2H)

Example 134. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Except that 37 mg of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid in step 1 of Example 100, In the same manner as in Example 100, 34 mg (yield: 63.6%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 7.98(s, 1H), 7.26(s, 2H), 7.17(s, 1H), 7.09(s, 1H), 5.04(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 2.94(t, 2H), 2.55(t, 2H), 2.27(s, 3H)

Example 135. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-8-methyl- 1H -quinolin-2-one

8-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -in step 1 of Example 100 instead of 4-acetylphenylboronic acid 33 mg (yield: 63.6%) of the title compound was prepared in the same manner as in Example 100, except that 40 mg of quinolin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.01 (s, 1H), 7.90 (d, 1H), 7.61 (d, 2H), 7.25 (s, 1H), 7.12 (s, 1H), 6.59 (d, 1H), 5.07(s, 2H), 4.60(s, 2H), 3.69(s, 2H), 2.47(s, 3H)

Example 136. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-8-fluoro-3,4-dihydro-1 H -quinolin-2-one

8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3, instead of 4-acetylphenylboronic acid in step 1 of Example 100, 29 mg (yield: 54.5 %) of the title compound was prepared in the same manner as in Example 100, except that 41 mg of 4-dihydro-1 H -quinolin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.26-7.24 (m, 3H), 7.11 (s, 1H), 5.05 (s, 2H), 4.59 (s, 2H), 3.68 ( s, 2H), 3.01 (t, 2H), 2.60 (t, 2H)

Example 137. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-8-fluoro-1 H -quinolin-2-one

8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H instead of 4-acetylphenylboronic acid in step 1 of Example 100 -30 mg (yield: 54.5%) of the title compound was prepared in the same manner as in Example 100, except that 40 mg of quinolin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.01(s, 1H), 7.95(d, 1H), 7.65(s, 1H), 7.60(d, 1H), 7.31(s, 1H), 7.13(s, 1H), 6.65(d, 1H), 5.08(s, 2H), 4.60(s, 2H), 3.68(s, 2H)

Example 138. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one

Except for using 37 mg of (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester in step 1 of Example 100 instead of 4-acetylphenylboronic acid Then, 41 mg (yield: 81.8 %) of the title compound was prepared in the same manner as in Example 100.

¹ H-NMR (MeOD, 400 MHz) δ 7.99(s, 1H), 7.48(d, 1H), 7.44(s, 1H), 7.22(s, 1H), 7.12(s, 2H), 5.05(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.34(s, 3H), 2.93(t, 2H), 2.62(t, 2H)

Example 139. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro- 2H- 1,4- Benzoxazine-6-yl)-2-thienyl]methyl]-1,2,4-triazole-3-one

(5-methyl-3,4-dihydro- 2H -benzo[b][1,4]oxazin-6-yl)boronic acid pinacol ester in step 1 of Example 100 instead of 4-acetylphenylboronic acid 32 mg (yield: 63.6%) of the title compound was prepared in the same manner as in Example 100, except that 38 mg was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.09 (d, 1H), 6.78 (d, 1H), 6.58 (s, 2H), 5.05 (s, 2H), 4.59 (s, 2H), 4.17(t, 2H), 3.68(s, 2H), 3.43(t, 2H), 2.10(s, 3H)

Example 140. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxazine- 7-day)-2-thienyl]methyl]-1,2,4-triazole-3-one

4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4 instead of 4-acetylphenylboronic acid in step 1 of Example 100 - dihydro -2 H -1,4- l, 38 mg, and, the same manner as in example 100 the title compound 27 mg (yield: 54.5%), and except for using to prepare a.

¹ H-NMR (MeOD, 400 MHz) δ 7.95 (s, 1H), 7.04 (s, 3H), 6.91 (s, 1H), 6.68 (d, 1H), 5.01 (s, 2H), 4.58 (s, 2H), 4.27(s, 2H), 3.66(s, 2H), 3.36-3.27(m, 6H), 2.90(s, 3H)

Example 141. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ] -2-Im carbonyl] -4 H -1,4- benzoxazin-3-one

In Step 1 of Example 100, instead of 4-acetylphenylboronic acid, 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -benzo[b] 11 mg (yield: 27.3%) of the title compound was prepared in the same manner as in Example 100, except that 30 mg of [1,4]oxazin-3(4 H )-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.21-7.12 (m, 4H), 6.96 (d, 1H), 5.05 (s, 2H), 4.59 (d, 4H), 3.59 ( s, 2H)

Example 142. 7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-1,4-dihydro-3,1-benzox-2-one

7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro- instead of 4-acetylphenylboronic acid in step 1 of Example 100 The title compound 35 mg (yield: 72.7%) was prepared in the same manner as in Example 100, except that 41 mg of 2 H -benzo[d][1,3]oxazin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.99 (s, 1H), 7.28 (s, 1H), 7.26 (d, 1H), 7.18 (d, 1H), 7.13 (d, 1H), 7.09 (s, 1H), 5.31(s, 2H), 5.06(s, 2H), 4.59(s, 2H), 3.68(s, 2H)

Example 143. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-1,4-dihydro-3,1-benzox-2-one

6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro- instead of 4-acetylphenylboronic acid in step 1 of Example 100 The title compound 31 mg (yield: 63.6%) was prepared in the same manner as in Example 100, except that 38 mg of 2 H -benzo[d][1,3]oxazin-2-one was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.49 (d, 1H), 7.43 (s, 1H), 7.21 (d, 1H), 7.11 (d, 1H), 6.89 (d, 1H), 5.33(s, 2H), 5.05(s, 2H), 4.59(s, 2H), 3.68(s, 2H)

Example 144. 7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-2-thienyl]-4-methyl-1,4-benzozin-3-one

4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzo[b][1,4]oxazin-7-boron in step 1 of Example 100 instead of 4-acetylphenylboronic acid 34 mg (yield: 63.6%) of the title compound was prepared in the same manner as in Example 100, except that 43 mg of the acid pinacol ester was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.28 (d, 1H), 7.20 (d, 2H), 7.12 (d, 2H), 5.05 (s, 2H), 4.62 (s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.34(s, 3H)

Example 145. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridine- 3-yl)-2-thienyl]methyl]-1,2,4-triazole-3-one

Except that in step 1 of Example 100, 36 mg of (5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)boronic acid pinacol ester was used instead of 4-acetylphenylboronic acid , 6 mg (yield: 18.2%) of the title compound was prepared in the same manner as in Example 100.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.92 (s, 1H), 7.69 (s, 1H), 7.17 (s, 1H), 7.12 (s, 1H), 5.05 (s, 2H), 4.58(s, 2H), 3.67(s, 2H), 3.50(d, 2H), 2.86(m, 2H), 1.95(m, 2H)

Example 146. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid 83 mg (yield: 87.0%) of the title compound was prepared in the same manner as in Example 100, except that 60 mg of 4-(methanesulfonyl)phenylboronic acid was used instead.

¹ H-NMR (MeOD, 400 MHz) δ 8.02-7.97 (m, 3H), 7.92-7.86 (m, 3H), 7.62 (s, 1H), 5.12 (s, 2H), 4.59 (s, 2H), 3.68(s, 2H), 3.15(s, 3H)

Example 147. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid Example 100, except that 83 mg of tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate was used instead 45 mg (yield: 56.3 %) of the title compound was prepared by the same method.

¹ H-NMR (MeOD, 400 MHz) δ 7.99 (s, 1H), 7.58-7.48 (m, 4H), 7.06 (d, 2H), 5.08 (s, 2H), 4.59 (s, 2H), 3.67 ( s, 2H), 3.45-3.32 (m, 8H)

Example 148. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-cy Enyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid 33 mg (yield: 35.6%) of the title compound was prepared in the same manner as in Example 100, except that 59 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used instead.

¹ H-NMR (MeOD, 400 MHz) δ 9.01(s, 1H), 8.29(d, 1H), 8.02(s, 1H), 7.97(s, 1H), 7.85(d, 1H), 7.66(s, 1H), 5.13(s, 2H), 4.59(s, 2H), 3.67(s, 2H)

Example 149. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thier Neil]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Enyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate mg was used, and instead of 4-acetylphenylboronic acid 35 mg (yield: 40.0%) of the title compound was prepared in the same manner as in Example 100, except that 53 mg of 6-(dimethylamino)pyridine-3-boronic acid was used.

¹ H-NMR (MeOD, 400 MHz) δ 8.20-8.17 (m, 2H), 8.00 (s, 1H), 7.68 (s, 1H), 7.51 (s, 1H), 7.16 (d, 1H), 5.10 ( s, 2H), 4.59 (s, 2H), 3.72 (s, 2H), 3.27 (s, 6H)

Example 150. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl ]Methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid 40 mg (yield: 45.8%) of the title compound was prepared in the same manner as in Example 100, except that 44 mg of 3,4-(methylenedioxy)phenyl boronic acid was used instead.

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.45 (d, 2H), 7.11 (d, 2H), 6.93 (s, 1H), 6.84 (d, 1H), 5.96 (s, 2H), 5.07(s, 2H), 4.58(s, 2H), 3.66(s, 2H)

Example 151. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-3-thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid 36 mg of the title compound in the same manner as in Example 100, except that 62 mg of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester was used instead. Yield: 37.6%).

MS (ESI) m/z= 444.1 (M + H)+

Example 152. 6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl ]-3-thienyl]-1-methyl-3,4-dihydroquinolin-2-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid The title compound was obtained in the same manner as in Example 100, except that 62 mg of (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester was used instead. 40 mg (Yield: 41.8%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.00 (s, 1H), 7.57-7.50 (m, 4H), 7.14 (d, 1H), 5.09 (s, 2H), 4.59 (s, 2H), 3.68 ( s, 2H), 3.35 (s, 3H), 2.95 (t, 2H), 2.63 (t, 2H)

Example 153. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl ]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]tert-butyl N -[2-[[4-(4-bromo-2-cy) prepared in Reference Example 42 instead of triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate Ethyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 100 mg was used, and 4-acetylphenylboronic acid The title compound 37 mg (yield: 45.2%) was prepared in the same manner as in Example 100, except that instead of using 48 mg of 1-ethylpyrazole-4-boronic acid pinacol ester.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.91 (s, 1H), 7.73 (s, 1H), 7.36 (d, 2H), 5.05 (s, 2H), 4.58 (s, 2H), 4.18 (q, 2H), 3.67 (s, 2H), 1.47 (t, 3H)

Example 154. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl] Methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- 21 mg (yield: 43.3%) of the title compound was prepared in the same manner as in Example 100, except that 21 mg of 4-(methanesulfonyl)phenylboronic acid was used instead of acetylphenylboronic acid.

¹ H-NMR (MeOD, 400 MHz) δ 7.99-7.92 (m, 3H), 7.81 (d, 2H), 7.38 (s, 1H), 5.03 (s, 2H), 4.59 (s, 2H), 3.68 ( s, 2H), 3.12 (s, 3H), 2.34 (s, 3H)

Example 155. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-cy Enyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- Except that 40 mg of tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate was used instead of acetylphenylboronic acid, In the same manner as in Example 100, 6 mg of the title compound (yield: 13.5%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 7.90 (s, 1H), 7.51 (d, 2H), 7.06-7.02 (m, 3H), 4.98 (s, 2H), 4.58 (s, 2H), 3.67 ( s, 2H), 3.45 (t, 4H), 3.38 (t, 4H), 2.30 (s, 3H)

Example 156. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl] -2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- 14 mg (yield: 30.8%) of the title compound was prepared in the same manner as in Example 100, except that 28 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used instead of acetylphenylboronic acid. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.92(s, 1H), 8.19(d, 1H), 7.97(s, 1H), 7.81(d, 1H), 7.45(s, 1H), 5.06(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 2.35(s, 3H)

Example 157. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl- 2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- 17 mg (yield: 38.5 %) of the title compound was prepared in the same manner as in Example 100, except that 26 mg of 6-(dimethylamino)pyridine-3-boronic acid was used instead of acetylphenylboronic acid.

¹ H-NMR (MeOD, 400 MHz) δ 8.11-8.07 (m, 2H), 7.92 (s, 1H), 7.18-7.14 (m, 2H), 5.10 (s, 2H), 4.58 (s, 2H), 3.68(s, 2H), 3.27(s, 6H), 2.32(s, 3H)

Example 158. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2 -Thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- Except using 26 mg of 2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan instead of acetylphenylboronic acid, 28 mg (yield: 62.5 %) of the title compound was prepared in the same manner as in Example 100.

¹ H-NMR (MeOD, 400 MHz) δ 7.89 (s, 1H), 7.05-7.00 (m, 2H), 6.80 (d, 1H), 5.95 (s, 2H), 4.96 (s, 2H), 4.58 ( s, 2H), 3.67 (s, 2H), 2.29 (s, 3H)

Example 159. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thi Enyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4- prepared in Reference Example 41 in Step 1 of Example 100 Triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate instead of tert-butyl N -[2-[[4-(5-bromo-3-methyl) prepared in Reference Example 43 50 mg of -2-thienyl)methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used, and 4- 10 mg (yield: 24.0%) of the title compound was prepared in the same manner as in Example 100, except that 23 mg of 1-ethylpyrazole-4-boronic acid pinacol ester was used instead of acetylphenylboronic acid.

¹ H-NMR (MeOD, 400 MHz) δ 7.88 (s, 1H), 7.86 (s, 1H), 7.64 (s, 1H), 6.91 (s, 1H), 4.96 (s, 2H), 4.58 (s, 2H), 4.18(q, 2H), 3.67(s, 2H), 2.28(s, 3H), 1.46(t, 3H)

Example 160. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2- Pyridyl]-1,2,4-triazole-3-one

Step 1: tert-butyl N -[3,3-difluoro-2-[[4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]- 5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

Tert-butyl N- [2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole-1-yl]methyl] prepared in Reference Example 31- 3,3-difluoro-allyl]carbamate 60 mg, 4-ethynyl-1-methyl-1 H -pyrazole 10 mg, tetrakis(triphenylphosphine)palladium (Pd(PPh ₃ ) ₄ ) 8 mg and 3 mg of copper iodide (CuI) were dissolved in 1 mL of N , N -dimethylformamide, 56.0 uL of triethylamine was added, and the mixture was stirred at 90°C overnight. The reaction mixture was filtered through a pad of celite, and the residue obtained by concentration under reduced pressure was dissolved in ethyl acetate, washed with distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 2/1) to prepare 51.7 mg (yield: 82.1 %) of the title compound as a yellow liquid.

MS (ESI) m/z= 372.0 (M + H)+

Step 2: 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyri Dill]-1,2,4-triazole-3-one

Tert-butyl N -[3,3-difluoro-2-[[4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl prepared in Step 1 ]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbomate 51.7 mg was dissolved in 1.0 mL of dichloromethane, 0.1 mL of trifluoroacetic acid was added, and then at room temperature for 2 hours. Stir for a while. After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 10 mg (yield: 24.5%) of the title compound as a white solid.

¹ H-NMR (MeOD, 400 MHz) δ 8.62(s, 1H), 8.19(d, 1H), 7.94(s, 2H), 7.70(s, 1H), 7.48(d, 1H), 4.61(s, 2H), 3.92(s, 3H), 3.40(s, 2H)

Example 161. 7-[( E )-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-tri Azole-4-yl]methyl]-2-thienyl]vinyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one

Example 100 Step 1 in place of 4-acetyl-phenylboronic acid 7 - [(E) -2-ethenyl (tetramethyl-1,3,2 dioxaborolan-2-yl)] -1 H, 2 H 17 mg of the title compound in the same manner as in Example 100, except that 42 mg of 3H -pyrido[2,3,b][1,4]oxazin-2-one was used (yield: 36.4%) ).

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.87 (s, 1H), 7.44 (s, 1H), 7.23 (d, 1H), 7.04 (d, 2H), 6.85 (d, 1H), 5.04(s, 2H), 4.84(s, 2H), 4.58(s, 2H), 3.60(s, 2H)

Example 162. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl ]-2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- 29 mg (yield: 54.5 %) of the title compound was prepared in the same manner as in Example 160, except that 39 mg of 5-ethynyl- N,N -dimethylpyridin-2-amine was used instead of 1 H -pyrazole. It was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.15(s, 1H), 7.98(s, 1H), 7.73(d, 1H), 7.17(s, 1H), 7.08(s, 1H), 6.90(d, 1H), 5.05(s, 2H), 4.59(s, 2H), 3.68(s, 2H), 3.20(s, 6H)

Example 163. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]- 2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- 42 mg (yield: 81.8%) of the title compound was prepared in the same manner as in Example 160, except that 51 mg of 4-(5-ethynylpyridin-2-yl)morpholine was used instead of 1 H -pyrazole. Did.

¹ H-NMR (MeOD, 400 MHz) δ 8.23 (s, 1H), 7.98 (s, 1H), 7.61 (d, 1H), 7.13 (s, 1H), 7.07 (s, 1H), 6.79 (d, 1H), 5.04(s, 2H), 4.59(s, 2H), 3.78(s, 4H), 3.67(s, 2H), 3.56(s, 4H)

Example 164. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro- 2H- 1,4-benzoic acid) Photo-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Conducted above, except that 70 mg of tert-butyl-6-ethynyl- 2H -benzo[b][1,4]oxazin-4( 3H )-carboxylate was used instead of 1 H -pyrazole 26 mg (yield: 81.8 %) of the title compound was prepared in the same manner as in Example 160.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.07 (d, 2H), 6.72 (s, 1H), 6.67 (t, 2H), 5.03 (s, 2H), 4.58 (s, 2H), 4.21(s, 2H), 3.67(s, 2H), 3.34-3.31(s, 2H)

Example 165. 6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- 1]methyl]-2-thienyl]ethynyl]-3,4-dihydro-1 H -quinolin-2-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- 38 mg of the title compound in the same manner as in Example 160, except that 46 mg of 6-ethynyl-1,2,3,4-tetrahydroquinolin-2-one was used instead of 1 H -pyrazole (yield: 72.7%).

¹ H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.30 (d, 2H), 7.14 (s, 1H), 7.07 (s, 1H), 6.86 (d, 1H), 5.04 (s, 2H), 4.59(s, 2H), 3.67(s, 2H), 2.96(t, 2H), 2.58(t, 2H)

Example 166. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2, 3-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Example 1 except that 43 mg of 7-ethynyl-2,3-dihydro- 1H -pyrido[2,,3-b][1,4]oxazin was used instead of 1 H -pyrazole 38 mg (yield: 81.8 %) of the title compound was prepared in the same manner as 160.

¹ H-NMR (MeOD, 400 MHz) δ 7.98(s, 1H), 7.52(s, 1H), 7.16(s, 1H), 7.07(s, 1H), 7.01(s, 1H), 5.05(s, 2H), 4.59(s, 2H), 4.39(s, 2H), 3.67(s, 2H), 3.38(s, 2H)

Example 167. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro- 2H -pyrido[3, 2-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Example 160, except that 43 mg of 7-ethynyl- 2H , 3H , 4H -pyrido[3,2-b][1,4]oxazin was used instead of 1 H -pyrazole 39 mg (yield: 72.7%) of the title compound was prepared in the same manner.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.69 (s, 1H), 7.12 (s, 1H), 7.05 (d, 2H), 5.04 (s, 2H), 4.58 (s, 2H), 4.18(s, 2H), 3.67(s, 2H), 3.55(s, 2H)

Example 168. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2, 3-b][1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Example 160, except that 43 mg of 6-ethynyl-2,3-dihydro-1 H -pyrido[2,3-b][1,4]oxazin was used instead of 1 H -pyrazole 26 mg (yield: 54.5 %) of the title compound was prepared by the same method.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.16 (s, 1H), 7.07 (s, 1H), 7.01 (d, 1H), 6.91 (d, 1H), 5.04 (s, 2H), 4.58(s, 2H), 4.36(s, 2H), 3.66(s, 2H), 3.41(s, 2H)

Example 169. 7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- 1]methyl]-2-thienyl]ethynyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Except that 47 mg of 7-ethynyl- 1H , 2H , 3H -pyrido[2,3-b][1,4]oxazin-2-one was used instead of 1 H -pyrazole 32 mg (yield: 63.6%) of the title compound were prepared in the same manner as in Example 160.

¹ H-NMR (MeOD, 400 MHz) δ 7.98(s, 1H), 7.93(s, 1H), 7.32(s, 1H), 7.21(s, 1H), 7.10(s, 1H), 5.06(s, 2H), 4.87(s, 2H), 4.59(s, 2H), 3.67(s, 2H)

Example 170. 7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- yl] methyl] -2-Im carbonyl] ethynyl] -4 H - pyrido [3,2-b] [1,4] oxazin-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate 50 mg was used, and 4-ethynyl-1-methyl- Except that 47 mg of 7-ethynyl- 2H , 3H , 4H -pyrido[3,2-b][1,4]oxazin-3-one instead of 1 H -pyrazole was used. In the same manner as in Example 160, 34 mg (yield: 63.6%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.37 (s, 1H), 7.20 (s, 1H), 7.09 (s, 1H), 5.06 (s, 2H), 4.68(s, 2H), 4.59(s, 2H), 3.67(s, 2H)

Example 171. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2 -Thienyl]methyl]-1,2,4-triazole-3-one

Tert-butyl N -[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazole- prepared in Reference Example 31 in Step 1 of Example 160 Tert-butyl N -[2-[[4-(5-bromo-2-thienyl) prepared in Reference Example 41 instead of 1-yl]methyl]-3,3-difluoro-allyl]carbamate. Same as in Example 160, except that 50 mg of methyl]-5-oxo-1,2,4-triazole-1-yl]methyl]-3,3-difluoro-allyl]carbamate was used. 32 mg (yield: 72.7%) of the title compound were prepared by the method.

¹ H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H), 7.84 (s, 1H), 7.61 (s, 1H), 7.08 (d, 2H), 5.04 (s, 2H), 4.58 (s, 2H), 3.90(s, 3H), 3.67(s, 2H)

Example 172. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazole-3 -On

Tert-butyl N -[3,3-difluoro-2-[[5-oxo-4-[2-(2-thienyl)ethyl]-1,2,4-trie prepared in Reference Example 44 43 mg of azole-1-yl]methyl]allyl]carbamate was dissolved in 5.0 mL of dichloromethane, and 0.5 mL of trifluoroacetic acid was added, followed by stirring at room temperature for 3 hours. After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 34 mg (yield: 100%) of the title compound as a white solid.

¹ H-NMR (MeOD, 400 MHz) δ 7.67 (s, 1H), 7.25 (s, 1H), 6.94 (s, 1H), 6.86 (s, 1H), 4.55 (s, 2H), 3.96 (t, 2H), 3.63(s, 2H), 3.27(t, 2H)

Example 173. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl] -1,2,4-triazole-3-one

Step 1: Tert-Butyl N- [3,3-difluoro-2-[[4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-5-oxo -1,2,4-triazole-1-yl]methyl]allyl]carbamate

Tert-butyl N- [2-[[4-(5-bromo-2-thienyl)ethyl]-5-oxo-1,2,4-triazole-1-yl prepared in Reference Example 45] Dissolve 60 mg of methyl]-3,3-difluoro-allyl]carbamate and 32 mg of 4-(methanesulfonyl)phenylboronic acid in 1.6 mL of 1,4-dioxane, 0.4 mL of 1 M potassium carbonate and palladium di 3 mg of [1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl ₂ (dppf)) was added and stirred at 90°C overnight. The reaction mixture was filtered through a pad of celite, and the residue obtained by concentration under reduced pressure was dissolved in ethyl acetate, washed with distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 1/2) to prepare 48 mg (yield: 69.2 %) of the title compound.

MS (ESI) m/z= 455.2 (M + H)+

Step 2: 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]- 1,2,4-triazole-3-one

Tert-Butyl N- [3,3-difluoro-2-[[4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl] prepared in Step 1-5 -48 mg of oxo-1,2,4-triazole-1-yl]methyl]allyl]carbamate was dissolved in 1.0 mL of dichloromethane, 0.1 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 2 hours. . After the reaction mixture was concentrated, dichloromethane was added, washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: dichloromethane/methanol = 10/1) to prepare 34 mg (yield: 59.2%) of the title compound.

¹ H-NMR (MeOD, 400 MHz) δ 7.94-7.92 (m, 2H), 7.82-7.77 (m, 3H), 7.44 (s, 1H), 6.92 (s, 1H), 4.56 (s, 2H), 3.99(t, 2H), 3.65(s, 2H), 3.36(s, 3H), 3.31(t, 2H)

Example 174. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl ]Ethyl]-1,2,4-triazole-3-one

Tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazin-1 instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 173 -9 mg (yield: 16.0%) of the title compound was prepared in the same manner as in Example 173, except that 49 mg of carboxylate was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.74 (s, 1H), 7.50 (d, 1H), 7.10 (s, 1H), 7.03 (d, 1H), 6.80 (s, 1H), 4.56 (s, 2H), 3.98(t, 2H), 3.59(s, 2H), 3.44(t, 4H), 3.37(t, 4H), 3.24(t, 2H)

Example 175. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2 -Thienyl]ethyl]-1,2,4-triazole-3-one

Same as Example 173, except that 34 mg of 2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronic acid in Step 1 of Example 173. By the method, 21 mg (yield: 37.6%) of the title compound was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.92(s, 1H), 8.19(d, 1H), 7.82(d, 1H), 7.79(s, 1H), 7.51(s, 1H), 6.97(s, 1H), 4.56(s, 2H), 4.01(t, 2H), 3.65(s, 2H), 3.36(s, 3H), 3.32(t, 2H)

Example 176. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2- Cyenyl]ethyl]-1,2,4-triazole-3-one

The title compound was prepared in the same manner as in Example 173, except that 31 mg of 6-(dimethylamino)pyridine-3-boronic acid was used instead of 4-(methanesulfonyl)phenylboronic acid in Step 1 of Example 173. 29 mg (yield: 35.2%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 8.10(s, 1H), 8.06(d, 1H), 7.76(s, 1H), 7.22(s, 1H), 7.13(d, 1H), 6.87(s, 1H), 4.56(s, 2H), 3.99(t, 2H), 3.65(s, 2H), 3.36(t, 2H), 3.27(s, 6H)

Example 177. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-cy Enyl] ethyl]-1,2,4-triazole-3-one

2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2 instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 173 -29 mg (yield: 55.2%) of the title compound was prepared in the same manner as in Example 173, except that 34 mg of dioxaborolan was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.73 (s, 1H), 7.06-7.02 (m, 3H), 6.82-6.77 (m, 2H), 5.97 (s, 2H), 4.59 (s, 2H), 3.97 (t, 2H), 3.63 (s, 2H), 3.23 (t, 2H)

Example 178. 6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl ]Ethyl]-2-thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one

Using 36 mg of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol ester instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 173 Except, the title compound 21 mg (yield: 36.0%) was prepared in the same manner as in Example 173.

¹ H-NMR (MeOD, 400 MHz) δ 7.75 (s, 1H), 7.24 (d, 1H), 7.13 (d, 1H), 6.80 (d, 1H), 4.56 (s, 2H), 3.97 (t, 2H), 3.63(s, 2H), 3.24(t, 2H), 2.94(t, 2H), 2.57(t, 2H), 2.27(s, 3H)

Example 179. 6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl ]Ethyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one

36 mg of (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacol ester instead of 4-(methanesulfonyl)phenylboronic acid in step 1 of Example 173 17 mg (yield: 30.4%) of the title compound was prepared in the same manner as in Example 173, except that was used.

¹ H-NMR (MeOD, 400 MHz) δ 7.75 (s, 1H), 7.47 (d, 1H), 7.43 (s, 1H), 7.18 (s, 1H), 7.12 (d, 1H), 6.83 (s, 1H), 4.56(s, 2H), 3.99(t, 2H), 3.64(s, 2H), 3.32(s, 3H), 3.26(t, 2H), 2.94(t, 2H), 2.64(t, 2H) )

Example 180. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl ]Ethyl]-1,2,4-triazole-3-one

The title compound was obtained in the same manner as in Example 173, except that 28 mg of 1-ethylpyrazole-4-boronic acid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronic acid in Step 1 of Example 173. 21 mg (Yield: 42.4%) was prepared.

¹ H-NMR (MeOD, 400 MHz) δ 7.84(s, 1H), 7.72(s, 1H), 7.63(s, 1H), 6.95(s, 1H), 6.75(s, 1H), 4.56(s, 2H), 4.19 (q, 2H), 3.96 (t, 2H), 3.63 (s, 2H), 3.22 (t, 2H), 1.47 (t, 3H)

Test Example 1: Activity evaluation for amine oxidases

Horseradish peroxidise (HPR) coupled reaction of the compounds according to the invention against recombinant human VAP-1 (recombinant human VAP-1, R&D systems) using Amplex Red Hydrogen Peroxide Assay Kit (Molecular Probes, Invitrogen, USA) It was evaluated by measuring the level of hydrogen peroxide at. The test was conducted at room temperature, and benzylamine was used as a substrate. Hydrogen peroxide oxidation of 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Red reagent) in the HRP coupling reaction produces a highly fluorescent compound, resorufin. . Briefly, the test compound was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 20 mM. Dose-response measurements made a 1:3 serial dilution in DMSO resulting in an 8-point curve. The top concentration was adjusted according to the efficacy of the compound, and then diluted with reaction buffer to obtain a <1% final DMSO concentration. Purified human VAP-1 in 50 mM sodium phosphate buffer (pH7.4) was added to each well in an assay 96 well plate. Test compounds dissolved in DMSO were incubated with human VAP-1 enzyme for 30 minutes at 37°C. After incubation for 30 minutes, a reaction mixture containing 200 uM Amplex Red reagent, 1 mM benzylamine, and 1 U/mL HRP prepared with 50 mM sodium phosphate buffer (pH7.4) was added to each well. Fluorescence was measured using a microplate reader (Flexstation3, Molecular Devices) at several time points for 1-2 hours under conditions of excitation at 545 nm and emission at 590 nm. Inhibition by compounds was measured as a% decrease in signal compared to the control without inhibitor (DMSO only diluted). Data were fixed to a four-variable logistic model and IC ₅₀ values were calculated using the GraphPad Prism program.

In addition, the activity of the compounds according to the present invention for recombinant human MAO-A (monoamine oxidase-A, Sigma-Aldrich) and recombinant human MAO-B (monoamine oxidase-B, Sigma-Aldrich) is 0.5 mM tyramine as a substrate. ) And 1 mM benzylamine, respectively, were evaluated in a similar manner to the activity evaluation method for recombinant human VAP-1. In addition, the activity of the compounds according to the present invention for the recombinant human DAO (diamine oxidase, R&D systems) as a substrate using 1 mM putrescine (putrescine), respectively, in a manner similar to the method for evaluating the activity for recombinant human VAP-1 Was evaluated.

The results obtained by evaluating the activity for the enzyme as described above are shown in Tables 1 to 3 below.

Example Inhibitory activity (IC ₅₀ , nM) human VAP-1 MAO-A MAO-B DAO One 2.0 >100,000 39,000 >10,000 3 4.0 >100,000 25,000 19,000 4 4.2 >100,000 2,300 58,000 5 2.5 >100,000 4,900 67,000 8 2.2 >100,000 >100,000 10,500 9 3.5 >100,000 >100,000 7,100 11 1.1 >100,000 57,000 >100,000 14 1.4 >100,000 40,000 4,100 15 3.0 >100,000 >100,000 >100,000 21 2.5 36,200 18,000 6,300 22 0.8 >100,000 >100,000 >10,000 23 3.1 >100,000 >100,000 8,400 25 1.7 6,280 >10,000 1,300 32 1.3 >100,000 17,000 670 37 0.5 >100,000 880 860 47 3.5 >100,000 >100,000 1,900 50 1.5 >100,000 13,000 1,200 51 0.6 >100,000 28,000 520 53 1.3 >100,000 >100,000 1,710 58 2.2 >100,000 >100,000 1,700 60 1.3 >100,000 >100,000 810 67 0.9 >100,000 8,300 490 68 0.5 >100,000 55,000 2,100 69 1.2 >100,000 >100,000 >100,000 70 0.7 >100,000 5,800 1,500 71 0.8 >100,000 >100,000 >100,000 72 0.5 >100,000 1,500 57,000 73 0.3 >100,000 7,200 6,100 74 0.3 >100,000 7,500 6,500 75 0.7 >100,000 >100,000 20,000 97 1.3 >100,000 20,000 >10,000 100 0.5 >100,000 11,000 >10,000

Example Inhibitory activity (IC ₅₀ , nM) human VAP-1 MAO-A MAO-B DAO 101 0.3 >100,000 67,000 21,000 102 0.4 >100,000 5,400 >10,000 103 0.9 >100,000 4,200 22,000 104 0.5 >100,000 >10,000 31,000 105 1.5 >100,000 6,500 >10,000 107 3.5 >100,000 46,000 12,000 108 2.0 >10,000 >10,000 42,000 109 1.4 >100,000 >100,000 84,000 110 1.3 >10,000 8,700 >100,000 111 0.4 >100,000 9,400 7,200 112 0.2 >100,000 26,000 >100,000 113 0.6 >100,000 2,700 19,000 115 0.8 >100,000 10,000 11,000 116 1.4 >100,000 >10,000 >100,000 117 1.1 >100,000 >100,000 7,100 118 3.5 >100,000 >100,000 40,000 119 0.5 >100,000 30,000 >10,000 121 0.9 >100,000 40,000 >10,000 122 0.4 >100,000 25,000 54,000 123 0.9 >100,000 56,000 59,000 125 2.5 >100,000 >100,000 >100,000 126 0.5 >100,000 760 >100,000 127 0.6 >100,000 1,070 >100,000 128 0.7 >100,000 >100,000 97,000 130 0.7 >100,000 >100,000 >100,000 131 0.4 7,800 12,000 >100,000 132 0.2 >100,000 >100,000 >100,000 133 0.2 >100,000 >100,000 >10,000 134 0.3 >100,000 22,000 >100,000 135 0.4 >100,000 >100,000 79,000 136 0.4 >100,000 >100,000 >100,000 137 0.3 >100,000 >100,000 >100,000 138 0.1 >100,000 15,000 13,000 139 1.0 21,000 21,000 73,000 140 0.8 6,600 8,000 6,800

Example Inhibitory activity (IC ₅₀ , nM) human VAP-1 MAO-A MAO-B DAO 141 0.6 8,100 20,000 16,000 142 0.2 >100,000 32,000 16,000 143 0.2 >100,000 6,400 >10,000 144 0.7 >100,000 >100,000 >10,000 145 0.8 >100,000 >100,000 >100,000 146 1.1 >100,000 33,000 9,200 148 0.7 >100,000 8,700 6,300 149 0.6 >100,000 >100,000 >10,000 150 2.9 >100,000 2,800 >10,000 151 0.3 >100,000 26,100 6,600 152 0.2 >100,000 13,400 3,500 153 1.3 >100,000 29,000 36,000 154 4.0 >100,000 >100,000 21,000 156 3.2 >100,000 17,000 9,100 157 2.3 >100,000 >100,000 >100,000 160 1.5 >100,000 15,600 5,090 161 0.2 >100,000 >100,000 54,000 162 0.7 >10,000 10,000 >10,000 163 0.4 >100,000 31,000 8,400 164 2.5 4,000 34,000 >10,000 165 0.5 >100,000 5,900 >10,000 166 0.9 >10,000 >10,000 >10,000 167 2.1 >100,000 41,000 >10,000 168 1.0 >10,000 45,000 >100,000 169 0.2 >100,000 >100,000 >100,000 170 0.8 >100,000 14,000 >10,000 171 1.8 >100,000 50,000 >100,000 176 0.5 >100,000 >100,000 1,100 177 1.2 >100,000 700 2,500 180 0.6 >100,000 61,000 1,900

From the results of Table 1 to Table 3, it can be seen that the compounds according to the present invention have excellent selective inhibitory activity against VAP-1 among various amine oxidase.

Claims (10)

A compound of Formula 1 or a pharmaceutically acceptable salt thereof:
<Formula 1>

Where,
n is 0, 1 or 2,
A is an aryl or heteroaryl group selected from the group consisting of phenyl, pyridine, pyrazine, and thiophene,
The aryl or heteroaryl group is optionally substituted with 1 or 2 substituents selected from the group consisting of C _1-3 alkyl, halogen, benzyloxy, -R, -CH=CH-R, and -C≡CR,
R is benzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole, indazole, 1,3-dihydroindole- 2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one, 3,4-dihydro-1,4-benzoxazine, 2 ,3-Dihydro-1,4-benzoxazine photo, 1,4-benzoxazine-3-one, 1,4-dihydro-3,1-benzoxazine-2-one, 5,6,7,8- Tetrahydronaphthyridine, triazolo[1,5-a]pyridine, 2,3-dihydro-pyrido[2,3-b][1,4]oxazine, 3,4-dihydro-pyrido [3,2-b][1,4]oxazin, pyrido[2,3-b][1,4]oxazin-2-one, and pyrido[3,2-b][1,4 ] Is a cyclic ring selected from the group consisting of oxazin-3-one,
The cyclic ring is halogen, C _1-6 alkyl, trifluoromethyl, C _1-6 alkoxy, amino, mono- or di-C _1-6 alkylamino, C _1-6 alkoxy-C _1-6 alkylamino, C _1-6 alkylcarbonylamino, mono-C _1-6 alkylaminocarbonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkylsulfonyl, C _1-6 alkylcarbonyl, It is optionally substituted with 1 to 3 substituents selected from the group consisting of morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl, and pyrazolyl. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein n is 0 or 1, and A is phenyl, pyridine or thiophene. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the aryl or heteroaryl group is substituted with 1 or 2 substituents selected from the group consisting of C _1-3 alkyl, halogen, and -R. The compound or a pharmaceutical thereof according to claim 3, wherein R is a cyclic ring selected from the group consisting of benzene, pyridine, pyridin-2-one, pyrazole and 3,4-dihydroquinolin-2-one. Acceptable salts. The compound according to claim 4, wherein the cyclic ring is substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl. Or a pharmaceutically acceptable salt thereof. According to claim 1,
n is 0,
A is phenyl,
The phenyl is substituted with 1 or 2 substituents selected from the group consisting of halogen and -R,
R is a cyclic ring selected from the group consisting of benzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole,
The cyclic ring is a compound characterized by being substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl, or a pharmaceutically acceptable compound thereof. Possible salts. According to claim 1,
n is 0,
A is pyridine,
The pyridine is substituted with 1 or 2 substituents selected from the group consisting of C 1-3 alkyl, halogen, and -R,
R is a cyclic ring selected from the group consisting of benzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole,
The cyclic ring is a compound characterized by being substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl, or a pharmaceutically acceptable compound thereof. Possible salts. According to claim 1,
n is 0,
A is a thiophene,
The thiophene is substituted with one or two cyclic rings selected from the group consisting of benzene, pyridine, pyridin-2-one, 3,4-dihydroquinolin-2-one and pyrazole,
The cyclic ring is a compound characterized by being substituted with a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkylsulfonyl, di-C _1-6 alkylamino, and piperazinyl, or a pharmaceutically acceptable compound thereof. Possible salts. The compound of claim 1, or a pharmaceutically acceptable salt thereof selected from the group consisting of:
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4-triazole-3 -On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazole-3 -On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2,4-tri Azole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4-triazole -3-one;
6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]phenyl]-8-methyl -3,4-dihydro-1 H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4-triazole-3 -On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole -3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro-phenyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl]-1, 2,4-triazole-3-one;
6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-fluoro- Phenyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]-1,2, 4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazole -3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro-phenyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl]-1, 2,4-triazole-3-one;
6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-fluoro- Phenyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]-1,2, 4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazole- 3-on;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]-1,2, 4-triazole-3-one;
6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazole- 3-on;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2, 4-triazole-3-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazole- 3-on;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2, 4-triazole-3-one;
6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-4-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4-triazole- 3-on;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]-1,2, 4-triazole-3-one;
6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-2-pyridyl] -1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-pyridyl] -1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2-pyridyl]- 1,2,4-triazole-3-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-methyl-3 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-methyl-3 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl] -1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3-pyridyl]- 1,2,4-triazole-3-one;
6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-methyl-2 -Pyridyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-3-methyl-2 -Pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2, 4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyri Dill]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-pyridyl] -1,2,4-triazole-3-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-fluoro- 3-pyridyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;
6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]-5-fluoro- 3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyridyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2,4-triazole -3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]-1,2, 4-triazole-3-one;
6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]pyrazin-2-yl] -1-methyl-3,4-dihydro-1 H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1,2,4- Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-triazole-3- On;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2,4-tri Azole-3-one;
4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-tri Azole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;
3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl] -N,N -dimethyl-benzenesulfonamide;
4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl] -N -methyl-benzamide;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro- Allyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]- 1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1 H -pyrazol-3-yl)phenyl]-2-thienyl] Methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl] -1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thi Enyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thier Neil]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl] Methyl]-1,2,4-triazole-3-one;
5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-methyl-pyridin-2-one;
5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-1-ethyl-pyridin-2-one;
5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-isopropyl-pyridin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro- 2H -pyridin-4-yl)-2 -Thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro- 2H -pyridin-4-yl)-2 -Thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]- 1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1 H -indazol-6-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazole[1,5-a]pyridin-7-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2-thienyl] Methyl]-1,2,4-triazole-3-one;
5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-7-fluoro-indolin-2-one;
N -[6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]-1,3-benzothiazol-2-yl]acetamide;
7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-3,4-dihydro- 2H -isoquinolin-1-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-3,4-dihydro-1 H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-8-methyl- 1H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-8-fluoro-3,4-dihydro-1 H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-8-fluoro-1 H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro- 2H- 1,4-benzoxazine-6 -Yl)-2-thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxa-7-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- in Im carbonyl] -4 H -1,4- benzoxazin-3-one;
7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1,4-dihydro-3,1-benzoxazine-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Thienyl]-1,4-dihydro-3,1-benzoxazine-2-one;
7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-2- Cyenyl]-4-methyl-1,4-benzoxazin-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl) -2-thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4 -Triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl] -1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]- 1,2,4-triazole-3-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-3- Thienyl]-8-methyl-3,4-dihydro- 1H -quinolin-2-one;
6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl]-3- Thienyl]-1-methyl-3,4-dihydroquinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1, 2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1 ,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thi Enyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thier Neil]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl ]Methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl ]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]- 1,2,4-triazole-3-one;
7-[( E )-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4- 1]methyl]-2-thienyl]vinyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2- Thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thier Neil]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2 H -1,4-benzoxazine-6- 1)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;
6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]ethynyl]-3,4-dihydro- 1H -quinolin-2-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2,3-b] [1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2 H -pyrido[3,2-b] [1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1 H -pyrido[2,3-b] [1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazole-3-one;
7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] -2-thienyl]ethynyl]-1 H -pyrido[2,3-b][1,4]oxazin-2-one;
7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]methyl] ethynyl -2-Im carbonyl]] -4 H - pyrido [3,2-b] [1,4] oxazin-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl ]Methyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-1,2 ,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl]ethyl]- 1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl ]Ethyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl] Ethyl]-1,2,4-triazole-3-one;
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-thienyl]ethyl ]-1,2,4-triazole-3-one;
6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]ethyl]- 2-thienyl]-8-methyl-3,4-dihydro-1 H -quinolin-2-one;
6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazole-4-yl]ethyl]- 2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one; And
2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]- 1,2,4-triazole-3-one. A method for selectively inhibiting vascular adhesion protein-1 comprising administering to a mammal a therapeutically effective amount of a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.