JP2018076234A - Pyrazolo[1,5-a]pyrimidine compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel compound that has anti-RSV activity and is useful for the prevention or treatment of infections associated with Pneumovirinae virus including respiratory syncytial virus, or a pharmaceutically acceptable salt thereof.SOLUTION: The present invention provides a compound represented by formula (I), or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Description

  The present invention relates to compounds useful for the prevention or treatment of infections involving viruses of the Pneumovirus subfamily and pharmaceutically acceptable salts thereof.

Pneumovirus subfamily viruses are negative sense single-stranded RNA viruses included in the Paramyxoviridae family. Pneumoviridae viruses, including respiratory syncytial virus (RSV), are involved in many epidemic human and animal diseases.
Human respiratory syncytial virus (HRSV) is one of the most common causes of respiratory infections in infants, and the severity of lower respiratory tract infections such as bronchiolitis and pneumonia also results in hospitalization and death. Particularly in high-risk groups such as low birth weight infants and infants with congenital heart or lung disease, the risk of seriousness and complications is high.
There are currently no effective therapeutics and vaccines for viral infections of the Pneumovirus subfamily. The humanized monoclonal antibody palivizumab having a high neutralizing ability is used as a preventive drug for suppressing the onset of serious lower respiratory tract infections caused by HRSV in high-risk infants, but the drug price is very high. Therefore, there is a need for effective therapeutic drugs or vaccines.

  Recently, compounds exhibiting anti-RSV activity and having a pyrazolo [1,5-a] pyrimidine skeleton have been disclosed in Patent Documents 1, 2, and 3, and Non-Patent Document 1. However, these documents do not disclose the structure of the compound of the present invention.

International Publication No. 2011-163518 Pamphlet International Publication No. 2013/096681 Pamphlet International Publication No. 2013/158877

Journal of Medicinal Chemistry vol. 58, p. 1630-1643 (2015)

  An object of the present invention is to provide a novel compound or a pharmaceutically acceptable salt thereof useful for the prevention or treatment of infections involving viruses of the Pneumovirinae family including respiratory syncytial virus (RSV). To do.

  As a result of intensive studies, the present inventors have found that a pyrazolo [1,5-a] pyrimidine compound represented by the following formula (I) has an excellent anti-RSV activity. The invention has been completed.

That is, the present invention
(1) Formula (I),

［ここで、式（Ｉ）中、
Ａ¹は、水素原子又はＣ_1-6アルキル基を示し、
Ａ²は、水素原子、Ｃ_1-6アルキル基、Ｃ_3-6シクロアルキル基、カルボキシ基、又はＣ_1-6アルコキシカルボニル基を示し、
Ａ³は、ハロゲン原子、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１個のアミノ基で置換されてもよい。）、ヘテロシクリルオキシ基、Ｃ_1-6アルキルアミノ基｛ここで、該Ｃ_1-6アルキルアミノ基は、アミノ基及びＣ_3-6シクロアルキル基（ここで、該Ｃ_3-6シクロアルキル基は、1個のアミノ基で置換されてもよい）からなる群から選ばれる同一又は異なる１〜２個の置換基で置換されてもよい。｝、Ｃ_3-6シクロアルキルアミノ基（ここで、 該Ｃ_3-6シクロアルキルアミノ基は、１個のアミノ基で置換されてもよい。）、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、ハロゲン原子、水酸基、アミノ基、及び１個のアミノ基で置換されたＣ_1-6アルキル基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。）を示し、
Ａ⁴は、水素原子、ハロゲン原子、Ｃ_1-6アルキル基、Ｃ_2-6アルキニル基（ここで、該Ｃ_2-6アルキニル基は、１個の水酸基で置換されてもよい。）、又はアリール基を示し、
Ｒ¹及びＲ²は、同一又は異なって、それぞれ水素原子、Ｃ_1-6アルキル基（ここで、該Ｃ_1-6アルキル基は、１個の水酸基で置換されてもよい。）、又はＣ_3-6シクロアルキル基を示すか、
又は、Ｒ¹及びＲ²は、隣接する炭素原子と一緒になって、Ｃ_3-6シクロアルカンを形成してもよく、
Ｒ³は、Ｃ_1-6アルキル基｛ここで、該Ｃ_1-6アルキル基は、ハロゲン原子、水酸基、アミノ基、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールオキシ基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基（ここで、該ヘテロシクリル基は、１〜２個のオキソで置換されてもよい。）、アリール基、及びヘテロアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝を示し、
Ｙは、アリール基、ヘテロアリール基｛ここで、該アリール基及びヘテロアリール基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基（ここで、該Ｃ_1-6アルキルスルホニルアミノ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基、アリール基、及びヘテロアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、１個のオキソで置換されてもよい。）を示し、
又は、Ｙは、下記式群（ＩＩ）のいずれかの構造を示し、

[Wherein in formula (I),
A ¹ represents a hydrogen atom or a C _1-6 alkyl group,
A ² represents a hydrogen atom, a C _1-6 alkyl group, a C _3-6 cycloalkyl group, a carboxy group, or a C _1-6 alkoxycarbonyl group,
A ³ represents a halogen atom, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a heterocyclyloxy group, a C _1-6 alkylamino group. A group {wherein the C _1-6 alkylamino group is an amino group and a C _3-6 cycloalkyl group (wherein the C _3-6 cycloalkyl group may be substituted with one amino group); ) May be substituted with the same or different 1 to 2 substituents selected from the group consisting of: }, A C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group may be substituted with one amino group), or a heterocyclyl group (wherein the heterocyclyl group is , A halogen atom, a hydroxyl group, an amino group, and a C _1-6 alkyl group substituted with one amino group may be substituted with 1 to 3 identical or different substituents. Show
A ⁴ represents a hydrogen atom, a halogen atom, a C _1-6 alkyl group, a C _2-6 alkynyl group (wherein the C _2-6 alkynyl group may be substituted with one hydroxyl group), or Represents an aryl group,
R ¹ and R ² are the same or different and are each a hydrogen atom, a C _1-6 alkyl group (wherein the C _1-6 alkyl group may be substituted with one hydroxyl group), or C _{Represents a 3-6} cycloalkyl group,
Or R ¹ and R ² may be taken together with adjacent carbon atoms to form a C _3-6 cycloalkane;
R ³ is a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, an amino group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 halogen atoms may be substituted), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group is 1 to And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of an aryl group and a heteroaryl group. },
Y is an aryl group, a heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group), a C _1-6 alkylsulfonylamino group (wherein the C _1-6 alkylsulfonyl group) The sulfonylamino group may be substituted with 1 to 3 halogen atoms.), An arylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group, an aryl group, and a heteroaryl group. It may be substituted with 1 to 3 identical or different substituents. }, Or a heterocyclyl group, wherein the heterocyclyl group may be substituted with one oxo,
Or, Y represents any structure of the following formula group (II),

環Qは、芳香族炭化水素環又はヘテロ芳香環（ここで、該芳香族炭化水素環及びヘテロ芳香環は、１個のＣ_1-6アルキル基で置換されてもよい。）を示し、
Ｗが単結合のとき、Ｚは、式（ＣＨ₂）ｎ又は式ＣＨ₂ＮＲ⁷を示し、
ｎは、２〜４の整数を示し、
Ｗが式ＣＨ₂のとき、Ｚは、式ＣＨ₂ＣＨ₂を示し、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴、及びＢ⁵は、同一又は異なって、それぞれ水素原子、ハロゲン原子、又はＣ_1-6アルキル基を示し、
Ｒ⁴及びＲ⁵は、同一又は異なって、それぞれ水素原子、Ｃ_1-6アルキル基を示すか、
又は、Ｒ⁴及びＲ⁵は、隣接する炭素原子と一緒になってＣ_3-6シクロアルカン｛ここで、該Ｃ_3-6シクロアルカンは、オキソ、水酸基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。｝を形成してもよく、さらに該Ｃ_3-6シクロアルカンは、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換されてもよく、
Ｒ⁶は、水素原子、アミノ基、Ｃ_1-6アルキル基（ここで、該Ｃ_1-6アルキル基は、Ｃ_3-6シクロアルキルカルボニル基、Ｃ_1-6アルキルスルホニル基、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルキルアミノ基（ここで、該Ｃ_1-6アルキルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、アミノ基、 スルファモイル基、Ｃ_3-6シクロアルキル基、Ｃ_1-6アルコキシ基、Ｃ_1-6アルキルアミノ基、Ｃ_2-6アルカノイルアミノ基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、Ｃ_1-6アルキルアミノスルホニル基、アリールスルホニル基、アリール基、及びヘテロアリール基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基（ここで、該Ｃ_1-6アルコキシカルボニルアミノ基は、１個のアリール基で置換されてもよい。）、又はＣ_1-6アルキルスルホニルアミノ基を示し、
Ｒ⁷は、水素原子又はＣ_1-6アルキル基を示し、
Ｒ⁸は、カルバモイル基、アミジノ基、Ｃ_2-6アルカノイル基（ここで、該Ｃ_2-6アルカノイル基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニル基（ここで、該Ｃ_1-6アルコキシカルボニル基は、１個のアリール基で置換されてもよい。）、又はＣ_1-6アルキルスルホニル基である。］
で表される化合物、又はその医薬上許容される塩、
（２）上記式（Ｉ）中、
Ｒ¹が、水素原子であり、
Ｒ²が、Ｃ_1-6アルキル基（ここで、該Ｃ_1-6アルキル基は、１個の水酸基で置換されてもよい。）、又はＣ_3-6シクロアルキル基であるか、
又は、Ｒ¹及びＲ²が、隣接する炭素原子と一緒になって、Ｃ_3-6シクロアルカンを形成してもよい、（１）に記載の化合物、又はその医薬上許容される塩、
（３）上記式（Ｉ）中、
Ｙが、アリール基、ヘテロアリール基｛ここで、該アリール基及びヘテロアリール基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基（ここで、該Ｃ_1-6アルキルスルホニルアミノ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基、アリール基、及びヘテロアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、１個のオキソで置換されてもよい。）である、（１）又は（２）に記載の化合物、又はその医薬上許容される塩、
（４）上記式（Ｉ）中、
Ａ¹が、水素原子又はＣ_1-6アルキル基であり、
Ａ²が、水素原子、Ｃ_1-6アルキル基、又はＣ_3-6シクロアルキル基であり、
Ａ³が、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１個のアミノ基で置換されてもよい。）、Ｃ_1-6アルキルアミノ基（ここで、該Ｃ_1-6アルキルアミノ基は、１個のアミノ基で置換されてもよい。）、Ｃ_3-6シクロアルキルアミノ基（ここで、 該Ｃ_3-6シクロアルキルアミノ基は、１個のアミノ基で置換されてもよい。）、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、１個のアミノ基で置換されてもよい。）であり、
Ａ⁴が、水素原子であり、
Ｒ¹が、水素原子であり、
Ｒ²が、Ｃ_1-6アルキル基又はＣ_3-6シクロアルキル基であり、
Ｒ³が、Ｃ_1-6アルキル基｛ここで、該Ｃ_1-6アルキル基は、ハロゲン原子、水酸基、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールオキシ基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基（ここで、該ヘテロシクリル基は、１〜２個のオキソで置換されてもよい。）、及びアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝であり、
Ｙが、アリール基、ヘテロアリール基｛ここで、該アリール基及びヘテロアリール基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基、アリールスルホニルアミノ基、及びヘテロアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、１個のオキソで置換されてもよい。）である（１）〜（３）いずれか１つに記載の化合物、又はその医薬上許容される塩、
（５）上記式（Ｉ）中、
Ａ¹が、水素原子であり、
Ａ²が、メチル基、エチル基、又はシクロプロピル基であり、
Ａ³が、下記式群（ＩＩＩ）のいずれかの構造であり、

Ring Q represents an aromatic hydrocarbon ring or a heteroaromatic ring (wherein the aromatic hydrocarbon ring and the heteroaromatic ring may be substituted with one C _1-6 alkyl group),
When W is a single bond, Z represents the formula (CH ₂ ) n or the formula CH ₂ NR ⁷ ,
n represents an integer of 2 to 4,
When W is of the formula CH ₂ , Z represents the formula CH ₂ CH ₂ ;
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are the same or different and each represents a hydrogen atom, a halogen atom, or a C _1-6 alkyl group,
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or a C _1-6 alkyl group,
Or R ⁴ and R ⁵ together with adjacent carbon atoms are C _3-6 cycloalkane {where C _3-6 cycloalkane is oxo, hydroxyl, C _2-6 alkanoylamino group (here And the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And one substitution selected from the group consisting of C _1-6 alkylsulfonylamino groups It may be substituted with a group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ represents a hydrogen atom, an amino group, a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a C _3-6 cycloalkylcarbonyl group, a C _1-6 alkylsulfonyl group, and a C _1- alkyl group). Which may be substituted with one substituent selected from the group consisting of ₆ alkylsulfonylamino groups), a C _1-6 alkylamino group (wherein the C _1-6 alkylamino group is one C _1-6 alkylsulfonyl group may be substituted), C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is an amino group, a sulfamoyl group, a C _3-6 cycloalkyl group, C _1-6 alkoxy group, C _1-6 alkylamino group, C _2-6 alkanoylamino group, C _1-6 alkylsulfonylamino group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, aryl Sulfonyl group, aryl group, and heteroaryl May be substituted with one substituent selected from the group consisting of.), By C _1-6 alkoxycarbonylamino group (wherein the C _1-6 alkoxycarbonylamino group, substituted with one aryl group Or a C _1-6 alkylsulfonylamino group,
R ⁷ represents a hydrogen atom or a C _1-6 alkyl group,
R ⁸ is carbamoyl group, amidino group, C (wherein said C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group.) _2-6 alkanoyl group, C _{1 A -6} alkoxycarbonyl group (wherein the C _1-6 alkoxycarbonyl group may be substituted with one aryl group), or a C _1-6 alkylsulfonyl group. ]
Or a pharmaceutically acceptable salt thereof,
(2) In the above formula (I),
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group (wherein the C _1-6 alkyl group may be substituted with one hydroxyl group), or a C _3-6 cycloalkyl group,
Or the compound according to (1), or a pharmaceutically acceptable salt thereof, wherein R ¹ and R ² may be combined with adjacent carbon atoms to form a C _3-6 cycloalkane;
(3) In the above formula (I),
Y is an aryl group, heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group), a C _1-6 alkylsulfonylamino group (wherein the C _1-6 alkylsulfonyl group) The sulfonylamino group may be substituted with 1 to 3 halogen atoms.), An arylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group, an aryl group, and a heteroaryl group. It may be substituted with 1 to 3 identical or different substituents. Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one oxo), or a pharmaceutically acceptable salt thereof,
(4) In the above formula (I),
A ¹ is a hydrogen atom or a C _1-6 alkyl group,
A ² is a hydrogen atom, a C _1-6 alkyl group, or a C _3-6 cycloalkyl group,
A ³ is a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a C _1-6 alkylamino group (wherein the C _{1-6 1-6} alkylamino group may be substituted with one amino group.), C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group is one amino group) Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one amino group),
A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group or a C _3-6 cycloalkyl group,
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 May be substituted with 1 halogen atom), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group has 1 to 2 And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of aryl groups. },
Y is an aryl group, heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), C _1-6 alkylsulfonylamino group, arylsulfonylamino group, and heteroaryl group May be substituted with the same or different 1 to 3 substituents selected from the group consisting of }, Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one oxo), or a pharmaceutically acceptable compound thereof, or any one thereof Salt,
(5) In the above formula (I),
A ¹ is a hydrogen atom,
A ² is a methyl group, an ethyl group, or a cyclopropyl group;
A ³ is any structure of the following formula group (III),

Ａ⁴が、水素原子であり、
Ｒ¹が、水素原子であり、
Ｒ²が、メチル基、エチル基、プロピル基、又はシクロプロピル基であり、
Ｒ³が、Ｃ_1-6アルキル基｛ここで、該Ｃ_1-6アルキル基は、ハロゲン原子、水酸基、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１〜３個のハロゲン原子で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基、及びヘテロシクリル基（ここで、該ヘテロシクリル基は、１〜２個のオキソで置換されてもよい。）からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝であり、
Ｙが、フェニル基又はピリジル基｛ここで、該フェニル基及びピリジル基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基、フェニルスルホニルアミノ基、及びＣ_1-6アルキルスルホニル基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝である（１）〜（４）いずれか１つに記載の化合物、又はその医薬上許容される塩、
（６）上記式（Ｉ）中、
Ｙが、上記式群（ＩＩ）のいずれかの構造であり、
環Qは、芳香族炭化水素環又はヘテロ芳香環（ここで、該芳香族炭化水素環及びヘテロ芳香環は、１個のＣ_1-6アルキル基で置換されてもよい。）であり、
Ｗが単結合のとき、Ｚが、式（ＣＨ₂）ｎ又は式ＣＨ₂ＮＲ⁷であり、
ｎが、２〜４の整数であり、
Ｗが式ＣＨ₂のとき、Ｚが、式ＣＨ₂ＣＨ₂であり、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴、及びＢ⁵が、同一又は異なって、それぞれ水素原子、ハロゲン原子、又はＣ_1-6アルキル基であり、
Ｒ⁴及びＲ⁵が、同一又は異なって、それぞれ水素原子、Ｃ_1-6アルキル基であるか、
又は、Ｒ⁴及びＲ⁵が、隣接する炭素原子と一緒になってＣ_3-6シクロアルカン｛ここで、該Ｃ_3-6シクロアルカンは、オキソ、水酸基、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。｝を形成してもよく、さらに該Ｃ_3-6シクロアルカンは、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換されてもよく、
Ｒ⁶が、水素原子、アミノ基、Ｃ_1-6アルキル基（ここで、該Ｃ_1-6アルキル基は、Ｃ_3-6シクロアルキルカルボニル基、Ｃ_1-6アルキルスルホニル基、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルキルアミノ基（ここで、該Ｃ_1-6アルキルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、アミノ基、 スルファモイル基、Ｃ_3-6シクロアルキル基、Ｃ_1-6アルコキシ基、Ｃ_1-6アルキルアミノ基、Ｃ_2-6アルカノイルアミノ基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、Ｃ_1-6アルキルアミノスルホニル基、アリールスルホニル基、アリール基、及びヘテロアリール基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基（ここで、該Ｃ_1-6アルコキシカルボニルアミノ基は、１個のアリール基で置換されてもよい。）、又はＣ_1-6アルキルスルホニルアミノ基であり、
Ｒ⁷が、水素原子又はＣ_1-6アルキル基であり、
Ｒ⁸が、カルバモイル基、アミジノ基、Ｃ_2-6アルカノイル基（ここで、該Ｃ_2-6アルカノイル基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニル基（ここで、該Ｃ_1-6アルコキシカルボニル基は、１個のアリール基で置換されてもよい。）、又はＣ_1-6アルキルスルホニル基である（１）又は（２）に記載の化合物、又はその医薬上許容される塩、
（７）上記式（Ｉ）中、
Ａ¹が、水素原子又はＣ_1-6アルキル基であり、
Ａ²が、水素原子、Ｃ_1-6アルキル基、又はＣ_3-6シクロアルキル基であり、
Ａ³が、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１個のアミノ基で置換されてもよい。）、Ｃ_1-6アルキルアミノ基（ここで、該Ｃ_1-6アルキルアミノ基は、１個のアミノ基で置換されてもよい。）、Ｃ_3-6シクロアルキルアミノ基（ここで、 該Ｃ_3-6シクロアルキルアミノ基は、１個のアミノ基で置換されてもよい。）、又はヘテロシクリル基（ここで、該ヘテロシクリル基は、１個のアミノ基で置換されてもよい。）であり、
Ａ⁴が、水素原子であり、
Ｒ¹が、水素原子であり、
Ｒ²が、Ｃ_1-6アルキル基又はＣ_3-6シクロアルキル基であり、
Ｒ³が、Ｃ_1-6アルキル基｛ここで、該Ｃ_1-6アルキル基は、ハロゲン原子、水酸基、Ｃ_1-6アルコキシ基（ここで、該Ｃ_1-6アルコキシ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールオキシ基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基（ここで、該ヘテロシクリル基は、１〜２個のオキソで置換されてもよい。）、及びアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝であり、
Ｙが、下記式群（ＩＶ）のいずれかの構造であり、

A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a methyl group, an ethyl group, a propyl group, or a cyclopropyl group;
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 A C _1-6 alkylsulfonylamino group, and a heterocyclyl group (wherein the heterocyclyl group may be substituted with 1 to 2 oxo groups). It may be substituted with 1 to 3 identical or different substituents selected from the group. },
Y is a phenyl group or a pyridyl group {wherein the phenyl group and the pyridyl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group (where The C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), C _1-6 alkylsulfonylamino group, phenylsulfonylamino group, and C _1-6 alkyl It may be substituted with 1 to 3 identical or different substituents selected from the group consisting of sulfonyl groups. } The compound according to any one of (1) to (4), or a pharmaceutically acceptable salt thereof,
(6) In the above formula (I),
Y is any structure of the above formula group (II),
Ring Q is an aromatic hydrocarbon ring or a heteroaromatic ring (wherein the aromatic hydrocarbon ring and the heteroaromatic ring may be substituted with one C _1-6 alkyl group),
When W is a single bond, Z is the formula (CH ₂ ) n or the formula CH ₂ NR ⁷ ;
n is an integer of 2 to 4,
When W is of formula CH ₂ , Z is of formula CH ₂ CH ₂ ;
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are the same or different and each is a hydrogen atom, a halogen atom, or a C _1-6 alkyl group,
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or a C _1-6 alkyl group,
Or R ⁴ and R ⁵ together with an adjacent carbon atom are C _3-6 cycloalkane {where C _3-6 cycloalkane is an oxo, hydroxyl group, C _2-6 alkanoylamino group (here And the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And one substitution selected from the group consisting of C _1-6 alkylsulfonylamino groups It may be substituted with a group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is a hydrogen atom, an amino group, a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a C _3-6 cycloalkylcarbonyl group, a C _1-6 alkylsulfonyl group, and a C _1- Which may be substituted with one substituent selected from the group consisting of ₆ alkylsulfonylamino groups), a C _1-6 alkylamino group (wherein the C _1-6 alkylamino group is one C _1-6 alkylsulfonyl group may be substituted), C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is an amino group, a sulfamoyl group, a C _3-6 cycloalkyl group, C _1-6 alkoxy group, C _1-6 alkylamino group, C _2-6 alkanoylamino group, C _1-6 alkylsulfonylamino group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, aryl Sulfonyl group, aryl group, and heteroaryl May be substituted with one substituent selected from the group consisting of.), By C _1-6 alkoxycarbonylamino group (wherein the C _1-6 alkoxycarbonylamino group, substituted with one aryl group Or a C _1-6 alkylsulfonylamino group,
R ⁷ is a hydrogen atom or a C _1-6 alkyl group,
R ⁸ is a carbamoyl group, an amidino group, a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group), C ₁ ( _{6) an} alkoxycarbonyl group (wherein the C _1-6 alkoxycarbonyl group may be substituted with one aryl group), or a C _1-6 alkylsulfonyl group (1) or (2) Or a pharmaceutically acceptable salt thereof,
(7) In the above formula (I),
A ¹ is a hydrogen atom or a C _1-6 alkyl group,
A ² is a hydrogen atom, a C _1-6 alkyl group, or a C _3-6 cycloalkyl group,
A ³ is a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a C _1-6 alkylamino group (wherein the C _{1-6 1-6} alkylamino group may be substituted with one amino group.), C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group is one amino group) Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one amino group),
A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group or a C _3-6 cycloalkyl group,
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 May be substituted with 1 halogen atom), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group has 1 to 2 And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of aryl groups. },
Y is any structure of the following formula group (IV),

Ｗが単結合のとき、Ｚが、式（ＣＨ₂）ｎであり、
ｎが、２〜４の整数であり、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴、及びＢ⁵が、それぞれ水素原子であり、
Ｂ⁶、Ｂ⁷、Ｂ⁸、及びＢ⁹が、同一又は異なって、それぞれ水素原子、又はＣ_1-6アルキル基であり、
Ｒ⁴及びＲ⁵が、隣接する炭素原子と一緒になってＣ_3-6シクロアルカン｛ここで、該Ｃ_3-6シクロアルカンは、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。｝を形成してもよく、さらに該Ｃ_3-6シクロアルカンは、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換されていてもよく、
Ｒ⁶が、アミノ基、Ｃ_1-6アルキル基（ここで、該Ｃ_1-6アルキル基はＣ_1-6アルキルスルホニル基及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、スルファモイル基、Ｃ_3-6シクロアルキル基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、Ｃ_1-6アルキルアミノスルホニル基、アリールスルホニル基、及びアリール基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基、又はＣ_1-6アルキルスルホニルアミノ基であり、
Ｒ⁸が、Ｃ_2-6アルカノイル基（ここで、該Ｃ_2-6アルカノイル基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、又はＣ_1-6アルキルスルホニル基である、（１）、（２）、又は（６）いずれか１つに記載の化合物、又はその医薬上許容される塩、
（８）上記式（Ｉ）中、
Ａ¹が、水素原子であり、
Ａ²が、メチル基であり、
Ａ³が、下記式（Ｖ）の構造であり、

When W is a single bond, Z is the formula (CH ₂ ) n;
n is an integer of 2 to 4,
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are each a hydrogen atom,
B ⁶ , B ⁷ , B ⁸ and B ⁹ are the same or different and each is a hydrogen atom or a C _1-6 alkyl group,
R ⁴ and R ^5, with C _3-6 cycloalkane {here together with the adjacent carbon atoms, the C _3-6 cycloalkane, C _2-6 at alkanoylamino group (wherein said C _{2- The 6} alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And may be substituted with one substituent selected from the group consisting of C _1-6 alkylsulfonylamino groups. Good. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is an amino group, with a C _1-6 alkyl group (wherein, the C _1-6 alkyl groups one selected from the group consisting of C _1-6 alkylsulfonyl group and a C _1-6 alkylsulfonylamino group A C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is a sulfamoyl group, a C _3-6 cycloalkyl group, a C _1-6 alkylsulfonylamino group). group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, may be substituted with an arylsulfonyl group 1 substituents selected from the group consisting of and aryl radicals,.), C _1-6 An alkoxycarbonylamino group, or a C _1-6 alkylsulfonylamino group,
R ⁸ represents a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group), or a C _1-6 alkylsulfonyl group The compound according to any one of (1), (2), or (6), or a pharmaceutically acceptable salt thereof,
(8) In the above formula (I),
A ¹ is a hydrogen atom,
A ² is a methyl group,
A ³ is a structure of the following formula (V),

Ａ⁴が、水素原子であり、
Ｒ¹が、水素原子であり、
Ｒ²が、メチル基又はエチル基であり、
Ｒ³が、メチル基であり、
Ｙが、上記式群（ＩＶ）のいずれかの構造であり、
Ｗが単結合のとき、Ｚが、式（ＣＨ₂）ｎであり、
ｎが、２〜４の整数であり、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴、Ｂ⁵、Ｂ⁶、Ｂ⁷、Ｂ⁸、及びＢ⁹が、水素原子であり、
Ｒ⁴及びＲ⁵が、隣接する炭素原子と一緒になってＣ_3-6シクロアルカン｛ここで、該Ｃ_3-6シクロアルカンは、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）で置換されてもよい。｝を形成してもよく、さらに該Ｃ_3-6シクロアルカンは、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換されてもよく、
Ｒ⁶が、Ｃ_2-6アルカノイルアミノ基（ここで、該Ｃ_2-6アルカノイルアミノ基は、スルファモイル基、Ｃ_1-6アルキルスルホニル基、及びＣ_1-6アルキルアミノスルホニル基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基、又はＣ_1-6アルキルスルホニルアミノ基であり、
Ｒ⁸が、Ｃ_2-6アルカノイル基（ここで、該Ｃ_2-6アルカノイル基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）である、（１）、（２）、（６）、又は（７）いずれか１つに記載の化合物又はその医薬上許容される塩、
（９）上記（１）〜（８）のいずれか１つに記載の化合物又はその医薬上許容される塩を有効成分として含有する医薬、
（１０）上記（１）〜（８）のいずれか１つに記載の化合物又はその医薬上許容される塩を有効成分として含有する、呼吸器合胞体ウイルス（ＲＳＶ）を含むニューモウイルス亜科のウイルスが関与する感染症の予防又は治療薬、
である。

A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a methyl group or an ethyl group,
R ³ is a methyl group,
Y is any structure of the above formula group (IV),
When W is a single bond, Z is the formula (CH ₂ ) n;
n is an integer of 2 to 4,
B ¹ , B ² , B ³ , B ⁴ , B ⁵ , B ⁶ , B ⁷ , B ⁸ , and B ⁹ are hydrogen atoms;
R ⁴ and R ^5, with C _3-6 cycloalkane {here together with the adjacent carbon atoms, the C _3-6 cycloalkane, C _2-6 at alkanoylamino group (wherein said C _{2- The 6} alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is a C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is selected from the group consisting of a sulfamoyl group, a C _1-6 alkylsulfonyl group, and a C _1-6 alkylaminosulfonyl group) And a C _1-6 alkoxycarbonylamino group, or a C _1-6 alkylsulfonylamino group,
R ⁸ is a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group), (1), (2 ), (6), or (7) any one of the compounds or pharmaceutically acceptable salts thereof,
(9) A medicament comprising the compound according to any one of (1) to (8) above or a pharmaceutically acceptable salt thereof as an active ingredient,
(10) Pneumovirus subfamily including respiratory syncytial virus (RSV), comprising as an active ingredient the compound according to any one of (1) to (8) above or a pharmaceutically acceptable salt thereof. Preventive or therapeutic agents for infections involving viruses,
It is.

  The compounds of the present invention have been shown to have anti-RSV activity. The medicament containing the compound of the present invention is useful as a preventive or therapeutic agent for infectious diseases involving viruses of the Pneumovirus subfamily including respiratory syncytial virus (RSV).

  The terms used in this specification are as defined below.

The “halogen atom” is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.
The “C _1-6 alkyl group” refers to a linear alkyl group or branched alkyl group having 1 to 6 carbon atoms. Examples of the linear alkyl group include methyl, ethyl, propyl, butyl, pentyl, and hexyl alkyl groups. Examples of the branched alkyl group include alkyl groups such as isopropyl, isobutyl, tert-butyl, isopentyl, 1-ethylpropyl, and isohexyl.
The “C _3-6 cycloalkyl group” refers to a cyclic alkyl group having 3 to 6 carbon atoms, and examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.
The “C _2-6 alkynyl group” refers to an alkynyl group having 2 to 6 carbon atoms, and examples thereof include ethynyl, propynyl, butynyl, pentynyl, hexynyl group and the like.
Examples of the “aryl group” include phenyl, 1-naphthyl, 2-naphthyl group and the like.
The “heteroaryl group” means a monocyclic heteroaryl group or a condensed heteroaryl group containing 1 to 4 heteroatoms which are the same or different from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. Pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, indolyl, benzofuranyl, benzothienyl, benzoimidazolyl, benzooxazolyl Examples thereof include oxazolyl, benzothiazolyl, benzoisothiazolyl, indazolyl, quinolyl, and isoquinolyl groups.
“C _3-6 cycloalkane” refers to a cyclic alkane having 3 to 6 carbon atoms, and examples thereof include cyclopropane, cyclobutane, cyclopentane, and cyclohexane.
“C _1-6 alkoxy group” refers to a linear or branched alkoxy group having 1 to 6 carbon atoms. Examples of the linear alkoxy group include methoxy, ethoxy, propoxy, butoxy, pentyloxy, and hexyloxy alkoxy groups. Examples of the branched alkoxy group include alkoxy groups such as isopropoxy, isobutoxy, tert-butoxy, isopentyloxy, 1-ethylpropoxy, isohexyloxy and the like.
The “C _2-6 alkanoyl group” refers to an alkanoyl group having 2 to 6 carbon atoms, and examples thereof include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl and the like.
The “C _2-6 alkanoylamino group” means a group in which the above “C _2-6 alkanoyl group” and an amino group are bonded. For example, acetylamino, propionylamino, butyrylamino, isobutyrylamino, valerylamino, iso Examples include valerylamino and pivaloylamino.
The “C _1-6 alkoxycarbonyl group” means a group in which the “C _1-6 alkoxy group” is bonded to a carbonyl group. For example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, Examples include isobutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl group and the like.
The “C _1-6 alkoxycarbonylamino group” means a group in which the “C _1-6 alkoxycarbonyl group” is bonded to an amino group, and examples thereof include methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxy Examples include carbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino group and the like.
The “C _1-6 alkylamino group” means a group in which one or two identical or different “C _1-6 alkyl groups” and an amino group are bonded to each other, and examples thereof include methylamino, ethylamino, Propylamino, butylamino, pentylamino, hexylamino, isopropylamino, isobutylamino, tert-butylamino, isopentylamino, 1-ethylpropylamino, isohexylamino, dimethylamino, diethylamino, dipropylamino, ethylmethylamino, Examples include methylpropylamino and ethylpropylamino groups.
The “C _1-6 alkylaminosulfonyl group” means a group in which the “C _1-6 alkylamino group” is bonded to a sulfonyl group, and examples thereof include methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, butylamino. Sulfonyl, pentylaminosulfonyl, hexylaminosulfonyl, isopropylaminosulfonyl, isobutylaminosulfonyl, tert-butylaminosulfonyl, isopentylaminosulfonyl, 1-ethylpropylaminosulfonyl, isohexylaminosulfonyl, dimethylaminosulfonyl, diethylaminosulfonyl, dipropyl Examples include aminosulfonyl, ethylmethylaminosulfonyl, methylpropylaminosulfonyl, and ethylpropylaminosulfonyl groups.
The “C _3-6 cycloalkylcarbonyl group” means a group in which the “C _3-6 cycloalkyl group” is bonded to a carbonyl group, and examples thereof include cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, and cyclohexylcarbonyl groups. It is done.
The “C _1-6 alkylsulfonyl group” means a group in which the “C _1-6 alkyl group” is bonded to a sulfonyl group, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, hexyl. Examples include sulfonyl, isopropylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, isopentylsulfonyl, 1-ethylpropylsulfonyl, and isohexylsulfonyl groups.
The “C _1-6 alkylsulfonylamino group” means a group in which the “C _1-6 alkylsulfonyl group” is bonded to an amino group, such as methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, butylsulfonyl. Examples include amino, pentylsulfonylamino, hexylsulfonylamino, isopropylsulfonylamino, isobutylsulfonylamino, tert-butylsulfonylamino, isopentylsulfonylamino, 1-ethylpropylsulfonylamino, isohexylsulfonylamino group and the like.
The “C _3-6 cycloalkylamino group” means a group in which the “C _3-6 cycloalkyl group” is bonded to an amino group, and examples thereof include cyclopropylamino, cyclobutylamino, cyclopentylamino, and cyclohexylamino groups. It is done.
The “aryloxy group” means a group in which the “aryl group” and the oxy group are bonded, and examples thereof include a phenoxy group, a 1-naphthoxy group, and a 2-naphthoxy group.
The “arylsulfonyl group” means a group in which the “aryl group” and the sulfonyl group are bonded, and examples thereof include phenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl group and the like.
The “arylsulfonylamino group” means a group in which the above “arylsulfonyl group” is bonded to an amino group, and examples thereof include phenylsulfonylamino, 1-naphthylsulfonylamino, 2-naphthylsulfonylamino groups and the like.
Examples of the “aromatic hydrocarbon ring” include a benzene ring and a naphthalene ring.
“Heteroaromatic ring” means a monocyclic heteroaromatic ring or a condensed heteroaromatic ring containing 1 to 4 heteroatoms which are the same or different from the group consisting of oxygen atom, nitrogen atom and sulfur atom. For example, pyrrole, furan, thiophene, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, triazole, tetrazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, triazine, indole, benzofuran, benzothiophene, benzimidazole Benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, indazole, quinoline, isoquinoline and the like.
"Heterocyclyl group" means a heterocyclyl group containing 1 to 3 heteroatoms which are the same or different from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, such as azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetrahydrofuranyl , Tetrahydropyranyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxidethiomorpholinyl, indolinyl, isoindolinyl, 3,4-dihydro-2H-benzoxazinyl group and the like.
“Heterocyclyloxy group” means a group in which the above “heterocyclyl group” is bonded to an oxy group. For example, azetidinyloxy, pyrrolidinyloxy, piperidinyloxy, oxetanyloxy, tetrahydrofuranyloxy, tetrahydropyranyl Ruoxy, piperazinyloxy, morpholinyloxy, thiomorpholinyloxy, 1,1-dioxidethiomorpholinyloxy, indolinyloxy, isoindolinyloxy, 3,4-dihydro-2H-benzoxa A dinyloxy group etc. are mentioned.

  Pneumovirinae virus including respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus included in Paramyxoviridae, human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV).

  Infectious diseases involving viruses of the Pneumovirinae family including respiratory syncytial virus (RSV) are epidemic in humans and animals, and include RSV infections and HMPV infections.

  When the compound (I) of the present invention forms a salt and it is used as a pharmaceutical, it is preferably a pharmaceutically acceptable salt. “Pharmaceutically acceptable salts” include, for example, salts with inorganic acids such as hydrochloride, sulfate, hydrobromide, nitrate and phosphate, or acetate, oxalate, lactate, citric acid. With organic acids such as acid, malate, tartrate, maleate, fumarate, succinate, methanesulfonate, ethanesulfonate, benzenesulfonate and p-toluenesulfonate Although a salt is used, it is not limited to these salts. Conversion from the educt to the salt can be performed by conventional methods.

  In addition, examples of the “pharmaceutically acceptable salt” include salts with inorganic bases and salts with organic bases. Suitable examples of the salt with an inorganic base include, for example, alkali metal salts (for example, sodium salts, potassium salts, etc.), alkaline earth metal salts (for example, calcium salts, magnesium salts, barium salts, etc.), aluminum salts and An ammonium salt etc. are mentioned. Preferable examples of the salt with an organic base include trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine and N, N-dibenzylethylenediamine.

Preferred embodiments of the compound of the present invention are listed below.
A ¹ is preferably a compound that is a hydrogen atom or a C _1-6 alkyl group, and more preferably a compound that is a hydrogen atom.
A ² is preferably a compound that is a hydrogen atom, a C _1-6 alkyl group, or a C _3-6 cycloalkyl group, and more preferably a compound that is a methyl group, an ethyl group, a propyl group, or a cyclopropyl group.
A ³ is a C _1-6 alkoxy group which may be substituted with one amino group, a C _1-6 alkylamino group which may be substituted with one amino group, or a single amino group. Preferred is a compound which is a C _3-6 cycloalkylamino group or a heterocyclyl group which may be substituted with one amino group, preferably a C _1-6 alkoxy group substituted with one amino group, one More preferably, the compound is a C _1-6 alkylamino group substituted with an amino group, a C _3-6 cycloalkylamino group substituted with one amino group, or a heterocyclyl group substituted with one amino group. Further, a compound having a structure of any one of the following formula group (III) is more preferable.

Ａ⁴は、水素原子である化合物が好ましい。
Ｒ¹は、水素原子である化合物が好ましい。
Ｒ²は、Ｃ_1-6アルキル基（該Ｃ_1-6アルキル基は、１個の水酸基で置換されてもよい。）、又はＣ_3-6シクロアルキル基である化合物が好ましく、Ｃ_1-6アルキル基、又はＣ_3-6シクロアルキル基である化合物がより好ましく、メチル基、エチル基、又はシクロプロピル基である化合物がさらに好ましい。
又は他の好ましい態様として、Ｒ¹及びＲ²が、隣接する炭素原子と一緒になって、Ｃ_3-6シクロアルカンを形成した化合物が好ましい。
Ｙは、アリール基、ヘテロアリール基｛該アリール基及びヘテロアリール基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基（該Ｃ_1-6アルキルスルホニルアミノ基は、１〜３個のハロゲン原子で置換されてもよい。）、アリールスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、ヘテロシクリル基、アリール基、及びヘテロアリール基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝、又はヘテロシクリル基（ここで、該シクロシクリル基は、１個のオキソで置換されてもよい。）である化合物が好ましく、フェニル基、ピリジル基｛該フェニル基及びピリジル基は、ハロゲン原子、アミノ基、Ｃ_1-6アルキル基、Ｃ_1-6アルコキシ基、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、Ｃ_1-6アルキルスルホニルアミノ基、フェニルスルホニルアミノ基、及びＣ_1-6アルキルスルホニル基からなる群から選ばれる同一又は異なる１〜３個の置換基で置換されてもよい。｝である化合物がより好ましい。
又は他の好ましい態様として、Ｙが、式群（ＩＶ）のいずれかの構造である化合物が好ましい。

A ⁴ is preferably a compound that is a hydrogen atom.
R ¹ is preferably a compound that is a hydrogen atom.
R ² is C _1-6 alkyl group (the C _1-6 alkyl group may be substituted with one hydroxy group.), Or C _3-6 is preferable compound is a cycloalkyl group, C _{1- A} compound that is a ₆ alkyl group or a C _3-6 cycloalkyl group is more preferable, and a compound that is a methyl group, an ethyl group, or a cyclopropyl group is more preferable.
Alternatively, as another preferred embodiment, a compound in which R ¹ and R ² are combined with adjacent carbon atoms to form a C _3-6 cycloalkane is preferred.
Y represents an aryl group, a heteroaryl group (the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group (the C _{2 -6} alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group), C _1-6 alkylsulfonylamino group (the C _1-6 alkylsulfonylamino group is 1 to 3 The same or different 1 to 3 substituents selected from the group consisting of an arylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group, an aryl group, and a heteroaryl group It may be substituted with a group. Or a heterocyclyl group (wherein the cyclocyclyl group may be substituted with one oxo group), a phenyl group, a pyridyl group {the phenyl group and the pyridyl group are a halogen atom, an amino group, Group, C _1-6 alkyl group, C _1-6 alkoxy group, C _2-6 alkanoylamino group (the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group) ), A C _1-6 alkylsulfonylamino group, a phenylsulfonylamino group, and a C _1-6 alkylsulfonyl group, the same or different 1 to 3 substituents may be substituted. } Is more preferable.
Or as another preferable aspect, the compound whose Y is a structure in any one of Formula group (IV) is preferable.

このとき、Ｗは単結合であり、Ｚは、式（ＣＨ₂）ｎであり、
ｎは、２〜４の整数である化合物か、
又はＷは式ＣＨ₂であり、Ｚは式ＣＨ₂ＣＨ₂である化合物が好ましく、Ｗは単結合であり、Ｚは、式（ＣＨ₂）ｎであり、ｎは、２〜４の整数である化合物がより好ましい。
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴、及びＢ⁵は、同一又は異なって、それぞれ水素原子、ハロゲン原子、又はＣ_1-6アルキル基である化合物が好ましく、水素原子である化合物がより好ましい。
Ｂ⁶、Ｂ⁷、Ｂ⁸、及びＢ⁹は、同一又は異なって、それぞれ水素原子又はＣ_1-6アルキル基である化合物が好ましく、水素原子である化合物がより好ましい。
Ｒ⁴及びＲ⁵は、隣接する炭素原子と一緒になってＣ_3-6シクロアルカン｛該Ｃ_3-6シクロアルカンは、オキソ、水酸基、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）、及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。｝を形成する化合物か、又は該Ｃ_3-6シクロアルカンが、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換された化合物が好ましく、Ｃ_3-6シクロアルカン｛該Ｃ_3-6シクロアルカンは、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、１個のＣ_1-6アルキルスルホニル基で置換されてもよい。）で置換されてもよい。｝を形成する化合物か、又は該Ｃ_3-6シクロアルカンが、環中の１個の式ＣＨ₂が式ＮＲ⁸で置換された化合物がより好ましい。
Ｒ⁶は、アミノ基、Ｃ_1-6アルキル基（該Ｃ_1-6アルキル基はＣ_1-6アルキルスルホニル基及びＣ_1-6アルキルスルホニルアミノ基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、スルファモイル基、Ｃ_3-6シクロアルキル基、Ｃ_1-6アルキルスルホニルアミノ基、Ｃ_1-6アルキルスルホニル基、Ｃ_1-6アルキルアミノスルホニル基、アリールスルホニル基、及びアリール基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基、又はＣ_1-6アルキルスルホニルアミノ基である化合物が好ましく、Ｃ_2-6アルカノイルアミノ基（該Ｃ_2-6アルカノイルアミノ基は、スルファモイル基、Ｃ_1-6アルキルスルホニル基、及びＣ_1-6アルキルアミノスルホニル基からなる群から選ばれる１個の置換基で置換されてもよい。）、Ｃ_1-6アルコキシカルボニルアミノ基、又はＣ_1-6アルキルスルホニルアミノ基である化合物がより好ましい。
Ｒ⁸は、１個のＣ_1-6アルキルスルホニル基で置換されたＣ_2-6アルカノイル基である化合物又はＣ_1-6アルキルスルホニル基である化合物が好ましく、１個のＣ_1-6アルキルスルホニル基で置換されたＣ_2-6アルカノイル基である化合物がより好ましい。

At this time, W is a single bond, Z is a formula (CH ₂ ) n,
n is a compound that is an integer of 2 to 4,
Or W is a formula CH _2, Z is preferably compounds of the formula CH ₂ CH _2, W is a single bond, Z is a formula (CH ₂₎ n, n is 2 to 4 integer Certain compounds are more preferred.
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are the same or different and are each preferably a hydrogen atom, a halogen atom, or a C _1-6 alkyl group, more preferably a compound that is a hydrogen atom. .
B ⁶ , B ⁷ , B ⁸ and B ⁹ are the same or different and are each preferably a hydrogen atom or a C _1-6 alkyl group, more preferably a hydrogen atom.
R ⁴ and R ⁵ together with the adjacent carbon atom are C _3-6 cycloalkane {the C _3-6 cycloalkane is an oxo, hydroxyl group, C _2-6 alkanoylamino group (the C _2-6 alkanoyl The amino group may be substituted with one C _1-6 alkylsulfonyl group.), And may be substituted with one substituent selected from the group consisting of C _1-6 alkylsulfonylamino groups. Or the C _3-6 cycloalkane is a compound in which one formula CH ₂ in the ring is substituted by the formula NR ⁸ , and the C _3-6 cycloalkane {the C _3-6 The cycloalkane may be substituted with a C _2-6 alkanoylamino group (the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group). Or a compound in which the C _3-6 cycloalkane is substituted with one formula CH ₂ in the ring with the formula NR ⁸ .
R ⁶ is an amino group, a C _1-6 alkyl group (the C _1-6 alkyl group with one substituent selected from the group consisting of C _1-6 alkylsulfonyl group and a C _1-6 alkylsulfonylamino group May be substituted), a C _2-6 alkanoylamino group (the C _2-6 alkanoylamino group is a sulfamoyl group, a C _3-6 cycloalkyl group, a C _1-6 alkylsulfonylamino group, a C _1-6). And may be substituted with one substituent selected from the group consisting of an alkylsulfonyl group, a C _1-6 alkylaminosulfonyl group, an arylsulfonyl group, and an aryl group), a C _1-6 alkoxycarbonylamino group, or C _1-6 compound is alkylsulfonylamino group are preferred, C _2-6 alkanoylamino group (said C _2-6 alkanoylamino group, a sulfamoyl group, C _1-6 alkylsulfonyl group, and C _1-6 alkyl With 1 substituent selected from the group consisting of Minosuruhoniru group may be substituted.), C _1-6 alkoxycarbonylamino group, or a C _1-6 compound is alkylsulfonylamino group is more preferred.
R ⁸ is one of C _1-6 compound alkylsulfonyl C _2-6 alkanoyl group substituted by a group or a C _1-6 compound alkylsulfonyl group is preferable, one C _1-6 alkylsulfonyl More preferred are compounds that are C _2-6 alkanoyl groups substituted with groups.

When this invention compound (I) contains an optical isomer, a stereoisomer, a positional isomer, and a rotational isomer, a single compound and its mixture are included as a compound of this invention. Moreover, when this invention compound (I) forms a hydrate or a solvate, these are also contained in the scope of the present invention. Similarly, pharmaceutically acceptable salts of hydrates or solvates of the compounds of the invention are also included within the scope of the invention. Further, the compound (I) of the present invention may be labeled with an isotope (for example, D, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ³⁵ S, ¹²⁵ I, etc.).

  The compound (I) of the present invention or a pharmaceutically acceptable salt is produced by formulating it as it is or with a pharmacologically acceptable carrier according to a method known per se. Examples of pharmacologically acceptable carriers include various organic or inorganic carrier substances commonly used as pharmaceutical materials, such as excipients in solid formulations (eg, lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, light Silicic anhydride, etc.), lubricants (eg, magnesium stearate, calcium stearate, talc, colloidal silica), binders (eg, crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose) , Polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, sodium carboxymethylcellulose, etc.), disintegrant (eg starch, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmello) Sodium, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, etc.) or solvents in liquid formulations (eg water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, etc.), solubilizers (eg polyethylene glycol) , Propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, etc.), suspending agents (eg, stearyltriethanolamine, sodium lauryl sulfate, lauryl) Surfactants such as aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, or, for example, polyvinyl alcohol, polyvinylidene Pyrrolidone, sodium carboxymethylcellulose, hydrophilic polymers such as methylcellulose, hydroxymethylcellulose, and hydroxypropylcellulose), isotonic agents (eg, glucose, D-sorbitol, sodium chloride, glycerin, D-mannitol, etc.), buffers ( For example, phosphates, acetates, carbonates, citrates, etc.), soothing agents (eg, benzyl alcohol, etc.) and the like. In addition, preservatives (for example, paraoxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.), antioxidants (for example, sulfites, Ascorbic acid and the like), colorants, sweeteners, adsorbents, wetting agents and the like can also be used.

  The compound (I) or pharmaceutically acceptable salt of the present invention can be administered orally or parenterally (for example, intravenous, topical, rectal administration, etc.). The dosage form includes, for example, tablets (including sugar-coated tablets and film-coated tablets), powders, granules, powders, troches, capsules (including soft capsules), liquids, injections (for example, subcutaneous injections, intravenous injections) Injections, intramuscular injections, intraperitoneal injections, etc.), external preparations (eg, nasal preparations, transdermal preparations, ointments, creams, etc.), suppositories (eg, rectal suppositories, vaginal suppositories, etc.) ), Sustained-release agents (eg, sustained-release microcapsules), pellets, infusions, etc., all of which can be produced by conventional formulation techniques (eg, the method described in the 16th revised Japanese Pharmacopoeia, etc.). it can.

  The dose of the compound (I) of the present invention or a pharmaceutically acceptable salt is appropriately selected depending on the administration subject, administration route, disease, patient age, weight and symptoms. For example, when treating an adult patient, the dosage is 1 to 5000 mg per day, and this amount is administered once or divided into several times a day.

The compound (I) of the present invention and pharmaceutically acceptable salts thereof can be synthesized using various organic synthesis methods known to those skilled in the art. For example, the production method is shown below, but is not limited to this synthesis method. In the following reaction formulas, R ¹ , R ² , R ³ , A ¹ , A ² , A ³ , A ⁴ and Y are as defined above.

  The compounds of the present invention are all novel compounds not described in publications, but can be produced by known methods described in publications or similar methods. Publications include, for example, Organic Functional Group Preparations (1968, SR Sandler et al., Academic Press Inc.), Synthetic Organic 61 (Synthetic Organic Chemistry 19). , SR Wagner et al., John Wiley Inc.), Comprehensive Organic Transformations (1989, RC Larlock, VCH Publishers, INC.). Of Regents for Organic Synth (Encyclopedia of Reagents for Organic Synthesis, 1995, LA Packet et al., Wiley INC.), Compendium of Organic Synthetic Method 9th Edition, Michael 9th Edition. B. Smith, Wiley Inc.).

  Examples of the “inert solvent” include aromatic solvents such as benzene, toluene, xylene and pyridine; hydrocarbon solvents such as hexane, pentane and cyclohexane; dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride and the like. Halogenated hydrocarbon solvents; ether solvents such as tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane; ester solvents such as ethyl acetate and ethyl formate; methanol, ethanol, isopropyl alcohol, tert- Alcohol solvents such as butyl alcohol and ethylene glycol; ketone solvents such as acetone and methyl ethyl ketone; amide solvents such as N, N-dimethylformamide, N-methylpyrrolidone and N, N-dimethylacetamide; sulfoxides such as dimethyl sulfoxide De solvents; acetonitrile, nitriles and water, such as propionitrile, and never is a these homogeneous and heterogeneous mixed solvents is not limited thereto. These inert solvents are appropriately selected according to various reaction conditions known to those skilled in the art.

  Examples of the “base” include hydrides of alkali metals or alkaline earth metals such as lithium hydride, sodium hydride, potassium hydride, calcium hydride; lithium amide, sodium amide, lithium diisopropylamide, lithium dicyclohexylamide, lithium Alkali metal or alkaline earth metal amides such as hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide; alkali metals such as sodium methoxide, sodium ethoxide, potassium tert-butoxide or alkaline earth Lower metal alkoxides; alkyl lithiums such as butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium; sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide Alkali metal or alkaline earth metal hydroxide such as sodium carbonate, potassium carbonate, cesium carbonate or other alkali metal or alkaline earth metal carbonate; Sodium hydrogen carbonate, potassium hydrogen carbonate or other alkali metal or alkaline earth Metal bicarbonate; triethylamine, N-methylmorpholine, N, N-diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1,5-diazabicyclo [4.3 0.0] amines such as non-5-ene (DBN) and N, N-dimethylaniline; basic heterocyclic compounds such as pyridine, imidazole and 2,6-lutidine, but not limited thereto. . These bases are appropriately selected according to various reaction conditions known to those skilled in the art.

  Examples of the “acid” include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, and organic acids such as p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, formic acid, and acetic acid. It is not limited to. These acids are appropriately selected according to various reaction conditions known to those skilled in the art.

[Production method 1]
The compound (I) of the present invention can be produced by the method shown in Scheme 1.
(Scheme 1)

In the formula, Lv represents a leaving group such as a methoxy group, an ethoxy group, or a methoxymethylamino group.
P ¹ represents an amino-protecting group such as a methoxycarbonyl group, an ethoxycarbonyl group, a tert-butoxycarbonyl group, a benzyloxycarbonyl group, an acetyl group or a benzyl group [Protective Groups in Organic Synthesis] , 4th Edition, 2006, TW Green et al., Wiley Inc.)].
X ¹ represents a leaving group such as a halogen atom or a trifluoromethanesulfonyloxy group.

Step 1-1: Compound (1) is alkylated with an alkyl halide such as methyl iodide and ethyl iodide in the presence of a base such as cesium carbonate in an inert solvent. -2) can be obtained. Alternatively, compound (1-2) can be obtained by reacting with an alkyl agent such as trimethylsilyldiazomethane in an inert solvent. Furthermore, a compound (1-2) can be obtained by acting an acid such as sulfuric acid in an alcohol solvent. Alternatively, the compound (1-2) is obtained by subjecting it to a dehydration condensation reaction with an alcohol such as methanol or ethanol or an alkoxyamine compound such as methoxymethylamine in the presence or absence of a base in an inert solvent. Can do. Here, the dehydration condensation reaction means N, N′-dicyclohexylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, diphenylphosphoryl azide, or in the presence or absence of a base in an inert solvent. Esterification reaction or amidation reaction using a condensing agent such as carbonyldiimidazole, esterification reaction or amidation reaction via mixed acid anhydride using ethyl chlorocarbonate, isobutyl chlorocarbonate or pivaloyl chloride, etc. Meaning [Refer to Peptide Synthesis Fundamentals and Experiments (1995, written by Michinori Waki et al., Maruzen Corporation)] Here, in the esterification reaction or amidation reaction using a condensing agent, additives such as 1-hydroxybenzotriazole can be used as necessary. Carboxylic acid (1-1) is available as a commercially available compound or a known compound. The carboxylic acid (1-1) can be synthesized from a commercially available compound or a known compound using various organic synthesis methods known to those skilled in the art.
Step 1-2: In an inert solvent, nitrile compounds such as acetonitrile and propionitrile are allowed to act on compound (1-2) in the presence of a base such as sodium hexamethyldisilazide and lithium hexamethyldisilazide. Thus, the compound (1-3) can be obtained.
Step 1-3: Compound (1-4) can be obtained by reacting compound (1-3) with hydrazine hydrate in an inert solvent in the presence or absence of an acid such as acetic acid.
Step 1-4: A compound (1-4) in an inert solvent in the presence or absence of a base such as cesium carbonate and an acrylic ester such as ethyl (2E) -3-ethoxy-2-methylprop-2-enoate To give compound (1-5). Various acrylic esters are available as commercially available compounds and known compounds. Various acrylic esters can be synthesized from commercially available compounds or known compounds using various organic synthesis methods known to those skilled in the art.
Step 1-5: When X ¹ of the compound (1-6) represents a halogen atom, the compound (1-5) is thionyl chloride, 3 in the presence or absence of a base in an inert solvent or without solvent. Compound (1-6) can be obtained by conducting a halogenation reaction using a halogenating agent such as phosphorus chloride, phosphorus pentachloride, phosphorus tribromide, phosphorus pentabromide, phosphorus oxychloride and the like. Alternatively, when X ¹ of compound (1-6) represents a trifluoromethanesulfonyloxy group, by reacting compound (1-5) with a trifluoromethanesulfonylating agent in an inert solvent in the presence or absence of a base. Compound (1-6) can be obtained. Here, the trifluoromethanesulfonylating agent is, for example, trifluoromethanesulfonic anhydride, N-phenyl-bis (trifluoromethanesulfonimide) or the like [Comprehensive Organic Transformations, 1989, RC RC Laroc, VCH Publishers, INC.)].
Step 1-6: Various protective methods known in the art for protecting the amino group P ¹ of the compound (1-6) in an inert solvent [Protective Groups in Organic Synthesis, Protective Groups in Organic Synthesis, 4th edition, 2006, TW Green et al., Wiley INC.)] To obtain the amine compound (1-7).
Step 1-7: Compound (1-8) by reacting compound (1-7) with an amine compound such as pyrrolidine or an alcohol compound such as methanol or ethanol in an inert solvent in the presence or absence of a base. Can be obtained. Alternatively, in an inert solvent, in the presence or absence of a base, in the presence of a transition metal catalyst, and optionally using a ligand, the compound (1-7) is converted into an amine compound, alcohol compound, organometallic compound, olefin compound. Alternatively, the compound (1-8) can be obtained by subjecting it to a coupling reaction with a terminal alkyne compound. Here, examples of the coupling reaction include coupling reaction conditions known to those skilled in the art. For example, Comprehensive Organic Transformations (1989) by RC Larlock, VCH Publishers. , INC.) And the like, a method according to the method, or a combination of these methods. Here, examples of the organometallic compound include a magnesium reactant, a zinc reactant, a boron reactant, a tin reactant, and the like, and are commercially available compounds, known compounds, or commercially available compounds using various organic synthesis techniques known to those skilled in the art. Alternatively, a compound synthesized from a known compound can be used. Here, as the olefin compound and the terminal alkyne compound, a commercially available compound, a known compound or a compound synthesized from a known compound using various organic synthesis methods known to those skilled in the art can be used. Examples of the transition metal catalyst include palladium (II) acetate, palladium (II) chloride, palladium (II) bis (triphenylphosphine) acetate, palladium (II) bis (triphenylphosphine) chloride, tris (dibenzylideneacetone). ) Dipalladium (0), bis (dibenzylideneacetone) palladium (0), tetrakistriphenylphosphine palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II), allyl palladium chloride (II), bis (acetonitrile) palladium chloride (II), [1,3-bis (2,6-diisopropylphenyl) imidazol-2-ylidene] (3-chloropyridyl) palladium (II) dichloride or [1,3 -Bis (2,6-diisopropylphenyl) imidazo Den] (3-chloropyridyl) palladium (II) dichloride, [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (1: 1), copper powder, copper (I) chloride, Examples thereof include copper (I) bromide, copper (I) iodide, and copper (I) acetate. Examples of the ligand include triphenylphosphine, tributylphosphine, tri (2-furyl) phosphine, 2,2-bis (diphenylphosphino) -1,1-binaphthyl (BINAP), 2- (di-tert-butylphosphine). Phino) biphenyl, 1,1-bis (diphenylphosphino) ferrocene, 1,10-phenanthroline, N, N′-dimethylethylenediamine or tetramethylethylenediamine.
Step 1-8: The present compound (I) is obtained by subjecting the amine compound (1-8) and an acid halide compound or carboxylic acid compound to an amidation reaction in an inert solvent in the presence or absence of a base. be able to. The acid halide compound or carboxylic acid compound is available as a commercially available compound or a known compound. Moreover, an acid halide compound or a carboxylic acid compound can be synthesized from a commercially available compound or a known compound using various organic synthesis methods known to those skilled in the art. Here, the amidation reaction means N, N′-dicyclohexylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, diphenylphosphoryl azide, or in the presence or absence of a base in an inert solvent. It means an amidation reaction using a condensing agent such as carbonyldiimidazole or an amidation reaction via a mixed acid anhydride using ethyl chlorocarbonate, isobutyl chlorocarbonate or pivaloyl chloride, etc. Experiment, (1995, written by Michinori Waki, Maruzen)]. Here, in the amidation reaction using a condensing agent, an additive such as 1-hydroxybenzotriazole can be used as necessary.
Step 1-9: The compound (1-7) can be converted to a compound (1-9) by the same method as in the above step 1-8.
Step 1-10: The compound (1-9) can be converted to the compound (I) of the present invention by the same method as in the above step 1-7.
Step 1-11: The compound (1-6) can be converted to a compound (1-10) by the same method as in the above step 1-7.
Step 1-12: The compound (1-10) can be converted to a compound (1-8) by the same method as in the above step 1-6.

The compound (I) of the present invention can also be produced by the method shown in Scheme 2.
(Scheme 2)

Step 2-1: Compound (2) by the same method as in Step 1-1 to Step 1-7 or the same method as in Step 1-1 to Step 1-5, Step 1-11, and Step 1-12 1) can be converted to compound (2-2).
Step 2-2: Compound (1) is reacted with an alkyl halide such as methyl iodide or ethyl iodide in an inert solvent in the presence or absence of a base such as potassium carbonate. -8) can be obtained. In addition, compound (2-2) is subjected to various reductive amination reactions [see Comprehensive Organic Transformations, 1989, RC Larlock, VCH Publishers, Inc.]. Can be converted to compound (1-8).
Step 2-3: Allowing a compound (2-2) to react with a trifluoroacetylating agent such as trifluoroacetic acid ester or trifluoroacetic anhydride in the presence of a base such as triethylamine in an inert solvent. Thus, the compound (2-3) can be obtained.
Step 2-4:
Various alkylation reactions known to those skilled in the art (see Comprehensive Organic Transformations, 1989, RC Larlock, VCH Publishers, Inc.) ] To convert to compound (2-4).
Step 2-5: Various hydrolysis reactions known to those skilled in the art [Protective Groups in Organic Synthesis, 4th edition, 2006, TW Green et al., Wiley INC.)] To convert the compound (1-8).
Step 2-6: The compound (1-8) can be converted to the compound (I) of the present invention by the same method as in the above step 1-8.

The compound (I) of the present invention can also be produced by the method shown in Scheme 3.
(Scheme 3)

In the formula, X ² represents a halogen atom.
When compound (1-5) and compound (1-8) are represented by compounds (3-1) and (3-4), respectively, they can be converted to the present compound (I) by the following method.
Step 3-1: By reacting a compound (3-1) with a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, Selectfluor (AIR Products and Chemicals) in an inert solvent. Compound (3-2) can be obtained.
Step 3-2: The compound (3-2) can be converted to a compound (3-3) by the same method as in the above step 1-5 to step 1-12.
Step 3-3: In an inert solvent, in the presence or absence of a base, in the presence of a transition metal catalyst, and optionally using a ligand, the compound (3-3) is converted into an organometallic compound, an olefin compound, or a terminal. The compound (I) of the present invention can be produced by subjecting it to a coupling reaction with an alkyne compound. Here, examples of the coupling reaction include coupling reaction conditions known to those skilled in the art. For example, Comprehensive Organic Transformations (1989) by RC Larlock, VCH Publishers. , INC.) And the like, a method according to the method, or a combination of these methods. Here, examples of the organometallic compound include a magnesium reactant, a zinc reactant, a boron reactant, a tin reactant, and the like, and are commercially available compounds, known compounds, or commercially available compounds using various organic synthesis techniques known to those skilled in the art. Alternatively, a compound synthesized from a known compound can be used. Here, as the olefin compound and the terminal alkyne compound, a commercially available compound, a known compound or a compound synthesized from a known compound using various organic synthesis methods known to those skilled in the art can be used. Examples of the transition metal catalyst include palladium (II) acetate, palladium (II) chloride, palladium (II) bis (triphenylphosphine) acetate, palladium (II) bis (triphenylphosphine) chloride, tris (dibenzylideneacetone). ) Dipalladium (0), bis (dibenzylideneacetone) palladium (0), tetrakistriphenylphosphine palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II), allyl palladium chloride (II), bis (acetonitrile) palladium chloride (II), [1,3-bis (2,6-diisopropylphenyl) imidazol-2-ylidene] (3-chloropyridyl) palladium (II) dichloride or [1,3 -Bis (2,6-diisopropylphenyl) imidazo Den] (3-chloropyridyl) palladium (II) dichloride, copper powder, copper chloride (I), copper bromide (I), copper iodide (I), copper (I) acetate, and the like. Examples of the ligand include triphenylphosphine, trifurylphosphine, tributylphosphine, 2,2-bis (diphenylphosphino) -1,1-binaphthyl (BINAP), 2- (di-tert-butylphosphino) biphenyl, Examples include 1,1-bis (diphenylphosphino) ferrocene, 1,10-phenanthroline, N, N′-dimethylethylenediamine, tetramethylethylenediamine, and the like.
Step 3-4: The compound (3-4) can be converted to a compound (3-5) by the same method as in the above step 3-1.
Step 3-5: The compound (3-5) can be converted to a compound (3-3) by the same method as in the above step 1-8.

Furthermore, by changing the order of carrying out the steps, adding a protective step to the hydroxy group or amino group, carrying out the reaction and carrying out the deprotection in a later step, adding a new step in the middle of each step, R ¹ , R ² , R ³ , A ¹ , A ² , A ³ , A ⁴ and Y are functionally converted using various organic synthesis methods known to those skilled in the art without departing from the present invention. The compound (I) of the present invention can also be produced.

Examples of amino-protecting groups include C _1-6 acyl groups (formyl, acetyl, propionyl, etc.) and C _2-12 alkoxycarbonyl groups (methoxycarbonyl, ethoxycarbonyl, tert-butoxy) generally used during peptide synthesis. Carbonyl, benzyloxycarbonyl, 9-fluorenylmethylenoxycarbonyl, etc.), arylcarbonyl group (benzoyl, etc.), trityl group, phthaloyl group, N, N-dimethylaminomethylene group, substituted silyl group (trimethylsilyl, triethylsilyl, Dimethylphenylsilyl, tert-butyldimethylsilyl, tert-butyldiethylsilyl, etc.) and C _2-6 alkenyl groups (1-allyl etc.). These groups may be substituted with one or more substituents selected from a halogen atom, a C _1-6 alkoxy group (methoxy, ethoxy, propoxy, etc.), and a nitro group.
Examples of the protecting group for the hydroxy group include C _1-6 alkyl groups (methyl, ethyl, tert-butyl, etc.), C _7-20 aralkyl groups (benzyl, trityl, etc.), phenyl groups, substituted silyl groups (trimethylsilyl, triethyl). Silyl, dimethylphenylsilyl, tert-butyldimethylsilyl, tert-butyldiethylsilyl, etc.), C _2-6 alkenyl group (1-allyl etc.), C _1-6 acyl group (formyl, acetyl, propionyl etc.), C _{2 -12} alkoxycarbonyl group (methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethylenoxycarbonyl etc.), arylcarbonyl group (benzoyl etc.), 2-tetrahydropyranyl group, 2- A tetrahydrofuranyl group is mentioned. These groups may be substituted with one or more substituents selected from a halogen atom, a C _1-6 alkoxy group (methoxy, ethoxy, propoxy, etc.), and a nitro group.

  The reaction temperature of the general production method of the compound of the present invention is −78 ° C. to 250 ° C., preferably −78 ° C. to 120 ° C. The reaction time is 5 minutes to 3 days, preferably 30 minutes to 18 hours. This production method can be carried out under normal pressure, under pressure, under microwave irradiation, or the like.

Hereinafter, the present invention will be described in more detail with reference examples, examples, and test examples. However, the present invention is not limited to these examples, and may be changed without departing from the scope of the present invention.
In the reference examples and examples, “Phase Separator” at the time of post-processing is ISOLUTE (registered trademark) Phase Separator manufactured by Biotage. When purified using silica gel column chromatography, Merck "Silica gel 60", Fuji Silysia Chemical "silica gel PSQ60", Kanto Chemical "silica gel 60", "Silica gel 60N", Fuji Silysia Chemical "Chromatolex NH", or Packed columns Biotage SNAP Cartridge KP-NH, Biotage SNAP Cartridge KP-Sil, Biotage SNAP Cartridge HP-Sil, GRACE REVELERISTM (Amino, 40 μM), GRACE REVELERISTM (Silica, 40 μM) and the like were used. Unless otherwise noted, Fuji Silysia Chemical "silica gel PSQ60", Kanto Chemical "silica gel 60N" or packed column was used. When purified using preparative thin layer chromatography (PTLC) was used Merck silica gel _{60F 254, 20 cm × 20 cm} . Water purification SFC30 was used for preparative purification by the supercritical fluid chromatography (SFC) method. For “reverse phase column chromatography” (hereinafter sometimes referred to as reverse phase preparative HPLC) during purification, Waters Sunfire prep C18 OBD, 5.0 μm, φ30 × 50 mm or YMC-Actus Triart C18, 5.0 μm, φ30 × 50 mm, Xbridge Prep C18 5.0 μm OBD, φ30 × 50 mm, Water XSlect CSH C18, 5.0 μm, φ30 × 50 mm (hereinafter sometimes referred to as reverse phase preparative HPLC). The preparative conditions were appropriately selected from the following three conditions for purification.

Preparative equipment: Agilent 1260 and Agilent 6130
Mobile phase A: water containing 0.1% formic acid, B: acetonitrile containing 0.1% formic acid,
Flow rate: 50 mL / min
Preparative condition 1:
0.0-0.5 min (A liquid / B liquid = 90/10)
0.5-7.5 min (A liquid / B liquid = 90/10 ~ 20/80)
7.5-7.9 5min (A liquid / B liquid = 20/80)
7.95-8.0 min (A liquid / B liquid = 20/80 to 5/95)
8.0-9.0 min (A liquid / B liquid = 5/95)
Preparative condition 2:
0.0-0.5 min (A liquid / B liquid = 95/5)
0.5-7.5 min (A liquid / B liquid = 95/5 ~ 50/50)
7.5-7.95 min (A liquid / B liquid = 50/50)
7.95-8.0 min (A liquid / B liquid = 50/50-5/95)
8.0-9.0 min (A liquid / B liquid = 5/95)
Preparative condition 3:
0.0-0.5 min (A liquid / B liquid = 80/20)
0.5-7.0 min (A liquid / B liquid = 80/20-5/95)
7.0-7.45 min (A / B = 5/95)
7.45-7.5 min (A liquid / B liquid = 5/95-1/99)
7.5-9.0 min (A liquid / B liquid = 1/99)

Each instrument data described in the following reference examples and examples was measured with the following measuring instruments.
NMR spectrum: JEOL JNM-ECA600 (600 MHz), JEOL JNM-ECA500 (500 MHz), Varian UNITYNOVA300 (300 MHz), Varian GEMINI2000 / 200 (200 MHz)
MS spectrum: Shimadzu LCMS-2010EV or micromass Platform LC
In the following Reference Examples and Examples, high performance liquid chromatography mass spectrum (LCMS) was measured under the following conditions.
Analysis condition 1
Measuring instrument: micromass Platform LC and Agilent Agilent 1100
Column: Waters SunFire C18, 2.5 μm, φ4.6 × 50 mm
Ionization method: Electron Spray Ionization: ESI
Solvent: Solution A; 0.1% trifluoroacetic acid-containing water, Solution B; 0.1% trifluoroacetic acid-containing acetonitrile Detection method: 254 nm, flow rate: 1 mL / min
Gradient: 0 min (A liquid / B liquid = 90/10), 0.5 min (A liquid / B liquid = 90/10), 5.5 min (A liquid / B liquid = 20/80), 6.0 min (A liquid / B solution = 1/99), 6.3 min (A solution / B solution = 1/99)
Analysis condition 2 (hereinafter referred to as mode H)
Measuring machine: Agilent 1290 and Agilent 6130
Column: Waters Acquity CSH C18, 1.7 μm, φ2.1 × 50 mm
Ionization method: Electron Spray Ionization: ESI
Solvent: Solution A; 0.1% formic acid-containing water, Solution B; 0.1% formic acid-containing acetonitrile Detection method: 254 nm
Flow rate and gradient: 0.8 mL / min, 0 min (A liquid / B liquid = 80/20) → 1.2 min (A liquid / B liquid = 50/50), 1.0 mL / min → 1.38 min (A liquid / B liquid = 3/97).
Analysis condition 3 (hereinafter referred to as mode N)
The measurement equipment, column, solvent, ionization method, and detection method are the same as in Analysis Condition 2.
Flow rate and gradient: 0.8 mL / min, 0 min (A liquid / B liquid = 80/20) → 1.2-1.4 min (A liquid / B liquid = 1/99).
Analysis condition 4 (hereinafter referred to as mode L)
Flow rate and gradient: 0 min (A / B solution = 70/30) → 0.8 min (A / B solution = 5/95), 1.5 mL / min → 1.0-1.4 min (A / B solution = 1 / 99)
In the following Reference Examples and Examples, Waters UPC2 was used for analysis by the supercritical fluid chromatography (SFC) method.
In the following Reference Examples and Examples, the compound names were named by ACD / Name (ACD / Labs 12.01, Advanced Chemistry Development Inc.).

In the present Reference Examples and Examples, the following terms and reagents are expressed as follows.
AcCl (acetyl chloride), AcOH (acetic acid), Boc (tert-butoxycarbonyl), Brine (saturated saline), br s (wide singlet), Bu (butyl), CDCl ₃ (deuterated chloroform), CD ₃ OD (deuterated methanol), CHCl ₃ (chloroform), CMBP (cyanomethylenetributylphosphorane), CO ₂ (carbon dioxide), cPr (cyclopropyl), Cs ₂ CO ₃ (cesium carbonate), CuI (iodide) Copper (I)), d (double wire), dd (double double wire), DIPEA (N, N-diisopropylethylamine), DMAP (N, N-dimethyl-4-aminopyridine), DMF (N, N-dimethylformamide), DMSO (dimethyl sulfoxide), DMSO-d ₆ (deuterated dimethyl sulfoxide), dt (double triplet), ee (enantiomeric excess), ESI (electrospray ionization), Et (ethyl) ), EtI (ethyl iodide), Et ₃ N (triethylamine), Et ₂ O ( Ethyl ether), EtOAc (ethyl acetate), EtOH (ethanol), H (proton), HATU [O- (7-azabenzotriazol-1-yl) -N, N, N ′, N′-tetramethyluronium Hexafluorophosphate], HCl (hydrogen chloride), HMDS (1,1,1,3,3,3-hexamethyldisilazane), HPLC (high performance liquid chromatography), Hz (hertz), IPA (isopropyl alcohol) , IPE (isopropyl ether), iPr (isopropyl), J (coupling constant), K ₂ CO ₃ (potassium carbonate), KOH (potassium hydroxide), LCMS (high performance liquid chromatography mass spectrum), m (multiple line) , M (mol / L), Me (methyl), MeCN (acetonitrile), MeI (methyl iodide), MeOH (methanol), MHz (megahertz), MgSO ₄ (anhydrous magnesium sulfate), min (min), MS ( Mass spectrometry), MsCl (meta chloride) Sulfonyl), m / z (mass-to-charge ratio), NaHCO ₃ (sodium bicarbonate), NaHMDS (sodium hexamethyldisilazane), NaOH (sodium hydroxide), NaOMe (sodium methoxide), NaOEt (sodium ethoxide) , Na ₂ SO ₄ (anhydrous sodium sulfate), NCS (N-chlorosuccinimide), NH ₄ Cl (ammonium chloride), NH ₄ OH (25-28% aqueous ammonia), NIS (N-iodosuccinimide), NMR (nuclear Magnetic resonance spectroscopy), PdCl ₂ (PPh ₃ ) ₂ [bis (triphenylphosphine) palladium (II) dichloride], PdCl ₂ (dppf) · CH ₂ Cl ₂ {[1,1'-bis (diphenylphos Fino) ferrocene] palladium (II) dichloride dichloromethane complex (1: 1)}, Pd ₂ (dba) ₃ [tris (dibenzylideneacetone) dipalladium (0)], Ph (phenyl), POCl ₃ (phosphorus oxychloride) , PPh ₃ (triphenylphosphine), Pr (flop Pill), q (quadruplex), s (singlestrand), SFC (supercritical fluid chromatography), t (triple), TBAF (tetrabutylammonium fluoride), TBDPSCl (tert-butyldiphenylchlorosilane) , Td (triple duplex), TFA (trifluoroacetic acid), TFP [tri (2-furyl) phosphine], THF (tetrahydrofuran), t _R (retention time), v / v (volume / volume), δ [Degree of low magnetic field from tetramethylsilane (parts per million)].

Reference Example 1: Synthesis of 1-methyl-4-[(methylsulfonyl) amino] -1H-pyrazole-5-carboxylic acid (1) Methyl 4-amino-1-methyl-1H-pyrazole-5-carboxylate (100 mg) in CHCl ₃ (2.0 mL) was added with Et ₃ N (0.90 mL) and MsCl (0.15 mL) under ice-cooling, and the mixture was stirred at 0 ° C. for 10 minutes. The reaction solution was concentrated under reduced pressure, EtOH (2.0 mL) and 20% NaOEt / EtOH solution (2.2 mL) were added thereto, and the mixture was stirred at room temperature for 15 minutes. 1 M HCl aqueous solution and CHCl ₃ were added to the reaction solution, and liquid separation operation was performed. The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by reverse phase preparative HPLC to give ethyl 1-methyl-4-[(methylsulfonyl) amino] -1H-pyrazole-5-carboxylate (120 mg, colorless oil) .
(2) To a solution of the compound (110 mg) obtained in Reference Example (1) in EtOH (2.0 mL) was added 1 M aqueous sodium hydroxide solution (0.9 mL), and the mixture was stirred at room temperature for 18 hours. To the reaction solution was added 1 M aqueous sodium hydroxide solution (0.9 mL), and the mixture was stirred at room temperature for 4 hours. A 1 M HCl aqueous solution and CHCl ₃ were added to the reaction solution to carry out a liquid separation operation. The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure to give the title compound (86 mg, white crystals).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.99 (s, 3H), 4.01 (s, 3H), 7.48 (s, 1H), 8.69 (br s, 1H), 13.90 (br s, 1H ).
LCMS (ESI) m / z 220 [M + H] ⁺ , t _R = 0.73 min, mode H.

Reference Example 2: 1-methyl-4-[(methylsulfonyl) amino] -1H-pyrazole-3-carboxylic acid Using the same procedure as in Reference Example 1, methyl 4-amino-1-methyl-1H-pyrazole- The title compound (45 mg, white crystals) was obtained from 3-carboxylate (100 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.98 (s, 3H), 3.87 (s, 3H), 7.78 (s, 1H), 8.61 (br s, 1H), 13.02 (br s, 1H ).
LCMS (ESI) m / z 218 [MH] ^- , t _R = 0.55 min, mode H.

Reference Example 3: Synthesis of 3-chloro-5-methyl-2-[(methylsulfonyl) amino] benzoic acid
NCS (76 mg) was added to a DMF (1.0 mL) solution of 5-methyl-2-[(methylsulfonyl) amino] benzoic acid (100 mg), and the mixture was stirred at room temperature for 17 hours. The reaction solution was purified by reverse phase preparative HPLC to give the title compound (34 mg, white crystals).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.33 (s, 3H), 3.02 (s, 3H), 7.53 (d, J = 1.7 Hz, 1H), 7.57 (d, J = 1.2 Hz, 1H), 9.43 (br s, 1H), 13.28 (br s, 1H).
LCMS (ESI) m / z 262 [MH] ^- , t _R = 0.70 min, mode N.

Reference Example 4: Synthesis of 1-{[(benzyloxy) carbonyl] amino} -2,3-dihydro-1H-indene-1-carboxylic acid (1) Potassium cyanide (4.93 g), ammonium carbonate (36.3 g) in water A solution of 1-indanone (5.00 g) in MeOH (50 mL) was added dropwise to the (50 mL) solution, and the mixture was stirred at 60 ° C. for 24 hours. After cooling the reaction solution to room temperature, water was added to the reaction solution and stirred. The resulting solid was collected by filtration, dried under reduced pressure, and 2 ', 3'-dihydro-2H, 5H-spiro [imidazolidine-4,1'-indene] -2,5-dione (6.47 g, colorless solid) )
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.12-2.18 (m, 1H), 2.50-2.56 (m, 1H), 2.95-3.05 (m, 2H), 7.15 (d, J = 7.4 Hz , 1H), 7.23-7.27 (m, 1H), 7.29-7.33 (m, 2H), 8.41 (s, 1H), 10.74 (br s, 1H).
LCMS (ESI) m / z 201 [MH] ^- , t _R = 0.50 min, mode N.
(2) The compound (6.47 g) obtained in Reference Example 4 (1) was dissolved in 5 M NaOH aqueous solution (40 mL), and stirred for 2 days while heating under reflux. After cooling the reaction solution to room temperature, a solution of NaOH (3.20 g) in water (20 mL) was added, and the mixture was stirred for 8 hours under reflux with heating. After cooling the reaction solution to room temperature, water (60 mL) and THF (120 mL) were added, and chloroformic acid benzyl ester (9.00 mL) was added dropwise under ice cooling. After stirring the reaction solution at room temperature for 16 hours, benzyl chloroformate (3.00 mL) was added dropwise under ice cooling, and the mixture was stirred at room temperature for 4 hours. The solution obtained by concentrating the reaction solution under reduced pressure was extracted three times with EtOAc. The aqueous layer was acidified with concentrated hydrochloric acid under ice-cooling, and the aqueous layer was extracted 3 times with CHCl ₃ . The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure to obtain the title compound (6.20 g, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.14-2.22 (m, 1H), 2.78-2.86 (m, 1H), 2.92-2.97 (m, 2H), 5.03 (s, 2H), 7.16 -7.21 (m, 1H), 7.24-7.27 (m, 2H), 7.29-7.39 (m, 5H), 7.45 (d, J = 7.8 Hz, 1H), 8.01 (s, 1H), 12.54 (br s, 1H).
LCMS (ESI) m / z 310 [MH] ^- , t _R = 0.95 min, mode N.

Reference Example 5: Synthesis of 1-{[(benzyloxy) carbonyl] amino} -6-methyl-2,3-dihydro-1H-indene-1-carboxylic acid In the same manner as in Reference Example 4, 6- The title compound (165 mg, pale yellow solid) was obtained from methyl-1-indanone (200 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.16 (dt, J = 12.7, 7.3 Hz, 1H), 2.27 (s, 3H), 2.80-2.86 (m, 1H), 2.87-2.91 (m , 2H), 5.00-5.07 (m, 2H), 7.07 (d, J = 7.4 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 7.25 (br s, 1H), 7.28-7.33 (m , 2H), 7.36 (d, J = 4.5 Hz, 4H), 7.96 (br s, 1H).
LCMS (ESI) m / z 324 [MH] ^- , t _R = 1.02 min, mode N.

Reference Example 6: Synthesis of 2- (tert-butoxycarbonyl) -1- [2- (ethylsulfonyl) ethyl] -2,3-dihydro-1H-isoindole-1-carboxylic acid (1) 2-tert-butyl To a solution of 1-methylisoindoline-1,2-dicarboxylate (100 mg) in THF (1.5 mL), add a 1.9 M NaHMDS / THF solution (0.25 mL) dropwise at -78 ° C and continue at the same temperature for 10 minutes. Stir. 1-Chloro-2- (ethylsulfonyl) ethane (92 μL) was added dropwise to the reaction solution, stirred at the same temperature for 30 minutes, then warmed to room temperature and stirred for 2 hours. Water was added to the reaction solution, and CHCl ₃ was added to separate the layers. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90 / 10-0 / 100; v / v) to give 2-tert-butyl 1 -Methyl 1- [2- (ethylsulfonyl) ethyl] -1,3-dihydro-2H-isoindole-1,2-dicarboxylate (131 mg, colorless oil) was obtained.
LCMS (ESI) m / z 420 [M + Na] ⁺ , t _R = 0.95 min, mode N.
(2) Lithium hydroxide monohydrate (48) was added to a 1,4-dioxane / water mixed solution (4.0 mL, 3/1; v / v) of the compound (115 mg) obtained in Reference Example 6 (1). mg) was added, and the mixture was stirred for 3 hours under reflux. The reaction mixture was cooled to room temperature, 1 M aqueous HCl was added dropwise to adjust the pH to 3-4, and the reaction mixture was extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure to obtain the title compound (54 mg, pale yellow solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.09 (q, J = 7.8 Hz, 3H), 1.42 (s, 6H), 1.46 (s, 3H), 2.20-2.30 (m, 1H), 2.56-2.63 (m, 1H), 2.70-2.79 (m, 1H), 2.88 (td, J = 13.5, 3.9 Hz, 0.6H), 2.96 (td, J = 13.5, 3.9 Hz, 0.4H), 3.01- 3.07 (m, 2H), 4.61-4.71 (m, 2H), 5.11 (br s, 1H), 7.26 (d, J = 7.4 Hz, 1H), 7.34-7.43 (m, 3H).
LCMS (ESI) m / z 406 [M + Na] ⁺ , t _R = 0.80 min, mode N.

Reference Example 7: Synthesis of 1- (2-cyclopropyl-2-oxoethyl) -2,3-dihydro-1H-indene-1-carboxylic acid In the same manner as in Reference Example 6, 2,3-dihydro- The title compound (102 mg, colorless solid) was obtained from 1H-indene-1-carboxylic acid methyl ester (50 mg) and 2-bromo-1-cyclopropylethane-1-one (93 μL).
LCMS (ESI) m / z 245 [M + H] ⁺ , t _R = 0.88 min, mode N.

Reference Example 8: Synthesis of 2-methyl-1- [2- (methylsulfonyl) ethyl] -2,3-dihydro-1H-isoindole-1-carboxylic acid (1) The same procedure as in Reference Example 6 (1) 1-methyl 2-tert-butyl isoindoline-1,2-dicarboxylate (100 mg), 2-bromoethyl-1-methylsulfone (100 μL) to 2-tert-butyl 1-methyl 1-methyl (2- (Methylsulfonyl) ethyl) isoindoline-1,2-dicarboxylate (39.3 mg, colorless oil) was obtained.
LCMS (ESI) m / z 406 [M + Na] ⁺ , t _R = 0.90 min, mode N.
(2) 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound (36 mg) obtained in Reference Example 8 (1) in 1,4-dioxane (1 mL), and the mixture was brought to room temperature. And stirred for 2 hours. The reaction solution was concentrated under reduced pressure to obtain methyl 1- [2- (methylsulfonyl) ethyl] -2,3-dihydro-1H-isoindole-1-carboxylate hydrochloride (39 mg, pale yellow amorphous).
(3) K ₂ CO ₃ (52 mg) and MeI (12 μL) were added to a DMF (1 mL) solution of the compound (30 mg) obtained in Reference Example 8 (2) and stirred at room temperature for 3 hours. . MeI (12 μL) was added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction mixture, and the mixture was stirred and extracted with EtOAc. The residue obtained by concentrating the organic layer under reduced pressure was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90 / 10-0 / 100; v / v), and methyl 1- [2- (Methylsulfonyl) ethyl] -2-methyl-2,3-dihydro-1H-isoindole-1-carboxylate (6.0 mg, yellow oil) was obtained.
(4) The title compound (2.5 mg, pale yellow solid) was obtained from the compound (6.0 mg) obtained in Reference Example 8 (3) using the same method as in Reference Example 6 (2).
LCMS (ESI) m / z 284 [M + H] ⁺ , t _R = 0.26 min, mode N.

Reference Example 9: Synthesis of 1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl] -2,3-dihydro-1H-indene-1-carboxylic acid Reference Example 6 Using the same procedure, the title compound (110 mg, colorless solid) was obtained from 2,3-dihydro-1H-indene-1-carboxylic acid methyl ester (100 mg) and N- (bromomethyl) phthalimide (204 mg). Obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.29 (m, 1H), 2.51-2.58 (m, 1H), 2.88-2.99 (m, 2H), 3.67 (dd, J = 13.4, 6.8 Hz , 1H), 3.77 (dd, J = 13.4, 6.8 Hz, 1H), 7.16-7.20 (m, 2H), 7.22 (td, J = 7.2, 1.2 Hz, 1H), 7.26 (d, J = 7.4 Hz, 1H), 7.34 (d, J = 7.4 Hz, 1H), 7.47 (td, J = 7.2, 1.2 Hz, 1H), 7.52 (td, J = 7.2, 1.2 Hz, 1H), 7.73 (dd, J = 7.4 , 1.2 Hz, 1H), 8.29 (t, J = 6.2 Hz, 1H).

Reference Example 10: Synthesis of 1-{[(benzyloxy) carbonyl] amino} -1,2,3,4-tetrahydronaphthalene-1-carboxylic acid
1-Amino-1,2,3,4-tetrahydro-1-naphthalenecarboxylic acid hydrochloride (397 mg) in 1 M aqueous sodium hydroxide / THF (20 mL, 1/1; v / v) Acid benzyl ester (0.37 mL) was added, and the mixture was stirred at room temperature for 16 hours. CHCl ₃ was added to the reaction solution for liquid separation, and 1M HCl aqueous solution was added dropwise to the aqueous layer to make it acidic, followed by extraction with EtOAc. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure to obtain the title compound (157 mg, pale yellow amorphous).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.70-1.78 (m, 1H), 1.81-1.90 (m, 1H), 2.23-2.29 (m, 1H), 2.32-2.40 (m, 1H) , 2.60-2.62 (m, 0.2H), 2.71-2.76 (m, 1.8H), 4.49 (d, J = 5.8 Hz, 0.5H), 4.96-5.04 (m, 2H), 5.16 (t, J = 5.8 Hz, 0.5H), 7.07-7.20 (m, 3H), 7.21-7.32 (m, 2H), 7.33-7.37 (m, 3H), 7.48 (d, J = 7.4 Hz, 1H), 7.63 (br s, 1H).
LCMS (ESI) m / z 348 [M + Na] ⁺ , t _R = 1.04 min, mode N.

Reference Example 11: Synthesis of 1-{[(benzyloxy) carbonyl] amino} -2,3-dihydro-1H-indene-1-carboxylic acid (single enantiomer) Compound obtained in Reference Example 4 (859 mg) (Preparation conditions: SFC method; column: CHIRALPAK AD-H / SFC (trademark of Daicel), column size: 5 μm 20 mm × 250 mm, mobile phase: MeOH / CO ₂ = 30/70 (v / v), flow rate: 30 mL / min, column temperature: 40 ° C., detection wavelength: 210 nM), the title compound (318 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 2.15-2.22 (m, 1H), 2.77-2.85 (m, 1H), 2.90-2.99 (m, 2H), 5.03 (s, 2H), 7.15 -7.21 (m, 1H), 7.23-7.27 (m, 2H), 7.28-7.38 (m, 5H), 7.44 (d, J = 7.0 Hz, 1H), 8.00 (br s, 1H), 12.55 (br s , 1H).
LCMS (ESI) m / z 310 [MH] ^- , t _R = 0.95 min, mode N.
t _R = 2.13 min, Analysis conditions: SFC method; Analyzer: waters UPC2; Column: CHIRALPAK AD-H / SFC (trademark of Daicel), column size: 5 μm 4.6 mm × 250 mm, mobile phase: MeOH / CO ₂ = 40/60 (v / v), flow rate: 3 mL / min, column temperature: 40 ° C, detection wavelength: 254 nm.
The structural formulas of the compounds obtained in Reference Examples 1 to 11 are shown in Table 1.

Example 1-1: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide
Step 1-1-1: To a toluene / MeOH mixed solution (125 mL, 3/2; v / v) of N- (tert-butoxycarbonyl) -N-methyl-L-alanine (25 g) under ice-cooling , 2 M trimethylsilyldiazomethane / Et ₂ O solution (92 mL) was added, and the mixture was stirred at room temperature for 1 hr. Acetic acid was added to the reaction solution until the reaction solution became clear. The reaction solution was diluted with CHCl _{3 and} washed with saturated aqueous NaHCO ₃ solution. The organic layer was dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure to obtain methyl N- (tert-butoxycarbonyl) -N-methyl-L-alaninate (27.5 g, colorless oil).
Step 1-1-2: To a THF (250 mL) solution of acetonitrile (20 mL), a 1.9 M NaHMDS / THF solution (200 mL) is added at -78 ° C, and then at -50 to -45 ° C for 20 minutes. Stir. Again, it cooled to -78 degreeC, the THF (150 mL) solution of the compound (27.5 g) obtained by process 1-1-1 was added, and it stirred at -50--45 degreeC for 1 hour. Again, it cooled to -78 degreeC, the acetic acid (22.5 mL) was added, and it heated up to room temperature. The reaction solution was poured into a saturated aqueous NH ₄ Cl solution and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , the solvent was concentrated, and tert-butyl [(2S) -4-cyano-3-oxobutan-2-yl] (methyl) carbamate (26.5 g, brown oil) Product).
Step 1-1-3: Compound (26.5 g) obtained in Step 1-1-2 under ice-cooling in a solution of hydrazine monohydrate (18.4 mL) and acetic acid (21.6 mL) in EtOH (160 mL) Of EtOH (100 mL) was added and stirred at room temperature for 2 days. After the reaction solution was concentrated under reduced pressure, the residue was diluted with CHCl ₃ , washed with a saturated aqueous NaHCO ₃ solution and Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by NH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 90/10; v / v). The obtained compound was subjected to preparative purification on a chiral column (preparation conditions: column: CHIRALPAK OZ-3 (Daicel Trademark), column size: 20 mm × 250 mm, mobile phase: hexane / IPA = 80/20 (v / v), flow rate: 14 mL / min), tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) ethyl] (methyl) carbamate (18.5 g, brown oil) and tert-Butyl [(1R) -1- (5-amino-1H-pyrazol-3-yl) ethyl] (methyl) carbamate (910 mg) was obtained.
tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) ethyl] (methyl) carbamate: ¹ H NMR (600 MHz, CDCl ₃ , δ): 1.44 (d, J = 7.0 Hz, 3H), 1.48 (s, 9H), 2.65 (s, 3H), 5.36 (br s, 1H), 5.55 (br s, 1H).
LCMS (ESI) m / z 241 [M + H] ⁺ , t _R = 0.46 min, mode N.
Step 1-1-4: To a solution of the compound obtained in Step 1-1-3 (1.65 g) in DMF (10 mL) was added ethyl ethyl (2E) -3-ethoxy-2-methylprop-2-enoate (1.63). g) and Cs ₂ CO ₃ (6.71 g) were added, and the mixture was stirred at 120 ° C. for 8 hours. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 90/10; v / v), and tert-butyl methyl [(1S) -1- (6- Methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] carbamate (1.35 g, brown amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.49 (s, 9H), 1.51 (d, J = 7.0 Hz, 3H), 2.10 (s, 3H), 2.67 (br s, 3H), 5.28-5.62 (m, 1H), 5.78 (s, 1H), 8.01 (s, 1H), 10.85 (br s, 1H).
LCMS (ESI) m / z 307 [M + H] ⁺ , t _R = 0.79 min, mode N.
Step 1-1-5: To a solution of the compound obtained in Step 1-1-4 (600 mg) in CHCl ₃ (8 mL), pyridine (790 μL) was added, and then ice-cooled trifluoromethylsulfone. Acid anhydride (659 μL) was added dropwise, and the mixture was stirred as it was for 10 minutes, then warmed to room temperature and stirred for 2 hours. A saturated aqueous NH ₄ Cl solution was added to the reaction solution, and the mixture was extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95 / 5-0 / 100; v / v) to give 2-{(1S) -1-[(tert-butoxy Carbonyl) (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (835 mg, yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.46-1.61 (m, 12H), 2.33 (s, 3H), 2.69 (br s, 3H), 5.44-5.79 (m, 1H), 6.50 (s, 1H), 8.54 (s, 1H).
Step 1-1-6: Compound (707 mg) obtained in Step 1-1-5, (3S)-(−)-3- (benzyloxycarbonylamino) -pyrrolidine (709 mg) in THF (8.0 mL) ) Et ₃ N (907 μL) was added to the solution and stirred at 80 ° C. for 30 minutes. After cooling the reaction solution to room temperature, water was added to separate the solution, and the aqueous layer was extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane: EtOAc = 95: 5 to 0: 100; v / v), and benzyl [(3S) -1- (2-{(1S ) -1-[(tert-Butoxycarbonyl) (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (693 mg, colorless amorphous) Obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.49 (s, 9H), 1.53 (d, J = 7.0 Hz, 3H), 1.91-2.00 (m, 1H), 2.18-2.27 (m, 1H), 2.32 (s, 3H), 2.66 (br s, 3H), 3.58 (m, 1H), 3.67-3.75 (m, 1H), 3.76-3.83 (m, 1H), 3.88-3.97 (m, 1H), 4.32 -4.40 (m, 1H), 4.92 (br s, 1H), 5.10 (br s, 2H), 5.38-5.71 (m, 1H), 5.98 (s, 1H), 7.29-7.41 (m, 5H), 8.07 (s, 1H).
LCMS (ESI) m / z 509 [M + H] ⁺ , t _R = 1.13 min, mode N.
Step 1-1-7: To a solution of the compound (690 mg) obtained in Step 1-1-6 in 1,4-dioxane (5.0 mL), 4 M HCl / 1,4-dioxane solution (5.0 mL) was added. The solution was added dropwise and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, dried under reduced pressure, and benzyl [(3S) -1- {6-methyl-2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidine -5-yl} pyrrolidin-3-yl] carbamate (858 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 409 [M + H] ⁺ , t _R = 0.52 min, mode N.
Step 1-1-8: To a solution of the compound obtained in Step 1-1-7 (186 mg) and 5-chloro-2-methanesulfonamidobenzenecarboxylic acid (116 mg) in DMF (2.0 mL), HATU (220 mg) and Et ₃ N (0.325 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure and azeotroped with toluene. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90 / 10-0: 100; v / v), and benzyl [(3S) -1- (2-{(1S ) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl ] Carbamate (186 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.60 (d, J = 7.0 Hz, 1.8H), 1.64 (d, J = 7.0 Hz, 1.2H), 1.92-2.00 (m, 1H), 2.20- 2.29 (m, 1H), 2.35 (br s, 1.2H), 2.36 (br s, 1.8H), 2.62 (s, 1.2H), 2.80 (s, 1.8H), 2.95 (s, 1.2H), 3.04 (s, 1.8H), 3.55-3.62 (m, 1H), 3.70-3.77 (m, 1H), 3.77-3.85 (m, 1H), 3.92-3.99 (m, 1H), 4.32-4.40 (m, 1H ), 4.88 (q, J = 7.0 Hz, 0.5H), 4.91-4.99 (m, 1H), 5.11 (br s, 2H), 6.00 (s, 0.6H), 6.01 (s, 0.4H), 6.22 ( q, J = 7.0 Hz, 0.5H), 7.28-7.40 (m, 5.5H), 7.60 (d, J = 8.7 Hz, 0.6H), 7.68 (d, J = 8.7 Hz, 0.4H), 8.36 (s , 0.5H), 8.39 (dd, J = 8.7, 1.2 Hz, 0.5H), 8.62-8.66 (m, 1H), 9.39 (br s, 0.5H).
LCMS (ESI) m / z 640 [M + H] ⁺ , t _R = 1.15 min, mode N.
Step 1-1-9: To a solution of the compound obtained in Step 1-1-8 (21 mg) in MeOH (1.0 mL) was added 10% palladium-carbon (2 mg), and the mixture was stirred under a hydrogen gas atmosphere for 6 hours. did. The reaction solution was filtered through Celite (registered trademark) and washed with MeOH, and the filtrate obtained was concentrated under reduced pressure. The obtained residue was purified by OH column chromatography (mobile phase: EtOAc to hexane / MeOH = 9: 1; v / v) to obtain the title compound (7.0 mg, colorless solid).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.59 (d, J = 7.0 Hz, 1.8H), 1.64 (d, J = 7.0 Hz, 1.2H), 1.76-1.86 (m, 1H), 2.11- 2.22 (m, 1H), 2.37 (s, 1.2H), 2.38 (s, 1.8H), 2.62 (s, 1.2H), 2.81 (s, 1.8H), 2.95 (s, 1.2H), 3.03 (s , 1.8H), 3.46 (dd, J = 10.9, 4.3 Hz, 1H), 3.66-3.78 (m, 2H), 3.88 (dd, J = 10.3, 4.5 Hz, 2H), 4.88 (q, J = 6.6 Hz , 0.6H), 5.98 (s, 0.6H), 5.99 (s, 0.4H), 6.22 (d, J = 7.0 Hz, 0.4H), 7.22-7.32 (m, 1H), 7.32-7.40 (m, 1H ), 7.61 (d, J = 8.7 Hz, 0.6H), 7.68 (d, J = 8.7 Hz, 0.4H), 8.34 (s, 0.6H), 8.61 (s, 0.4H).
LCMS (ESI) m / z 506.2 [M + H] ⁺ , t _R = 0.58 min, mode N.

Example 1-2: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N-propylbenzamide Hydrochloride Synthesis Step 1-2-1: Using the same method as in Step 1-1-2 and Step 1-1-3 From methyl N- (tert-butoxycarbonyl) -L-alaninate (25.0 g), tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) ethyl] carbamate (21.9 g , Pale yellow amorphous).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.43-1.49 (m, 12H), 4.71-4.81 (m, 1H), 4.85 (br s, 1H), 5.49 (s, 1H), 5.64 (br s , 1H).
LCMS (ESI) m / z 227 [M + H] ⁺ , t _R = 0.28 min, mode N.
Step 1-2-2: Ethyl (2E) -3-ethoxy-2-methylprop-2-enoate (23 mL) was added to EtOH (320 mL) of the compound (21.9 g) obtained in Step 1-2-1. 2.94 M NaOEt / EtOH solution (115 mL) was added, and the mixture was stirred for 30 hours with heating under reflux. EtOAc was added to the reaction solution, and a liquid separation operation was performed with a saturated aqueous NaHCO ₃ solution. The aqueous layer was separated using Brine and MgSO ₄ , and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: CHCl ₃ : MeOH = 100: 0 to 95: 5; v / v), and tert-butyl [(1S) -1- (6-methyl-5-oxo- 4,5-Dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] carbamate (6.2 g, pale yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.45 (s, 9H), 1.50 (d, J = 6.6 Hz, 3H), 2.09 (s, 3H), 4.88 (br s, 1H), 5.06 (br s, 1H), 5.81 (s, 1H), 7.96 (s, 1H), 10.23 (br s, 1H).
LCMS (ESI) m / z 293 [M + H] ⁺ , t _R = 0.68 min, mode N.
Step 1-2-3: To a solution of the compound (6.2 g) obtained in Step 1-2-2 in 1,4-dioxane (26 mL), add 4 M HCl / 1,4-dioxane solution (26 mL). The solution was added dropwise and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and dried under reduced pressure to give 2-[(1S) -1-aminoethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride as a crude product (brown As a solid).
LCMS (ESI) m / z 193 [M + H] ⁺ , t _R = 0.18 min, mode N.
Step 1-2-4: POCl ₃ (40 mL) was added to the compound obtained in Step 1-2-3, and the mixture was stirred at 100 ° C. for 1.5 hr. The reaction solution was concentrated under reduced pressure to obtain (1S) -1- (5-chloro-6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethanamine hydrochloride as a crude product (brown amorphous).
LCMS (ESI) m / z 211 [M + H] ⁺ , t _R = 0.56 min, mode N.
Step 1-2-5: To a solution of the compound obtained in Step 1-2-4 in MeOH (90 mL), (3S)-(−)-3- (tert-butoxycarbonylamino) pyrrolidine (19.6 g), Et ₃ N (23.6 mL) was added, and the mixture was stirred at 80 ° C. for 1 hr. The reaction mixture was poured into water and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (CHCl ₃ / MeOH = 95/5 to 85/15; v / v) and silica gel column chromatography (mobile phase: hexane / EtOAc = 5/95 to 0/100 to CHCl ₃ / MeOH = 95/5) and tert-butyl [(3S) -1- {2-[(1S) -1-aminoethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl } Pyrrolidin-3-yl] carbamate (3.7 g, pale yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.41-1.50 (m, 12H), 1.89-1.95 (m, 1H), 2.18-2.24 (m, 1H), 2.33 (m, 3H), 3.53 (dd , J = 11.4, 3.9 Hz, 1H), 3.68-3.74 (m, 1H), 3.77-3.83 (m, 1H), 3.88-3.95 (m, 1H), 4.20 (q, J = 6.9 Hz, 1H), 4.30 (br s, 1H), 4.69 (br s, 1H), 6.02 (s, 1H), 8.02 (s, 1H).
LCMS (ESI) m / z 361 [M + H] ⁺ , t _R = 0.85 min, mode H.
Step 1-2-6: 1-iodopropane (16 μL) and K ₂ CO ₃ (29 mg) were added to a DMF (1 mL) solution of the compound (30 mg) obtained in Step 1-2-5. , And stirred at 80 ° C. for 1 hour. The reaction solution was purified by reverse phase preparative HPLC, and tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- (propylamino) ethyl] pyrazolo [1,5-a ] Pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (13 mg, colorless solid) was obtained.
Step 1-2-7: To a solution of propyl (13 mg) in DMF (1.0 mL), 5-chloro-2-methanesulfonamidobenzenecarboxylic acid (9.5 mg), HATU (16 mg) and Et ₃ N (22 μL) was added and stirred at room temperature for 3 days. The reaction solution was purified by reverse phase preparative HPLC, and tert-butyl [(3S) -1- (2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (Propyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (13 mg, colorless solid) was obtained.
LCMS (ESI) m / z 634 [M + H] ⁺ , t _R = 1.26 min, mode N.
Step 1-2-8: To a solution of the compound obtained in Step 1-2-7 (21 mg) in 1,4-dioxane (1.0 mL) was added 4 M HCl / 1,4-dioxane solution (1 mL). Stir at room temperature overnight. The reaction mixture was concentrated under reduced pressure to obtain the title compound (15 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.53 (t, J = 7.2 Hz, 1H), 0.77 (t, J = 7.4 Hz, 2H), 1.21-1.54 (m, 4H), 1.57 ( d, J = 7.0 Hz, 2H), 1.66 (d, J = 7.0 Hz, 1H), 2.00-2.10 (m, 1H), 2.20-2.30 (m, 1H), 2.34-2.38 (m, 3H), 2.85 -2.98 (m, 2H), 3.04 (s, 3H), 3.81-3.96 (m, 5H), 4.74-4.82 (m, 0.7H), 5.73 (br s, 0.3H), 6.13 (s, 1H), 7.43-7.58 (m, 3H), 8.18 (br s, 3H), 8.52 (s, 0.5H), 9.34 (s, 0.5H).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.62 min, mode N.

Example 1-3: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-3-1: Using the same method as in Step 1-1-1 to Step 1-1-3 From (2S) -2-[(tert-butoxycarbonyl) amino] butanoic acid (25.0 g), tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) propyl] Carbamate (17.5 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.95-1.06 (m, 3H), 1.43-1.46 (m, 9H), 1.63-1.77 (m, 1H), 1.83-1.98 (m, 1H), 4.35 -4.58 (m, 1H), 4.61-4.90 (m, 1H), 5.49 (s, 1H).
LCMS (ESI) m / z 241 [M + H] ⁺ , t _R = 0.33 min, mode N.
Analytical data of another lot of tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) propyl] carbamate synthesized by the same method is shown below.
t _R = 6.62 min (98.8% ee), Analysis conditions: Column: CHIRALPAK IC3 (trademark of Daicel), Column size: 5 μm 4.6 mm × 250 mm, Mobile phase: Hexane / EtOH = 80/20 (v / v) , Flow rate: 1 mL / min, Column temperature: 40 ° C, Detection wavelength: 210 nm.
Analytical data of tert-butyl [(1R) -1- (5-amino-1H-pyrazol-3-yl) propyl] carbamate synthesized by the same method is shown below.
t _R = 5.13 min, Analysis conditions: Column: CHIRALPAK IC3 (trademark of Daicel), Column size: 5 μm 4.6 mm × 250 mm, Mobile phase: Hexane / EtOH = 80/20 (v / v), Flow rate: 1 mL / min, column temperature: 40 ° C, detection wavelength: 210 nm.
Step 1-3-2: Using a method similar to that in Step 1-2-2, tert-butyl [(1S) -1- (6) from the compound (16.5 g) obtained in Step 1-3-1. -Methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) propyl] carbamate (5.80 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.88-0.97 (m, 3H), 1.39-1.51 (m, 9H), 1.78 (dt, J = 13.8, 7.1 Hz, 1H), 1.90 (dd, J = 13.6, 7.0 Hz, 1H), 2.07-2.14 (m, 3H), 4.72 (d, J = 6.2 Hz, 1H), 5.06 (d, J = 7.0 Hz, 1H), 5.82 (s, 1H), 7.98 (d, J = 0.8 Hz, 1H), 10.81 (br s, 1H).
LCMS (ESI) m / z 307 [M + H] ⁺ , t _R = 0.74 min, mode N.
Step 1-3-3: Using the same method as in Step 1-2-3, from the compound (5.4 g) obtained in Step 1-3-2, 2-[(1S) -1-aminopropyl] -6-methylpyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride (4.7 g, yellow solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.78-0.89 (m, 3H), 1.77-2.01 (m, 5H), 4.07-4.25 (m, 1H), 5.97-6.10 (m, 1H) , 8.38-8.48 (m, 1H), 8.57 (br s, 3H), 12.29 (br s, 1H).
Step 1-3-4: Using a method similar to that in Step 1-2-4, from the compound (4.7 g) obtained in Step 1-3-3, (1S) -1- (5-chloro-6 -Methylpyrazolo [1,5-a] pyrimidin-2-yl) propan-1-amine hydrochloride (5.0 g, brown amorphous) was obtained.
Step 1-3-5: Using a method similar to that in Step 1-2-5, from the compound (16.5 g) obtained in Step 1-3-4, tert-butyl [(3S) -1- {2 -[(1S) -1-Aminopropyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (4.5 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.88-0.99 (m, 3H), 1.45 (s, 9H), 1.72-1.97 (m, 3H), 2.16-2.25 (m, 1H), 2.33 (s , 3H), 3.53 (dd, J = 10.7, 3.7 Hz, 1H), 3.71 (ddd, J = 10.7, 7.8, 5.8 Hz, 1H), 3.80 (dt, J = 10.7, 7.4 Hz, 1H), 3.88- 3.97 (m, 2H), 4.30 (br s, 1H), 4.71 (br s, 1H), 5.91-6.09 (m, 1H), 8.02 (s, 1H).
LCMS (ESI) m / z 375 [M + H] ⁺ , t _R = 0.48 min, mode N.
Step 1-3-6: From the compound (3.60 g) obtained in Step 1-3-5 and MeI (300 μL) using the same method as in Step 1-2-6 and Step 1-2-7 Tert-butyl [(3S) -1- (2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] propyl} -6-methylpyrazolo [ 1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (758 mg, pale yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.06 (t, J = 7.4 Hz, 2H), 1.13 (t, J = 7.2 Hz, 1H), 1.45 (s, 9H), 1.86-1.95 (m, 1H), 2.01-2.06 (m, 1H), 2.15-2.27 (m, 1H), 2.36 (s, 1H), 2.37 (s, 2H), 2.58 (s, 1H), 2.77 (s, 2H), 2.95 (s, 1H), 3.03 (s, 2H), 3.54 (dd, J = 11.4, 4.3 Hz, 1H), 3.69-3.76 (m, 1H), 3.77-3.83 (m, 1H), 3.94 (br s, 1H), 4.30 (br s, 1H), 4.57-4.64 (m, 1H), 4.67 (br s, 1H), 5.99 (s, 0.7H), 6.02 (s, 0.3H), 7.24-7.28 (m, 0.7H), 7.29 (d, J = 2.5 Hz, 0.3H), 7.35 (dd, J = 8.7, 2.5 Hz, 0.7H), 7.38 (dd, J = 8.9, 2.3 Hz, 0.3H), 7.60 (d , J = 8.7 Hz, 0.7H), 7.68 (d, J = 8.7 Hz, 0.3H), 8.38 (s, 0.7H), 8.63 (s, 0.3H), 9.37-9.48 (m, 0.3H), 11.26 (br s, 0.7H).
LCMS (ESI) m / z 620 [M + H] ⁺ , t _R = 1.21 min, mode N.
Step 1-3-7: The title compound (623 mg, colorless solid) was obtained from the compound (637 mg) obtained in Step 1-3-6 using the same method as in Step 1-2-8. .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.91 (br s, 1.5H), 1.03 (t, J = 7.4 Hz, 1.5H), 1.82-2.11 (m, 3H), 2.12-2.30 ( m, 2H), 2.35 (s, 1.5H), 2.37 (s, 1.5H), 2.58 (s, 1.5H), 2.72 (br s, 1.5H), 2.97-3.06 (m, 3H), 3.71-3.82 (m, 2H), 3.82-3.90 (m, 2H), 3.90-3.98 (m, 1H), 4.54 (dd, J = 9.9, 5.0 Hz, 0.5H), 5.73 (dd, J = 10.3, 5.4 Hz, 0.5H), 6.13 (s, 1H), 7.36-7.57 (m, 3H), 8.34 (br s, 3H), 8.51 (s, 0.5H), 9.21 (s, 0.5H).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 1.07 min, mode H.

Example 1-4: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N, 5-Dimethyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-4-1: Compound (4.3 g) MeOH (48 mL) obtained in Step 1-3-5 Ethyl trifluoroacetate (2.1 g) and Et ₃ N (2.5 mL) were added to the solution, and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and tert-butyl [(3S) -1- (6-methyl-2-{(1S) -1-[(trifluoroacetyl) amino] propyl} pyrazolo [1,5-a] Pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (6.5 g, pale yellow solid) was obtained.
LCMS (ESI) m / z 471 [M + H] ⁺ , t _R = 0.98 min, mode N.
Step 1-4-2: MeI (2.2 mL) and Cs ₂ CO ₃ (15 g) were added to a DMF (50 mL) solution of the compound (5.4 g) obtained in Step 1-4-1 at 65 ° C. For 2 hours. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , the filtrate was concentrated under reduced pressure, and tert-butyl [(3S) -1- (6-methyl-2-{(1S) -1- [methyl (tri Fluoroacetyl) amino] propyl} pyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (5.6 g, pale yellow oil) was obtained.
LCMS (ESI) m / z 485 [M + H] ⁺ , t _R = 1.10 min, mode N.
Step 1-4-3: 1M NaOH aqueous solution (40 mL) was added to a THF / MeOH mixed solution (80 mL, 1/1; v / v) of the compound (5.5 g) obtained in Step 1-4-2. And stirred at room temperature for 1 hour. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure to give tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- (methylamino)]. Propyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (4.3 g, brown amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.88 (t, J = 7.4 Hz, 3H), 1.45 (s, 9H), 1.68-1.98 (m, 3H), 2.14-2.25 (m, 1H), 2.28-2.42 (m, 6H), 3.48-3.63 (m, 2H), 3.66-3.85 (m, 2H), 3.87-3.98 (m, 1H), 4.30 (br s, 1H), 4.59-4.78 (m, 1H), 5.91-6.07 (m, 1H), 7.96-8.10 (m, 1H).
LCMS (ESI) m / z 389 [M + H] ⁺ , t _R = 0.50 min, mode N.
Step 1-4-4: Using a method similar to that of Step 1-2-7 and Step 1-2-8, the compound (30 mg) obtained in Step 1-4-3 and 5-methyl-2- The title compound (30 mg, colorless solid) was obtained from [(methylsulfonyl) amino] benzoic acid (26 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.91 (br s, 1.5H), 1.02 (t, J = 7.2 Hz, 1.5H), 1.84-2.29 (m, 4H), 2.30-2.38 ( m, 6H), 2.55-2.58 (m, 1.5H), 2.72 (br s, 1.5H), 2.97 (s, 3H), 3.70-3.98 (m, 5H), 4.49-4.59 (m, 0.5H), 5.74-5.80 (m, 0.5H), 6.11 (s, 1H), 7.14 (s, 1H), 7.22-7.30 (m, 1H), 7.30-7.38 (m, 1H), 8.30-8.39 (m, 3H) , 8.51 (s, 0.5H), 8.97 (s, 0.5H).
LCMS (ESI) m / z 500 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 1-5: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-ethyl-5-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride Synthesis of step 1-3-6 to step 1-2-8 using the same method as in step 1-3-3- The title compound (907 mg, colorless solid) was obtained from the compound obtained in 5 (1.50 g), 5-methyl-2-[(methylsulfonyl) amino] benzoic acid (1.10 g) and EtI (320 μL). .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.80 (t, J = 6.8 Hz, 1H), 0.86-1.00 (m, 4H), 1.07 (t, J = 7.2 Hz, 1H), 1.93- 2.10 (m, 3H), 2.21-2.29 (m, 2H), 2.32-2.38 (m, 6H), 2.91-3.05 (m, 4H), 3.25-3.33 (m, 1H), 3.72-3.82 (m, 2H ), 3.82-3.90 (m, 2H), 3.90-3.97 (m, 1H), 4.51 (br s, 0.5H), 5.56 (br s, 0.5H), 6.12-6.23 (m, 1H), 7.09-7.40 (m, 3H), 8.30 (br s, 3H), 8.52 (s, 0.5H), 8.97 (s, 0.5H).
LCMS (ESI) m / z 514 [M + H] ⁺ , t _R = 1.08 min, mode H.

Example 1-6: N-[(1S) -1- {5-[(3S) -3-Aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} butyl ] -N, 5-dimethyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-6-1: Using the same method as in Step 1-1-2 and Step 1-1-3, From methyl N- (tert-butoxycarbonyl) -L-norvalinate (5800 mg), tert-butyl [(1S) -1- (5-amino-1H-pyrazol-3-yl) butyl] carbamate (4600 mg) Obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.89-0.98 (m, 3H), 1.31-1.48 (m, 1H), 1.63-1.85 (m, 2H), 4.55-4.67 (m, 1H), 4.85 (br s, 1H), 5.49 (s, 1H).
LCMS (ESI) m / z 255 [M + H] ⁺ , t _R = 0.51 min, mode N.
Step 1-6-2: Using a method similar to that of Step 1-2-2, tert-butyl [(1S) -1- (6) from the compound (4600 mg) obtained in Step 1-6-1 -Methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) butyl] carbamate (2000 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.90-0.96 (m, 3H), 1.30-1.47 (m, 11H), 1.68-1.89 (m, 2H), 2.10 (s, 3H), 4.73-4.83 (m, 1H), 4.97- 5.09 (m, 1H), 5.83 (s, 1H), 7.98 (s, 1H), 11.04 (br s, 1H).
LCMS (ESI) m / z 321 [M + H] ⁺ , t _R = 0.86 min, mode N.
Step 1-6-3: Using a method similar to that of Step 1-2-3, 2-[(1S) -1-aminobutyl] from the compound (500 mg) obtained in Step 1-6-2 -6-methylpyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride (460 mg) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.87 (t, J = 7.4 Hz, 3H), 1.19-1.30 (m, 2H), 1.79-1.90 (m, 2H), 1.93- 1.96 (m , 3H), 4.23-4.29 (m, 1H), 6.01 (s, 1H), 8.43 (s, 1H), 8.50 (br s, 3), 12.27 (br s, 1H).
LCMS (ESI) m / z 221 [M + H] ⁺ , t _R = 0.54 min, mode H.
Step 1-6-4: Using a method similar to that of Step 1-2-4, from the compound (400 mg) obtained in Step 1-6-3, (1S) -1- (5-chloro-6 -Methylpyrazolo [1,5-a] pyrimidin-2-yl) butan-1-amine hydrochloride was obtained as a crude product.
LCMS (ESI) m / z 239 [M + H] ⁺ , t _R = 0.78 min, mode H.
Step 1-6-5: Using a method similar to that of Step 1-2-5, tert-butyl [(3S) -1- {2] from the compound (430 mg) obtained in Step 1-6-4 -[(1S) -1-Aminobutyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (400 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.90-0.95 (m, 3H), 1.30-1.51 (m, 11H), 1.68-1.82 (m, 2H), 1.88-1.97 (m, 1H), 2.16 -2.25 (m, 1H), 2.33 (s, 3H), 3.49-3.56 (m, 1H), 3.67-3.74 (m, 1H), 3.76-3.83 (m, 1H), 3.88-3.95 (m, 1H) , 4.02 (t, J = 7.0 Hz, 1H), 4.30 (br s, 1H), 4.70 (br s, 1H), 6.02 (s, 1H), 8.02 (s, 1H).
LCMS (ESI) m / z 389 [M + H] ⁺ , t _R = 1.01 min, mode H.
Step 1-6-6: Using the same method as in Step 1-2-6 and Step 1-2-7, the compound (0.27 g) obtained in Step 1-6-5, 5-methyl-2- From [(methylsulfonyl) amino] benzoic acid (96 mg) and MeI (0.11 mL), tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- (methyl {5- Methyl-2-[(methylsulfonyl) amino] benzoyl} amino) butyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (49 mg) was obtained.
LCMS (ESI) m / z 614 [M + H] ⁺ , t _R = 1.26 min, mode N.
Step 1-6-7: Using the same method as in Step 1-2-8, the title compound (42 mg, colorless solid) was obtained from the compound (45 mg) obtained in Step 1-6-6. .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.86 (br s, 1.5H), 1.00 (t, J = 7.4 Hz, 1.5H), 1.20-1.57 (m, 2H), 1.83-1.98 ( m, 1H), 2.01-2.14 (m, 1H), 2.21-2.37 (m, 8H), 2.56 (s, 1.5H), 2.72 (br s, 1.5H), 2.96 (s, 3H), 3.64-3.95 (m, 5H), 4.57-4.69 (m, 0.5H), 5.84-5.92 (m, 0.5H), 6.07-6.14 (m, 1H), 7.09-7.39 (m, 3H), 8.13-8.37 (m, 3H), 8.51 (s, 0.5H), 8.96 (s, 0.5H).
LCMS (ESI) m / z 514 [M + H] ⁺ , t _R = 0.63 min, mode N.

Example 1-7: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} butyl ] -N-ethyl-5-methyl-2-[(methylsulfonyl) amino] benzamide Step 1-6 using the same method as in Step 1-2-6 to Step 1-2-8 The title compound (2.5 mg, colorless amorphous) was obtained from the compound obtained in 5 (0.13 g), 5-methyl-2-[(methylsulfonyl) amino] benzoic acid (46 mg) and EtI (54 μL). .
LCMS (ESI) m / z 528 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 1-8: N-({5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} methyl) -5-chloro- N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 1-8-1: Using the same method as in step 1-1-1 to step 1-1-3, N- (tert -Butoxycarbonyl) -N-methylglycine (4.00 g) gave tert-butyl [(5-amino-1H-pyrazol-3-yl) methyl] (methyl) carbamate (1.35 g, yellow amorphous).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.41-1.57 (m, 9H), 2.75-3.01 (m, 3H), 4.26 (br s, 2H), 5.59 (s, 1H).
LCMS (ESI) m / z 227 [M + H] ⁺ , t _R = 0.37 min, mode N.
Step 1-8-2: Using a method similar to that in Step 1-1-4, tert-butyl methyl [(6-methyl-5- Oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) methyl] carbamate (0.41 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.39-1.54 (m, 9H), 2.09 (s, 3H), 2.78-2.95 (m, 3H), 4.31-4.51 (m, 2H), 5.72-5.90 (m, 1H), 7.96 (s, 1H), 10.77 (br s, 1H).
LCMS (ESI) m / z 291 [MH] ^- , t _R = 0.74 min, mode N.
Step 1-8-3: Using a method similar to that of Step 1-1-5, from the compound obtained in Step 1-8-2 (410 mg), 2-{[(tert-butoxycarbonyl) (methyl ) Amino] methyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (590 mg, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.49 (s, 9H), 2.34 (s, 3H), 2.90 (d, J = 15.7 Hz, 3H), 4.53-4.69 (m, 2H), 6.54 ( d, J = 15.3 Hz, 1H), 8.47-8.58 (m, 1H).
Step 1-8-4: Using a method similar to that of Step 1-2-3, from the compound (590 mg) obtained in Step 1-8-3, 6-methyl-2-[(methylamino) methyl Pyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (500 mg, yellow oil) was obtained.
Step 1-8-5: Using a method similar to that of Step 1-1-8, the compound (500 mg) obtained in Step 1-8-4 was used to give 2-{[{5-chloro-2- [ (Methylsulfonyl) amino] benzoyl} (methyl) amino] methyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (590 mg, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 2.36-2.42 (m, 3H), 2.83-3.14 (m, 6H), 4.58 (br s, 0.6H), 5.02 (br s, 1.4H), 6.37 -6.51 (m, 1H), 7.15-7.78 (m, 3H), 8.72-8.87 (m, 1H), 9.08 (s, 0.7H), 10.09 (s, 0.3H).
Step 1-8-6: Using a method similar to that in Step 1-2-5, from the compound obtained in Step 1-8-5 (60 mg), tert-butyl [(3S) -1- (2 -{[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] methyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (55 mg, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.39-1.48 (m, 9H), 1.92 (dd, J = 12.6, 6.4 Hz, 1H), 2.17-2.26 (m, 1H), 2.36 (d, J = 9.5 Hz, 3H), 2.82-3.11 (m, 6H), 3.55 (d, J = 12.0 Hz, 1H), 3.68-3.86 (m, 2H), 3.93 (br s, 1H), 4.29 (br s, 1H), 4.44 (br s, 1H), 4.66 (br s, 1H), 4.92 (br s, 1H), 5.88-6.05 (m, 1H), 7.27-7.45 (m, 2H), 7.56-7.63 (m , 0.5H), 7.66-7.77 (m, 0.5H), 8.35 (s, 0.5H), 8.62 (s, 0.5H), 9.26 (s, 0.5H), 10.89 (s, 0.5H).
LCMS (ESI) m / z 592 [M + H] ⁺ , t _R = 1.30 min, mode N.
Step 1-8-7: Using the same method as in Step 1-2-8, the title compound (45 mg, colorless solid) was obtained from the compound (55 mg) obtained in Step 1-8-6. .
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.46 min, mode N.

Example 1-9: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl}- Synthesis of 2-methylpropyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide N- (tert The title compound (15 mg, colorless solid) was obtained from -butoxycarbonyl) -N-methyl-L-valine (5.0 g).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.66 min, mode N.

Example 1-10: N- (1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} cyclopropyl) -5 Step 1-10-1 for Synthesis of 1-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide: Using the same method as in Step 1-1-1 to Step 1-1-3, (tert-Butoxycarbonyl) amino] cyclopropanecarboxylic acid (4.0 g) gave tert-butyl [1- (5-amino-1H-pyrazol-3-yl) cyclopropyl] carbamate (4.7 g, yellow amorphous) It was.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.14 (s, 4H), 1.44 (s, 9H), 5.26 (br s, 1H), 5.35 (br s, 1H).
Step 1-10-2: Ethyl (2E) -3-ethoxy-2-methylprop-2-enoate (3.7 mL) and EtOH (110 mL) of the compound (2.5 g) obtained in Step 1-10-1 and 28% NaOEt / EtOH solution (7.3 mL) was added, and the mixture was stirred at 90 ° C. for 30 hr. EtOAc was added to the reaction solution, and a liquid separation operation was performed with a saturated aqueous NaHCO ₃ solution. The aqueous layer was washed with Brine, the organic layer was dried with MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by OH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100: 0 to 95/5; v / v), and tert-butyl [1- (6-methyl-5-oxo-4, 5-Dihydropyrazolo [1,5-a] pyrimidin-2-yl) cyclopropyl] carbamate (2.0 g, brown solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.09-1.54 (m, 13H), 2.06 (s, 3H), 4.06-4.29 (m, 1H), 5.36 (s, 1H), 5.76 (br s, 1H), 7.89 (s, 1H), 10.71 (br s, 1H).
LCMS (ESI) m / z 305 [M + H] ⁺ , t _R = 0.66 min, mode N.
Step 1-10-3: Using a method similar to that of Step 1-1-5, 2- {1-[(tert-butoxycarbonyl) amino from the compound (1.9 g) obtained in Step 1-10-2 ] Cyclopropyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (0.69 g, yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.28-1.54 (m, 13H), 2.30 (s, 3H), 5.39 (br s, 1H), 6.49 (s, 1H), 8.43 (s, 1H) .
Step 1-10-4: Using a method similar to that of Step 1-1-6, benzyl [(3S) -1- (2- {1] from the compound (100 mg) obtained in Step 1-10-3 -[(tert-Butoxycarbonyl) amino] cyclopropyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (120 mg, pale yellow solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.17-1.51 (m, 13H), 1.89-2.00 (m, 1H), 2.17-2.35 (m, 4H), 3.51-3.60 (m, 1H), 3.65 -3.73 (m, 1H), 3.74-3.82 (m, 1H), 3.86-3.96 (m, 1H), 4.30-4.40 (m, 1H), 4.88-4.98 (m, 1H), 5.11 (br s, 2H ), 5.36 (br s, 1H), 5.99 (s, 1H), 7.29-7.41 (m, 5H), 7.96 (s, 1H).
Step 1-10-5: Using a method similar to that of Step 1-1-7, benzyl {(3S) -1- [2- (1) from the compound (120 mg) obtained in Step 1-10-4 -Aminocyclopropyl) -6-methylpyrazolo [1,5-a] pyrimidin-5-yl] pyrrolidin-3-yl} carbamate hydrochloride (110 mg, pale yellow solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.22-1.28 (m, 2H), 1.41-1.46 (m, 2H), 1.83-1.90 (m, 1H), 2.04-2.13 (m, 1H) , 2.34 (s, 3H), 3.47-3.89 (m, 4H), 4.06-4.17 (m, 1H), 5.03 (s, 2H), 5.96 (s, 1H), 7.30-7.40 (m, 4H), 7.60 -7.67 (m, 1H), 8.43 (s, 1H), 8.87 (br s, 3H).
LCMS (ESI) m / z 407 [M + H] ⁺ , t _R = 0.52 min, mode N.
Step 1-10-6: Using a method similar to that of Step 1-2-6 and Step 1-2-7, the compound (88 mg) obtained in Step 1-10-5, 5-chloro-2- [ From (methylsulfonyl) amino] benzoic acid (28 mg) and MeI (12 μL), benzyl [(3S) -1- (2- {1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl } (Methyl) amino] cyclopropyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (27 mg, pale yellow solid) was obtained.
LCMS (ESI) m / z 652 [M + H] ⁺ , t _R = 1.15 min, mode N.
Step 1-10-7: Using the same method as in Step 1-1-9, the title compound (8.0 mg, white solid) was obtained from the compound (27 mg) obtained in Step 1-10-6. .
LCMS (ESI) m / z 518 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 1-11: N-[(S)-{5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} (cyclopropyl ) Methyl] -5-chloro-N-ethyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-11-1: Procedure similar to Step 1-1-1 to Step 1-1-3 From (2S)-[(tert-butoxycarbonyl) amino] (cyclopropyl) acetic acid (2.0 g) to tert-butyl [(S)-(5-amino-1H-pyrazol-3-yl) ( Cyclopropyl) methyl] carbamate (1.65 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.30-0.76 (m, 4H), 1.16 (dt, J = 8.4, 4.3 Hz, 1H), 1.37-1.52 (m, 9H), 3.94 (dd, J = 9.1, 7.4 Hz, 1H), 5.00 (br s, 1H), 5.63 (s, 1H).
LCMS (ESI) m / z 253 [M + H] ⁺ , t _R = 0.369 min, mode N.
Step 1-11-2: Using a method similar to that of Step 1-2-2, tert-butyl [(S) -cyclopropyl (6) from the compound (1.65 g) obtained in Step 1-11-1 -Methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) methyl] carbamate (0.31 g, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.36-0.59 (m, 4H), 1.13-1.21 (m, 1H), 1.43-1.46 (m, 9H), 2.10 (d, J = 1.2 Hz, 3H ), 4.27 (br s, 1H), 5.22 (d, J = 7.8 Hz, 1H), 5.87 (s, 1H), 7.99 (s, 1H), 10.57-11.23 (m, 1H).
LCMS (ESI) m / z 319 [M + H] ⁺ , t _R = 0.75 min, mode N.
Step 1-11-3: Using the same method as in Step 1-2-3, from the compound (310 mg) obtained in Step 1-11-2, 2-[(S) -amino (cyclopropyl) Methyl] -6-methylpyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride (250 mg, yellow solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.38-0.72 (m, 4H), 1.22-1.36 (m, 1H), 1.86-1.97 (m, 3H), 3.63-3.75 (m, 1H) , 6.02 (s, 1H), 8.38-8.48 (m, 1H), 8.57 (br s, 3H), 12.28 (br s, 1H).
LCMS (ESI) m / z 202 [M-NH ₂ ] ⁺ , t _R = 0.34 min, mode N.
Step 1-11-4: Using the same method as in Step 1-2-4, from the compound (250 mg) obtained in Step 1-11-3, (S) -1- (5-chloro-6 -Methylpyrazolo [1,5-a] pyrimidin-2-yl) -1-cyclopropylmethanamine hydrochloride (260 mg, brown amorphous) was obtained.
LCMS (ESI) m / z 221 [M-NH ₂ ] ⁺ , t _R = 0.659 min, mode H.
Step 1-11-5: Using the same method as in Step 1-2-5, from the compound (260 mg) obtained in Step 1-11-4, tert-butyl [(3S) -1- {2 -[(S) -Amino (cyclopropyl) methyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (235 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.30-0.41 (m, 2H), 0.48-0.63 (m, 2H), 1.15-1.22 (m, 1H), 1.45 (s, 9H), 1.89-1.96 (m, 1H), 2.17-2.25 (m, 1H), 2.33 (d, J = 0.8 Hz, 3H), 3.38 (d, J = 8.7 Hz, 1H), 3.53 (dd, J = 11.1, 3.7 Hz, 1H), 3.66-3.74 (m, 1H), 3.80 (dt, J = 10.7, 7.4 Hz, 1H), 3.92 (dd, J = 10.3, 5.8 Hz, 1H), 4.30 (br s, 1H), 4.71 ( br s, 1H), 6.12 (s, 1H), 8.04 (s, 1H).
LCMS (ESI) m / z 370 [M-NH ₂ ] ⁺ , t _R = 0.49 min, mode N.
Step 1-11-6: Using the same method as in Step 1-2-6 and Step 1-2-7, the compound (235 mg) obtained in Step 1-11-1-5, 5-chloro-2- From [(methylsulfonyl) amino] benzoic acid (99 mg) and EtI (48 μL), tert-butyl [(3S) -1- {2-[(S)-[{5-chloro-2-[(methyl Sulfonyl) amino] benzoyl} (ethyl) amino] (cyclopropyl) methyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (100 mg, pale yellow solid) Obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.21-1.36 (m, 8H), 1.45 (s, 9H), 1.92 (dd, J = 12.2, 6.0 Hz, 1H), 2.15-2.27 (m, 1H ), 2.37 (d, J = 8.3 Hz, 3H), 2.87-3.13 (m, 5H), 3.49-3.59 (m, 1H), 3.65-3.84 (m, 3H), 3.94 (br s, 1H), 4.30 (br s, 1H), 4.67 (br s, 1H), 6.15-6.37 (m, 1H), 6.98-7.74 (m, 3H), 8.37 (s, 0.5H), 8.66 (s, 0.5H), 9.61 (br s, 0.5H), 11.20 (br s, 0.5H).
Step 1-11-7: Using the same method as in Step 1-2-8, the title compound (70 mg, colorless solid) was obtained from the compound (100 mg) obtained in Step 1-11-6. .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.26 (br s, 1H), 0.48-0.83 (m, 3H), 0.91-1.17 (m, 3H), 1.44-1.62 (m, 1H), 2.03-2.12 (m, 1H), 2.20-2.31 (m, 1H), 2.32-2.40 (m, 3H), 3.00 (s, 3H), 3.05-3.19 (m, 2H), 3.69-4.01 (m, 5H ), 4.87 (br s, 1H), 6.21-6.32 (m, 1H), 7.33-7.58 (m, 3H), 8.36-8.45 (m, 3H), 8.53 (s, 0.5H), 9.24 (s, 0.5 H).
LCMS (ESI) m / z 546 [M + H] ⁺ , t _R = 0.64 min, mode N.

Example 1-12: N-[(1R) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl}- 2-Hydroxyethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-12-1: Using the same method as in Step 1-1-1, Methyl N- (tert-butoxycarbonyl) -N-methyl-L-selinate (5.6 g, colorless oil) was obtained from-(tert-butoxycarbonyl) -N-methyl-L-serine (5.0 g).
Step 1-12-2: To a DMF (50 mL) solution of the compound obtained in Step 1-12-1 (5.50 g), TBDPSCl (7.58 g) and imidazole (3.42 g) were added, and overnight at room temperature. Stir. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v), and methyl N- (tert-butoxycarbonyl) -O- [tert- Butyl (diphenyl) silyl] -N-methyl-L-selinate (12.2 g, colorless oil) was obtained.
Step 1-12-3: Using a method similar to that in Step 1-1-2 and Step 1-1-3, from the compound (12 g) obtained in Step 1-12-2, tert-butyl [( 1R) -1- (5-Amino-1H-pyrazol-3-yl) -2-{[tert-butyl (diphenyl) silyl] oxy} ethyl] (methyl) carbamate (8.5 g, pale yellow amorphous) was obtained. .
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.06 (br s, 9H), 1.42-1.53 (m, 9H), 2.73 (s, 3H), 3.88-4.06 (m, 2H), 5.17-5.32 ( m, 1H), 5.44 (s, 1H), 7.34-7.46 (m, 6H), 7.60-7.68 (m, 4H).
LCMS (ESI) m / z 495 [M + H] ⁺ , t _R = 1.22 min, mode N.
Step 1-12-4: Using a method similar to that in Step 1-1-4, the compound (3.85 g) obtained in Step 1-12-3 was used to obtain tert-butyl [(1R) -2-{[[ tert-butyl (diphenyl) silyl] oxy} -1- (6-methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamate (150 mg, yellow amorphous).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.01-1.09 (m, 9H), 1.45-1.54 (m, 9H), 2.01-2.12 (m, 3H), 2.75 (d, J = 14.0 Hz, 3H ), 3.96-4.24 (m, 2H), 5.36-5.83 (m, 2H), 7.33-7.48 (m, 6H), 7.68 (d, J = 6.2 Hz, 4H), 7.90 (s, 1H), 10.28 ( br s, 1H).
Step 1-12-5: Using a method similar to that of Step 1-1-5, from the compound (145 mg) obtained in Step 1-12-4, 6-methyl-2-[(6R) -2 , 2,7,10,10-Pentamethyl-8-oxo-3,3-diphenyl-4,9-dioxa-7-aza-3-silaundecan-6-yl] pyrazolo [1,5-a] pyrimidine- 5-yl trifluoromethanesulfonate (150 mg, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.06 (br s, 9H), 1.46-1.53 (m, 9H), 2.30 (br s, 3H), 2.77 (d, J = 16.9 Hz, 3H), 4.06-4.26 (m, 2H), 5.48-5.86 (m, 1H), 6.42-6.51 (m, 1H), 7.35-7.45 (m, 6H), 7.68 (d, J = 6.6 Hz, 4H), 8.44 ( br s, 1H).
Step 1-12-6: Using a method similar to that of Step 1-2-3, from the compound (150 mg) obtained in Step 1-12-5, 2-[(1R) -2-{[tert -Butyl (diphenyl) silyl] oxy} -1- (methylamino) ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate hydrochloride (150 mg, yellow oil) It was.
Step 1-12-7: Using a method similar to that of Step 1-1-8, the compound (150 mg) obtained in Step 1-12-6 was used to give 2-{(1R) -2-{[tert -Butyl (diphenyl) silyl] oxy} -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidine-5 -Il trifluoromethanesulfonate (100 mg, yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.05-1.18 (m, 9H), 2.25-2.49 (m, 3H), 2.67-2.85 (m, 3H), 2.88-3.14 (m, 3H), 3.98 -4.41 (m, 2H), 5.07 (dd, J = 8.9, 5.6 Hz, 0.5H), 6.21-6.38 (m, 1.5H), 7.32-7.78 (m, 13H), 8.71-8.86 (m, 1H) , 9.03 (s, 0.5H), 10.21 (br s, 0.5H).
Step 1-12-8: Using a method similar to that of Step 1-2-5, from the compound (100 mg) obtained in Step 1-12-7, tert-butyl [(3S) -1- (2 -{(1R) -2-{[tert-butyl (diphenyl) silyl] oxy} -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6- Methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (100 mg, yellow amorphous) was obtained.
Step 1-12-9: 1M TBAF / THF solution (0.24 mL) was added to a THF (3 mL) solution of the compound (100 mg) obtained in Step 1-12-8, and the mixture was stirred at 65 ° C. for 4 hours. did. After the reaction solution was concentrated under reduced pressure, the obtained residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 50 / 50-0 / 100; v / v), and tert-butyl [(3S) -1 -(2-{(1R) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] -2-hydroxyethyl} -6-methylpyrazolo [1,5-a] Pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (75 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.46 (s, 9H), 1.92 (d, J = 5.8 Hz, 1H), 2.22 (br s, 1H), 2.37 (d, J = 5.8 Hz, 3H ), 2.78-3.04 (m, 6H), 3.50-3.59 (m, 1H), 3.55 (d, J = 10.7 Hz, 1H), 3.68-3.85 (m, 2H), 3.94 (br s, 1H), 4.07 -4.21 (m, 2H), 4.25-4.35 (m, 1H), 4.68 (br s, 1H), 4.94 (t, J = 7.2 Hz, 0.5H), 5.88-6.04 (m, 1H), 6.08 (br s, 0.5H), 7.30-7.72 (m, 3H), 8.32 (br s, 0.5H), 8.50 (s, 0.5H).
LCMS (ESI) m / z 622 [M + H] ⁺ , t _R = 0.96 min, mode N.
Step 1-12-10: Using the same method as in Step 1-2-8, the title compound (50 mg, white solid) was obtained from the compound (73 mg) obtained in Step 1-12-9. .
LCMS (ESI) m / z 522 [M + H] ⁺ , t _R = 0.42 min, mode N.

Example 2-1 N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of —N-methyl-2-[(methylsulfonyl) amino] benzamide The compound obtained in Step 1-1-7 using the same method as in Step 1-1-8 and Step 1-1-9 ( The title compound (6.9 mg, colorless amorphous) was obtained from 30 mg) and 2-[(methylsulfonyl) amino] benzoic acid (16 mg).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.65-1.75 (m, 3H), 2.36-2.44 (m, 3H), 2.66 (s, 2H), 2.81 (s, 1H), 2.96 (s, 2H ), 3.05 (s, 1H), 4.97-5.03 (m, 0.5H), 6.31 (q, J = 7.2 Hz, 1H), 6.43-6.47 (m, 1H), 7.28-7.48 (m, 3H), 7.59 -7.75 (m, 1H), 8.76-9.13 (m, 1H).
LCMS (ESI) m / z 472 [M + H] ⁺ , t _R = 0.40 min, mode N.

Example 2-2: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of] -3-Chloro-N-methylbenzamide
In the same manner as in Step 1-1-8 and Step 1-1-9, the title compound (0.9 mg) was obtained from the compound (30 mg) obtained in Step 1-1-7 and 3-chlorobenzoic acid (12 mg). mg, colorless amorphous).
LCMS (ESI) m / z 413 [M + H] ⁺ , t _R = 0.48 min, mode N.

Example 2-3: 2-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -5-chloro-N-methylbenzamide synthesis The compound obtained in Step 1-1-7 using the same method as in Step 1-1-8 and Step 1-1-9 (60 mg ) And 2-amino-5-chlorobenzoic acid (26 mg) to give the title compound (3.9 mg, colorless amorphous).
LCMS (ESI) m / z 428 [M + H] ⁺ , t _R = 0.46 min, mode N.

Example 2-4: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methylbenzamide synthesis step 1-1-8 and step 1-1-9 were used in the same manner as in step 1-1-7 to obtain the compound (40 mg) and benzoic acid (12 mg). This gave the title compound (8.0 mg).
LCMS (ESI) m / z 379 [M + H] ⁺ , t _R = 0.34 min, mode N.

Example 2-5: 2-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -5-methoxy-N-methylbenzamide synthesis step 1-1-8 and the compound obtained in step 1-1-7 using the same method as in step 1-1-9 (40 mg ) And 2-amino-5-methoxybenzoic acid (17 mg) to give the title compound (6.6 mg).
LCMS (ESI) m / z 424 [M + H] ⁺ , t _R = 0.25 min, mode N.

Example 2-6: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N, 5-dimethyl-2-[(methylsulfonyl) amino] benzamide was obtained in Step 1-1-7 using the same method as in Step 1-1-8 and Step 1-1-9. The title compound (3.1 mg) was obtained from the compound (40 mg) and 5-methyl-2-[(methylsulfonyl) amino] benzoic acid (22 mg).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.73-1.80 (m, 1H), 2.11-2.19 (m, 1H), 2.33-2.37 (m, 6H), 2.37-2.41 (m, 1.8H), 2.59-2.66 (m, 1.2H), 2.78-3.03 (m, 6H), 3.30-4.05 (m, 5H), 4.88-4.96 (m, 0.6H), 5.96-6.05 (m, 1H), 6.16-6.25 (m, 0.4H), 7.07-7.29 (m, 2H), 7.48-7.63 (m, 1H), 8.36 (br s, 0.6H), 8.64 (br s, 0.4H).
LCMS (ESI) m / z 486 [M + H] ⁺ , t _R = 0.49 min, mode N.

Example 2-7: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -2- (1,1-dioxidethiomorpholin-4-yl) -N-methylbenzamide is synthesized in the same manner as in Step 1-1-1 using the same procedure as in Step 1-1-8 and Step 1-1-9. The title compound (13 mg) was obtained from the compound obtained in -7 (40 mg) and 2- (1,1-dioxidethiomorpholin-4-yl) benzoic acid (25 mg).
LCMS (ESI) m / z 512 [M + H] ⁺ , t _R = 0.36 min, mode N.

Example 2-8: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -2-Chloro-N-methylbenzamide Synthesis Using the same method as in Step 1-1-8 and Step 1-1-9, the compound (40 mg) obtained in Step 1-1-7 and 2- The title compound (4.6 mg) was obtained from chlorobenzoic acid (15 mg).
LCMS (ESI) m / z 413 [M + H] ⁺ , t _R = 0.45 min, mode N.

Example 2-9: N-[(1R) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Synthesis of hydrochloride
Step 2-9-1: Using a method similar to that of Step 1-1-7, from the compound (861 mg) obtained in Step 1-1-5, 6-methyl-2-[(1S) -1 -(Methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate hydrochloride (1.07 g) was obtained.
LCMS (ESI) m / z 339 [M + H] ⁺ , t _R = 0.52 min, mode N.
Step 2-9-2: Using a method similar to that of Step 1-2-7, from the compound (1.07 g) obtained in Step 2-9-1, 2-{(1S) -1-[{5 -Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (709 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.68 (d, J = 7.4 Hz, 1.4H), 1.72 (d, J = 7.4 Hz, 1.6H), 2.39 (s, 1.8H), 2.40 (s , 1.2H), 2.66 (s, 1.6H), 2.80 (s, 1.4H), 2.96 (s, 1.8H), 3.05 (s, 1.2H), 5.00 (q, J = 7.4 Hz, 0.5H), 6.31 (q, J = 7.4 Hz, 0.5H), 6.45 (s, 0.5H), 6.46 (s, 0.5H), 7.28-7.34 (m, 1H), 7.35-7.42 (m, 1H), 7.62 (d , J = 8.7 Hz, 0.5H), 7.71 (d, J = 8.7 Hz, 0.5H), 8.79 (s, 1H), 8.93 (s, 0.5H), 9.10 (s, 0.5H).
Step 2-9-3: Using a method similar to that of Step 1-1-6, the compound (702 mg) obtained in Step 2-9-2 and (3S)-(-)-3- (tert- From butoxycarbonylamino) pyrrolidine (459 mg), tert-butyl [(3S) -1- (2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl ) Amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (732 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.45 (s, 9H), 1.60 (d, J = 7.0 Hz, 2H), 1.64 (d, J = 7.0 Hz, 1H), 1.86-1.97 (m, 1H), 2.16-2.27 (m, 1H), 2.35-2.39 (m, 3H), 2.63 (s, 1H), 2.81 (s, 2H), 2.95 (s, 1H), 3.03 (s, 2H), 3.50 -3.58 (m, 1H), 3.69-3.76 (m, 1H), 3.77-3.85 (m, 1H), 3.90-3.97 (m, 1H), 4.24-4.34 (m, 1H), 4.67 (br s, 1H ), 4.88 (q, J = 7.0 Hz, 0.5H), 5.97-6.04 (m, 1H), 6.23 (q, J = 7.0 Hz, 0.5H), 7.27-7.31 (m, 1H), 7.33-7.40 ( m, 1H), 7.61 (d, J = 8.7 Hz, 0.6H), 7.69 (d, J = 8.7 Hz, 0.4H), 8.36 (s, 1H), 8.64 (s, 0.5H), 9.40 (s, 0.5H).
LCMS (ESI) m / z 606 [M + H] ⁺ , t _R = 1.15 min, mode N.
Step 2-9-4: The compound (730 mg) obtained in Step 2-9-3 was subjected to preparative purification using a chiral column (preparation conditions: column: CHIRALPAK AD-H (Daicel), column size: By concentrating the fraction eluted at 20 mm x 250 mm, mobile phase: hexane / EtOH = 20/80 (v / v), flow rate: 10 mL / min), retention time 20.0 min-27.0 min under reduced pressure, tert-butyl [(3S) -1- (2-{(1R) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1 , 5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (70.4 mg) and the fraction eluted with a retention time of 10.5 to 16.0 minutes were concentrated under reduced pressure to give tert-butyl [(3S) -1- (2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidine- 5-yl) pyrrolidin-3-yl] carbamate (685 mg) was obtained.
tert-butyl [(3S) -1- (2-{(1R) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1 , 5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate: LCMS (ESI) m / z 606 [M + H] ⁺ , t _R = 1.147 min, mode N.
Step 2-9-5: Using a method similar to that of Step 1-1-7, tert-butyl [(3S) -1- (2-{(1R) -1- [{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (63.0 mg) gave the title compound (69.5 mg, colorless amorphous).
LCMS (ESI) m / z 506 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 2-10: 4-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} propyl] -N-methylpyridine-3-carboxamide hydrochloride The compound obtained in Step 1-4-3 using the same method as in Step 1-2-7 and Step 1-2-8 ( The title compound (16 mg, colorless solid) was obtained from 50 mg) and 4-aminopyridine-3-carboxylic acid (21 mg).
LCMS (ESI) m / z 409 [M + H] ⁺ , t _R = 0.35 min, mode N.

Example 2-11: 3-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} propyl] -N-methylpyridine-2-carboxamide hydrochloride The compound obtained in Step 1-4-3 using the same method as in Step 1-2-7 and Step 1-2-8 ( The title compound (12 mg, colorless solid) was obtained from 50 mg) and 3-aminopyridine-2-carboxylic acid (21 mg).
LCMS (ESI) m / z 409 [M + H] ⁺ , t _R = 0.65 min, mode H.

Example 2-12: 5-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} propyl] -2-chloro-N-methylpyridine-4-carboxamide hydrochloride In step 1-4-3 using the same procedure as in step 1-2-7 and step 1-2-8 The title compound (14 mg, colorless solid) was obtained from the obtained compound (50 mg) and 5-amino-2-chloropyridine-4-carboxylic acid (26 mg).
LCMS (ESI) m / z 443 [M + H] ⁺ , t _R = 0.79 min, mode H.

Example 2-13: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-3-[(methylsulfonyl) amino] thiophene-2-carboxamide hydrochloride Synthesis of Step 1-4-4 using the same method as in Step 1-2-7 and Step 1-2-8 The title compound (17 mg, colorless solid) was obtained from the compound obtained in 3 (30 mg) and 3-[(methylsulfonyl) amino] thiophene-2-carboxylic acid (20 mg).
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.87 min, mode H.

Example 2-14: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2-[(methylsulfonyl) amino] thiophene-3-carboxamide hydrochloride Synthesis of step 1-4-4 using the same procedure as in step 1-2-7 and step 1-2-8 The title compound (20 mg, colorless solid) was obtained from the compound obtained in 3 (30 mg) and 2-[(methylsulfonyl) amino] thiophene-3-carboxylic acid (20 mg).
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.86 min, mode H.

Example 2-15: 2-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Yl} propyl] -5-chloro-N-methylbenzamide hydrochloride synthesis
Using the same method as in Step 1-2-7 and Step 1-2-8, from the compound obtained in Step 1-4-3 (50 mg) and 2-amino-5-chlorobenzoic acid (26 mg) To give the title compound (9.5 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.76-1.03 (m, 3H), 1.83-1.93 (m, 1H), 2.00-2.29 (m, 3H), 2.35 (s, 3H), 2.58 -2.79 (m, 3H), 3.69-3.95 (m, 5H), 5.74 (br s, 1H), 6.07 (s, 1H), 6.77 (d, J = 8.7 Hz, 1H), 6.98-7.25 (m, 2H), 8.28 (br s, 3H), 8.44-8.59 (m, 1H).
LCMS (ESI) m / z 442 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 2-16: N-[(1S) -1- {5-[(3S) -3-Aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride obtained in Step 1-4-3 using the same method as in Step 1-2-7 and Step 1-2-8. The title compound (21 mg, colorless solid) was obtained from the compound (30 mg) and 2-[(methylsulfonyl) amino] benzoic acid (24 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.85-1.06 (m, 3H), 1.86-2.30 (m, 4H), 2.33-2.40 (m, 3H), 2.57 (s, 1.5H), 2.73 (br s, 1.5H), 3.02 (s, 3H), 3.76 (br s, 2H), 3.82-3.89 (m, 2H), 3.90-3.99 (m, 1H), 4.55 (br s, 0.5H) , 5.77 (dd, J = 9.7, 5.6 Hz, 0.5H), 6.12 (s, 1H), 7.26-7.39 (m, 2H), 7.41-7.52 (m, 2H), 8.39 (br s, 3H), 8.51 (s, 0.5H), 9.08 (s, 0.5H).
LCMS (ESI) m / z 486 [M + H] ⁺ , t _R = 0.49 min, mode N.

Example 2-17: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methylbenzamide Hydrochloride Synthesis of the compound obtained in Step 1-4-3 (30 mg) and benzoic acid (14) using the same method as in Step 1-2-7 and Step 1-2-8 mg) gave the title compound (18 mg, colorless solid).
LCMS (ESI) m / z 393 [M + H] ⁺ , t _R = 0.43 min, mode N.

Example 2-18: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2-oxo-2,3-dihydro-1H-indole-7-carboxamide Hydrochloride Synthesis Step 1-2-7 and Step 1-2-8 The title compound (26 mg, colorless solid) was obtained from the compound (30 mg) obtained in -4--3 and 2-oxo-2,3-dihydro-1H-indole-7-carboxylic acid (20 mg).
LCMS (ESI) m / z 448 [M + H] ⁺ , t _R = 0.38 min, mode N.

Example 2-19: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-1H-indazole-7-carboxamide hydrochloride The compound obtained in Step 1-4-3 using the same method as in Step 1-2-7 and Step 1-2-8 (30 mg) and 1H-indazole-7-carboxylic acid (18 mg) gave the title compound (31 mg, colorless solid).
LCMS (ESI) m / z 433 [M + H] ⁺ , t _R = 0.43 in, mode N.

Example 2-20: N-[(1S) -1- {5-[(3S) -3-Aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2- (1H-pyrazol-1-yl) benzamide hydrochloride in step 1-4-3 using the same method as in step 1-2-7 and step 1-2-8 The title compound (26 mg, colorless solid) was obtained from the obtained compound (30 mg) and 2- (1H-pyrazol-1-yl) benzoic acid (21 mg).
LCMS (ESI) m / z 459 [M + H] ⁺ , t _R = 0.85 in, mode H.

Example 2-21: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methylbiphenyl-2-carboxamide Hydrochloride Synthesis Using the same method as in Step 1-2-7 and Step 1-2-8, the compound obtained in Step 1-4-3 (30 mg) and The title compound (25 mg, colorless solid) was obtained from biphenyl-2-carboxylic acid (22 mg).
LCMS (ESI) m / z 469 [M + H] ⁺ , t _R = 0.60 min, mode N.

Example 2-22: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2- (1H-tetrazol-1-yl) benzamide Hydrochloride Synthesis Step 1-2-3 using the same method as in Step 1-2-7 and Step 1-2-8 The title compound (25 mg, colorless solid) was obtained from the obtained compound (30 mg) and 2- (1H-tetrazol-1-yl) benzoic acid (22 mg).
LCMS (ESI) m / z 461 [M + H] ⁺ , t _R = 0.340 min, mode N.

Example 2-23: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -3-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-4 Using the same procedure as in Step 1-2-7 and Step 1-2-8 The title compound (10 mg, colorless solid) was obtained from the compound (10 mg) obtained in 3 and 3-chloro-2-[(methylsulfonyl) amino] benzoic acid (6.4 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.79-1.05 (m, 3H), 1.84-2.30 (m, 4H), 2.33-2.42 (m, 3H), 2.43-2.59 (m, 3H) , 2.98-3.17 (m, 3H), 3.68-4.01 (m, 5H), 4.37 (br s, 0.5H), 5.75 (br s, 0.5H), 6.06-6.25 (m, 1H), 7.23-7.67 ( m, 3H), 8.17-8.27 (m, 3H), 8.51 (s, 0.5H), 9.43 (br s, 0.5H).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.46 min, mode N.

Example 2-24: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -3,5-Dichloro-N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride Using the same procedure as in Step 1-2-7 and Step 1-2-8, Step 1- The title compound (34 mg, colorless solid) was obtained from the compound (30 mg) obtained in 4-3 and 3,5-dichloro-2-[(methylsulfonyl) amino] benzoic acid (24 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.80-1.06 (m, 3H), 1.83-2.30 (m, 4H), 2.31-2.41 (m, 3H), 2.46-2.61 (m, 3H) , 2.89-3.16 (m, 3H), 3.70-3.81 (m, 2H), 3.81-3.90 (m, 2H), 3.90-3.98 (m, 1H), 5.72 (br s, 1H), 6.15 (br s, 1H), 7.31-7.47 (m, 1H), 7.78-7.86 (m, 1H), 8.30-8.57 (m, 3H), 9.48 (br s, 1H).
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 0.58 min, mode N.

Example 2-25: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-2-{[(trifluoromethyl) sulfonyl] amino} benzamide Hydrochloride Synthesis Step 1-2-4 Using the same method as in Step 1-2-7 and Step 1-2-8 The title compound (7.2 mg, colorless solid) was obtained from the compound (30 mg) obtained in 3 and 2-{[(trifluoromethyl) sulfonyl] amino} benzoic acid (25 mg).
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.61 min, mode N.

Example 2-26: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N-methyl-2-[(phenylsulfonyl) amino] benzamide Hydrochloride Synthesis Using the same method as in Step 1-2-7 and Step 1-2-8, Step 1-4-4- The title compound (29 mg, colorless solid) was obtained from the compound (30 mg) obtained in 3 and 5-chloro-2-[(phenylsulfonyl) amino] benzoic acid (29 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.83 (br s, 1H), 1.01 (t, J = 7.2 Hz, 2H), 1.84-2.30 (m, 4H), 2.34-2.38 (m, 3H), 2.54-2.74 (m, 3H), 3.69-3.99 (m, 5H), 4.51 (dd, J = 9.5, 5.8 Hz, 0.5H), 5.69 (dd, J = 9.5, 5.8 Hz, 0.5H) , 6.13 (s, 1H), 7.04-7.82 (m, 8H), 8.22 (br s, 3H), 8.58 (s, 0.5H), 9.61 (s, 0.5H).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 2-27: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide Similar procedure to steps 1-2-7 and 1-2-8 From the compound obtained in Step 1-4-3 (35 mg) and 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxylic acid (16 mg) to give the title compound ( 30 mg, a colorless solid) was obtained.
LCMS (ESI) m / z 464 [M + H] ⁺ , t _R = 0.73 min, mode N.

Example 2-28: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N, 1-Dimethyl-4-[(methylsulfonyl) amino] -1H-pyrazole-5-carboxamide Hydrochloride Synthesis using the same method as in Step 1-2-7 and Step 1-2-8, From the compound obtained in Step 1-4-3 (30 mg) and 1-methyl-4-[(methylsulfonyl) amino] -1H-pyrazole-5-carboxylic acid (19 mg), the title compound (23 mg, colorless Solid) was obtained.
LCMS (ESI) m / z 490 [M + H] ⁺ , t _R = 0.71 min, mode H.

Example 2-29: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -3-Chloro-N, 5-dimethyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-7 and Step 1-2-8 The title compound (37 mg, colorless solid) was obtained from the compound obtained in 4-3 (30 mg) and 3-chloro-5-methyl-2-[(methylsulfonyl) amino] benzoic acid (22 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.75-1.04 (m, 3H), 1.84-2.29 (m, 4H), 2.31-2.41 (m, 6H), 2.53-2.72 (m, 3H) , 2.88-3.13 (m, 3H), 3.69-3.98 (m, 5H), 5.74 (br s, 1H), 6.11 (br s, 1H), 7.00-7.15 (m, 1H), 7.42-7.50 (m, 1H), 8.24-8.33 (m, 3H), 8.46-8.55 (m, 0.5H), 9.29 (br s, 0.5H).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.97 min, mode H.

Example 2-30: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N, 1-Dimethyl-4-[(methylsulfonyl) amino] -1H-pyrazole-3-carboxamide Hydrochloride Synthesis using the same method as in Step 1-2-7 and Step 1-2-8, From the compound obtained in Step 1-4-3 (30 mg) and 1-methyl-4-[(methylsulfonyl) amino] -1H-pyrazole-3-carboxylic acid (18 mg), the title compound (29 mg, colorless Solid) was obtained.
LCMS (ESI) m / z 490 [M + H] ⁺ , t _R = 0.73 min, mode H.

Example 2-31: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] Synthesis step 2-31-1 of 5-chloro-2-[(ethylsulfonyl) amino] -N-methylbenzamide: In step 1-1-7, using the same method as in step 1-1-8 From the obtained compound (100 mg) and 2-amino-5-chlorobenzoic acid (43 mg), benzyl [(3S) -1- (2-{(1S) -1-[(2-amino-5- Chlorobenzoyl) (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (63 mg) was obtained.
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 1.06 min, mode N.
Step 2-31-2: The compound (28 mg) obtained in Step 2-3-1 was dissolved in THF (1.0 mL), Et ₃ N (42 μL) and ethanesulfonyl chloride (28 μL) were added, and room temperature was added. For 4 hours. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to OH type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) NH type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 95/5; v / v) and purified by benzyl [(3S) -1- (2-{(1S) -1-[{5-chloro-2-[(ethylsulfonyl) amino] benzoyl} (methyl) amino] ethyl } -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (12 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 654 [M + H] ⁺ , t _R = 1.19 min, mode N.
Step 2-31-3: Using the same method as in Step 1-1-9, the title compound (1.62 mg, colorless amorphous) was obtained from the compound (11.8 mg) obtained in Step 2-31-2. .
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 2-32: 2- (acetylamino) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] Pyrimidin-2-yl} ethyl] -5-chloro-N-methylbenzamide Step 2-32-1: Obtained in Step 1-1-7 using a method similar to Step 1-1-8. From the compound (60 mg) and 2-amino-5-chlorobenzoic acid (26 mg), benzyl [(3S) -1- (2-{(1S) -1-[(2-amino-5-chlorobenzoyl) (Methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (46 mg) was obtained.
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 1.05 min, mode N.
Step 2-32-2: in CHCl ₃ (1.0 mL) solution of the compound obtained in step 2-32-1 (28 mg), under _{ice-cooling, Et 3 N (42 μL)} , AcCl a (10 [mu] L) In addition, the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95 / 5-0 / 100; v / v), and benzyl [(3S) -1- {2-[(1S ) -1-{[2- (acetylamino) -5-chlorobenzoyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate ( 24 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 604 [M + H] ⁺ , t _R = 1.00 min, mode N.

Step 2-332: Using the same method as in Step 1-1-9, the title compound (4.6 mg, colorless solid) was obtained from the compound (24 mg) obtained in Step 2-3-2.
LCMS (ESI) m / z 470 [M + H] ⁺ , t _R = 0.39 min, mode N.

Example 2-33: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Ethyl-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Method 1-1-8, Step 2-3-2 and Step 1-2-8 The title compound (30 mg, colorless solid) was obtained from the compound (64 mg) obtained in Step 1-4-3, 2-amino-5-ethylbenzoic acid (38 mg) and MsCl (36 μL). It was.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.85-0.96 (m, 1.5H), 1.03 (t, J = 7.2 Hz, 1.5H), 1.14-1.22 (m, 3H), 1.82-2.32 (m, 4H), 2.33-2.38 (m, 3H), 2.57 (s, 1.5H), 2.59-2.68 (m, 2H), 2.72 (br s, 1.5H), 2.97 (s, 3H), 3.69- 4.05 (m, 5H), 4.50-4.57 (m, 0.5H), 5.75-5.80 (m, 0.5H), 6.12 (s, 1H), 7.15 (s, 1H), 7.26-7.33 (m, 1H), 7.33-7.40 (m, 1H), 8.30-8.39 (m, 3H), 8.51 (s, 0.5H), 8.98 (s, 0.5H).
LCMS (ESI) m / z 514 [M + H] ⁺ , t _R = 0.59 min, mode N.

Example 2-34: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N, 4-Dimethyl-2-[(methylsulfonyl) amino] benzamide hydrochloride Synthesis step 1-1-8, step 2-31-2 and step 1-2-8 The title compound (25 mg, colorless solid) was obtained from the compound (45 mg) obtained in Step 1-4-3, 2-amino-4-methylbenzoic acid (21 mg) and MsCl (36 μL).
LCMS (ESI) m / z 500 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 2-35: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Methoxy-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride has the same method as in Step 1-1-8, Step 2-31-2 and Step 1-2-8 From the wisdom, the compound obtained in Step 1-4-3 (45 mg), 2-amino-5-methoxybenzoic acid (23 mg) and MsCl (36 μL), the title compound (19 mg, colorless solid) was obtained. It was.
LCMS (ESI) m / z 516 [M + H] ⁺ , t _R = 0.50 min, mode N.

Example 2-36: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-3-[(methylsulfonyl) amino] pyridine-2-carboxamide hydrochloride synthesis step 2-36-1: using a method similar to that of step 1-1-8, step 1-4-4 From the compound (50 mg) obtained in 3 and 3-aminopyridine-2-carboxylic acid (21 mg), tert-butyl [(3S) -1- {2-[(1S) -1-{[(3 -Aminopyridin-2-yl) carbonyl] (methyl) amino} propyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (33 mg) was obtained.
Step 2-36-2: Et ₃ N (57 μL) and MsCl (9.5 μL) were added to a solution of the compound obtained in Step 2-36-1 (20 mg) in CHCl ₃ (1.0 mL) at room temperature. For 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in EtOH (1 mL), 2.94 M NaOEt / EtOH solution (50 μL) was added, and the mixture was stirred at room temperature for 30 min. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by reverse phase preparative HPLC, and tert-butyl [(3S) -1- (6-methyl-2-{(1S) -1- [methyl ({3-[(methylsulfonyl)) Amino] pyridin-2-yl} carbonyl) amino] propyl} pyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (16 mg, colorless amorphous) was obtained.
Step 2-36-3: Using the same method as in Step 1-2-8, the title compound (15 mg, colorless solid) was obtained from the compound (16 mg) obtained in Step 2-3-6. .
LCMS (ESI) m / z 487 [M + H] ⁺ , t _R = 0.77 min, mode H.

Example 2-37: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-3-[(methylsulfonyl) amino] pyridine-4-carboxamide Hydrochloride Synthesis Using the same method as in Step 1-1-8, Step 2-3-2 and Step 1-2-8 Then, the title compound (19 mg, colorless solid) was obtained from the compound obtained in Step 1-4-3 (50 mg) and 3-aminopyridine-4-carboxylic acid (21 mg).
LCMS (ESI) m / z 487 [M + H] ⁺ , t _R = 0.72 min, mode H.

Example 2-38: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -2-Chloro-N-methyl-5-[(methylsulfonyl) amino] pyridine-4-carboxamide Similar to Step 1-1-8, Step 2-36-2 and Step 1-2-8 of hydrochloride The title compound (19 mg, colorless solid) was obtained from the compound (50 mg) obtained in Step 1-4-3 and 5-amino-2-chloropyridine-4-carboxylic acid (21 mg) using the procedure of Got.
LCMS (ESI) m / z 521 [M + H] ⁺ , t _R = 0.92 min, mode H.

Example 2-39: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-4-[(methylsulfonyl) amino] -1,2-thiazole-3-carboxamide Hydrochloride Synthesis Step 1-1-8, Step 2-3-6 and Step 1-2-8 Using a similar method, the title compound (16 mg, colorless) was obtained from the compound obtained in Step 1-4-3 (50 mg) and 4-amino-1,2-thiazole-3-carboxylic acid (28 mg). Solid) was obtained.
LCMS (ESI) m / z 493 [M + H] ⁺ , t _R = 0.82 min, mode H.

Example 2-40: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -6-Chloro-N-methyl-3-[(methylsulfonyl) amino] pyridine-2-carboxamide Hydrochloride Synthesis Step 1-1-8, Step 2-3-2 and Step 1-2-8 From the compound obtained in Step 1-4-3 and 3-amino-6-chloropyridine-2-carboxylic acid (27 mg), the title compound (27 mg, colorless solid) Got.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.89-1.03 (m, 3H), 1.88-2.30 (m, 4H), 2.33-2.38 (m, 3H), 2.62 (s, 1.5H), 2.74 (s, 1.5H), 3.07-3.14 (m, 3H), 3.69-4.08 (m, 5H), 4.60 (dd, J = 9.7, 5.6 Hz, 0.5H), 5.72 (dd, J = 9.3, 6.0 Hz, 0.5H), 6.10-6.17 (m, 1H), 7.63 (t, J = 9.1 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 8.28 (br s, 3H), 8.52 (s , 0.5H), 9.56 (s, 0.5H).
LCMS (ESI) m / z 521 [M + H] ⁺ , t _R = 0.95 min, mode H.

Example 2-41: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -4-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Using the same method as in Step 1-1-8, Step 2-36-2 and Step 1-2-8 of hydrochloride The title compound (35 mg, colorless solid) was obtained from the compound (50 mg) obtained in Step 1-4-3 and 2-amino-4-chlorobenzoic acid (26 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.86-0.92 (m, 1.5H), 1.02 (t, J = 7.2 Hz, 1.5H), 1.86-2.30 (m, 4H), 2.33-2.38 (m, 3H), 2.58 (s, 1.5H), 2.73 (br s, 1.5H), 3.01-3.12 (m, 3H), 3.68-4.15 (m, 5H), 4.56 (dd, J = 9.9, 4.5 Hz, 0.5H), 5.73 (dd, J = 10.1, 5.6 Hz, 0.5H), 6.11 (s, 1H), 7.39 (s, 2H), 7.49 (d, J = 11.6 Hz, 1H), 8.23 (br s, 3H), 8.51 (s, 0.5H), 9.28 (s, 0.5H).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 1.04 min, mode H.

Example 2-42: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -2-Fluoro-N-methyl-6-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Method 1-1-8, Step 2-3-2 and Step 1-2-8 The title compound (25 mg, colorless solid) was obtained from the compound obtained in Step 1-4-3 (45 mg) and 2-amino-6-fluorobenzoic acid (21 mg).
LCMS (ESI) m / z 504 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 2-43: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N-methyl-2-{[(methylsulfonyl) acetyl] amino} benzamide Hydrochloride Synthesis Step 2-43-1: Compound (50 mg) obtained in Step 1-4-3 and HATU (63 mg) and Et ₃ N (89 μL) were added to a solution of 5-chloro-anthranilic acid (26 mg) in DMF (1 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was purified by reverse phase preparative HPLC and tert-butyl [(3S) -1- (2-{(1S) -1-[(2-amino-5-chlorobenzoyl) (methyl) amino] propyl. } -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (37 mg, colorless solid) was obtained.
Step 2-43-2: A solution of the compound obtained in Step 2-43-1 (25 mg) and methanesulfonylacetic acid (7 mg) in DMF (1 mL) was added to HATU (22 mg), Et ₃ N (31 μL). ) Was added and stirred at room temperature for 30 minutes. The reaction solution was purified by reverse phase preparative HPLC, and tert-butyl [(3S) -1- (2-{(1S) -1-[(5-chloro-2-{[(methylsulfonyl) acetyl] amino } Benzoyl) (methyl) amino] propyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (16 mg, colorless solid) was obtained.
Step 2-43-3: The title compound (15 mg, colorless solid) was obtained from the compound (17 mg) obtained in Step 2-43-2 using the same method as in Step 1-2-8. .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.71-0.89 (m, 1.5H), 0.98 (t, J = 7.2 Hz, 1.5H), 1.82-2.30 (m, 4H), 2.31 -2.37 (m, 3H), 2.53-2.54 (m, 1.5H), 2.82 (br s, 1.5H), 3.15 (s, 3H), 3.81-3.95 (m, 5H), 4.23-4.35 (m, 1.5H) , 4.47 (br s, 1H), 5.65-5.73 (m, 0.5H), 6.02-6.17 (m, 1H), 7.34-7.57 (m, 3H), 8.22 (br s, 3H), 8.52 (s, 0.5 H), 10.21 (s, 0.5H).
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 0.91 min, mode H.

Example 2-44: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of] -5-chloro-N-ethyl-2-[(methylsulfonyl) amino] benzamide
Step 2-44-1: Using a method similar to that of Step 1-1-5 to Step 1-1-7, from the compound (540 mg) obtained in Step 1-2-2, benzyl ((3S) -1- (2-((1S) -1-aminoethyl) -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl) carbamate (296 mg) was obtained.
Step 2-44-2: Compound (0.10 g) obtained in Step 2-44-1 using the same method as in Step 1-2-6, Step 1-2-7 and Step 1-1-9 And EtI (46 μL) gave the title compound (25 mg, colorless amorphous).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.83 (t, J = 6.6 Hz, 1H), 1.00 (t, J = 7.0 Hz, 2H), 1.52-1.68 (m, 3H), 1.77 ( br s, 1H), 2.01-2.10 (m, 1H), 2.33 (s, 3H), 2.79-2.94 (m, 3H), 2.94-3.17 (m, 2H), 3.45 (dd, J = 11.1, 4.1 Hz , 1H), 3.57-3.73 (m, 2H), 3.74-3.85 (m, 2H), 4.73-4.83 (m, 0.7H), 5.78 (br s, 0.3H), 6.16 (s, 1H), 7.21- 7.49 (m, 3H), 8.31 (s, 0.5H), 8.46 (s, 0.5H).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 2-45: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -3-Chloro-N- (propan-2-yl) benzamide synthesis step 2-451: A solution of the compound obtained in step 24-1 (100 mg) in THF (2 mL) was added to acetone. (20 μL), AcOH (39 μL), Et 3 N (64 μL) and sodium triacetoxyborohydride (123 mg) were added, and the mixture was stirred at room temperature for 5 hours. The reaction solution was poured into a saturated aqueous NaHCO ₃ solution and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 95/5 to 80/20; v / v) to obtain benzyl [(3S) -1- {6-methyl- 2-[(1S) -1- (propan-2-ylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (73 mg, pale yellow solid) was obtained. .
Step 2-45-2: To a solution of the compound obtained in Step 2-45-1 (62 mg) in CHCl ₃ (2 mL), add 3-chlorobenzoyl chloride (22 μL) and Et ₃ N (99 μL). The mixture was further stirred at room temperature for 18 hours. EtOAc was added to the reaction solution, and a liquid separation operation was performed with a saturated aqueous NaHCO ₃ solution. The aqueous layer was washed with Brine, the organic layer was dried with MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 70 / 30-30 / 70; v / v), and benzyl [(3S) -1- (2-{(1S) -1- [(3-Chlorobenzoyl) (propan-2-yl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (35 mg, colorless solid) Obtained.
Step 2-45-3: Using the same method as in Step 1-1-9, the title compound (10 mg, colorless amorphous) was obtained from the compound (34 mg) obtained in Step 2-45-2.
LCMS (ESI) m / z 441 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 2-46: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-butyl-5-chloro-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-6 to Step 1-2-8 The title compound (15 mg, colorless solid) was obtained from the compound obtained in 5 (30 mg) and 1-iodobutane (19 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.55 (t, J = 7.2 Hz, 1H), 0.81 (t, J = 7.4 Hz, 2H), 0.84-1.52 (m, 6H), 1.57 ( d, J = 7.0 Hz, 2H), 1.66 (d, J = 7.0 Hz, 1H), 2.00-2.10 (m, 1H), 2.22-2.29 (m, 1H), 2.33-2.38 (m, 3H), 2.85 -3.08 (m, 5H), 3.69-3.95 (m, 5H), 4.74-4.82 (m, 0.7H), 5.74 (br s, 0.3H), 6.13 (s, 1H), 7.42-7.57 (m, 3H ), 8.17 (br s, 3H), 8.52 (s, 0.5H), 9.34 (s, 0.5H).
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 2-47: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (2-methylbutyl) -2-[(methylsulfonyl) amino] benzamide hydrochloride Synthesis step 1-2-6 to step 1-2-8 The title compound (12 mg, colorless solid) was obtained from the compound obtained in 1-2-5 (30 mg) and 1-iodo-2-methylbutane (21 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.55-1.07 (m, 8H), 1.08-1.77 (m, 6H), 2.01-2.11 (m, 1H), 2.21-2.31 (m, 1H) , 2.33-2.38 (m, 3H), 2.76-3.36 (m, 5H), 3.69-3.95 (m, 5H), 4.80-4.89 (m, 1H), 6.04-6.16 (m, 1H), 7.31-7.58 ( m, 3H), 8.16 (br s, 3H), 8.30 (br s, 0.5H), 8.51 (s, 0.5H).
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 0.72 min, mode N.

Example 2-48: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N-pentylbenzamide Step 1-2-6 using the same method as in Step 1-2-6 to Step 1-2-8 The title compound (12 mg, colorless solid) was obtained from the compound obtained in 5 (30 mg) and 1-iodopentane (22 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.62 (t, J = 7.0 Hz, 1H), 0.77 (t, J = 7.0 Hz, 2H), 0.80-1.48 (m, 6H), 1.53 ( d, J = 7.0 Hz, 2H), 1.62 (d, J = 6.6 Hz, 1H), 1.97-2.05 (m, 1H), 2.17-2.25 (m, 1H), 2.27-2.34 (m, 3H), 2.82 -3.05 (m, 3H), 3.24-3.60 (m, 4H), 3.78-3.92 (m, 3H), 4.68-4.78 (m, 0.7H), 5.70 (s, 0.3H), 6.09 (s, 1H) , 7.36-7.55 (m, 3H), 8.13 (br s, 3H), 8.48 (s, 0.5H), 9.30 (s, 0.5H).
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 1.27 min, mode H.

Example 2-49: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (2-fluoroethyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (14 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 1-iodo-2-fluoroethane (13 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.50-1.73 (m, 3H), 2.00-2.10 (m, 1H), 2.20-2.30 (m, 1H), 2.32-2.40 (m, 3H) , 2.99-3.13 (m, 3H), 3.43-3.96 (m, 8H), 4.19-4.87 (m, 2H), 6.07-6.17 (m, 1H), 7.38-7.61 (m, 3H), 8.19 (br s , 3H), 8.52 (s, 0.5H), 9.37 (s, 0.5H).
LCMS (ESI) m / z 538 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 2-50: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (3-fluoropropyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (11 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 1-iodo-3-fluoropropane (17 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.52-1.97 (m, 5H), 2.00-2.10 (m, 1H), 2.20-2.30 (m, 1H), 2.32-2.40 (m, 3H) , 2.97-3.17 (m, 5H), 3.42-3.96 (m, 5H), 4.10-4.56 (m, 2.5H), 4.77-4.83 (m, 1H), 6.05-6.18 (m, 1H), 7.44-7.75 (m, 3H), 8.15 (br s, 3H), 8.52 (s, 0.5H), 9.34 (s, 1H).
LCMS (ESI) m / z 552 [M + H] ⁺ , t _R = 0.59 min, mode N.

Example 2-51: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- (2-phenylethyl) benzamide hydrochloride In the same manner as in Step 1-2-6 to Step 1-2-8, The title compound (12 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and (2-bromoethyl) benzene (22 μL).
LCMS (ESI) m / z 596 [M + H] ⁺ , t _R = 1.26 min, mode H.

Example 2-52: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- (3-phenylpropyl) benzamide Using the same method as in Step 1-2-6 to Step 1-2-8 of hydrochloride, The title compound (18 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and (3-bromopropyl) benzene (25 μL).
LCMS (ESI) m / z 610 [M + H] ⁺ , t _R = 1.29 min, mode H.

Example 2-53: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (2-methoxyethyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (10 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 2-bromoethyl methyl ether (16 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.52-1.72 (m, 3H), 2.00-2.07 (m, 1H), 2.20-2.32 (m, 1H), 2.32-2.38 (m, 3H) , 2.97-3.10 (m, 5H), 3.12-3.35 (m, 5H), 3.65-3.95 (m, 7H), 4.74-4.82 (m, 0.5H), 5.61 (br s, 0.5H), 6.12 (br s, 1H), 7.41-7.58 (m, 3H), 8.06-8.22 (m, 3H), 8.52 (s, 0.5H), 9.22 (s, 0.5H).
LCMS (ESI) m / z 550 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 2-54: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (3-methoxypropyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (13 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 1-bromo-3-methoxypropane (18 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.45-1.78 (m, 5H), 2.00-2.09 (m, 1H), 2.20-2.32 (m, 1H), 2.32-2.40 (m, 3H) , 2.95-3.18 (m, 6H), 3.21-3.52 (m, 4H), 3.65-3.95 (m, 5H), 4.78 (q, J = 6.9 Hz, 0.5H), 5.74 (br s, 0.5H), 6.06-6.16 (s, 1H), 7.43-7.60 (m, 3H), 8.14 (br s, 3H), 8.52 (s, 0.5H), 9.33 (s, 0.5H).
LCMS (ESI) m / z 564 [M + H] ⁺ , t _R = 0.58 min, mode N.

Example 2-55: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- [2- (2,2,2-trifluoroethoxy) ethyl] benzamide Synthesis of Hydrochloride Step 1-2-6 to Step 1-2 Using the same method as for -8, from the compound obtained in Step 1-2-5 (30 mg) and 2- (2-bromoethoxy) -1,1,1-trifluoroethane (35 mg), the title Compound (11 mg, colorless solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.52-1.73 (m, 3H), 1.99-2.09 (m, 1H), 2.20-2.32 (m, 1H), 2.33-2.38 (m, 3H) , 2.98-3.13 (m, 5H), 3.41-4.10 (m, 9H), 4.76-4.84 (m, 1H), 6.05-6.18 (m, 1H), 7.39-7.59 (m, 3H), 8.14 (br s , 3H), 8.51 (s, 0.5H), 9.36 (s, 0.5H).
LCMS (ESI) m / z 618 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 2-56: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- (2-phenoxyethyl) benzamide Hydrochloride Synthesis Using the same method as in Step 1-2-6 to Step 1-2-8, The title compound (15 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and (2-bromoethoxy) benzene (33 mg).
LCMS (ESI) m / z 612 [M + H] ⁺ , t _R = 0.70 min, mode N.

Example 2-57: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- [2- (1H-pyrazol-1-yl) ethyl] benzamide Synthesis Step 1-2-6 to Step 1-2-8 of Hydrochloride Using the same procedure as above, the title compound (4.1 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 1- (2-bromoethyl) -1H-pyrazole (18 μL). Obtained.
LCMS (ESI) m / z 586 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 2-58: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- [3- (methylsulfonyl) propyl] benzamide The same procedure as in Synthesis step 1-2-6 to Step 1-2-8 of hydrochloride The title compound (17 mg, colorless solid) was obtained from the compound (30 mg) obtained in Step 1-2-5 and 1-bromo-3- (methylsulfonyl) propane (35 mg).
LCMS (ESI) m / z 612 [M + H] ⁺ , t _R = 0.95 min, mode H.

Example 2-59: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of Step-5-6-chloro-N- (2-hydroxyethyl) -2-[(methylsulfonyl) amino] benzamide Step 1-2-6 to Step 1-2-8 The title compound (13 mg, colorless amorphous) was obtained from the compound obtained in 2-5 (30 mg) and 2-bromoethanol (12 μL).
LCMS (ESI) m / z 536 [M + H] ⁺ , t _R = 0.90 min, mode H.

Example 2-60: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N-[(2S) -3-hydroxy-2-methylpropyl] -2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-6 to Step 1-2-8 In the same manner as above, from the compound (30 mg) obtained in Step 1-2-5 and (2R) -3-bromo-2-methylpropan-1-ol (17 μL), the title compound (2.7 mg , Colorless solid).
LCMS (ESI) m / z 564 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 2-61: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N-[(2R) -3-hydroxy-2-methylpropyl] -2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-6 to Step 1-2-8 The title compound (2.2 mg) was prepared from the compound (30 mg) obtained in Step 1-2-5 and (2S) -3-bromo-2-methylpropan-1-ol (17 μL) using the same procedure as described above. , Colorless solid).
LCMS (ESI) m / z 564 [M + H] ⁺ , t _R = 0.53 min, mode N.

Example 2-62: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (3-hydroxypropyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (18 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 2- (3-bromopropoxy) tetrahydro-2H-pyran (28 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.53-1.71 (m, 5H), 2.00-2.10 (m, 1H), 2.20-2.29 (m, 1H), 2.32-2.38 (m, 3H) , 2.92-3.18 (m, 5H), 3.28-3.52 (m, 2H), 3.64-3.96 (m, 5H), 4.75-4.82 (m, 0.5H), 5.76 (br s, 0.5H), 6.06-6.17 (m, 1H), 7.42-7.58 (m, 3H), 8.23 (br s, 3H), 8.52 (s, 0.5H), 9.32 (s, 0.5H).
LCMS (ESI) m / z 550 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 2-63: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N- (4-hydroxybutyl) -2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 2-63-1: Step 1-2-6 and Step 1-2-7 Using a similar method, 4-([((1S) -1- (5-{(3S)) was obtained from the compound obtained in Step 1-2-5 (30 mg) and 4-bromobutyl acetate (24 μL). -3-[(tert-Butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] {5-chloro-2-[(methylsulfonyl) amino ] Benzoyl} amino) butyl acetate (18 mg, colorless solid) was obtained.
LCMS (ESI) m / z 706 [M + H] ⁺ , t _R = 1.19 min, mode N.
Step 2-63-2: K ₂ CO ₃ (8.0 mg) was added to a solution of the compound obtained in Step 2-63-1 (17 mg) in MeOH (2.0 mL), and the mixture was stirred at room temperature for 4 hours. The reaction solution was extracted by adding CHCl ₃ and water. The aqueous layer was separated using a Phase Separator, and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 30/70 to 1/99; v / v) and tert-butyl [(3S) -1- (2-{(1S) -1- [{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (4-hydroxybutyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] Carbamate (16 mg, colorless solid) was obtained.
LCMS (ESI) m / z 664 [M + H] ⁺ , t _R = 1.07 min, mode N.
Step 2-63-3: The title compound (16 mg, colorless solid) was obtained from the compound (15 mg) obtained in Step 2-63-2 using the same method as in Step 1-2-8.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.00-1.55 (m, 4H), 1.55-1.71 (m, 3H), 2.01-2.10 (m, 1H), 2.20-2.30 (m, 1H) , 2.34-2.38 (m, 3H), 2.92-3.13 (m, 5H), 3.29-3.96 (m, 7H), 4.74-4.82 (m, 0.5H), 5.71 (br s, 0.5H), 6.07-6.16 (m, 1H), 7.43-7.58 (m, 3H), 8.24 (br s, 3H), 8.52 (s, 0.5H), 9.34 (s, 0.5H).
LCMS (ESI) m / z 564 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 2-64: N- (3-aminopropyl) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5- a] Pyrimidin-2-yl} ethyl] -5-chloro-2-[(methylsulfonyl) amino] benzamide Using the same procedure as in Step 1-2-6 to Step 1-2-8 of hydrochloride, The title compound (23 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (30 mg) and tert-butyl (3-bromopropyl) carbamate (39 mg).
LCMS (ESI) m / z 549 [M + H] ⁺ , t _R = 0.69 min, mode H.

Example 2-65: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- {3-[(methylsulfonyl) amino] propyl} benzamide Similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride Was used to obtain the title compound (12 mg, colorless solid) from the compound (30 mg) obtained in Step 1-2-5 and N- (3-bromopropyl) methanesulfonamide (36 mg). .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.52-1.74 (m, 5H), 2.00-2.10 (m, 1H), 2.20-2.29 (m, 1H), 2.33-2.38 (m, 3H) , 2.71-2.96 (m, 5H), 3.00-3.07 (m, 3H), 3.35-3.97 (m, 7H), 4.11-4.15 (m, 0.5H), 4.75-4.82 (m, 0.5H), 6.06- 6.17 (m, 1H), 6.92-6.98 (m, 1H), 7.43-7.62 (m, 3H), 8.16 (br s, 3H), 8.52 (s, 0.5H), 9.32 (s, 0.5H).
LCMS (ESI) m / z 627 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 2-66: N- (3-aminopropyl) -5-chloro-N-{(1S) -1- [6-methyl-5- (pyrrolidin-1-yl) pyrazolo [1,5-a] Pyrimidin-2-yl] propyl} -2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 2-66-1: Step 1-3-4 using the same method as in Step 1-2-5 (1S) -1- [6-Methyl-5- (pyrrolidin-1-yl) pyrazolo [1,5-a] pyrimidin-2-yl was obtained from the compound (930 mg) and pyrrolidine (2.50 mL) obtained in 1 ] Propan-1-amine (380 mg, brown oil) was obtained.
LCMS (ESI) m / z 260 [M + H] ⁺ , t _R = 0.67 min, mode H.
Step 2-66-2: Using a method similar to that in Step 1-2-6 and Step 1-2-7, the compound (30 mg) obtained in Step 2-66-1 and tert-butyl (3- From bromopropyl) carbamate (55 mg), tert-butyl [3-({5-chloro-2-[(methylsulfonyl) amino] benzoyl} {(1S) -1- [6-methyl-5- (pyrrolidine- 1-yl) pyrazolo [1,5-a] pyrimidin-2-yl] propyl} amino) propyl] carbamate (10 mg, white solid) was obtained.
LCMS (ESI) m / z 648 [M + H] ⁺ , t _R = 1.32 min, mode N.
Step 2-66-3: Using the same method as in Step 1-2-8, the title compound (11 mg, colorless solid) was obtained from the compound (10 mg) obtained in Step 2-66-2.
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.71 min, mode N.

Example 2-67: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of] -5-chloro-N- [4- (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) butyl] -2-[(methylsulfonyl) amino] benzamide hydrochloride Step 2-67-1: Using a method similar to that of Step 1-2-6 and Step 1-2-7, the compound (150 mg) obtained in Step 1-2-5 and 2- (4-bromobutyl) ) -1H-isoindole-1,3 (2H) -dione (234 mg), tert-butyl [(3S) -1- {2-[(1S) -1-({5-chloro-2- [ (Methylsulfonyl) amino] benzoyl} [4- (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) butyl] amino) ethyl] -6-methylpyrazolo [1,5-a] Pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (138 mg, colorless solid) was obtained.
LCMS (ESI) m / z 793 [M + H] ⁺ , t _R = 1.25 min, mode N.
Step 2-67-2: Using the same method as in Step 1-2-8, the title compound (15 mg, colorless solid) was obtained from the compound (15 mg) obtained in Step 2-67-1.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.20-1.68 (m, 7H), 2.01-2.10 (m, 1H), 2.21-2.30 (m, 1H), 2.35 (s, 3H), 2.91 -3.06 (m, 5H), 3.28-3.75 (m, 7H), 4.72-4.80 (m, 1H), 6.02-6.10 (m, 1H), 7.40-7.58 (m, 3H), 7.80-7.86 (m, 4H), 8.23 (br s, 3H), 8.48 (s, 0.5H), 9.32 (s, 0.5H).
LCMS (ESI) m / z 693 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 2-68: N- (4-aminobutyl) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5- a] pyrimidin-2-yl} ethyl] -5-chloro-2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 2-68-1: compound obtained in step 2-67-1 (0.12 g ) In EtOH (2.0 mL) was added hydrazine monohydrate (37 μL) and stirred at 60 ° C. for 4 hours. A saturated aqueous NH ₄ Cl solution was added to the reaction solution, and the mixture was extracted with CHCl ₃ . The aqueous layer was separated using a Phase Separator, and the organic layer was concentrated under reduced pressure. The residue was purified by NH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 97/3 to 90/10; v / v), and tert-butyl [(3S) -1- (2-{(1S) -1-[(4-aminobutyl) {5-chloro-2-[(methylsulfonyl) amino] benzoyl} amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidine-3 -Il] carbamate (71 mg, colorless solid) was obtained.
LCMS (ESI) m / z 663 [M + H] ⁺ , t _R = 0.72 min, mode N.
Step 2-68-2: Using the same method as in Step 1-2-8, the title compound (18 mg, colorless solid) was obtained from the compound (15 mg) obtained in Step 2-68-1.
LCMS (ESI) m / z 563 [M + H] ⁺ , t _R = 0.74 min, mode H.

Example 2-69: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- {4-[(methylsulfonyl) amino] butyl} benzamide Hydrochloride Synthesis Step 2-69-1: Obtained in Step 2-68-1 Et ₃ N (33 μL) and MsCl (7.4 μL) were added to a CHCl ₃ (2.0 mL) solution of the obtained compound (53 mg) under ice cooling, and the mixture was stirred at room temperature for 30 minutes. A saturated aqueous NaHCO ₃ solution was added to the reaction solution, and the mixture was extracted with CHCl ₃ . The aqueous layer was separated using a Phase Separator, and the organic layer was concentrated under reduced pressure. Purification by OH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 97/3; v / v) and tert-butyl [(3S) -1- {2-[(1S) -1 -({5-Chloro-2-[(methylsulfonyl) amino] benzoyl} {4-[(methylsulfonyl) amino] butyl} amino) ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl } Pyrrolidin-3-yl] carbamate (56 mg, colorless solid) was obtained.
LCMS (ESI) m / z 741 [M + H] ⁺ , t _R = 1.09 min, mode N.
Step 2-69-2: The title compound (54 mg, colorless solid) was obtained from the compound (54 mg) obtained in Step 2-69-1 using the same method as in Step 1-2-8.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.06-1.56 (m, 4H), 1.56-1.71 (m, 3H), 2.02-2.12 (m, 1H), 2.20-2.30 (m, 1H) , 2.32-2.38 (m, 3H), 2.60-2.67 (m, 1H), 2.75-2.89 (m, 4H), 2.92-3.09 (m, 4H), 3.33-3.52 (m, 1H), 3.70-3.98 ( m, 5H), 4.78 (q, J = 6.6 Hz, 1H), 6.06-6.17 (m, 1H), 6.80-6.97 (m, 1H), 7.42-7.57 (m, 3H), 8.31 (br s, 3H ), 8.51 (s, 0.5H), 9.36 (s, 0.5H).
LCMS (ESI) m / z 641 [M + H] ⁺ , t _R = 0.99 min, mode H.

Example 2-70: 2- (acetylamino) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] Pyrimidin-2-yl} propyl] -5-chloro-N-methylbenzamide Step 2-70-1: Obtained in Step 1-4-3 using a method similar to that of Step 1-1-8. From the compound (50 mg) and 2-amino-5-chlorobenzoic acid (26 mg), tert-butyl [(3S) -1- (2-{(1S) -1-[(2-amino-5-chloro Benzoyl) (methyl) amino] propyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (41 mg) was obtained.
Step 2-70-2: To a solution of the compound (41 mg) obtained in Step 2-70-1 in CHCl ₃ (1.0 mL) was added pyridine (32 μL) and acetic anhydride (21 μL) under ice-cooling. And stirred at room temperature for 2 hours. The reaction solution was poured into water and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse phase preparative HPLC and tert-butyl [(3S) -1- {2-[(1S) -1-{[2- (acetylamino) -5-chlorobenzoyl] ( Methyl) amino} propyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (34 mg, colorless solid) was obtained.
Step 2-70-3: TFA (1 mL) was added to a solution of the compound obtained in Step 2-70-2 (34 mg) in CHCl ₃ (1 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into a saturated aqueous NaHCO ₃ solution and extracted with CHCl ₃ . The organic layer was filtered through a phase separator, and the filtrate was concentrated under reduced pressure to obtain the title compound (34 mg, colorless amorphous).
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.80-1.13 (m, 3H), 1.74-1.82 (m, 1H), 1.90-2.09 (m, 2H), 2.10-2.20 (m, 4H), 2.34 -2.43 (m, 3H), 2.73 (br s, 1H), 2.86-2.96 (m, 2H), 3.43 (dd, J = 10.5, 4.3 Hz, 1H), 3.66-3.79 (m, 2H), 3.89 ( br s, 2H), 4.83 (br s, 0.5H), 5.89-6.08 (m, 1.5H), 7.17-7.40 (m, 1H), 7.94-8.23 (m, 2H), 8.62-9.04 (m, 1H ).
LCMS (ESI) m / z 484 [M + H] ⁺ , t _R = 0.46 min, mode N.

Example 2-71: 2- (acetylamino) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] Pyrimidin-2-yl} propyl] -N, 5-dimethylbenzamide in the same manner as in Step 1-1-8, Step 2-70-2 and Step 2-70-3, Step 1-4-3 The title compound (21 mg, colorless amorphous) was obtained from the compound (50 mg) obtained in 1 and 2-amino-5-methylbenzoic acid (23 mg).
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.77-1.13 (m, 3H), 1.75-2.24 (m, 7H), 2.25-2.34 (m, 3H), 2.38 (br s, 3H), 2.67- 2.97 (m, 3H), 3.44 (dd, J = 10.9, 4.3 Hz, 1H), 3.66-3.78 (m, 2H), 3.89 (br s, 2H), 4.90 (br s, 0.5H), 5.88-6.18 (m, 1.5H), 7.00-7.23 (m, 1.5H), 8.01 (br s, 1.5H), 8.55 (br s, 0.5H), 8.83 (br s, 0.5H) .LCMS (ESI) m / z 464 [M + H] ⁺ , t _R = 0.38 min, mode N.

Example 2-72: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-2-[(methylsulfonyl) amino] -N- (4,4,4-trifluorobutyl) benzamide Similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride Using the method, the title compound (30 mg, colorless solid) was obtained from the compound obtained in Step 1-2-5 (80 mg) and 4-bromo-1,1,1-trifluorobutane (42 mg). It was.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.43-1.97 (m, 5H), 2.02-2.12 (m, 1H), 2.17-2.32 (m, 3H), 2.32-2.40 (m, 3H) , 2.98-3.11 (m, 3H), 3.41-4.00 (m, 7H), 4.79 (q, J = 6.9 Hz, 1H), 6.04-6.18 (m, 1H), 7.43-7.65 (m, 3H), 8.35 (br s, 3H), 8.49-8.55 (m, 0.5H), 9.33 (s, 0.5H) .LCMS (ESI) m / z 602 [M + H] ⁺ , t _R = 0.67 min, mode N.

Example 2-73: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-methyl-2- (methylsulfonyl) benzamide Compound synthesized in Step 1-4-3 using the same method as in Step 1-2-7 and Step 1-2-8 of hydrochloride (30) mg) and 2- (methylsulfonyl) benzoic acid (17 mg) gave the title compound (28 mg).
LCMS (ESI) m / z 471 [M + H] ⁺ , t _R = 0.80 min, mode H.

Example 2-74: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-3-fluoro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-7 and Step 1-2-8 The title compound (40 mg, colorless solid) was obtained from the compound obtained in 1-4-3 (40 mg) and 5-chloro-3-fluoro-2-[(methylsulfonyl) amino] benzoic acid (33 mg). It was.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.87 (br s, 1H), 1.01 (t, J = 7.2 Hz, 2H), 1.83-2.30 (m, 4H), 2.33-2.40 (m, 3H), 2.56 (s, 1.5H), 2.66-2.74 (m, 0.5H), 2.98-3.07 (m, 3H), 3.67-3.99 (m, 5H), 4.46 (br s, 0.3H), 5.73 ( dd, J = 9.5, 6.2 Hz, 0.7H), 6.14 (s, 0.7H), 6.21 (br s, 0.3H), 7.24-7.34 (m, 1H), 7.63-7.69 (m, 1H), 8.22- 8.42 (m, 3H), 8.50 (s, 0.7H), 9.46 (br s, 0.3H)
LCMS (ESI) m / z 538 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 2-75: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N-ethyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-6 to Step 1-2-8 The title compound (15 mg, colorless solid) was obtained from the compound (50 mg) obtained in 5 and EtI (10 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.80-1.10 (m, 6H), 1.94-2.31 (m, 4H), 2.34-2.38 (m, 3H), 2.96-3.05 (m, 4H) , 3.25-3.33 (m, 1H), 3.69-4.00 (m, 5H), 4.51 (br s, 0.7H), 5.51 (s, 0.3H), 6.15-6.22 (m, 1H), 7.45-7.55 (m , 3H), 8.21 (br s, 3H), 8.52 (s, 0.5H), 9.20 (s, 0.5H)
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 1.11 min, mode H.

Example 2-76: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N- (3-fluoropropyl) -2-[(methylsulfonyl) amino] benzamide Using a method similar to the synthesis steps 1-2-6 to 1-2-8 of hydrochloride, The title compound (11 mg, colorless solid) was obtained from the compound obtained in Step 1-3-5 (50 mg) and 1-iodo-3-fluoropropane (27 μL).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.87-1.10 (m, 3H), 1.64-2.30 (m, 6H), 2.34-2.38 (m, 3H), 2.97-3.12 (m, 4H) , 3.30-3.37 (m, 1H), 4.29-4.49 (m, 2H), 4.51-4.57 (m, 1H), 6.17 (s, 1H), 7.44-7.57 (m, 3H), 8.19 (br s, 3H ), 8.53 (s, 0.5H), 9.25 (s, 0.5H)
LCMS (ESI) m / z 566 [M + H] ⁺ , t _R = 1.13 min, mode H.

Example 2-77: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-Chloro-N- (4-hydroxybutyl) -2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-2-6, Step 1-2-7, Step 2-63-2 and Using the same method as in Step 1-2-8, the title compound (13 mg, colorless solid) was obtained from the compound obtained in Step 1-3-5 (50 mg) and 4-bromobutyl acetate (38 μL). It was.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.87-1.53 (m, 7H), 1.94-2.30 (m, 4H), 2.34-2.38 (m, 3H), 2.87-3.09 (m, 5H) , 3.22-3.32 (m, 2H), 3.63-3.97 (m, 5H), 4.51 (br s, 1H), 6.15 (s, 1H), 7.45-7.56 (m, 3H), 8.20 (br s, 3H) , 8.52 (s, 0.5H), 9.23 (s, 0.5H)
LCMS (ESI) m / z 578 [M + H] ⁺ , t _R = 1.03 min, mode H.

Example 2-78: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -5-chloro-N- (5-hydroxypentyl) -2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 1-2-6, step 1-2-7, step 2-63-2 and Using the same method as in Step 1-2-8, the title compound (13 mg, colorless solid) was obtained from the compound obtained in Step 1-3-5 (50 mg) and 5-bromopentyl acetate (42 μL). Obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.78-1.49 (m, 9H), 1.93-2.30 (m, 4H), 2.33-2.38 (m, 3H), 2.84-3.33 (m, 7H) , 3.61-3.96 (m, 5H), 4.52 (br s, 1H), 6.16 (s, 1H), 7.44-7.55 (m, 3H), 8.20 (br s, 3H), 8.52 (s, 0.5H), 9.24 (s, 0.5H)
LCMS (ESI) m / z 592 [M + H] ⁺ , t _R = 1.07 min, mode H.

Example 3-1 N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-[(methylsulfonyl) amino] -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-1-1: Obtained in Step 1-1-4 A 4M HCl / 1,4-dioxane solution (30 mL) was added dropwise to a solution of the compound (4.73 g) in 1,4-dioxane (30 mL), and the mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure, and 6-methyl-2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride (3.81 g, colorless Solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.55 (d, J = 7.0 Hz, 3H), 1.95 (br s, 3H), 2.46 (t, J = 5.4 Hz, 3H), 4.34-4.42 (m, 1H), 6.04 (s, 1H), 8.43 (s, 1H), 9.11-9.38 (m, 1H), 12.28 (s, 1H).
LCMS (ESI) m / z 207 [M + H] ⁺ , t _R = 0.22 min, mode H.
Step 3-1-2: The compound (3.81 g) obtained in Step 3-1-1 was suspended in POCl ₃ (29 mL), and stirred for 2.5 hours under heating to reflux. The reaction solution was concentrated under reduced pressure, and (1S) -1- (5-chloro-6-methylpyrazolo [1,5-a] pyrimidin-2-yl) -N-methylethanamine hydrochloride (4.62 g, brown solid) Got.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.64 (d, J = 6.2 Hz, 3H), 2.34 (s, 3H), 4.59 (br s, 1H), 6.88 (s, 1H), 6.95 -7.62 (m, 3H), 9.19 (s, 1H), 9.26-9.53 (m, 1H).
LCMS (ESI) m / z 225 [M + H] ⁺ , t _R = 0.56 min, mode H.
Step 3-1-3: A solution of the compound (4.50 g) obtained in Step 3-1-2 in a solution of (3S)-(−)-3- (tert-butoxycarbonylamino) pyrrolidine (14.4) in MeOH (60 mL). g), Et ₃ N (17.2 mL) was added, and the mixture was stirred for 2 hours under reflux with heating and then for 14 hours at room temperature. The reaction solution was concentrated under reduced pressure, and the resulting residue was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with a saturated aqueous NaHCO ₃ solution, dried over MgSO ₄ and filtered, and then the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH / NH ₄ OH = 100/0/0 to 80/20/2; v / v / v), and tert-butyl [(3S) -1- {6-Methyl-2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (6.16 g, pale yellow amorphous).
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.42-1.48 (m, 12H), 1.88-1.95 (m, 1H), 2.17-2.24 (m, 1H), 2.33 (br s, 3H), 2.39 ( s, 3H), 3.53 (dd, J = 10.9, 3.9 Hz, 1H), 3.68-3.74 (m, 1H), 3.76-3.82 (m, 1H), 3.80 (dt, J = 10.7, 7.4 Hz, 1H) , 3.84 (q, J = 6.6 Hz, 1H), 3.88-3.95 (m, 1H), 4.30 (br s, 1H), 4.69 (br s, 1H), 6.04 (s, 1H), 8.02 (s, 1H ).
LCMS (ESI) m / z 375 [M + H] ⁺ , t _R = 0.46 min, mode N.
Step 3-1-4: HATU (1.66 g), Et in a DMF (20 mL) solution of the compound obtained in Step 3-1-3 (606 mg) and the compound obtained in Reference Example 4 (705 mg) ₃ N (1.35 mL) was added, and the mixture was stirred at room temperature for 4 days. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) to obtain benzyl (1-{[(1S) -1- (5 -{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -2, 3-Dihydro-1H-inden-1-yl) carbamate (1.10 g, light brown amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.79-0.89 (m, 1H), 1.37-1.62 (m, 13H), 1.86-1.96 (m, 1H), 2.10-2.25 (m, 1H), 2.32 (br s, 3H), 2.57-3.11 (m, 5H), 3.49-3.55 (m, 1H), 3.66-3.73 (m, 1H), 3.74-3.83 (m, 1H), 3.87-3.96 (m, 1H ), 4.23-4.34 (m, 1H), 4.61-4.71 (m, 1H), 4.85-4.96 (m, 1H), 4.97-5.05 (m, 1H), 5.90-5.97 (m, 0.5H), 6.11- 6.18 (m, 0.5H), 7.12-8.01 (m, 10H).
LCMS (ESI) m / z 668 [M + H] ⁺ , t _R = 1.17 min, mode N.
Step 3-1-5: To a solution of the compound obtained in Step 3-1-4 (856 mg) in MeOH (20 mL) was added 10% palladium-carbon (428 mg), and the reaction was performed at room temperature under a hydrogen atmosphere. Stir for hours. After the reaction solution was filtered through Celite (registered trademark), the filtrate was concentrated under reduced pressure, and tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-2,3- Dihydro-1H-inden-1-yl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (681 mg, colorless amorphous) Got.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.96-1.04 (m, 1H), 1.40-1.58 (m, 10H), 1.87-1.98 (m, 1H), 2.12-2.21 (m, 1H), 2.22-2.33 (m, 2H), 2.38 (br s, 3H), 2.66-2.83 (m, 6H), 3.49-3.57 (m, 1H), 3.71-3.78 (m, 1H), 3.79-3.86 (m, 1H), 3.87-3.96 (m, 1H), 4.11-4.19 (m, 1H), 4.55-4.66 (m, 0.5H), 5.82-5.96 (m, 1H), 6.04-6.11 (m, 0.5H), 7.17-7.46 (m, 4H), 8.08-8.15 (m, 1H).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.62 min, mode N.
Step 3-1-6: Et ₃ N (24 μL) and MsCl (6.0 μL) were added to a CHCl ₃ (1 mL) solution of the compound (31 mg) obtained in Step 3-1-5 under ice cooling. And stirred for 30 minutes at room temperature. The reaction solution was partitioned between CHCl ₃ and saturated NaHCO ₃ aqueous solution, and the aqueous layer was extracted with CHCl ₃ . The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) to obtain tert-butyl [(3S ) -1- (6-Methyl-2-{(1S) -1- [methyl ({1-[(methylsulfonyl) amino] -2,3-dihydro-1H-inden-1-yl} carbonyl) amino] Ethyl} pyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (27 mg, colorless oil) was obtained.
LCMS (ESI) m / z 612 [M + H] ⁺ , t _R = 0.97, 0.99 min, mode N.
Step 3-1-7: The title compound (22.4 mg, colorless solid) was obtained from the compound (26.0 mg) obtained in Step 3-1-6 using the same method as in Step 3-1-1.
LCMS (ESI) m / z 512 [M + H] ⁺ , t _R = 0.84 min, mode H.

Example 3-2: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-[(Ethylsulfonyl) amino] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Similar procedure as in step 3-1-6 and step 3-1-1 for the synthesis of hydrochloride Was used to give the title compound (6.8 mg, colorless solid) from the compound (30 mg) obtained in Step 3-1-5 and ethanesulfonyl chloride (16 μL).
LCMS (ESI) m / z 526 [M + H] ⁺ , t _R = 0.50 min, mode N.

Example 3-3: benzyl (1-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate In step 3-1-4 using the same procedure as in step 3-1-1 for the synthesis of hydrochloride The title compound (8.7 mg, colorless solid) was obtained from the obtained compound (10 mg).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 1.09 min, mode H.

Example 3-4: tert-butyl (1-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine- 2-yl} ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate using the same procedure as in Steps 3-1-4 and 3-1-5, The title compound (2.9 mg, colorless amorphous) was obtained from the compound obtained in Step 1-1-7 (65 mg) and N-tert-butoxycarbonyl-1-aminoindan-1-carboxylic acid (0.11 g).
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.78-0.90 (m, 1H), 1.32 (br s, 3H), 1.49-1.67 (br s, 9H), 1.70-1.80 (m, 1H), 2.08 -2.16 (m, 1H), 2.17-3.05 (m, 6H), 2.32 (br s, 3H), 3.40 (dd, J = 10.5, 4.3 Hz, 1H), 3.61-3.75 (m, 2H), 3.77- 3.91 (m, 2H), 4.62-4.73 (m, 0.5H), 5.78-6.25 (m, 1.5H), 7.11-7.30 (m, 4H), 7.98 (s, 1H).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.59 min, mode H.

Example 3-5: 1-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide obtained in Example 3-4 using the same procedure as in Synthesis step 3-1-1 of hydrochloride. The title compound (1.6 mg, colorless solid) was obtained from the compound (1.5 mg).
LCMS (ESI) m / z 434 [M + H] ⁺ , t _R = 0.54 min, mode H.

Example 3-6: 1- (acetylamino) -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] Pyrimidin-2-yl} ethyl] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide hydrochloride synthesis step 3-6-1: compound obtained in step 3-1-5 (20 mg) in CHCl ₃ (1 mL) was added with Et ₃ N (16 μL) and AcCl (3.5 μL) under ice cooling, followed by stirring at the same temperature for 1 hour. The reaction solution was partitioned between CHCl ₃ and saturated NaHCO ₃ aqueous solution, and the aqueous layer was extracted with CHCl ₃ . The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) to obtain tert-butyl [(3S ) -1- (2-{(1S) -1-[{[1- (acetylamino) -2,3-dihydro-1H-inden-1-yl] carbonyl} (methyl) amino] ethyl} -6- Methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (14 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 576 [M + H] ⁺ , t _R = 0.90 min, mode N.
Step 3-6-2: The title compound (13.3 mg, colorless solid) was obtained from the compound (13.5 mg) obtained in Step 3-6-1 using the same method as in Step 3-1-1.
LCMS (ESI) m / z 476 [M + H] ⁺ , t _R = 0.76 min, mode H.

Example 3-7: Methyl (1-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate hydrochloride using the same procedure as in Steps 3-6-1 and 3-1-1, The title compound (7.3 mg, colorless solid) was obtained from the compound obtained in Step 3-1-5 (20 mg) and chloroformic acid methyl ester (4.0 μL).
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.85 min, mode H.

Example 3-8: Propan-2-yl (1-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] Synthesis of Pyrimidin-2-yl} ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate Step 3-8-1: Using the same method as in Step 3-6-1 From the compound (30 mg) obtained in Step 3-1-5 and chloroformic acid isopropyl ester (19 μL), propan-2-yl (1-{[(1S) -1- (5-{(3S ) -3-[(tert-Butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -2,3-dihydro- 1H-Inden-1-yl) carbamate (6.9 mg, pale yellow amorphous) was obtained.
LCMS (ESI) m / z 620 [M + H] ⁺ , t _R = 1.11, 1.13 min, mode N.
Step 3-8-2: A 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound obtained in Step 3-8-1 (6.9 mg) in 1,4-dioxane (1 mL). The mixture was stirred at room temperature for 2 hours. The reaction solution was partitioned between CHCl ₃ and saturated NaHCO ₃ aqueous solution, and the aqueous layer was extracted with CHCl ₃ . The organic layer was concentrated under reduced pressure to obtain the title compound (6.3 mg, colorless amorphous).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 3-9: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-[(2-methylpropanoyl) amino] -2,3-dihydro-1H-indene-1-carboxamide similar to steps 3-6-1 and 3-8-2 Using the method, the title compound (2.6 mg, colorless amorphous) was obtained from the compound obtained in Step 3-1-5 (30 mg) and isobutyryl chloride (18 μL).
LCMS (ESI) m / z 504 [M + H] ⁺ , t _R = 0.49 min, mode N.

Example 3-10: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-[(phenylacetyl) amino] -2,3-dihydro-1H-indene-1-carboxamide was synthesized in the same manner as in Steps 3-6-1 and 3-8-2. Thus, the title compound (9.2 mg, colorless amorphous) was obtained from the compound (25 mg) obtained in Step 3-1-5 and phenylacetyl chloride (12 μL).
LCMS (ESI) m / z 552 [M + H] ⁺ , t _R = 1.00 min, mode H.

Example 3-11: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[2- (methylsulfonyl) ethyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-11-1: Step 3-1 Methyl vinyl sulfone (7.0 μL) was added to a solution of the compound obtained in 5 (20 mg) in MeOH (1 mL) and stirred at room temperature for 6 hours. Methyl vinyl sulfone (14 μL) was added to the reaction solution, and the mixture was stirred at room temperature for 3 days. Methyl vinyl sulfone (14 μL) was added to the reaction solution, and the mixture was stirred at 50 ° C. for 8 hours and at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure, and the resulting residue was subjected to NH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100 to EtOAc / MeOH = 100/0 to 90/10; v / v ) Tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[2- (methylsulfonyl) ethyl] amino} -2 , 3-Dihydro-1H-inden-1-yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (5.5 mg, colorless amorphous) was obtained. .
LCMS (ESI) m / z 640 [M + H] ⁺ , t _R = 0.65 min, mode N.
Step 3-11-2: Using the same method as in Step 3-1-1, the title compound (8.0 mg, colorless solid) was obtained from the compound (5.3 mg) obtained in Step 3-11-1.
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.58 min, mode H.

Example 3-12: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1-carboxamide hydrochloride synthesis step 3-12-1: in step 3-1-5 HATU (28 mg) and Et ₃ N (31 μL) were added to a DMF (1 mL) solution of the obtained compound (20 mg) and methanesulfonylacetic acid (10 mg), and the mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100 to EtOAc / MeOH = 100/0 to 95/5; v / v), and tert- Butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1 -Yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (9.1 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 654 [M + H] ⁺ , t _R = 0.92, 0.93 min, mode N.
Step 3-12-2: 4 M HCl / 1,4-dioxane solution (1.0 mL) was added dropwise to a solution of the compound obtained in Step 3-12-1 (8.8 mg) in 1,4-dioxane (0.5 mL). And stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (9.0 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.39 (br s, 3H), 1.98-2.09 (m, 1H), 2.19-2.29 (m, 1H), 2.34 (s, 3H), 2.40- 3.19 (m, 10H), 3.44-3.52 (m, 1H), 3.58-3.93 (m, 4H), 4.00-4.24 (m, 2H), 5.79-5.96 (m, 2H), 7.14-7.21 (m, 1H ), 7.25 (br s, 2H), 7.44-7.51 (m, 1H), 8.18 (br s, 3H), 8.50 (br s, 0.5H), 9.17 (br s, 0.5H).
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 0.78 min, mode H.

Example 3-13: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-{[N- (Ethylsulfonyl) glycyl] amino} -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as Example 3-12 The title compound (13 mg, colorless solid) was obtained from the compound (20 mg) obtained in Step 3-1-5 and [(ethylsulfonyl) amino] acetic acid (13 mg).
LCMS (ESI) m / z 583 [M + H] ⁺ , t _R = 0.82 min, mode H.

Example 3-14: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-{[(Ethylsulfonyl) acetyl] amino} -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as in Example 3-12, The title compound (13 mg, colorless solid) was obtained from the compound obtained in 3-1-5 (25 mg) and 2- (ethanesulfonyl) acetic acid (9 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.19 (br s, 3H), 1.41 (br s, 3H), 2.01-2.10 (m, 1H), 2.18-2.28 (m, 1H), 2.34 (s, 3H), 2.41-3.30 (m, 9H), 3.69-3.95 (m, 5H), 3.96-4.33 (m, 2H), 5.81-5.94 (m, 2H), 7.12-7.20 (m, 1H) , 7.24 (br s, 2H), 7.43-7.52 (m, 1H), 8.33 (br s, 3H), 8.51 (br s, 0.5H), 9.25 (m, 0.5H).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 0.42 min, mode N.

Example 3-15: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-({[(2-methylpropyl) sulfonyl] acetyl} amino) -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Method Similar to Example 3-12 Was used to give the title compound (15 mg, colorless solid) from the compound obtained in Step 3-1-5 (25 mg) and 2- (2-methylpropylsulfonyl) acetic acid (10 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.93-1.06 (m, 6H), 1.41 (br s, 3H), 2.00-2.09 (m, 1H), 2.18-2.28 (m, 2H), 2.34 (s, 3H), 2.40-3.26 (m, 9H), 3.68-4.18 (m, 7H), 5.79-5.93 (m, 2H), 7.13-7.28 (m, 3H), 7.42-7.51 (m, 1H ), 8.28 (br s, 3H), 8.50 (br s, 0.5H), 9.16-9.24 (m, 0.5H).
LCMS (ESI) m / z 596 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 3-16: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-[(3,3-Dimethylbutanoyl) amino] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as Example 3-12 The title compound (2 mg, colorless solid) was obtained from the compound (25 mg) obtained in Step 3-1-5 and tert-butylacetic acid (7 mg).
LCMS (ESI) m / z 532 [M + H] ⁺ , t _R = 0.60 min, mode N.

Example 3-17: 1-[(N-acetylglycyl) amino] -N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [ 1,5-a] pyrimidin-2-yl} ethyl] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as in Example 3-12, The title compound (13 mg, colorless solid) was obtained from the compound (25 mg) obtained in 3-1-5 and N-acetylglycine (11 mg).
LCMS (ESI) m / z 533 [M + H] ⁺ , t _R = 0.72 min, mode H.

Example 3-18: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-[(N, N-dimethylglycyl) amino] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as Example 3-12 The title compound (12 mg, colorless solid) was obtained from the compound obtained in Step 3-1-5 (25 mg) and N, N-dimethylglycine hydrochloride (13 mg).
LCMS (ESI) m / z 519 [M + H] ⁺ , t _R = 0.58 min, mode H.

Example 3-19: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-[(Methoxyacetyl) amino] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as in Example 3-12, step 3-1 The title compound (14 mg, light brown solid) was obtained from the compound obtained in -5 (25 mg) and methoxyacetic acid (8 mg).
LCMS (ESI) m / z 506 [M + H] ⁺ , t _R = 0.84 min, mode H.

Example 3-20: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis of] -N-methyl-1-[(sulfamoylacetyl) amino] -2,3-dihydro-1H-indene-1-carboxamide hydrochloride Step 3 was carried out using the same procedure as in Example 3-12. The title compound (19 mg, colorless solid) was obtained from the compound obtained in -1-5 (22 mg) and 2-sulfamoyl acetic acid (11 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.32-1.52 (m, 3H), 2.00-2.08 (m, 1H), 2.24 (m, 1H), 2.30-2.36 (m, 3H), 2.37 -3.16 (m, 7H), 3.40-3.99 (m, 7H), 5.76-5.96 (m, 2H), 6.79-7.54 (m, 4H), 8.21 (br s, 3H), 8.51 (br s, 0.5H ), 8.87-9.09 (m, 0.5H).
LCMS (ESI) m / z 555 [M + H] ⁺ , t _R = 0.79 min, mode H.

Example 3-21: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[(phenylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as in Example 3-12, The title compound (23 mg, colorless solid) was obtained from the compound obtained in 3-1-5 (22 mg) and phenylsulfonylacetic acid (17 mg).
LCMS (ESI) m / z 616 [M + H] ⁺ , t _R = 0.99 min, mode H.

Example 3-22: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-[(1H-1,2,4-triazol-1-ylacetyl) amino] -2,3-dihydro-1H-indene-1-carboxamide Synthesis Example 3-12 with hydrochloride Using the same method, the title compound (20 mg, colorless solid) was obtained from the compound obtained in Step 3-1-5 (22 mg) and 1,2,4-triazole-1-acetic acid (10 mg). It was.
LCMS (ESI) m / z 543 [M + H] ⁺ , t _R = 0.79 min, mode H.

Example 3-23: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[3- (methylsulfonyl) propanoyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as Example 3-12 The title compound (24 mg, colorless solid) was obtained from the compound (21 mg) obtained in Step 3-1-5 and 3- (methylsulfonyl) propanoic acid (10 mg).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 0.77 min, mode H.

Example 3-24: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[2-methyl-2- (methylsulfonyl) propanoyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Synthesis of hydrochloride Similar to Example 3-12 Using the method, the title compound (5 mg, pale yellow solid) was obtained from the compound (20 mg) obtained in Step 3-1-5 and 2-methanesulfonyl-2-methylpropanoic acid (7 mg).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.69 min, mode N.

Example 3-25: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-{[(Dimethylsulfamoyl) acetyl] amino} -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Using the same procedure as Example 3-12 The title compound (21 mg, colorless solid) was obtained from the compound obtained in Step 3-1-5 (20 mg) and 2- (dimethylsulfamoyl) acetic acid (8 mg).
LCMS (ESI) m / z 583 [M + H] ⁺ , t _R = 0.66 min, mode N.

Example 3-26: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-[(Cyclopropylacetyl) amino] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide in the same manner as in Steps 3-12-1 and 3-8-2 The title compound (9 mg, colorless amorphous) was obtained from the compound (22 mg) obtained in Step 3-1-5 and cyclopropylacetic acid (8 mg).
LCMS (ESI) m / z 516 [M + H] ⁺ , t _R = 0.91 min, mode H.

Example 3-27: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- (Glycylamino) -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-27-1: Steps 3-12-1 and 3-1-5 Using a similar method, the compound (75 mg) obtained in Step 3-1-5, benzyloxycarbonylglycine (44 mg) and tert-butyl [(3S) -1- (2-{(1S)- 1-[{[1- (Glycylamino) -2,3-dihydro-1H-inden-1-yl] carbonyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl ) Pyrrolidin-3-yl] carbamate (34 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 591 [M + H] ⁺ , t _R = 0.61 min, mode N.
Step 3-27-2: Using the same method as in Step 3-1-1, the title compound (7.2 mg, colorless solid) was obtained from the compound (5.7 mg) obtained in Step 3-27-1.
LCMS (ESI) m / z 491 [M + H] ⁺ , t _R = 0.56 min, mode H.

Example 3-28: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[N- (methylsulfonyl) glycyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Steps 3-1-6 and 3-1 1 was used to give the title compound (4.8 mg, colorless amorphous) from the compound (27 mg) obtained in Step 3-27-1.
LCMS (ESI) m / z 569 [M + H] ⁺ , t _R = 0.78 min, mode H.

Example 3-29: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N, 6-Dimethyl-1-[(methylsulfonyl) amino] -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-29-1: Obtained in Step 3-1-3 HATU (117 mg) and Et ₃ N (130 μL) were added to a DMF (1 mL) solution of the obtained compound (69 mg) and the compound (50 mg) obtained in Reference Example 5 and stirred at 50 ° C. for 6 hours. did. Water was added to the reaction mixture and stirred, followed by extraction with EtOAc. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90/10 to 0/100; v / v) to obtain benzyl (1-{[ (1S) -1- (5-{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (Methyl) carbamoyl} -6-methyl-2,3-dihydro-1H-inden-1-yl) carbamate (57 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.22, 1.23 min, mode N.
Step 3-29-2: Using a method similar to that of Step 3-1-5, tert-butyl [(3S) -1- {2-] from the compound (37 mg) obtained in Step 3-29-1 [(1S) -1-{[(1-Amino-6-methyl-2,3-dihydro-1H-inden-1-yl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5- a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (30 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.66, 0.68 min, mode N.
Step 3-29-3: Using a method similar to that of Step 3-1-6 and Step 3-1-1, the title compound (15 mg, A colorless solid was obtained.
LCMS (ESI) m / z 526 [M + H] ⁺ , t _R = 0.51 min, mode N.

Example 3-30: benzyl (1-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] (methyl) carbamoyl} -6-methyl-2,3-dihydro-1H-inden-1-yl) carbamate hydrochloride using the same procedure as in step 3-1-1, The title compound (15.9 mg, colorless solid) was obtained from the compound (14.7 mg) obtained in 29-1.
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.68 min, mode N.

Example 3-31: 1-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N, 6-dimethyl-2,3-dihydro-1H-indene-1-carboxamide hydrochloride in step 3-29-2 using the same procedure as in step 3-1-1 The title compound (8.8 mg, colorless solid) was obtained from the obtained compound (8.2 mg).
LCMS (ESI) m / z 448 [M + H] ⁺ , t _R = 0.18 min, mode N.

Example 3-32: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- [2- (Ethylsulfonyl) ethyl] -N-methyl-2,3-dihydro-1H-isoindole-1-carboxamide Hydrochloride Synthesis Steps 3-29-1 and 3-1-1 Using the same method, the title compound (27 mg, colorless solid) was obtained from the compound (59 mg) obtained in Step 3-1-3 and the compound (50 mg) obtained in Reference Example 6.
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.20 min, mode N.

Example 3-33: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] Synthetic step 3-33-1 of step -3-3-1: step 3-29-1 of 2- (2-cyclopropyl-2-oxoethyl) -N-methyl-2,3-dihydro-1H-indene-1-carboxamide From the compound obtained in Step 3-1-3 (90 mg) and the compound obtained in Reference Example 7 (69 mg), tert-butyl [(3S) -1- (2-{(1S ) -1-[{[1- (2-Cyclopropyl-2-oxoethyl) -2,3-dihydro-1H-inden-1-yl] carbonyl} (methyl) amino] ethyl} -6-methylpyrazolo [1, 5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (40 mg, colorless solid) was obtained.
LCMS (ESI) m / z 601 [M + H] ⁺ , t _R = 1.16 min, mode N.
Step 3-33-2: TFA (0.5 mL) was added dropwise to a solution of the compound obtained in Step 3-33-1 (18 mg) in CHCl ₃ (0.5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was separated with CHCl ₃ and saturated NaHCO ₃ aqueous solution. The organic layer was concentrated under reduced pressure to obtain the title compound (15 mg, colorless solid).
LCMS (ESI) m / z 501 [M + H] ⁺ , t _R = 0.61 min, mode N.

Example 3-34: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis steps 3-29-1 and 3-33-2 of] -N, 2-dimethyl-1- [2- (methylsulfonyl) ethyl] -2,3-dihydro-1H-isoindole-1-carboxamide Using the same method, the title compound (1.9 mg, orange amorphous) was obtained from the compound (4.0 mg) obtained in Step 3-1-3 and the compound (2.5 mg) obtained in Reference Example 8.
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.49 min, mode N.

Example 3-35: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-{[(methylsulfonyl) amino] methyl} -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-35-1: Step 3-29-1 and Using a similar method, the compound obtained in Step 3-1-3 (137 mg) and the compound obtained in Reference Example 9 (107 mg) were tert-butyl [(3S) -1- (2- { (1S) -1-[({1-[(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl] -2,3-dihydro-1H-inden-1-yl} Carbonyl) (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (31 mg, pale yellow amorphous) was obtained.
LCMS (ESI) m / z 678 [M + H] ⁺ , t _R = 1.18 min, mode N.
Step 3-35-2: Hydrazine monohydrate (15 mg) was added to a solution of the compound obtained in Step 3-35-1 (31 mg) in EtOH (1.0 mL), and the mixture was stirred at 60 ° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and CHCl ₃ was added to the resulting residue to precipitate a solid. The solid was filtered off and the filtrate obtained by washing with CHCl ₃ was concentrated under reduced pressure, and tert-butyl [(3S) -1- (2-{(1S) -1-[{[1- (aminomethyl) -2,3-dihydro-1H-inden-1-yl] carbonyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidin-3-yl] carbamate (26 mg, colorless amorphous).
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.68 min, mode N.
Step 3-35-3: Using a method similar to that of Step 3-1-6 and Step 3-1-1, the title compound (3.2 mg, A colorless solid was obtained.
LCMS (ESI) m / z 526 [M + H] ⁺ , t _R = 0.51 min, mode N.

Example 3-36: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N, 1-dimethyl-2,3-dihydro-1H-indene-1-carboxamide Hydrochloride Synthesis Step 3-3-1 using the same procedure as in Step 3-29-1 and Step 3-1-1 The title compound (83 mg, light green solid) was obtained from the compound obtained in -3 (78 mg) and 1-methyl-2,3-dihydro-1H-indene-1-carboxylic acid (31 mg).
LCMS (ESI) m / z 433 [M + H] ⁺ , t _R = 0.58 min, mode N.

Example 3-37: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- [2- (Ethylsulfonyl) ethyl] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Similar to Synthesis Steps 3-29-1 and 3-1-1 of hydrochloride salt The compound obtained in Step 3-1-3 (64 mg) and 1- [2- (ethanesulfonyl) ethyl] -2,3-dihydro-1H-indene-1-carboxylic acid (40 mg) gave the title compound (83 mg, pale green solid).
LCMS (ESI) m / z 539 [M + H] ⁺ , t _R = 0.53 min, mode N.

Example 3-38: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1- [3- (methylsulfonyl) propyl] -2,3-dihydro-1H-indene-1-carboxamide Similar to Steps 3-29-1 and 3-1-1 of Synthesis of Hydrochloride The compound obtained in Step 3-1-3 (28 mg) and 1- [3- (methanesulfonyl) propyl] -2,3-dihydro-1H-indene-1-carboxylic acid (20 mg) gave the title compound (5.3 mg, green amorphous).
LCMS (ESI) m / z 539 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 3-39: 1-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide hydrochloride (single diastereomer) synthesis step 3-39-1: obtained in step 3-1-4 The compound (210 mg) was subjected to preparative purification on a chiral column (preparation conditions: column: CHIRALPAK IB (Daicel Trademark), column size: 20 mm × 250 mm, mobile phase: hexane / EtOH = 80/20 (v / v), flow rate: 10 mL / min, column temperature: 25 ° C., detection wavelength: 254 nm), benzyl (1-{[(1S) -1- (5-{(3S) -3-[(tert- Butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) The carbamate diastereomer A (87.5 mg) and diastereomer B (76.7 mg) were obtained.
Diastereomer A: ¹ H NMR (600 MHz, CD ₃ OD, δ): 1.36-1.53 (m, 12H), 1.84-1.97 (m, 1H), 2.10-2.22 (m, 1H), 2.25-2.44 ( m, 3H), 2.46-3.38 (m, 7H), 3.45-3.96 (m, 4H), 4.08-4.22 (m, 1H), 4.91-5.15 (m, 2H), 5.45-5.60 (m, 0.5H) , 5.82-6.07 (m, 1.5H), 7.02-7.40 (m, 7H), 7.49-7.65 (m, 1H), 7.86-7.93 (m, 1H), 8.12 (br s, 1H).
LCMS (ESI) m / z 668 [M + H] ⁺ , t _R = 1.18 min, mode N.
Diastereomer B: LCMS (ESI) m / z 668 [M + H] ⁺ , t _R = 1.17 min, mode N.

Step 3-39-2: The benzyl (1-{[(1S) -1- (5-{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidine-) obtained in Step 3-39-1 1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate diastereomer A ( To a solution of 78 mg) in MeOH (2 mL) was added 10% palladium-carbon (39 mg), and the mixture was stirred at room temperature for 3 hours in a hydrogen atmosphere. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to NH silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100-CHCl ₃ / MeOH). = 100/0 to 70/30; v / v), and tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-2,3-dihydro -1H-Inden-1-yl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (single diastereomer) ( 48 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): (br s, 1.5H), 1.38-1.57 (m, 10.5H), 1.90-1.97 (m, 1H), 2.13-2.22 (m, 2H), 2.29 (br s, 1H), 2.39 (s, 3H), 2.56-3.16 (m, 4H), 3.24-3.39 (m, 3H), 3.55 (dd, J = 10.7, 4.5 Hz, 1H), 3.72-3.79 (m, 1H), 3.80-3.87 (m, 1H), 3.89-3.95 (m, 1H), 4.13-4.19 (m, 1H), 4.55-4.76 (m, 0.5H), 5.83-5.94 (m, 1H ), 6.05-6.12 (m, 0.5H), 7.21-7.38 (m, 4H), 8.13 (s, 1H).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.67 min, mode N.

Step 3-39-3: The title compound (27.3 mg, colorless solid) was obtained from the compound (23.8 mg) obtained in Step 3-39-2 using the same method as in Step 3-1-1.
LCMS (ESI) m / z 434 [M + H] ⁺ , t _R = 0.54 min, mode H.

Example 3-40: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-[(methylsulfonyl) amino] -2,3-dihydro-1H-indene-1-carboxamide Synthesis Steps 3-1-6 and Step 3- of Hydrochloride (Single Diastereomer) The title compound (23.1 mg, colorless solid) was obtained from the compound (23.6 mg) obtained in Step 3-39-2 using a method similar to 1-1.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.20-1.48 (m, 3H), 2.00-2.08 (m, 1H), 2.19-2.26 (m, 1H), 2.28-3.23 (m, 10H) , 2.34 (s, 3H), 3.44-4.04 (m, 5H), 5.81-6.16 (m, 2H), 7.19-7.56 (m, 4H), 7.93 (br s, 0.5H), 8.22 (br s, 3H ), 8.51 (br s, 0.5H).
LCMS (ESI) m / z 512 [M + H] ⁺ , t _R = 0.84 min, mode H.

Example 3-41: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-[(methylsulfonyl) amino] -2,3-dihydro-1H-indene-1-carboxamide Hydrochloride (single diastereomer) synthesis step 3-41-1: step 3- Using the same method as for 39-2, the benzyl (1-{[(1S) -1- (5-{(3S) -3-[(tert-butoxycarbonyl)) obtained in Step 3-39-1 was used. Amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -2,3-dihydro-1H-inden-1-yl) carbamate dia From stereomer B (68 mg) tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-2,3-dihydro-1H-inden-1-yl) carbonyl ] (Methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (single diastere Omar) (48 mg, to obtain a colorless amorphous).
LCMS (ESI) m / z 534 [M + H] ⁺ , t _R = 0.61 min, mode N.
Step 3-41-2: Using a method similar to that of Step 3-1-6 and Step 3-1-1, the title compound (18.5 mg, A colorless solid was obtained.
LCMS (ESI) m / z 512 [M + H] ⁺ , t _R = 0.84 min, mode H.

Example 3-42: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1-carboxamide Step 3-42-1 for Synthesis of Hydrochloride (Single Diastereomer): HATU (100 mg) and Et ₃ N (110 μL) were added to a DMF (1 mL) solution of the compound obtained in Step 3-1-5 (70 mg) and methanesulfonylacetic acid (36 mg) at room temperature. Stir for 16 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100 to EtOAc / MeOH = 100/0 to 90/10; v / v), and tert- Butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1 -Il) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate diastereomer A (24 mg, colorless amorphous) and diastereomer B (20 mg , Colorless amorphous).
Diastereomer A: ¹ H NMR (600 MHz, CD ₃ OD, δ): 1.38-1.61 (m, 12H), 1.88-1.96 (m, 1H), 2.11-2.23 (m, 1H), 2.38 (br s , 3H), 2.51-3.12 (m, 10H), 3.50-3.57 (m, 2H), 3.71-3.78 (m, 1H), 3.79-3.86 (m, 1H), 3.88-3.94 (m, 1H), 3.96 -4.03 (m, 1H), 4.12-4.20 (m, 1H), 4.95-5.07 (m, 0.5H), 5.92 (br s, 1H), 5.99-6.10 (m, 0.5H), 7.14-7.57 (m , 4H), 8.10-8.19 (m, 1H).
LCMS (ESI) m / z 654 [M + H] ⁺ , t _R = 0.93 min, mode N.
Diastereomer B: LCMS (ESI) m / z 654 [M + H] ⁺ , t _R = 0.91 min, mode N.
Step 3-42-2: tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[( Methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-inden-1-yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate To a 1,4-dioxane (0.5 mL) solution of diastereomer A (23.2 mg), 4M HCl / 1,4-dioxane solution (1.0 mL) was added dropwise, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (23.6 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.97-1.51 (m, 3H), 1.98-2.10 (m, 1H), 2.17-2.28 (m, 1H), 2.33 (s, 3H), 2.37 -3.17 (m, 10H), 3.40-3.94 (m, 5H), 3.99-4.23 (m, 2H), 5.78-5.95 (m, 2H), 7.10-7.53 (m, 4H), 8.16 (br s, 3H ), 8.50 (br s, 0.5H), 9.01-9.23 (m, 0.5H).
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 0.78 min, mode H.

Example 3-43: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl Synthesis step 3-1-1 of] -N-methyl-1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1-carboxamide hydrochloride (single diastereomer) Using a similar procedure, tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[(methyl Sulfonyl) acetyl] amino} -2,3-dihydro-1H-inden-1-yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate The title compound (18 mg, colorless solid) was obtained from stereomer B (19 mg).
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 0.78 min, mode H.

Example 3-44: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-2,3-dihydro-1H-indene-1-carboxamide hydrochloride Synthesis step 3-1-4 and step 3-1-1 The title compound (27 mg, colorless solid) was obtained from the compound obtained in (20 mg) and 2,3-dihydro-1H-indene-1-carboxylic acid (10 mg).
LCMS (ESI) m / z 419 [M + H] ⁺ , t _R = 0.92 min, mode H.

Example 3-45: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-phenylcyclopropanecarboxamide hydrochloride The compound (25) obtained in Step 3-1-3 using the same method as in Step 3-1-4 and Step 3-1-1 mg) and 1-phenyl-1-cyclopropanecarboxylic acid (13 mg) gave the title compound (34 mg, colorless solid).
LCMS (ESI) m / z 419 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 3-46: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N, 2-dimethyl-2-phenylpropanamide hydrochloride The compound obtained in Step 3-1-3 using the same method as in Step 3-1-4 and Step 3-1-1 ( The title compound (24 mg, colorless solid) was obtained from 20 mg) and 2-phenylisobutyric acid (12 mg).
LCMS (ESI) m / z 421 [M + H] ⁺ , t _R = 0.96 min, mode H.

Example 3-47: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1- (3-methylphenyl) cyclopropanecarboxamide obtained in Step 3-1-3 using the same procedure as in Step 3-1-4 and Step 3-1-1 of hydrochloride The title compound (17 mg, colorless solid) was obtained from the obtained compound (25 mg) and 1- (3-methylphenyl) cyclopropane-1-carboxylic acid (18 mg).
LCMS (ESI) m / z 433 [M + H] ⁺ , t _R = 0.98 min, mode H.

Example 3-48: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- (3-Fluorophenyl) -N-methylcyclopropanecarboxamide Obtained in Step 3-1-3 using the same method as in Synthesis Step 3-1-4 and Step 3-1-1 of hydrochloride The title compound (11 mg, colorless solid) was obtained from the obtained compound (25 mg) and 1- (3-fluorophenyl) cyclopropane-1-carboxylic acid (18 mg).
LCMS (ESI) m / z 437 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 3-49: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-5,6,7,8-tetrahydroimidazo [1,2-a] pyridine-8-carboxamide Hydrochloric acid salt The same procedure as in Step 3-1-4 and Step 3-1-1 The title compound (30 mg) obtained from Step 1-4-3 and 5,6,7,8-tetrahydroimidazo [1,2-a] pyridine-8-carboxylic acid (29 mg) were used. 25 mg, a colorless solid) was obtained.
LCMS (ESI) m / z 437 [M + H] ⁺ , t _R = 0.49 min, mode H.

Example 3-50: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- (Ethylsulfonyl) -N-methyl-4-phenylpiperidine-4-carboxamide Hydrochloride Synthesis using the same method as in Step 3-29-1 and Step 3-1-1, Step 3-1 The title compound (48 mg, colorless solid) was obtained from the compound obtained in -3 (40 mg) and 1- (ethanesulfonyl) -4-phenylpiperidine-4-carboxylic acid (64 mg).
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 1.00 min, mode H.

Example 3-51: 1-acetyl-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N-methyl-4-phenylpiperidine-4-carboxamide Hydrochloride Synthesis in Step 3-1-3 using the same method as in Step 3-29-1 and Step 3-1-1 The title compound (66 mg, brown amorphous) was obtained from the obtained compound (42 mg) and 1-acetyl-4-phenylpiperidine-4-carboxylic acid (55 mg).
LCMS (ESI) m / z 504 [M + H] ⁺ , t _R = 0.47 min, mode N.

Example 3-52: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1- (3-Chlorophenyl) -N-methylcyclopropanecarboxamide Obtained in Step 3-1-3 using the same method as in Step 3-29-1 and Step 3-1-1 of hydrochloride The title compound (51 mg, pink amorphous) was obtained from the compound (30 mg) and 1- (3-chlorophenyl) cyclopropane-1-carboxylic acid (32 mg).
LCMS (ESI) m / z 453 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 3-53: tert-butyl 4-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] (methyl) carbamoyl} -4-phenylpiperidine-1-carboxylate in Step 1-1-7 using the same procedure as in Steps 3-29-1 and 3-1-5 The title compound (9.8 mg, colorless oil) was obtained from the obtained compound (50 mg) and 1- (tert-butoxycarbonyl) -4-phenylpiperidine-4-carboxylic acid (0.13 g).
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 0.67 min, mode H.

Example 3-54: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1- (methylsulfonyl) -4-phenylpiperidine-4-carboxamide Hydrochloride Synthesis Step 3-54-1: The same procedure as in Steps 3-29-1 and 3-1-5 is used. Tert-butyl [(3S) from the compound (240 mg) obtained in Step 3-1-3 and 1-[(benzyloxy) carbonyl] -4-phenylpiperidine-4-carboxylic acid (435 mg). -1- {6-methyl-2-[(1S) -1- {methyl [(4-phenylpiperidin-4-yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} Pyrrolidin-3-yl] carbamate (155 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 0.63 min, mode N.
Step 3-54-2: Using a method similar to that of Step 3-1-6 and Step 3-1-1, the title compound (31 mg, Colorless amorphous) was obtained.
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 3-55: N4-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N4-Methyl-4-phenylpiperidine-1,4-dicarboxamide Step 3-55-1: To a solution of the compound obtained in Step 3-54-1 (20 mg) in CHCl ₃ (1 mL) Trimethylsilyl isocyanate (9.0 μL) was added, and the mixture was stirred at room temperature for 2 days. The reaction solution was separated with CHCl ₃ and water. The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure and tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-carbamoyl-4-phenylpiperidin-4-yl) carbonyl] (methyl) amino } Ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (22 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 605 [M + H] ⁺ , t _R = 0.91 min, mode N.
Step 3-55-2: 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound obtained in Step 3-55-1 (22 mg) in 1,4-dioxane (1 mL). The mixture was stirred at room temperature for 24 hours. The residue obtained by concentrating the reaction solution under reduced pressure was purified by NH column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 80/20; v / v) to give the title compound (8.8 mg , Colorless amorphous).
LCMS (ESI) m / z 505 [M + H] ⁺ , t _R = 0.41 min, mode N.

Example 3-56: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -1-Carbamimidoyl-N-methyl-4-phenylpiperidine-4-carboxamide Step 3-56-1: EtOH (1 mL) of the compound (20 mg) obtained in Step 3-54-1 ) Cyanamide (7 mg) was added to the solution and stirred at 80 ° C. for 2 hours. Cyanamide (20 mg) was added to the reaction solution, and the mixture was stirred at 80 ° C. for 16 hours. The reaction solution was filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 95/5; v / v) and tert-butyl. [(3S) -1- {2-[(1S) -1-{[(1-carbamimidoyl-4-phenylpiperidin-4-yl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [ 1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (7.4 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 604 [M + H] ⁺ , t _R = 0.69 min, mode N.
Step 3-56-2: The title compound (5.1 mg, colorless amorphous) was obtained from the compound (7.4 mg) obtained in Step 3-56-1 using the same method as in Step 3-55-2.
LCMS (ESI) m / z 504 [M + H] ⁺ , t _R = 0.17 min, mode N.

Example 3-57: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-1-[(methylsulfonyl) acetyl] -3-phenylpyrrolidine-3-carboxamide hydrochloride synthesis step 3-57-1: using the same method as in step 3-1-4, The compound (100 mg) obtained in 3-1-3 and 1-[(benzyloxy) carbonyl] -3- obtained by the method described in the literature (Tetrahedron Letters, 2005, 46, 8463) Benzyl 3-{[(1S) -1- (5-{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6 from phenylpyrrolidine-3-carboxylic acid (130 mg) -Methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamoyl} -3-phenylpyrrolidine-1-carboxylate (160 mg, light brown amorphous) was obtained.
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.20 min, mode N.
Step 3-57-2: Using a method similar to that of Step 3-1-5, tert-butyl [(3S) -1- {6- Methyl-2-[(1S) -1- {methyl [(3-phenylpyrrolidin-3-yl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] Carbamate (92.1 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.63 min, mode N.
Step 3-57-3: The title compound (22 mg, colorless solid) was obtained from the compound (23 mg) obtained in Step 3-57-2 using the same method as in Example 3-12.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.76-1.42 (m, 3H), 1.98-2.07 (m, 1H), 2.16-3.18 (m, 9H), 2.32 (s, 3H), 3.29 -3.91 (m, 9H), 4.25-4.47 (m, 2H), 5.49-5.98 (m, 2H), 7.23-7.48 (m, 5H), 8.16 (br s, 2H), 8.48 (s, 1H).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 0.83 min, mode H.

Example 3-58: benzyl 3-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl } Ethyl] (methyl) carbamoyl} -3-phenylpyrrolidine-1-carboxylate The compound obtained in Step 3-57-1 (13.7 mg) using the same method as in Synthesis Step 3-1-1 of hydrochloride ) Afforded the title compound (13.0 mg, colorless solid).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 1.16, 1.18 min, mode H.

Example 3-59: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1- (methylsulfonyl) -3-phenylpyrrolidine-3-carboxamide Hydrochloride Synthesis Step 3-59-1: CHCl _{3 of} the compound (20 mg) obtained in Step 3-57-2 To the (1 mL) solution, Et ₃ N (20 μL) and methanesulfonic anhydride (8.0 mg) were added under ice-cooling, and the mixture was stirred at the same temperature for 1 hour. The reaction solution was partitioned between CHCl ₃ and saturated NaHCO ₃ aqueous solution, and the aqueous layer was extracted with CHCl ₃ . The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure, and the obtained residue was subjected to OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100 to EtOAc / MeOH = 100/0 to 90/10; v / v ) Tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- (methyl {[1- (methylsulfonyl) -3-phenylpyrrolidin-3-yl] Carbonyl} amino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (23 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 626 [M + H] ⁺ , t _R = 1.02 min, mode N.
Step 3-59-2: The title compound (22.4 mg, colorless solid) was obtained from the compound (22.5 mg) obtained in Step 3-59-1 using the same method as in Step 3-1-1.
LCMS (ESI) m / z 526 [M + H] ⁺ , t _R = 0.90 min, mode H.

Example 3-60: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -3- (Ethylsulfonyl) -N-methyl-3-phenylpyrrolidine-3-carboxamide Hydrochloride Synthesis Step 3-1-6 and Step 3-1-1 were performed in the same manner as in Step 3-57. The title compound (20 mg, colorless solid) was obtained from the compound obtained in -2 (20 mg) and ethanesulfonyl chloride (4.5 μL).
LCMS (ESI) m / z 540 [M + H] ⁺ , t _R = 0.94 min, mode H.

Example 3-61: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-4-oxo-1-phenylcyclohexanecarboxamide synthesis step 3-61-1: Using a method similar to that in step 3-29-1, the compound obtained in step 3-1-3 ( 100 mg) and 4-oxo-1-phenylcyclohexanecarboxylic acid (117 mg) from tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(4-oxo 1-Phenylcyclohexyl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (94.0 mg, pale yellow amorphous) was obtained.
LCMS (ESI) m / z 575 [M + H] ⁺ , t _R = 1.07 min, mode N.
Step 3-61-2: Using the same method as in Step 3-33-2, the title compound (14 mg, pale yellow amorphous) was obtained from the compound (18 mg) obtained in Step 3-61-1. .
LCMS (ESI) m / z 475 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 3-62: trans-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl } Ethyl] -4-hydroxy-N-methyl-1-phenylcyclohexanecarboxamide Hydrochloride Synthesis Step 3-62-1: A solution of the compound obtained in Step 3-61-1 (300 mg) in MeOH (5 mL) Was added with sodium borohydride (30 mg), and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution under ice cooling, and CHCl ₃ was added to separate the layers. The organic layer was filtered with a Phase Separator. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 50 / 50-30 / 70; v / v), and tert-butyl [(3S ) -1- {2-[(1S) -1-{[(trans-4-hydroxy-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidine- 5-yl} pyrrolidin-3-yl] carbamate (24.6 mg, colorless amorphous) and tert-butyl [(3S) -1- {2-[(1S) -1-{[(cis-4-hydroxy-1- Phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (174 mg, colorless amorphous) was obtained.
tert-butyl [(3S) -1- {2-[(1S) -1-{[(trans-4-hydroxy-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1, 5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate: LCMS (ESI) m / z 577 [M + H] ⁺ , t _R = 0.94 min, mode N.
tert-butyl [(3S) -1- {2-[(1S) -1-{[(cis-4-hydroxy-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1, 5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate: LCMS (ESI) m / z 577 [M + H] ⁺ , t _R = 1.01 min, mode N.
Step 3-62-2: Using a method similar to that of Step 3-1-1, tert-butyl [(3S) -1- {2-[(1S) -1] obtained in Step 3-62-1 was used. -{[(trans-4-hydroxy-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (6.0 mg) gave the title compound (2.4 mg, colorless solid).
LCMS (ESI) m / z 477 [M + H] ⁺ , t _R = 0.44 min, mode N.

Example 3-63: cis-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl } Ethyl] -4-hydroxy-N-methyl-1-phenylcyclohexanecarboxamide hydrochloride Using the same method as in Synthesis step 3-1-1, tert-butyl obtained in step 3-62-1 [( 3S) -1- {2-[(1S) -1-{[(cis-4-hydroxy-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidine The title compound (10.9 mg, colorless solid) was obtained from -5-yl} pyrrolidin-3-yl] carbamate (15.0 mg).
LCMS (ESI) m / z 477 [M + H] ⁺ , t _R = 0.51 min, mode N.

Example 3-64: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-4-[(methylsulfonyl) amino] -1-phenylcyclohexanecarboxamide Hydrochloride Synthesis Step 3-64-1: Compound (100 mg) obtained in Step 3-61-1 in MeOH / Ammonium acetate (268 mg) was added to a CHCl ₃ mixed solution (2 mL, 1/1; v / v), and the mixture was stirred at room temperature for 30 minutes. Sodium cyanoborohydride (17 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. A saturated aqueous NaHCO ₃ solution was added to the reaction solution, and CHCl ₃ was added to separate the layers. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by NH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v) to obtain tert-butyl [(3S ) -1- {2-[(1S) -1-{[(4-Amino-1-phenylcyclohexyl) carbonyl] (methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidine-5- Ir} pyrrolidin-3-yl] carbamate (71 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 576 [M + H] ⁺ , t _R = 0.65, 0.69 min, mode N.
Step 3-64-2: Using a method similar to that of Step 3-1-6 and Step 3-1-1, the title compound (14 mg, A colorless solid was obtained.
LCMS (ESI) m / z 554 [M + H] ⁺ , t _R = 0.50, 0.56 min, mode N.

Example 3-65: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-methyl-4-[(methylsulfonyl) amino] -1-phenylcyclohexanecarboxamide hydrochloride (single diastereomer) synthesis step 3-65-1: compound obtained in step 3-64-1 HATU (20 mg) and Et ₃ N (22 μL) were added to a DMF (1 mL) solution of (15 mg) and methanesulfonylacetic acid (5 mg), and the mixture was stirred at 60 ° C. for 2 hours. Water was added to the reaction mixture, and the mixture was stirred and extracted with EtOAc. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90/10 to 0/100; v / v) to obtain tert-butyl [( 3S) -1- {6-methyl-2-[(1S) -1- {methyl [(4-{[(methylsulfonyl) acetyl] amino} -1-phenylcyclohexyl) carbonyl] amino} ethyl] pyrazolo [1 , 5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate diastereomer A (15 mg, colorless amorphous) and diastereomer B (2.7 mg, colorless amorphous) were obtained.
Diastereomer A: LCMS (ESI) m / z 696 [M + H] ⁺ , t _R = 1.18 min, mode N.
Diastereomer B: LCMS (ESI) m / z 696 [M + H] ⁺ , t _R = 1.13 min, mode N.
Step 3-65-2: Using a method similar to that of Step 3-1-1, tert-butyl [(3S) -1- {6-methyl-2-[( 1S) -1- {Methyl [(4-{[(methylsulfonyl) acetyl] amino} -1-phenylcyclohexyl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidine-3 The title compound (5.7 mg, colorless solid) was obtained from diastereomer A (15 mg) of -yl] carbamate.
LCMS (ESI) m / z 596 [M + H] ⁺ , t _R = 0.50 min, mode N.

Example 3-66: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-4-{[(methylsulfonyl) acetyl] amino} -1-phenylcyclohexanecarboxamide hydrochloride (single diastereomer) synthesis step 3-1-1 using the same procedure Tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(4-{[(methylsulfonyl) acetyl] amino}-] obtained from 3-65-1 1-Phenylcyclohexyl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate diastereomer B (3 mg), title compound (0.6 mg, colorless solid) )
LCMS (ESI) m / z 596 [M + H] ⁺ , t _R = 0.45 min, mode N.

Example 3-67: benzyl 3-{[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl } Ethyl] (methyl) carbamoyl} -3-phenylazetidine-1-carboxylate Synthesis Step 3-1-3 (17 mg) and the 1-[(benzyloxy) carbonyl] -3-phenylazetidine-3-carboxylic acid (14 mg) to give the title compound (4.4 mg, colorless solid).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 1.18 min, mode N.

Example 3-68: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-3-oxo-1-phenylcyclobutanecarboxamide synthesis step 3-68-1: Using a method similar to that in step 3-29-1, the compound obtained in step 3-1-3 ( 0.10 g) and 3-oxo-1-phenylcyclobutane-1-carboxylic acid (61 mg), tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [( 3-Oxo-1-phenylcyclobutyl) carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (0.15 g, pale yellow amorphous) was obtained.
LCMS (ESI) m / z 547 [M + H] ⁺ , t _R = 1.04 min, mode N.
Step 3-68-2: The title compound (14.9 mg, colorless solid) was obtained from the compound (20.6 mg) obtained in Step 3-68-1 using the same method as in Step 3-33-2.
LCMS (ESI) m / z 447 [M + H] ⁺ , t _R = 0.48 min, mode N.

Example 3-69: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -3-Hydroxy-N-methyl-1-phenylcyclobutanecarboxamide obtained in Step 3-68-1 using the same method as in Step 3-64-1 and Step 3-1-1 of hydrochloride The title compound (12.5 mg, colorless solid) was obtained from the compound (130 mg).
LCMS (ESI) m / z 449 [M + H] ⁺ , t _R = 0.39 min, mode N.

Example 3-70: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -N-Methyl-1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalene-1-carboxamide Hydrochloride Synthesis Step 3-70-1: Step 3-1-3 HATU (137 mg) and Et ₃ N (0.15 mL) were added to a DMF (1 mL) solution of the compound (81 mg) obtained in Example 10 and the compound (59 mg) obtained in Reference Example 10 at 60 ° C. Stir for 6 hours. Water was added to the reaction mixture, and the mixture was stirred and extracted with EtOAc. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90/10 to 0/100; v / v) to obtain benzyl (1- { [(1S) -1- (5-{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl ] (Methyl) carbamoyl} -1,2,3,4-tetrahydronaphthalen-1-yl) carbamate (24 mg, pale yellow amorphous) was obtained.
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.27 min, mode N.
Step 3-70-2: 10% palladium-carbon (12 mg) was added to a solution of the compound obtained in Step 3-70-1 (24 mg) in MeOH (1 mL) and added at room temperature under a hydrogen atmosphere at room temperature. Stir for hours. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to NH silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v) Tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-1,2,3,4-tetrahydronaphthalen-1-yl) carbonyl] ( Methyl) amino} ethyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (8.8 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.66 min, mode N.
Step 3-70-3: To a solution of the compound obtained in Step 3-70-2 (8.8 mg) and methanesulfonylacetic acid (4.0 mg) in DMF (1 mL), HATU (12 mg), Et ₃ N (14 μL ) Was added and stirred at 60 ° C. for 1.5 hours. Water was added to the reaction mixture, and the mixture was stirred and extracted with EtOAc. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 90/10 to 0/100; v / v) to obtain tert-butyl [( 3S) -1- {6-Methyl-2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalen-1-yl ) Carbonyl] amino} ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (9.7 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 668 [M + H] ⁺ , t _R = 1.00 min, mode N.
Step 3-70-4: 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound obtained in Step 3-70-3 (9.7 mg) in 1,4-dioxane (1 mL). And stirred at room temperature for 2 hours. The reaction mixture was filtered, and the collected solid was dried under reduced pressure to give the title compound (6.6 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.33-1.49 (m, 3H), 1.71-1.82 (m, 1H), 1.89-2.01 (m, 1H), 2.02-2.09 (m, 1H) , 2.19-2.29 (m, 1H), 2.31-3.13 (m, 13H), 3.65-3.94 (m, 5H), 4.18 (s, 2H), 4.62-4.76 (m, 0.5H), 5.78-5.99 (m , 1.5H), 7.06-7.33 (m, 4H), 8.22 (br s, 3H), 8.38-8.54 (m, 1H).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 0.47 min, mode N.

Example 3-71: 1-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxamide obtained in Step 3-70-2 using a method similar to that of Synthesis Step 3-70-4 of hydrochloride. The title compound (8.5 mg, colorless solid) was obtained from the obtained compound (7.9 mg).
LCMS (ESI) m / z 448 [M + H] ⁺ , t _R = 0.59 min, mode H.

Example 3-72: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl Synthesis step 3-72-1 of] -N-methyl-1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-indene-1-carboxamide hydrochloride (single diastereomer): HATU (88 mg) and Et ₃ N (0.13 mL) were added to a DMF (2 mL) solution of the compound obtained in Step 1-4-3 (60 mg) and the compound obtained in Reference Example 11 (63 mg). The mixture was further stirred at room temperature for 3 days. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) to obtain benzyl (1-{[(1S) -1- (5 -{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) propyl] (methyl) carbamoyl} -2, 3-Dihydro-1H-inden-1-yl) carbamate (single diastereomer) (89 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.66-0.97 (m, 3H), 1.44 (br s, 9H), 1.75-1.96 (m, 2H), 2.01-2.20 (m, 2H), 2.31 (br s, 1H), 2.38 (br s, 2H), 2.42-3.21 (m, 7H), 3.45-3.57 (m, 1H), 3.71-3.78 (m, 1H), 3.78-3.86 (m, 1H) , 3.87-3.94 (m, 1H), 4.07-4.19 (m, 1H), 4.98-5.10 (m, 2H), 5.10-5.14 (m, 0.5H), 5.76-5.83 (m, 0.5H), 5.86- 6.02 (m, 1H), 7.02-7.38 (m, 8H), 7.51-7.60 (m, 1H), 8.05-8.15 (m, 1H).
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.23 min, mode N.
Step 3-72-2: To a solution of the compound obtained in Step 3-72-1 (85 mg) in MeOH (2 mL) was added 10% palladium-carbon (43 mg), and 1.5% at room temperature under a hydrogen atmosphere. Stir for hours. The reaction solution was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to NH silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 80/20; v / v ) Tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-2,3-dihydro-1H-inden-1-yl) carbonyl] ( Methyl) amino} propyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (single diastereomer) (52 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.91-1.01 (m, 2H), 1.24-1.34 (m, 1H), 1.45 (br s, 9H), 1.84-1.97 (m, 2H), 2.05 -2.23 (m, 2H), 2.28 (br s, 1H), 2.38 (br s, 2H), 2.62-2.73 (m, 1H), 2.88 (br s, 1H), 3.07-3.16 (m, 1H), 3.16-3.39 (m, 4H), 3.49-3.59 (m, 1H), 3.70-3.79 (m, 1H), 3.79-3.87 (m, 1H), 3.87-3.96 (m, 1H), 4.11-4.21 (m , 1H), 5.91 (br s, 2H), 7.15-7.42 (m, 4H), 8.09-8.19 (m, 1H).
LCMS (ESI) m / z 548 [M + H] ⁺ , t _R = 0.65 min, mode N.
Step 3-72-3: A solution of the compound obtained in Step 3-72-2 (19 mg) and methanesulfonylacetic acid (7.7 mg) in DMF (1 mL) was added to HATU (21 mg), Et ₃ N (29 μL ) Was added and stirred at room temperature for 1 hour. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95 / 5-0 / 100; v / v), and tert-butyl [(3S) -1- {6-methyl -2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -2,3-dihydro-1H-inden-1-yl) carbonyl] amino} propyl] pyrazolo [1 , 5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (single diastereomer) (20 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.94-1.03 (m, 3H), 1.45 (br s, 9H), 1.88-1.97 (m, 2H), 2.09-2.22 (m, 2H), 2.39 (br s, 3H), 2.51-2.76 (m, 2H), 2.77-2.94 (m, 4H), 2.97-3.11 (m, 4H), 3.24-3.41 (m, 2H), 3.52-3.58 (m, 1H ), 3.71-3.79 (m, 1H), 3.80-3.88 (m, 1H), 3.88-3.95 (m, 1H), 4.12-4.21 (m, 1H), 5.81-6.01 (m, 2H), 7.16-7.40 (m, 3H), 7.50-7.56 (m, 0.7H), 7.98 (br s, 0.3H), 8.13 (br s, 0.7H), 8.18-8.23 (m, 0.3H).
LCMS (ESI) m / z 668 [M + H] ⁺ , t _R = 0.98 min, mode N.
Step 3-72-4: To a solution of the compound (19.0 mg) obtained in Step 3-72-3 in 1,4-dioxane (0.5 mL), 4M HCl / 1,4-dioxane solution (1 mL) was added dropwise. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (18.5 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.88 (t, J = 7.4 Hz, 3H), 1.70-1.80 (m, 1H), 1.98-2.10 (m, 2H), 2.18-2.28 (m , 1H), 2.33 (s, 3H), 2.36-3.13 (m, 10H), 3.43-4.02 (m, 5H), 4.03-4.22 (m, 2H), 5.65-6.06 (m, 2H), 7.12-7.55 (m, 4H), 8.23 (br s, 3H), 8.48 (s, 0.5H), 9.20 (s, 0.5H).
LCMS (ESI) m / z 568 [M + H] ⁺ , t _R = 0.85 min, mode H.

Example 3-73: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -1-{[(Ethylsulfonyl) acetyl] amino} -N-methyl-2,3-dihydro-1H-indene-1-carboxamide Step 373-1 for Synthesis of Hydrochloride (Single Diastereomer): HATU (18 mg) and Et ₃ N (24 μL) were added to a DMF (1 mL) solution of the compound obtained in step 3-72-2 (16 mg) and 2- (ethanesulfonyl) acetic acid (7.1 mg). The mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v), and tert-butyl [(3S) -1- {2- [ (1S) -1-{[(1-{[(Ethylsulfonyl) acetyl] amino} -2,3-dihydro-1H-inden-1-yl) carbonyl] (methyl) amino} propyl] -6-methylpyrazolo [ 1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (single diastereomer) (16 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.97 (t, J = 7.4 Hz, 2H), 1.24 (t, J = 7.4 Hz, 1H), 1.26-1.36 (m, 3H), 1.45 (s , 9H), 1.86-1.97 (m, 2H), 2.09-2.21 (m, 2H), 2.38 (s, 3H), 2.49-3.39 (m, 11H), 3.50-3.58 (m, 1H), 3.70-3.79 (m, 1H), 3.79-3.87 (m, 1H), 3.88-3.94 (m, 1H), 4.12-4.18 (m, 1H), 5.79-6.01 (m, 2H), 7.15-7.38 (m, 3H) , 7.52 (d, J = 7.4 Hz, 1H), 7.98 (s, 0.5H), 8.13 (br s, 0.5H).
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.01 min, mode N.
Step 3-73-2: 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound obtained in Step 3-73-1 (14.8 mg) in 1,4-dioxane (0.5 mL). And stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (14.8 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.86 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.4 Hz, 3H), 1.71-1.80 (m, 1H), 1.99- 2.10 (m, 2H), 2.19-2.28 (m, 1H), 2.33 (s, 3H), 2.36-3.27 (m, 9H), 3.44-3.95 (m, 5H), 4.01-4.18 (m, 2H), 5.65-5.83 (m, 2H), 7.13-7.52 (m, 4H), 8.19 (br s, 3H), 8.48 (s, 0.5H), 9.20 (s, 0.5H).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.89 min, mode H.

Example 3-74: 1-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} propyl] -N-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxamide hydrochloride synthesis step 3-74-1: compound obtained in step 1-4-3 (100 mg) HATU (196 mg), DMAP (63 mg), and DIPEA (269 μL) were added to a DMF (2 mL) solution of the compound (167 mg) obtained in Reference Example 10 and stirred at 80 ° C. for 20 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95/5 to 0/100; v / v) to obtain benzyl (1-{[(1S) -1- (5 -{(3S) -3-[(tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) propyl] (methyl) carbamoyl} -1, 2,3,4-Tetrahydronaphthalen-1-yl) carbamate (55 mg, pale yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.90-0.99 (m, 3H), 1.45 (br s, 9H), 1.72-3.06 (m, 13H), 2.29-2.34 (m, 3H), 3.47- 4.34 (m, 5H), 4.56-4.70 (m, 1H), 4.90-5.01 (m, 2H), 5.89-6.02 (m, 1H), 7.05-7.36 (m, 9H), 7.98-8.04 (m, 1H ).
LCMS (ESI) m / z 696 [M + H] ⁺ , t _R = 1.42 min, mode N.
Step 3-74-2: 10% palladium-carbon (20 mg) was added to a solution of the compound obtained in Step 3-74-1 (50 mg) in MeOH (1 mL) and added at room temperature under a hydrogen atmosphere at room temperature. Stir for hours. After the reaction solution was filtered through Celite (registered trademark), the filtrate was concentrated under reduced pressure, and tert-butyl [(3S) -1- {2-[(1S) -1-{[(1-amino-1,2, 3,4-Tetrahydronaphthalen-1-yl) carbonyl] (methyl) amino} propyl] -6-methylpyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (39 mg, colorless amorphous )
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.94-1.00 (m, 3H), 1.45 (br s, 9H), 1.72-2.26 (m, 9H), 2.30-2.34 (m, 3H), 2.48- 3.02 (m, 4H), 3.48-3.55 (m, 1H), 3.67-3.73 (m, 1H), 3.75-3.83 (m, 1H), 3.87-3.97 (m, 1H), 4.23-4.36 (m, 1H ), 4.64-4.74 (m, 1H), 5.90-6.08 (m, 1H), 7.05-7.20 (m, 4H), 7.97-8.05 (m, 1H).
LCMS (ESI) m / z 562 [M + H] ⁺ , t _R = 0.90 min, mode N.
Step 3-74-3: 4M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound obtained in Step 3-74-2 (18.6 mg) in 1,4-dioxane (1 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was collected by filtration, and the filtrate was dried under reduced pressure to give the title compound (19.9 mg, colorless solid).
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.94-1.00 (m, 3H), 1.45 (br s, 9H), 1.72-2.26 (m, 9H), 2.30-2.34 (m, 3H), 2.48- 3.02 (m, 4H), 3.48-3.55 (m, 1H), 3.67-3.73 (m, 1H), 3.75-3.83 (m, 1H), 3.87-3.97 (m, 1H), 4.23-4.36 (m, 1H ), 4.64-4.74 (m, 1H), 5.90-6.08 (m, 1H), 7.05-7.20 (m, 4H), 7.97-8.05 (m, 1H).
LCMS (ESI) m / z 462 [M + H] ⁺ , t _R = 0.62 min, mode H.

Example 3-75: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalene-1-carboxamide Hydrochloride Synthesis Step 3-75-1: Step 3-74-2 HATU (42 mg) and Et ₃ N (46 μL) were added to a DMF (1 mL) solution of the compound obtained in (32.0 mg) and methanesulfonylacetic acid (15 mg), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO ₃ solution. The organic layer was washed with Brine, dried over MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc = 95 / 5-0 / 100; v / v), and tert-butyl [(3S) -1- {6-methyl -2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalen-1-yl) carbonyl] amino} propyl] pyrazolo [ 1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (27 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CD ₃ OD, δ): 0.90-1.04 (m, 3H), 1.45 (br s, 9H), 1.82-2.28 (m, 9H), 2.32-2.40 (m, 3H), 2.72 -3.44 (m, 9H), 3.50-3.58 (m, 1H), 3.72-3.78 (m, 1H), 3.80-3.87 (m, 1H), 3.89-3.95 (m, 1H), 4.03-4.10 (m, 1H), 4.13-4.20 (m, 1H), 4.57-4.95 (m, 1H), 5.81-6.01 (m, 1H), 7.09-7.32 (m, 4H), 7.94-8.16 (m, 1H).
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.05 min, mode N.
Step 3-75-2: 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of the compound (11.6 mg) obtained in Step 3-75-1 in 1,4-dioxane (0.5 mL). And stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (10.5 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.79-0.95 (m, 3H), 1.68-2.29 (m, 6H), 2.31-2.35 (m, 3H), 2.36-3.11 (m, 10H) , 3.42-3.94 (m, 5H), 4.13-4.21 (m, 2H), 5.69-6.04 (m, 2H), 7.08-7.30 (m, 2H), 8.11-8.26 (m, 2H), 8.35-8.50 ( m, 1H).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 3-76: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalene-1-carboxamide Hydrochloride (Single Diastereomer) Synthesis Step 3-76-1 : Preparative purification of the compound (12 mg) obtained in Step 3-75-1 using a chiral column (Preparation conditions: Column: CHIRALPAK IC (Daicel)), column size: 20 mm × 250 mm, migration Phase: hexane / EtOH = 10/90 (v / v), flow rate: 10 mL / mL), fractions eluted with a retention time of 16-18 min were concentrated under reduced pressure to give tert-butyl [(3S) -1- {6-Methyl-2-[(1S) -1- {methyl [(1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalen-1-yl) carbonyl ] Amino} propyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-y ] The fraction eluted with carbamate diastereomer A (6.5 mg), retention time 32 min to 37 min, was concentrated under reduced pressure to give tert-butyl [(3S) -1- {6-methyl-2- [ (1S) -1- {Methyl [(1-{[(methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalen-1-yl) carbonyl] amino} propyl] pyrazolo [1,5- a] Pyrimidin-5-yl} pyrrolidin-3-yl] carbamate diastereomer B (3.1 mg) was obtained.
Diastereomer A: ¹ H NMR (600 MHz, CD ₃ OD, δ): 0.92-1.03 (m, 3H), 1.45 (br s, 9H), 1.80-2.29 (m, 9H), 2.33-2.41 (m , 3H), 2.81-3.46 (m, 9H), 3.50-3.59 (m, 1H), 3.70-3.79 (m, 1H), 3.79-3.87 (m, 1H), 3.88-3.96 (m, 1H), 4.11 -4.23 (m, 1H), 4.58-4.71 (m, 1H), 5.72-6.06 (m, 1H), 7.05-7.33 (m, 4H), 8.01-8.23 (m, 1H).
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.05 min, mode N.
Diastereomer B: LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 1.05 min, mode N.
Step 3-76-2: tert-butyl [(3S) -1- {6-methyl-2-[(1S) -1- {methyl [(1-{[( Methylsulfonyl) acetyl] amino} -1,2,3,4-tetrahydronaphthalen-1-yl) carbonyl] amino} propyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate 4 M HCl / 1,4-dioxane solution (1 mL) was added dropwise to a solution of diastereomer A (5.8 mg) in 1,4-dioxane (0.5 mL), and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound (6.9 mg, colorless solid).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.81-0.95 (m, 3H), 1.68-2.28 (m, 6H), 2.30-2.36 (m, 3H), 2.38-3.14 (m, 10H) , 3.52-3.94 (m, 5H), 4.11-4.22 (m, 2H), 5.67-6.05 (m, 2H), 7.06-7.32 (m, 2H), 8.22-8.34 (m, 2H), 8.37-8.56 ( m, 1H).
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.93 min, mode H.

Example 3-77: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} propyl ] -N-Methyl-5-{[(methylsulfonyl) acetyl] amino} -6,7,8,9-tetrahydro-5H-benzo [7] annulene-5-carboxamide Hydrochloride Synthesis Step 3-1-4 Using the same method as in Step 3-12-1 and Step 3-1-1, the compound (30 mg) obtained in Step 1-4-3 and 5-amino-6,7,8,9- The title compound (5.5 mg, colorless solid) was obtained from tetrahydro-5H-benzo [7] annulene-5-carboxylic acid hydrochloride (21 mg).
LCMS (ESI) m / z 596 [M + H] ⁺ , t _R = 0.88, 0.98 min, mode H.

Example 3-78: 2-amino-N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} propyl] -N-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxamide hydrochloride using the same procedure as in Steps 3-29-1 and 3-1-1 From the compound (11 mg) obtained in 1-4-3 and 2-[(tert-butoxycarbonyl) amino] -1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (7.9 mg), the title compound ( 2.1 mg, a pale yellow solid).
LCMS (ESI) m / z 462 [M + H] ⁺ , t _R = 0.50 min, mode N.

Example 4-1 N-{(1S) -1- [5- (2-aminoethoxy) -6-methylpyrazolo [1,5-a] pyrimidin-2-yl] ethyl} -5-chloro-N- Synthesis step 4-1-1 of methyl-2-[(methylsulfonyl) amino] benzamide: (70 mg) of the compound obtained in step 1-1-4 and benzyl (2-hydroxyethyl) carbamate (67 mg) CMBP (0.18 mL) was added to the THF suspension (1 mL), and the mixture was stirred at 80 ° C. for 2.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by OH-type silica gel column chromatography (mobile phase: hexane / EtOAc) to give benzyl {2-[(2-{(1S) -1-[(tert -Butoxycarbonyl) (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) oxy] ethyl} carbamate (39 mg, light brown oil) was obtained.
LCMS (ESI) m / z 484 [M + H] ⁺ .
Step 4-1-2: Compound obtained in Step 4-1-1 (37 mg) using the same method as in Step 1-2-8, Step 1-1-8 and Step 1-1-9 The title compound (15 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 481 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 4-2: N-{(1S) -1- [5- (azetidin-3-yloxy) -6-methylpyrazolo [1,5-a] pyrimidin-2-yl] ethyl} -5-chloro-N Synthesis of 4-methyl-2-[(methylsulfonyl) amino] benzamide using the same method as in Step 4-1-1, Step 2-70-3, Step 1-1-8 and Step 1-1-9, The title compound (17 mg, colorless amorphous) was obtained from the compound (70 mg) obtained in Step 1-1-4 and benzyl (3-hydroxyazetidine) -1-carboxylate (71 mg).
LCMS (ESI) m / z 493 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 4-3: N-{(1S) -1- [5- (3-aminoazetidin-1-yl) -6-methylpyrazolo [1,5-a] pyrimidin-2-yl] ethyl} -5 Step 4-3-1: Synthesis of 4-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide obtained in Step 2-9-2 using the same method as in Step 1-1-6. Compound (20 mg) and tert-butyl azetidin-3-ylcarbamate methanesulfonate (47 mg) from tert-butyl [1- (2-{(1S) -1-[{5-chloro-2- [ (Methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) azetidin-3-yl] carbamate (17 mg) was obtained.
LCMS (ESI) m / z 592 [M + H] ⁺ , t _R = 1.10 min, mode N.
Step 4-3-2: Using the same method as in Step 2-70-3, the title compound (14 mg, colorless amorphous) was obtained from the compound (17 mg) obtained in Step 4-3-1.
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.53 min, mode N.

Example 4-4: N-[(1S) -1- (5-{[(1-aminocyclobutyl) methyl] amino} -6-methylpyrazolo [1,5-a] pyrimidin-2-yl) ethyl] Synthesis of 4-5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Step 4-4-1: Obtained in Step 2-9-2 using the same method as in Step 1-1-6. From the obtained compound (20 mg) and tert-butyl (1-[(aminomethyl) cyclobutyl] carbamate (35 mg), tert-butyl (1-{[(2-{(1S) -1-[{5-chloro -2-[(Methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl) amino] methyl} cyclobutyl) carbamate (11 mg) was obtained. .
LCMS (ESI) m / z 620 [M + H] ⁺ , t _R = 1.26 min, mode N.
Step 4-4-2: The title compound (8.0 mg) was obtained from the compound (10 mg) obtained in Step 4-4-1 using the same method as in Step 2-70-3.
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.58 min, mode N.

Example 4-5: 5-chloro-N-methyl-N-{(1S) -1- [6-methyl-5- (piperazin-1-yl) pyrazolo [1,5-a] pyrimidin-2-yl Ethyl} -2-[(methylsulfonyl) amino] benzamide Compound obtained in Step 2-9-2 using the same method as in Step 1-1-6 and Step 1-1-7 of hydrochloride The title compound (17 mg, colorless amorphous) was obtained from (20 mg) and 1-tert-butoxycarbonylpiperazine (33 mg).
LCMS (ESI) m / z 506 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 4-6: N-[(1S) -1- {5-[(2-aminoethyl) amino] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl] -5-chloro -N-methyl-2-[(methylsulfonyl) amino] benzamide obtained in Step 2-9-2 using the same procedure as in Step 1-1-6 and Step 1-1-7 of hydrochloride The title compound (7 mg, pale yellow solid) was obtained from the compound (22 mg) and tert-butyl (2-aminoethyl) carbamate (12 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.51-1.63 (m, 3H), 2.11 (s, 1.5H), 2.11 (s, 1.5H), 2.60 (s, 1.5H), 2.92- 3.11 (m, 3H), 3.05 (s, 1.5H), 3.43-3.72 (m, 4H), 4.74-4.83 (m, 0.5H), 5.89-5.96 (m, 0.5H), 5.98-6.11 (m, 1H), 7.35-7.57 (m, 3H), 7.89 (br s, 1H), 7.98 (br s, 3H), 8.46 (s, 0.5H), 9.25 (s, 0.5H).
LCMS (ESI) m / z 480 [M + H] ⁺ , t _R = 0.52 min, mode N.

Example 4-7: N-[(1S) -1- {5-[(trans-3-aminocyclobutyl) amino] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl]- 5-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide In the step 2-9-2, using the same procedure as in Step 1-1-6 and Step 1-1-7 The title compound (19 mg, colorless amorphous) was obtained from the obtained compound (20 mg) and trans-tert-butyl (-3-aminocyclobutyl) carbamate (33 mg).
LCMS (ESI) m / z 506 [M + H] ⁺ , t _R = 0.55 min, mode N.

Example 4-8: N-[(1S) -1- {5-[(3-aminopropyl) amino] -6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl] -5-chloro -N-methyl-2-[(methylsulfonyl) amino] benzamide obtained in Step 2-9-2 using the same procedure as in Step 1-1-6 and Step 1-1-7 of hydrochloride The title compound (21 mg, colorless amorphous) was obtained from the compound (20 mg) and tert-butyl (3-aminopropyl) carbamate (31 mg).
LCMS (ESI) m / z 494 [M + H] ⁺ , t _R = 0.54 min, mode N.

Example 4-9: N-[(1S) -1- {5-[(3R) -3- (aminomethyl) pyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-1-6 and Step 1-1-7 using the same procedure as in Step 2 The title compound (19 mg, colorless amorphous) was obtained from the compound (20 mg) obtained in -9-2 and (S) -tert-butyl (pyrrolidin-3-ylmethyl) carbamate (35 mg).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 4-10: N-[(1S) -1- {5-[(3S) -3- (aminomethyl) pyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-1-6 and Step 1-1-7 using the same procedure as in Step 2 The title compound (20 mg, colorless amorphous) was obtained from the compound obtained in -9-2 (20 mg) and (R) -tert-butyl (pyrrolidin-3-ylmethyl) carbamate (35 mg).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 4-11: 5-chloro-N-[(1S) -1- {5-[(3S) -3-hydroxypyrrolidin-1-yl] -6-methylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -N-methyl-2-[(methylsulfonyl) amino] benzamide, using the same method as in Step 1-1-6, the compound obtained in Step 2-9-2 (20 mg ) And (S) -3-pyrrolidinol (15 mg) to give the title compound (22 mg).
LCMS (ESI) m / z 507 [M + H] ⁺ , t _R = 0.85 min, mode N.

Example 4-12: 5-chloro-N-{(1S) -1- [5- (3,3-difluoropyrrolidin-1-yl) -6-methylpyrazolo [1,5-a] pyrimidin-2-yl Synthesis of ethyl] -N-methyl-2-[(methylsulfonyl) amino] benzamide Using the same method as in Step 1-1-6, the compound (20 mg) obtained in Step 2-9-2 and The title compound (16 mg, colorless amorphous) was obtained from 3,3-difluoropyrrolidine (25 mg).
LCMS (ESI) m / z 527 [M + H] ⁺ , t _R = 1.17 min, mode N.

Example 4-13: 5-chloro-N-{(1S) -1- [5- (3,3-difluoroazetidin-1-yl) -6-methylpyrazolo [1,5-a] pyrimidine-2- Yl] ethyl} -N-methyl-2-[(methylsulfonyl) amino] benzamide Compound (20 mg) obtained in Step 2-9-2 using the same method as in Step 1-1-6. The title compound (18 mg, colorless amorphous) was obtained from 3,3-difluoroazetidine (23 mg).
LCMS (ESI) m / z 513 [M + H] ⁺ , t _R = 1.13 min, mode N.

Example 5-1: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -3-chloro-6-methylpyrazolo [1,5-a] pyrimidine-2 -Yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 5-1-1: compound obtained in step 1-1-4 (170 mg) NCS (78 mg) was added to a DMF (5 mL) solution, and the mixture was stirred at room temperature for 4 hours. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v), and tert-butyl [(1S) -1- (3-chloro-6- Methyl-5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamate (90 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.45-1.55 (m, 12H), 2.02-2.21 (m, 3H), 2.64 (br s, 3H), 7.93 (d, J = 1.2 Hz, 1H) , 9.95 (br s, 1H).
LCMS (ESI) m / z 341 [M + H] ⁺ .
Step 5-1-2: Using a method similar to that of Step 1-1-5, the compound (90 mg) obtained in Step 5-1-1 was used to give 2-{(1S) -1-[(tert -Butoxycarbonyl) (methyl) amino] ethyl} -3-chloro-6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (115 mg) was obtained.
LCMS (ESI) m / z 373 [M + H-Boc] +, t _R = 1.30 min, mode N.
Step 5-1-3: Using the same method as in Step 1-1-6, 3-chloro-6-methyl-2-[((1)) was obtained from the compound (0.11 g) obtained in Step 5-1-2. 1S) -1- (Methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (90 mg) was obtained.
LCMS (ESI) m / z 373 [M + H] ⁺ , t _R = 0.59 min, mode N.
Step 5-1-4: Using a method similar to that of Step 1-1-7, 3-chloro-2-{(1S) -1 from the compound (90 mg) obtained in Step 5-1-3 -[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (70 mg) Obtained.
Step 5-1-5: Using a method similar to that of Step 1-1-8, from the compound obtained in Step 5-1-4 (70 mg), tert-butyl [(3S) -1- (3 -Chloro-2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methylpyrazolo [1,5-a] pyrimidine-5 -Yl) pyrrolidin-3-yl] carbamate (61 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.46 (s, 9H), 1.78 (d, J = 7.4 Hz, 3H), 1.90-1.98 (m, 1H), 2.22 (d, J = 5.0 Hz, 1H), 2.37 (s, 3H), 2.78-3.06 (m, 6H), 3.62 (dd, J = 11.1, 4.1 Hz, 1H), 3.77-3.92 (m, 1H), 4.00 (dd, J = 10.7, 5.4 Hz, 1H), 4.31 (br s, 1H), 4.67 (br s, 1H), 5.03 (br s, 1H), 6.15 (d, J = 7.4 Hz, 1H), 7.28-7.76 (m, 3H) , 8.36 (s, 1H), 8.77 (br s, 1H).
LCMS (ESI) m / z 640 [M + H] ⁺ , t _R = 1.19 min, mode N.
Step 5-1-6: Using the same method as in Step 1-2-8, the title compound (42 mg, colorless solid) was obtained from the compound (56 mg) obtained in Step 5-1-5. .
LCMS (ESI) m / z 541 [M + H] +, t _R = 0.56 min, mode N.

Example 5-2: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -3,6-dimethylpyrazolo [1,5-a] pyrimidine-2 -Il} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 5-2-1: compound obtained in step 3-1-3 (400 mg) NIS (256 mg) was added to a DMF (8 mL) solution, and the mixture was stirred at room temperature for 4 hours. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v), and tert-butyl [(3S) -1- {3-iodo-6- Methyl-2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (510 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 501 [M + H] ⁺ , t _R = 0.60 min, mode N.
Step 5-2-2: Using a method similar to that of Step 1-1-7, tert-butyl [(3S) -1- (2) from the compound (510 mg) obtained in Step 5-2-1. -{(1S) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -3-iodo-6-methylpyrazolo [1,5-a] pyrimidine-5 -Yl) pyrrolidin-3-yl] carbamate (460 mg) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.44 (s, 9H), 1.71-1.82 (m, 3H), 1.93 (dd, J = 12.0, 6.6 Hz, 1H), 2.17-2.27 (m, 1H ), 2.37 (s, 3H), 2.77-3.04 (m, 6H), 3.62 (d, J = 7.0 Hz, 1H), 3.75-3.91 (m, 2H), 3.99 (dd, J = 10.9, 6.0 Hz, 1H), 4.31 (br s, 1H), 4.68 (br s, 1H), 4.99 (br s, 0.2H), 5.99 (d, J = 7.0 Hz, 0.8H), 7.27-7.70 (m, 3H), 8.03 (s, 1H), 8.19-8.32 (m, 0.2H), 8.57 (br s, 0.8H).
LCMS (ESI) m / z 732 [M + H] ⁺ , t _R = 1.22 min, mode N.
Step 5-2-3: To a DMF (5 mL) solution of the compound (200 mg) obtained in Step 5-2-2, add 2,4,6-trimethylboroxine (102 mg), PdCl ₂ (dppf) _{· CH 2 Cl 2 (33 mg} ), K 2 CO 3 to (188 mg) was added and stirred for 3 hours at 110 ° C.. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v), and tert-butyl [(3S) -1- (2-{(1S ) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -3,6-dimethylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidine -3-yl] carbamate (43 mg, colorless amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.44 (s, 9H), 1.63-1.74 (m, 3H), 1.86-1.95 (m, 1H), 2.20 (d, J = 13.2 Hz, 4H), 2.33 (d, J = 9.1 Hz, 3H), 2.72-3.05 (m, 6H), 3.55 (dd, J = 10.9, 3.9 Hz, 1H), 3.67-3.84 (m, 2H), 3.92 (br s, 1H ), 4.30 (br s, 1H), 4.70 (br s, 1H), 4.99 (d, J = 7.0 Hz, 0.4H), 6.08-6.21 (m, 0.6H), 7.20-7.70 (m, 3H), 8.24-8.44 (m, 1H), 9.19 (s, 0.6H), 10.93 (br s, 0.4H).
LCMS (ESI) m / z 620 [M + H] ⁺ , t _R = 1.21 min, mode N.
Step 5-2-4: Using a method similar to that of Step 1-2-8, the title compound (32 mg, colorless solid) was obtained from 43 mg (43 mg).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.56 min, mode N.

Example 5-3: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-methyl-3-phenylpyrazolo [1,5-a] pyrimidine 2-yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 5-3-1: Compound (60) obtained in Step 5-2-2 mg) in 1,4-dioxane / water mixed solution (3.3 mL, 10/1; v / v), phenylboronic acid (30 mg), Pd ₂ (dba) ₃ (7.5 mg), TFP (11 mg) , Cs ₂ CO ₃ (80 mg) was added, and the mixture was stirred at 90 ° C. for 2 hr. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v) and tert-butyl [(3S) -1- (2-{(1S) -1 -[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-methyl-3-phenylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidine- 3-yl] carbamate (25 mg, colorless amorphous) was obtained.
LCMS (ESI) m / z 682 [M + H] ⁺ , t _R = 0.82 min, mode N.
Step 5-3-2: The title compound (28 mg, colorless solid) was obtained from the compound (34 mg) obtained in Step 5-3-1 using the same method as in Step 1-2-8. .
LCMS (ESI) m / z 582 [M + H] ⁺ , t _R = 0.62 min, mode N.

Example 5-4: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -3- (4-hydroxybut-1-in-1-yl)- Synthesis Step 5-4-1: Step 5-2 of 6-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide -2 compound (50 mg) in DMF / Et ₃ N mixed solution (4.5 mL, 2/1; v / v) was added 4-hydroxy-1-butyne (14 mg), PdCl ₂ (Ph ₃ P) ₂ (4.8 mg), CuI (1.3 mg), Ph ₃ P (3.6 mg), and HMDS (22 μL) were added, and the mixture was stirred at 110 ° C. for 2 hours. The reaction solution was poured into water and extracted with EtOAc. The organic layer was washed with Brine, dried and filtered with MgSO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 80 / 20-0 / 100; v / v) and tert-butyl {(3S) -1- [2-{(1S) -1 -[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -3- (4-hydroxybut-1-in-1-yl) -6-methylpyrazolo [1,5 -a] pyrimidin-5-yl] pyrrolidin-3-yl} carbamate (12 mg, colorless amorphous) was obtained.
Step 5-4-2: Using the same method as in Step 1-2-8, the title compound (3.0 mg, colorless solid) was obtained from the compound (12 mg) obtained in Step 5-4-1. .
LCMS (ESI) m / z 574 [M + H] ⁺ , t _R = 0.53 min, mode N.

Example 5-5: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] pyrazolo [1,5-a] pyrimidin-2-yl} ethyl] -5 -Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide hydrochloride synthesis step 1-2-2, step 1-1-5, step 1-1-7, step 1-1-8, step Using the same method as in 1-2-5 and step 1-2-8, the title compound (147 mg, 147 mg,) was obtained from the compound (1.00 g) obtained in step 1-1-3 and dimethyluracil (700 mg). A colorless solid was obtained.
LCMS (ESI) m / z 492 [M + H] ⁺ , t _R = 0.92 min, mode H.

Example 5-6: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -7-methylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 1-1-4, Step 1-1-5, Step 1-1-7, Step 1-1 8. Using the same method as in Step 1-2-5 and Step 1-2-8, the compound obtained in Step 1-1-3 (1.31 g) and ethyl 3-ethoxy-2-butenoate (1.55 g ) Afforded the title compound (65.0 mg, colorless solid).
LCMS (ESI) m / z 506 [M + H] ⁺ , t _R = 0.89 min, mode H.

Example 5-7: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-ethylpyrazolo [1,5-a] pyrimidin-2-yl} ethyl ] -5-Chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 5-7-1: EtOH (8.0 mg) of the compound obtained in Step 1-1-3 (390 mg) To the solution, ethyl (2E) -2- (methoxymethylidene) butanoate (380 mg) and 28% NaOMe / MeOH solution (1.1 mL) were added, and the mixture was stirred at 90 ° C. for 21 hours. EtOAc was added to the reaction solution, and a liquid separation operation was performed with a saturated aqueous NaHCO ₃ solution. The aqueous layer was separated using Brine and MgSO ₄ , and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane / EtOAc = 70/30 to 35/65; v / v), and tert-butyl [(1S) -1- (6-ethyl-5-oxo- 4,5-Dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamate (96 mg, brown oil) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.23 (t, J = 7.4 Hz, 3H), 1.50 (s, 9H), 1.52 (d, J = 7.0 Hz, 3H), 2.50-2.55 (m, 2H), 2.67 (br s, 3H), 5.25-5.65 (m, 1H), 5.75 (s, 1H), 7.96 (s, 1H), 9.97 (br s, 1H).
LCMS (ESI) m / z 321 [M + H] ⁺ , t _R = 0.86 min, mode N.
Step 5-7-2: Using a method similar to that of Step 1-1-5, from the compound (92 mg) obtained in Step 5-7-1, 2-{(1S) -1-[(tert -Butoxycarbonyl) (methyl) amino] ethyl} -6-ethylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (100 mg, brown oil) was obtained.
Step 5-7-3: Using a method similar to that of Step 1-2-3, from the compound (0.10 g) obtained in Step 5-7-2, 6-ethyl-2-[(1S) -1 -(Methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate hydrochloride (90 mg, pale yellow substance) was obtained.
Step 5-7-4: Using a method similar to that of Step 1-1-8, from the compound obtained in Step 5-7-3 (90 mg), 2-{(1S) -1-[{5 -Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-ethylpyrazolo [1,5-a] pyrimidin-5-yl trifluoromethanesulfonate (65 mg, white solid) was obtained. It was.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.32-1.40 (m, 3H), 1.65-1.75 (m, 3H), 2.67 (s, 2H), 2.73-2.86 (m, 4H), 2.96 (s , 2H), 3.06 (s, 1H), 4.97-5.04 (m, 0.4H), 6.31 (q, J = 7.2 Hz, 0.6H), 6.42-6.48 (m, 1H), 7.24-7.42 (m, 2H ), 7.62 (d, J = 8.3 Hz, 0.4H), 7.72 (d, J = 8.7 Hz, 0.6H), 8.80 (s, 0.4H), 8.95 (s, 0.6H), 9.10 (s, 0.6H ), 10.43 (br s, 0.4H).
Step 5-7-5: Using a method similar to that of Step 1-2-5, from the compound (58 mg) obtained in Step 5-7-4, tert-butyl [(3S) -1- (2 -{(1S) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-ethylpyrazolo [1,5-a] pyrimidin-5-yl) pyrrolidine -3-yl] carbamate (71 mg, colorless solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.26-1.30 (m, 3H), 1.45 (br s, 9H), 1.61 (d, J = 7.0 Hz, 2H), 1.65 (d, J = 7.4 Hz , 1H), 1.88-1.96 (m, 1H), 2.18-2.26 (m, 1H), 2.64 (s, 1H), 2.69-2.78 (m, 2H), 2.82 (s, 2H), 2.95 (s, 1H ), 3.03 (s, 2H), 3.48 -3.55 (m, 1H), 3.65-3.82 (m, 2H), 3.87-3.94 (m, 1H), 4.30 (br s, 1H), 4.66 (br s, 1H ), 4.87-4.93 (m, 0.6H), 5.97-6.04 (m, 1H), 6.19-6.27 (m, 0.4H), 7.24-7.40 (m, 2H), 7.62 (d, J = 8.7 Hz, 0.6 H), 7.69 (d, J = 9.1 Hz, 0.4H), 8.44 (s, 0.6H), 8.70 (s, 0.4H), 9.41 (s, 0.4H), 11.13 (br s, 0.6H).
Step 5-7-6: Using the same method as in Step 1-2-8, Step 5-7-5: Obtaining in Step 5-7-4 using the same method as in Step 1-2-5 The title compound (60 mg, white solid) was obtained from the compound (69 mg) obtained in the obtained compound (58 mg).
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 1.21 (t, J = 7.2 Hz, 3H), 1.52-1.62 (m, 3H), 2.01-2.11 (m, 1H), 2.21-2.31 (m , 1H), 2.57-2.63 (m, 1.5H), 2.69-2.80 (m, 3.5H), 2.99-3.09 (m, 3H), 3.65-3.76 (m, 2H), 3.81-3.92 (m, 3H) , 4.77-4.84 (m, 0.5H), 5.95 (q, J = 7.4 Hz, 0.5H), 6.08-6.18 (m, 1H), 7.44-7.57 (m, 3H), 8.25-8.44 (m, 3H) , 8.53 (s, 0.5H), 9.26 (s, 0.5H).
LCMS (ESI) m / z 520 [M + H] ⁺ , t _R = 0.57 min, mode N.

Example 5-8: N-[(1S) -1- {5-[(3S) -3-aminopyrrolidin-1-yl] -6-cyclopropylpyrazolo [1,5-a] pyrimidine-2- Yl} ethyl] -5-chloro-N-methyl-2-[(methylsulfonyl) amino] benzamide Hydrochloride Synthesis Step 5-8-1: Using a method similar to Step 1-1-4, Step 1 From the compound (350 mg) obtained in 1-3, and (E) -ethyl 2-cyclopropyl-3-methoxyacrylate (370 mg), tert-butyl [(1S) -1- (6-cyclopropyl- 5-Oxo-4,5-dihydropyrazolo [1,5-a] pyrimidin-2-yl) ethyl] (methyl) carbamate (250 mg, pale yellow amorphous) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.59-0.64 (m, 2H), 0.94-1.01 (m, 2H), 1.46-1.54 (m, 12H), 1.88-1.98 (m, 1H), 2.66 (br s, 3H), 5.26-5.62 (m, 1H), 5.78 (br s, 1H), 7.81 (s, 1H), 10.61 (br s, 1H).
LCMS (ESI) m / z 333 [M + H] ⁺ , t _R = 0.88 min, mode N.
Step 5-8-2: Using a method similar to that of Step 1-2-3, from the compound (240 mg) obtained in Step 5-8-1, 6-cyclopropyl-2-[(1S)- 1- (Methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5 (4H) -one hydrochloride (190 mg, pale yellow solid) was obtained.
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.70-0.76 (m, 2H), 0.79-0.85 (m, 2H), 1.54 (d, J = 7.0 Hz, 3H), 1.77-1.84 (m , 1H), 2.46 (t, J = 5.2 Hz, 3H), 4.32-4.41 (m, 1H), 6.03 (s, 1H), 8.15 (s, 1H), 9.13 (br s, 1H), 9.30 (br s, 1H), 12.29 (s, 1H).
LCMS (ESI) m / z 233 [M + H] ⁺ , t _R = 0.39 min, mode H.
Step 5-8-3: Using a method similar to that of Step 1-2-4, from the compound (190 mg) obtained in Step 5-8-2, (1S) -1- (5-chloro-6 -Cyclopropylpyrazolo [1,5-a] pyrimidin-2-yl) -N-methylethanamine hydrochloride (200 mg, brown oil) was obtained.
LCMS (ESI) m / z 251 [M + H] ⁺ , t _R = 0.75 min, mode H.
Step 5-8-4: Using a method similar to that in Step 1-2-5, from the compound (200 mg) obtained in Step 5-8-3, tert-butyl [(3S) -1- {6 -Cyclopropyl-2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidin-5-yl} pyrrolidin-3-yl] carbamate (240 mg, brown solid) was obtained. .
¹ H NMR (600 MHz, CDCl ₃ , δ): 0.67-0.75 (m, 2H), 0.93-1.01 (m, 2H), 1.42-1.50 (m, 12H), 1.88-1.98 (m, 2H), 2.18 -2.27 (m, 1H), 2.40 (s, 3H), 3.71-3.80 (m, 1H), 3.81-3.97 (m, 3H), 4.03-4.11 (m, 1H), 4.31 (br s, 1H), 4.68 (br s, 1H), 6.03 (s, 1H), 8.07 (s, 1H).
LCMS (ESI) m / z 401 [M + H] ⁺ , t _R = 0.55 min, mode N.
Step 5-8-5: Using a method similar to that of Step 1-2-7, from the compound obtained in Step 5-8-4 (20 mg), tert-butyl [(3S) -1- (2 -{(1S) -1-[{5-Chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} -6-cyclopropylpyrazolo [1,5-a] pyrimidine-5- Yl) pyrrolidin-3-yl] carbamate (24 mg, white solid) was obtained.
LCMS (ESI) m / z 632 [M + H] ⁺ , t _R = 1.21 min, mode N.
Step 5-8-6: Using a method similar to that of Step 1-2-8, the title compound (24 mg, white solid) was obtained from the compound (24 mg) obtained in Step 5-8-5. .
¹ H NMR (600 MHz, DMSO-d ₆ , δ): 0.72-1.00 (m, 4H), 1.53-1.60 (m, 3H), 2.00-2.11 (m, 1H), 2.21-2.34 (m, 1H) , 2.59 (s, 1.5H), 2.74 (br s, 1.5H), 3.00-3.07 (m, 3H), 3.59-4.09 (m, 5H), 4.75-4.83 (m, 0.5H), 5.89-5.97 ( m, 0.5H), 6.05-6.13 (m, 1H), 7.44-7.57 (m, 3H), 8.15-8.36 (m, 3H), 8.47 (s, 0.5H), 9.22 (s, 0.5H).
LCMS (ESI) m / z 532 [M + H] ⁺ , t _R = 0.61 min, mode N.

Example 5-9: ethyl 5-[(3S) -3-aminopyrrolidin-1-yl] -2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (Methyl) amino] ethyl} pyrazolo [1,5-a] pyrimidine-6-carboxylate hydrochloride synthesis step 5-9-1: using the same method as in step 5-7-1, step 1-1 2-((1S) -1-[(tert-butoxycarbonyl) (methyl) amino] ethyl} -5-oxo from the compound (1.0 g) obtained in -3 and diethyl ethoxymethylenemalonate (1.6 mL) -4,5-dihydropyrazolo [1,5-a] pyrimidine-6-carboxylate (210 mg, brown solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.39 (t, J = 7.2 Hz, 3H), 1.49 (s, 9H), 1.53 (d, J = 7.0 Hz, 3H), 2.68 (br s, 3H ), 4.40 (q, J = 7.0 Hz, 2H), 5.28-5.68 (m, 1H), 5.92 (br s, 1H), 9.00 (s, 1H), 10.72 (br s, 1H).
LCMS (ESI) m / z 365 [M + H] ⁺ , t _R = 0.84 min, mode N.
Step 5-9-2: Using a method similar to that of Step 1-2-3, from the compound (200 mg) obtained in Step 5-9-1, ethyl 2-[(1S) -1- (methyl Amino) ethyl] -5-oxo-4,5-dihydropyrazolo [1,5-a] pyrimidine-6-carboxylate hydrochloride (170 mg, brown solid) was obtained.
LCMS (ESI) m / z 265 [M + H] ⁺ , t _R = 0.35 min, mode H.
Step 5-9-3: Using a method similar to that in Step 1-2-4, from the compound obtained in Step 5-9-2 (170 mg), ethyl 5-chloro-2-[(1S)- 1- (Methylamino) ethyl] pyrazolo [1,5-a] pyrimidine-6-carboxylate hydrochloride (160 mg, brown oil) was obtained.
LCMS (ESI) m / z 283 [M + H] ⁺ , t _R = 0.68 min, mode H.
Step 5-9-4: Using a method similar to that of Step 1-2-5, from the compound (160 mg) obtained in Step 5-9-3, ethyl 5-{(3S) -3-[( tert-Butoxycarbonyl) amino] pyrrolidin-1-yl} -2-[(1S) -1- (methylamino) ethyl] pyrazolo [1,5-a] pyrimidine-6-carboxylate (230 mg, brown solid) Got.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.38 (t, J = 7.2 Hz, 3H), 1.41-1.46 (m, 12H), 1.92 (br s, 1H), 2.16-2.24 (m, 1H) , 2.40 (s, 3H), 3.27-3.34 (m, 1H), 3.53- 3.61 (m, 1H), 3.65-3.79 (m, 2H), 4.29 (br s, 1H), 4.36 (q, J = 7.3 Hz, 2H), 4.67 (br s, 1H), 6.05 (s, 1H), 8.82 (s, 1H).
LCMS (ESI) m / z 433 [M + H] ⁺ , t _R = 0.53 min, mode N.
Step 5-9-5: Using a method similar to that of Step 1-2-7, from the compound (220 mg) obtained in Step 5-9-4, ethyl 5-{(3S) -3-[( tert-butoxycarbonyl) amino] pyrrolidin-1-yl} -2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} pyrazolo [1 , 5-a] pyrimidine-6-carboxylate (200 mg, white solid) was obtained.
¹ H NMR (600 MHz, CDCl ₃ , δ): 1.42-1.46 (m, 15H), 1.63 (d, J = 7.0 Hz, 1H), 1.66 (d, J = 7.4 Hz, 2H), 1.92 (br s , 1H), 2.16-2.27 (m, 1H), 2.67 (s, 2H), 2.83 (s, 1H), 2.94 (s, 2H), 3.04 (s, 1H), 3.30-3.37 (m, 1H), 3.54-3.62 (m, 1H), 3.64-3.76 (m, 2H), 4.29 (br s, 1H), 4.34-4.43 (m, 2H), 4.65 (br s, 1H), 4.88-4.97 (m, 0.4 H), 5.99-6.05 (m, 1H), 6.20-6.27 (m, 0.6H), 7.22-7.41 (m, 2H), 7.61 (d, J = 8.3 Hz, 0.4H), 7.70 (d, J = 9.1 Hz, 0.6H), 9.10-9.19 (m, 1H), 9.45 (s, 0.6H), 10.70 (br s, 0.4H).
LCMS (ESI) m / z 664 [M + H] ⁺ , t _R = 1.17 min, mode N.
Step 5-9-6: Using a method similar to that of Step 1-2-8, the title compound (10 mg, white solid) was obtained from the compound (10 mg) obtained in Step 5-9-5.
LCMS (ESI) m / z 564 [M + H] ⁺ , t _R = 0.59 min, mode N.

Example 5-10: 5-[(3S) -3-aminopyrrolidin-1-yl] -2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} ( Methyl) amino] ethyl} pyrazolo [1,5-a] pyrimidine-6-carboxylic acid hydrochloride synthesis step 5-10-1: THF (1.0 mg) of the compound (100 mg) obtained in step 5-9-5 MeOH (0.5 mL) and 2M aqueous KOH solution (150 μL) were added to the solution, and the mixture was stirred at room temperature for 3 hours. A saturated aqueous NH ₄ Cl solution was added to the reaction solution, and extraction was performed with CHCl ₃ . After washing the organic layer with Brine, the aqueous layer was separated using Phase Separator, and the organic layer was concentrated under reduced pressure. After purification by OH type silica gel column chromatography (mobile phase: CHCl ₃ / MeOH = 100/0 to 80/20; v / v), purification by reverse phase preparative HPLC was performed, and 5-[(3S) -3- Aminopyrrolidin-1-yl] -2-{(1S) -1-[{5-chloro-2-[(methylsulfonyl) amino] benzoyl} (methyl) amino] ethyl} pyrazolo [1,5-a] pyrimidine -6-carboxylic acid hydrochloride (60 mg, white solid) was obtained.
LCMS (ESI) m / z 636 [M + H] ⁺ , t _R = 0.81 min, mode N.
Step 5-10-2: Using the same method as in Step 1-2-8, the title compound (9.0 mg, white solid) was obtained from the compound (8.0 mg) obtained in Step 5-10-1. .
LCMS (ESI) m / z 536 [M + H] ⁺ , t _R = 0.53 min, mode N.
The structural formulas of the compounds obtained in Examples 1-1 to 1-12 are shown in Table 2, the structural formulas of the compounds obtained in Examples 2-1 to 2-78 are shown in Tables 3-1 to 3-8, The structural formulas of the compounds obtained in Examples 3-1 to 3-78 are shown in Tables 4-1 to 4-8, and the structural formulas of the compounds obtained in Examples 4-1 to 4-13 are shown in Table 5. Table 6 shows the structural formulas of the compounds obtained in Examples 5-1 to 5-10.

Test Example 1 (In vitro anti-RSV activity evaluation test)
The antiviral activity against RSV of the compounds of the present invention was determined by cytopathic effect (CPE) inhibition test.
Hep2 cells were obtained from DS Pharma Biomedical Co., Ltd. and cultured in a growth medium (MEM medium supplemented with 10% fetal bovine serum and gentamicin). RSV A2 strain was obtained from ATCC, amplified with Hep2 cells as a host, and stored at −80 ° C. Prior to testing, the appropriate dilution factor of RSV A2 strain virus solution that produces the desired cytopathic effect in Hep2 cells was determined.
For the CPE inhibition test, Hep2 cells were seeded in a 96-well plate at a density of 1.0 × 10 ⁴ cells / well one day before the test. A dilution series of the compound was prepared in a separate 96-well plate using assay medium (MEM medium supplemented with 2% fetal bovine serum and streptomycin / penicillin), and added to the cells from which the growth medium had been removed at 50 μL / well. Subsequently, RSV A2 strain virus solution appropriately diluted with assay medium was added to a test plate containing cells and compounds at 50 μL / well. Each plate was provided with wells of infected untreated cells and uninfected cells as 0% and 100% virus inhibition controls. After infection with RSV, test plates were cultured for 4 days at 37 ° C. and 5% CO ₂ . After culture, cytopathic effect by RSV was determined using XTT cell proliferation assay kit (Biological Industries, Cosmo Bio). Absorbance at two wavelengths (450 and 655 nm) was measured using a microplate reader, and the absorbance at 655 nm was subtracted from the absorbance at 450 nm to eliminate the effect of non-specific absorption. The compound concentration that inhibited CPE by 50% (EC ₅₀ ) was determined by non-linear regression.
EC ₅₀ values in the compounds of the present invention are classified as shown below and shown in Tables 2 to 6.
A: EC ₅₀ <100 nM, B: 100 nM ≤ EC ₅₀ <1000 nM, C: EC ₅₀ ≥ 1000 nM. Furthermore, EC ₅₀ values are shown in Table 7 for some of the compounds of the present invention.

  The compound (I) of the present invention or a pharmaceutically acceptable salt thereof has anti-RSV activity and is useful for prevention of infections involving viruses of the Pneumovirus subfamily including respiratory syncytial virus (RSV). It can be used as a medicine or therapeutic agent.

Claims (10)

Formula (I),

[Wherein in formula (I),
A ¹ represents a hydrogen atom or a C _1-6 alkyl group,
A ² represents a hydrogen atom, a C _1-6 alkyl group, a C _3-6 cycloalkyl group, a carboxy group, or a C _1-6 alkoxycarbonyl group,
A ³ represents a halogen atom, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a heterocyclyloxy group, a C _1-6 alkylamino group. A group {wherein the C _1-6 alkylamino group is an amino group and a C _3-6 cycloalkyl group (wherein the C _3-6 cycloalkyl group may be substituted with one amino group); ) May be substituted with the same or different 1 to 2 substituents selected from the group consisting of: }, A C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group may be substituted with one amino group), or a heterocyclyl group (wherein the heterocyclyl group is , A halogen atom, a hydroxyl group, an amino group, and a C _1-6 alkyl group substituted with one amino group may be substituted with 1 to 3 identical or different substituents. Show
A ⁴ represents a hydrogen atom, a halogen atom, a C _1-6 alkyl group, a C _2-6 alkynyl group (wherein the C _2-6 alkynyl group may be substituted with one hydroxyl group), or Represents an aryl group,
R ¹ and R ² are the same or different and are each a hydrogen atom, a C _1-6 alkyl group (wherein the C _1-6 alkyl group may be substituted with one hydroxyl group), or C _{Represents a 3-6} cycloalkyl group,
Or R ¹ and R ² may be taken together with adjacent carbon atoms to form a C _3-6 cycloalkane;
R ³ is a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, an amino group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 halogen atoms may be substituted), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group is 1 to And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of an aryl group and a heteroaryl group. },
Y is an aryl group, a heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group), a C _1-6 alkylsulfonylamino group (wherein the C _1-6 alkylsulfonyl group) The sulfonylamino group may be substituted with 1 to 3 halogen atoms.), An arylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group, an aryl group, and a heteroaryl group. It may be substituted with 1 to 3 identical or different substituents. }, Or a heterocyclyl group, wherein the heterocyclyl group may be substituted with one oxo,
Or, Y represents any structure of the following formula group (II),

Ring Q represents an aromatic hydrocarbon ring or a heteroaromatic ring (wherein the aromatic hydrocarbon ring and the heteroaromatic ring may be substituted with one C _1-6 alkyl group),
When W is a single bond, Z represents the formula (CH ₂ ) n or the formula CH ₂ NR ⁷ ,
n represents an integer of 2 to 4,
When W is of the formula CH ₂ , Z represents the formula CH ₂ CH ₂ ;
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are the same or different and each represents a hydrogen atom, a halogen atom, or a C _1-6 alkyl group,
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or a C _1-6 alkyl group,
Or R ⁴ and R ⁵ together with adjacent carbon atoms are C _3-6 cycloalkane {where C _3-6 cycloalkane is oxo, hydroxyl, C _2-6 alkanoylamino group (here And the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And one substitution selected from the group consisting of C _1-6 alkylsulfonylamino groups It may be substituted with a group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ represents a hydrogen atom, an amino group, a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a C _3-6 cycloalkylcarbonyl group, a C _1-6 alkylsulfonyl group, and a C _1- alkyl group). Which may be substituted with one substituent selected from the group consisting of ₆ alkylsulfonylamino groups), a C _1-6 alkylamino group (wherein the C _1-6 alkylamino group is one C _1-6 alkylsulfonyl group may be substituted), C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is an amino group, a sulfamoyl group, a C _3-6 cycloalkyl group, C _1-6 alkoxy group, C _1-6 alkylamino group, C _2-6 alkanoylamino group, C _1-6 alkylsulfonylamino group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, aryl Sulfonyl group, aryl group, and heteroaryl May be substituted with one substituent selected from the group consisting of.), By C _1-6 alkoxycarbonylamino group (wherein the C _1-6 alkoxycarbonylamino group, substituted with one aryl group Or a C _1-6 alkylsulfonylamino group,
R ⁷ represents a hydrogen atom or a C _1-6 alkyl group,
R ⁸ is carbamoyl group, amidino group, C (wherein said C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group.) _2-6 alkanoyl group, C _{1 A -6} alkoxycarbonyl group (wherein the C _1-6 alkoxycarbonyl group may be substituted with one aryl group), or a C _1-6 alkylsulfonyl group. ]
Or a pharmaceutically acceptable salt thereof. In the above formula (I),
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group (wherein the C _1-6 alkyl group may be substituted with one hydroxyl group), or a C _3-6 cycloalkyl group,
Or R ¹ and R ² together with adjacent carbon atoms may form a C _3-6 cycloalkane,
The compound according to claim 1, or a pharmaceutically acceptable salt thereof. In the above formula (I),
Y is an aryl group, heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group), a C _1-6 alkylsulfonylamino group (wherein the C _1-6 alkylsulfonyl group) The sulfonylamino group may be substituted with 1 to 3 halogen atoms.), An arylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group, an aryl group, and a heteroaryl group. It may be substituted with 1 to 3 identical or different substituents. Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one oxo).
The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof. In the above formula (I),
A ¹ is a hydrogen atom or a C _1-6 alkyl group,
A ² is a hydrogen atom, a C _1-6 alkyl group, or a C _3-6 cycloalkyl group,
A ³ is a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a C _1-6 alkylamino group (wherein the C _{1-6 1-6} alkylamino group may be substituted with one amino group.), C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group is one amino group) Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one amino group),
A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group or a C _3-6 cycloalkyl group,
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 May be substituted with 1 halogen atom), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group has 1 to 2 And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of aryl groups. },
Y is an aryl group, heteroaryl group {wherein the aryl group and heteroaryl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group ( Here, the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), C _1-6 alkylsulfonylamino group, arylsulfonylamino group, and heteroaryl group May be substituted with the same or different 1 to 3 substituents selected from the group consisting of Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one oxo), or a pharmaceutically acceptable salt thereof. . In the above formula (I),
A ¹ is a hydrogen atom,
A ² is a methyl group, an ethyl group, or a cyclopropyl group;
A ³ is any structure of the following formula group (III),

A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a methyl group, an ethyl group, a propyl group, or a cyclopropyl group;
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 A C _1-6 alkylsulfonylamino group, and a heterocyclyl group (wherein the heterocyclyl group may be substituted with 1 to 2 oxo groups). It may be substituted with 1 to 3 identical or different substituents selected from the group. },
Y is a phenyl group or a pyridyl group {wherein the phenyl group and the pyridyl group are a halogen atom, an amino group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-6 alkanoylamino group (where The C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), C _1-6 alkylsulfonylamino group, phenylsulfonylamino group, and C _1-6 alkyl It may be substituted with 1 to 3 identical or different substituents selected from the group consisting of sulfonyl groups. } The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof. In the above formula (I),
Y is any structure of the above formula group (II),
Ring Q is an aromatic hydrocarbon ring or a heteroaromatic ring (wherein the aromatic hydrocarbon ring and the heteroaromatic ring may be substituted with one C _1-6 alkyl group),
When W is a single bond, Z is the formula (CH ₂ ) n or the formula CH ₂ NR ⁷ ;
n is an integer of 2 to 4,
When W is of formula CH ₂ , Z is of formula CH ₂ CH ₂ ;
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are the same or different and each is a hydrogen atom, a halogen atom, or a C _1-6 alkyl group,
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or a C _1-6 alkyl group,
Or R ⁴ and R ⁵ together with an adjacent carbon atom are C _3-6 cycloalkane {where C _3-6 cycloalkane is an oxo, hydroxyl group, C _2-6 alkanoylamino group (here And the C _2-6 alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And one substitution selected from the group consisting of C _1-6 alkylsulfonylamino groups It may be substituted with a group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is a hydrogen atom, an amino group, a C _1-6 alkyl group (wherein the C _1-6 alkyl group is a C _3-6 cycloalkylcarbonyl group, a C _1-6 alkylsulfonyl group, and a C _1- Which may be substituted with one substituent selected from the group consisting of ₆ alkylsulfonylamino groups), a C _1-6 alkylamino group (wherein the C _1-6 alkylamino group is one C _1-6 alkylsulfonyl group may be substituted), C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is an amino group, a sulfamoyl group, a C _3-6 cycloalkyl group, C _1-6 alkoxy group, C _1-6 alkylamino group, C _2-6 alkanoylamino group, C _1-6 alkylsulfonylamino group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, aryl Sulfonyl group, aryl group, and heteroaryl May be substituted with one substituent selected from the group consisting of.), By C _1-6 alkoxycarbonylamino group (wherein the C _1-6 alkoxycarbonylamino group, substituted with one aryl group Or a C _1-6 alkylsulfonylamino group,
R ⁷ is a hydrogen atom or a C _1-6 alkyl group,
R ⁸ is a carbamoyl group, an amidino group, a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group), C _{1 The -6} alkoxycarbonyl group (wherein the C _1-6 alkoxycarbonyl group may be substituted with one aryl group) or a C _1-6 alkylsulfonyl group. Or a pharmaceutically acceptable salt thereof. In the above formula (I),
A ¹ is a hydrogen atom or a C _1-6 alkyl group,
A ² is a hydrogen atom, a C _1-6 alkyl group, or a C _3-6 cycloalkyl group,
A ³ is a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group may be substituted with one amino group), a C _1-6 alkylamino group (wherein the C _{1-6 1-6} alkylamino group may be substituted with one amino group.), C _3-6 cycloalkylamino group (wherein the C _3-6 cycloalkylamino group is one amino group) Or a heterocyclyl group (wherein the heterocyclyl group may be substituted with one amino group),
A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a C _1-6 alkyl group or a C _3-6 cycloalkyl group,
R ³ is a C _1-6 alkyl group {wherein the C _1-6 alkyl group is a halogen atom, a hydroxyl group, a C _1-6 alkoxy group (wherein the C _1-6 alkoxy group is 1 to 3 May be substituted with 1 halogen atom), an aryloxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylsulfonyl group, a heterocyclyl group (wherein the heterocyclyl group has 1 to 2 And may be substituted with 1 to 3 identical or different substituents selected from the group consisting of aryl groups. },
Y is any structure of the following formula group (IV),

When W is a single bond, Z is the formula (CH ₂ ) n;
n is an integer of 2 to 4,
B ¹ , B ² , B ³ , B ⁴ , and B ⁵ are each a hydrogen atom,
B ⁶ , B ⁷ , B ⁸ and B ⁹ are the same or different and each is a hydrogen atom or a C _1-6 alkyl group,
R ⁴ and R ^5, with C _3-6 cycloalkane {here together with the adjacent carbon atoms, the C _3-6 cycloalkane, C _2-6 at alkanoylamino group (wherein said C _{2- The 6} alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group.), And may be substituted with one substituent selected from the group consisting of C _1-6 alkylsulfonylamino groups. Good. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is an amino group, with a C _1-6 alkyl group (wherein, the C _1-6 alkyl groups one selected from the group consisting of C _1-6 alkylsulfonyl group and a C _1-6 alkylsulfonylamino group A C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is a sulfamoyl group, a C _3-6 cycloalkyl group, a C _1-6 alkylsulfonylamino group). group, C _1-6 alkylsulfonyl group, C _1-6 alkylaminosulfonyl group, may be substituted with an arylsulfonyl group 1 substituents selected from the group consisting of and aryl radicals,.), C _1-6 An alkoxycarbonylamino group, or a C _1-6 alkylsulfonylamino group,
R ⁸ represents a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group), or a C _1-6 alkylsulfonyl group The compound according to any one of claims 1, 2, and 6, or a pharmaceutically acceptable salt thereof. In the above formula (I),
A ¹ is a hydrogen atom,
A ² is a methyl group,
A ³ is a structure of the following formula (V),

A ⁴ is a hydrogen atom,
R ¹ is a hydrogen atom,
R ² is a methyl group or an ethyl group,
R ³ is a methyl group,
Y is any structure of the above formula group (IV),
When W is a single bond, Z is the formula (CH ₂ ) n;
n is an integer of 2 to 4,
B ¹ , B ² , B ³ , B ⁴ , B ⁵ , B ⁶ , B ⁷ , B ⁸ , and B ⁹ are hydrogen atoms;
R ⁴ and R ^5, with C _3-6 cycloalkane {here together with the adjacent carbon atoms, the C _3-6 cycloalkane, C _2-6 at alkanoylamino group (wherein said C _{2- The 6} alkanoylamino group may be substituted with one C _1-6 alkylsulfonyl group. Furthermore, the C _3-6 cycloalkane may have one formula CH ₂ in the ring substituted with the formula NR ⁸ ,
R ⁶ is a C _2-6 alkanoylamino group (wherein the C _2-6 alkanoylamino group is selected from the group consisting of a sulfamoyl group, a C _1-6 alkylsulfonyl group, and a C _1-6 alkylaminosulfonyl group) And a C _1-6 alkoxycarbonylamino group, or a C _1-6 alkylsulfonylamino group,
R ⁸ is a C _2-6 alkanoyl group (wherein the C _2-6 alkanoyl group may be substituted with one C _1-6 alkylsulfonyl group). Or the compound according to any one of 7 or a pharmaceutically acceptable salt thereof. The pharmaceutical which contains the compound or its pharmaceutically acceptable salt of any one of Claims 1-8 as an active ingredient. Infectious disease involving pneumovirus subfamily viruses including respiratory syncytial virus (RSV), comprising as an active ingredient the compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof. Preventive or therapeutic drug.