BR112018000698B1 - RET INHIBITORS, THEIR USES, PHARMACEUTICAL COMPOSITIONS AND ANTITUMOR AGENT - Google Patents

Abstract

The purpose of the present invention is to provide a novel RET inhibitor and a prophylactic or therapeutic agent for diseases that can be prevented or treated with the aid of a RET inhibitory activity (e.g., malignant tumors) each of which contains, as an active ingredient, a compound that is not heretofore known to have RET inhibition activity, or a salt of the compound. A RET inhibitor containing, as an active ingredient, a compound represented by formula (I) [wherein A, R1 to R3, X and n are as defined in the description] or a salt thereof.

Description

Technical Field Cross Reference to Related Patent Applications

[001] The present application claims priority to Japanese Patent Application No. 2015-177073 filed on September 8, 2015, which is incorporated by reference in its entirety. The present invention relates to a new fused pyrimidine compound having RET inhibitory activity or a salt thereof, and to a pharmaceutical composition containing the compound or salt.

Background Technique

[002] Several protein kinases are present in vivo and are known to be involved in a wide range of functional regulations. RET is a receptor tyrosine kinase identified as one of the proto-oncogenes. RET binds to glial cell strain-derived neurotrophic factor (GDNF) and GDNF receptor to form a complex, which enables RET to perform physiological functions through intracellular phosphorylation signaling (Non-Patent Literature 1). One study reports that in normal tissues, RET contributes to kidney development and neurogenesis during fetal life (Non-Patent Literature 2). Some studies indicate that in cancers, such as lung cancer, thyroid cancer, breast cancer, pancreatic cancer, and prostate cancer, translocation, mutation, or overexpression of the RET gene enhances its activation to thereby contribute to growth. cellular, tumor formation, or tissue infiltration (Non-Patent Literature 3, 4, 5, 6, 7, and 8). Furthermore, RET is known to be an adverse prognostic factor in cancer, as indicated in some reports that RET translocation and its enhanced activation level are also inversely correlated with prognosis in cancer (Non-Patent Literature 9, 10, 11 , and 12).

[003] Therefore, an inhibitor capable of inhibiting RET activity is believed to be useful as a therapeutic agent for diseases associated with abnormally enhanced RET signaling pathways.

[004] It is believed, for example, that in cancers involving translocated, mutated, and overexpressed RET genes, the administration of a drug capable of specifically inhibiting RET selectively and intensively will suppress the proliferation of cancer cells and contribute to the treatment , prolonging life, and improving the quality of life of cancer patients.

[005] As an example of such compounds having RET inhibitory activity, PP1 is known (Non-Patent Literature 13). PP1 is known to exhibit high inhibitory activity against not only RET but also SRC (Non-Patent Literature 14), c-Kit, Bcr-Abl (Non-Patent Literature 15 and 16), and others. For example, as side effects, SRC inhibition can lead to abnormally enhanced bone formation, and LCK inhibition can suppress T cells (Non-Patent Literature 17 and 18). Since multikinase inhibitors inhibit not only RET, but also several signaling pathways, inhibition of cell growth and other functions, the inhibitors raise concerns about possible various side effects, which may require dose reduction or drug intervals, such as mode leading to insufficient RET inhibitory activity. From a side effect reduction perspective, there is a demand for a RET inhibitor having high inhibitory activity against RET, while exhibiting low inhibitory activity against other kinases.

Citation List Patent Literature

[006] Patent Literature 1: US Patent No. 5665721

[007] Patent Literature 2: WO 96/40686A1

[008] Non-Patent Literature

[009] Non-Patent Literature 1: Lois M. Mulligan, Nature Rev., 14(3): pp. 173-186, (2014)

[0010] Non-Patent Literature 2: Carlos F. Ibanez, Cold Spring Harb Perspect Biol., 5(2): pp. 1-10, (2013) Non-Patent Literature 3: Takashi Kohno, Nature Med., 18(3): pp. 375-377, (2012)

[0011] Non-Patent Literature 4: Massimo Santoro, Eur J Endo crinol., 155: pp. 645-653, (2006)

[0012] Non-Patent Literature 5: Marjan Zarif Yeganeh, Asian Pac J Cancer Prev., 16(6): pp. 2107-2117, (2015)

[0013] Non-Patent Literature 6: Albana Gattelli, EMBO Mol Med., 5: pp. 1335-1350, (2013)

[0014] Non-Patent Literature 7: Yoshinori Ito, Surgery, 138: pp. 788-794, (2005)

[0015] Non-Patent Literature 8: Dawn M. Dawson, J Natl Can cer Inst., 90(7): pp. 519-523, (1998)

[0016] Non-Patent Literature 9: Weijing Cai, Cancer, 119: pp. 1486-1494, (2013)

[0017] Non-Patent Literature 10: Rossella Elisei, J Clin Endo crinol Metab., 93(3): pp. 682-687, (2008)

[0018] Non-Patent Literature 11: Albana Gattelli, EMBO Mol Med., 5: pp. 1335-1350, (2013)

[0019] Non-Patent Literature 12: Q Zeng, J. Int. Med. Res., 36: pp. 656-664, (2008)

[0020] Non-Patent Literature 13: Francesca Carlomagno, Can cer Res., 62(4): pp. 1077-1082, (2002)

[0021] Non-Patent Literature 14: Johannes Waltenberger, Circ Res., 85(1): pp. 12-22, (1999)

[0022] Non-Patent Literature 15: Louise Tatton, J Biol Chem., 278(7): pp. 4847-4853, (2003)

[0023] Non-Patent Literature 16: Markus Warmuth, Blood. 101(2): pp. 664-672, (2003)

[0024] Non-Patent Literature 17: Carolyn Lowe, Proc Natl Acad Sci USA, 90(10): pp. 4485-4489, (1993)

[0025] Non-Patent Literature 18: Thierry Molina, Nature, 357(6374): pp. 161-164, (1992)

Summary of the Invention Technical problem

[0026] An object of the present invention is to provide a new RET inhibitor comprising, as an active ingredient, a compound or a salt thereof that has not been known to have RET inhibitory activity, and also to provide an agent for preventing or treat diseases (e.g., malignant tumors) that can be prevented or treated by RET inhibitory activity. Another object of the present invention is to provide a new compound or a salt thereof that selectively and potentially inhibits RET.

Solution to the Problem

[0027] The present inventors conducted extensive research to achieve the aforementioned objectives, and consequently discovered that the groups of compounds represented by formulas (I) and (I') below showed excellent inhibitory activity against RET and kinase selectivity, and were useful as a pharmaceutical preparation for treating RET-related diseases, such as malignant tumors. In this way, the present invention has been completed.

[0028] Specifically, the present invention provides a compound represented by formula (I) below or a salt thereof:

[0029] where A is pyrazolyl substituted by number n of R1;

[0030] R1 is

[0031] halogen,

[0032] cyan,

[0033] C1-C6 substituted or unsubstituted alkyl,

[0034] C3-C7 substituted or unsubstituted cycloalkyl,

[0035] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0036] a substituted or unsubstituted monocyclic or polycyclic saturated or unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[0037] R2 is

[0038] C1-C10 substituted or unsubstituted alkyl,

[0039] C3-C7 substituted or unsubstituted cycloalkyl,

[0040] C2-C6 substituted or unsubstituted alkenyl,

[0041] C3-C7 substituted or unsubstituted cycloalkenyl,

[0042] C4-C12 substituted or unsubstituted bridged cycloalkyl,

[0043] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0044] a substituted or unsubstituted monocyclic or polycyclic saturated or unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[0045] X is

[0046] N or

[0047] CR3, where R3 is

[0048] hydrogen,

[0049] halogen,

[0050] cyan,

[0051] C1-C6 substituted or unsubstituted alkyl,

[0052] C2-C6 substituted or unsubstituted alkenyl,

[0053] C2-C6 substituted or unsubstituted alkynyl,

[0054] C1-C6 substituted or unsubstituted alkoxy,

[0055] substituted or unsubstituted amino,

[0056] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0057] a substituted or unsubstituted monocyclic or polycyclic unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[0058] n is an integer from 0 to 3,

[0059] wherein when n is 2 or 3, R1 can be identical or different from each other.

[0060] The present invention also provides a compound represented by formula (I') below or a salt thereof:

[0061] where A is pyrazolyl substituted by number n of R1;

[0062] R1 is

[0063] halogen,

[0064] cyan,

[0065] C1-C6 substituted or unsubstituted alkyl,

[0066] C3-C7 substituted or unsubstituted cycloalkyl,

[0067] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0068] a substituted or unsubstituted monocyclic or polycyclic saturated or unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[0069] R2 is

[0070] C1-C10 substituted or unsubstituted alkyl,

[0071] C3-C4 substituted or unsubstituted cycloalkyl,

[0072] C2-C6 substituted or unsubstituted alkenyl,

[0073] C3-C4 substituted or unsubstituted cycloalkenyl,

[0074] C4-C12 substituted or unsubstituted bridged cycloalkyl,

[0075] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0076] a substituted or unsubstituted monocyclic or polycyclic saturated or unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[0077] X is

[0078] N or

[0079] CR3, where R3 is

[0080] hydrogen,

[0081] halogen,

[0082] cyan,

[0083] C1-C6 substituted or unsubstituted alkyl,

[0084] C2-C6 substituted or unsubstituted alkenyl,

[0085] C2-C6 substituted or unsubstituted alkynyl,

[0086] C1-C6 substituted or unsubstituted alkoxy,

[0087] substituted or unsubstituted amino,

[0088] C6-C14 substituted or unsubstituted aromatic hydrocarbon, or

[0089] a substituted or unsubstituted monocyclic or polycyclic unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[0090] n is an integer from 0 to 3,

[0091] where when n is 2 or 3, R1 can be identical or different from each other.

[0092] The present invention also provides a RET inhibitor comprising a compound represented by formula (I) or (I') above or a salt thereof as an active ingredient.

[0093] The present invention also provides a pharmaceutical composition comprising a compound represented by formula (I) or (I') above or a salt thereof.

[0094] The present invention also provides a pharmaceutical composition comprising a compound represented by formula (I) or (I') above or a salt thereof, wherein the pharmaceutical composition prevents or treats a disease that can be treated by inhibition of RET .

[0095] The present invention also provides an antitumor agent comprising a compound represented by formula (I) or (I') above or a salt thereof.

[0096] The present invention also provides an antitumor agent comprising a compound represented by formula (I) or (I') above or a salt thereof, wherein the antitumor agent treats a malignant tumor with enhanced RET activation.

[0097] The present invention also provides a compound represented by formula (I) or (I') above or a salt thereof for use in preventing or treating a malignant tumor.

[0098] The present invention also provides a compound represented by formula (I) or (I') above or a salt thereof for use in preventing or treating a malignant tumor, wherein the malignant tumor is a malignant tumor with activation highlighted from RET.

[0099] The present invention also provides the use of a compound represented by formula (I) or (I') above or a salt thereof to produce an antitumor agent.

[00100] The present invention also provides the use of a compound represented by formula (I) or (I') above or a salt thereof to produce an antitumor agent, wherein the antitumor agent is an antitumor agent for treating a malignant tumor with enhanced activation of RET.

[00101] The present invention also provides the use of a compound represented by formula (I) or (I') above or a salt thereof to produce a RET inhibitor.

[00102] The present invention also provides a method for preventing or treating a malignant tumor, comprising administering a compound represented by formula (I) or (I') above or a salt thereof to a mammal.

[00103] The present invention also provides a method for preventing or treating a malignant tumor, comprising administering a compound represented by formula (I) or (I') above or a salt thereof to a mammal, wherein the malignant tumor is a malignant tumor with enhanced RET activation.

[00104] The present invention also provides a method of inhibiting RET comprising administering a compound represented by formula (I) or (I') above or a salt thereof to a mammal.

[00105] Patent Literature 1 and 2 do not suggest RET inhibitory activity or antitumor effects.

[00106] Above-mentioned PP1 is known as a compound having RET inhibitory activity. In PP1, a p-toluyl group is attached to a fused ring pyrimidine skeleton; however, its structure is significantly different from the present invention in that PP1 does not have a continuous pyrazolyl group with an amide bond, which is the characteristic of the compound of the present invention. Furthermore, as shown in the Test Examples provided below, the compound or a salt thereof of the present invention has the characteristic of high RET selectivity, which is different from PP1.

Advantageous Effects of the Invention

[00107] The present invention can provide a new RET inhibitor and an agent for preventing or treating diseases (e.g., malignant tumors) that can be prevented or treated by RET inhibitory activity, using, as its active ingredients, compounds represented by formulas (I) and (I') or salts thereof, which have not been known for their RET inhibitory activity. In particular, a new compound represented by Formula (I') or a salt thereof, etc., are preferred.

[00108] It has been revealed that the compound or a salt thereof of the present invention has excellent selective RET inhibitory activity and a cancer cell growth inhibitory effect.

[00109] RET is known as an oncogene and known to be activated by translocation, mutation, or overexpression of the RET gene in many types of cancer (Non-Patent Literatures 3, 4, 5, 6, 7, and 8). Thus, the compound or a salt thereof of the present invention, both of which have a high RET inhibitory activity, are useful as an agent for preventing and/or treating cancer.

[00110] Furthermore, the compound or a salt thereof of the present invention selectively and potentially inhibits RET, rather than other kinases, such as SRC and LCK; therefore, side effects can be reduced, and improvements in safety can be expected.

[00111] Furthermore, the compound or a salt thereof of the present invention is advantageous in that it has excellent stability in liver microsomes, excellent exposure in the blood can be expected, and there is no concern about Cyp inhibition.

Brief Description of Drawings

[00112] Figure 1 illustrates changes in relative tumor volume during testing in Test Example 5.

[00113] Figure 2 illustrates changes in relative tumor volume during testing in Test Example 5

[00114] Figure 3 illustrates changes in body weight during testing in Test Example 5.

[00115] Figure 4 illustrates changes in body weight during testing in Test Example 5.

Description of Modalities

[00116] The compounds of the present invention represented by formulas (I) and (I') above are compounds having a ring pyrimidine skeleton fused with a pyrazolyl group through an amide bond, and they have not been known to its RET inhibitory activity. In particular, the compound represented by Formula (I') above or a salt thereof, etc., are new compounds that are not described in any of the above-mentioned prior art documents.

[00117] In the present invention, the compounds represented by formulas (I) and (I') are also referred to simply as "Compound (I)" and "Compound (I')," respectively.

[00118] In the present specification, unless otherwise specified, examples of the "substituent" include halogen, hydroxy, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkyl-alkyl, bridged cycloalkyl, aralkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, cycloalkoxy, cycloalkyl-alkoxy, aralkyloxy, alkylthio, cycloalkyl-alkylthio, amino, mono- or dialkylamino, cycloalkyl-alkylamino, acyl, acyloxy, oxo, carboxyl, alkoxycarbonyl, aralkyl loxycarbonyl, carbamoyl, saturated or unsaturated heterocyclic group, aromatic hydrocarbon, saturated heterocyclic oxy, etc. (These substituents are also referred to as “Substituents B.”) When a substituent listed above is present, its number is typically one, two or three.

[00119] In the present specification, examples of "halogen" include fluorine, chlorine, bromine, and iodine.

[00120] In the present specification, "alkyl" can be linear or branched. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, 1-methylpropyl, n-pentyl, isopentyl, n-hexyl, 1,1-dimethylpropyl, 1,1,2,2- tetramethylethyl, n-heptyl, 1,1,2,2-tetramethylpropyl, n-octyl, n-nonyl, n-decyl, etc.; and specifically include C1-C10 alkyl, C1-C6 alkyl, etc.

[00121] In the present specification, examples of "haloalkyl" include linear or branched C1-C10 alkyl having one or more (e.g., 1 to 10, 1 to 7, or 1 to 5) halogen atoms (C1 halogen -C10 alkyl). Examples include fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, fluoroethyl, 1,1,1-trifluoroethyl, monofluoro-n-propyl, perfluoro-n-propyl, perfluoroisopropyl, monofluoro-n-butyl, monofluoro-n -pentyl, monofluoro-n-hexyl, etc.; and specifically include C1-C6 alkyl halo, C1-C4 alkyl halo, etc.

[00122] In the present specification, examples of "hydroxyalkyl" include linear or branched C1-C10 alkyl having one or more (e.g., 1 to 5, 1 to 3, or 1) hydroxy groups (C1-C10 hydroxy alkyl ).Examples include hydroxymethyl, hydroxyethyl (1-hydroxyethyl or 2-hydroxyethyl), hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, etc.; and specifically include hydroxy C1-C6 alkyl, hydroxy C1-C4 alkyl, etc.

[00123] In the present specification, examples of "alkoxyalkyl" include alkoxyalkyl in which the alkoxy moiety is linear or branched C1-C6 alkoxy, and the alkyl moiety is linear or branched C1-C10 alkyl (C1-C6 alkoxy C1-C10 alkyl ).Examples of linear or branched C1-C6 alkoxy include those in which the alkyl moiety is C1-C6 alkoxy among the examples of the alkyl mentioned above. Examples of the alkoxyalkyl include methoxymethyl, ethoxymethyl, n-propoxymethyl, n-butoxymethyl, 2 -methoxyethyl, 1-methoxy-n-propyl, 3-methoxy-n-propyl, 2-ethoxy-n-butyl, 4-methoxy-n-butyl, 5-methoxy-n-pentyl, 6-methoxy-n-hexyl , etc.; and specifically include C1-C4 alkoxy C1-C6 alkyl, C1-C4 alkoxy C1-C4 alkyl, etc.

[00124] In the present specification, specific examples of "cycloalkyl" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.; and specifically include C3-C7 cycloalkyl, C3-C5 cycloalkyl, C3-C4 cycloalkyl, etc. In the present invention, "cycloalkyl" must be specified independently of "bridged cycloalkyl" described later. Therefore, in the present invention, "bridged cycloalkyl" is excluded from "cycloalkyl".

[00125] In the present specification, examples of "cycloalkyl-alkyl" include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, etc.; and specifically include C1C10 alkyl substituted by C3-C7 cycloalkyl, C1-C6 alkyl substituted by C3-C5 cycloalkyl, etc.

[00126] In the present specification, "bridged cycloalkyl" refers to a bridged cyclic hydrocarbon in which the carbocyclic ring constituting the bridged cyclic hydrocarbon has a saturated structure. In the present specification, examples of "bridged cycloalkyl” include bicyclo [1.1.0]butyl (bicyclo [1.1.0]butan-1-yl or bicyclo [1.1.0]butan-2-yl), bicyclo [1.1.1]pentyl (bicyclo [1.1.1] pentan-1-yl or bicyclo [1.1.1]pentan-2-yl), bicyclo [3.1.0]hexyl (bicyclo [3.1.0]hexan-1-yl, bicyclo [3.1.0]hexan-2-yl , bicyclo [3.1.0]hexan-3-yl, or bicyclo [3.1.0]hexan-6-yl), bicyclo [2.2.1]heptyl (bicyclo [2.2.1]heptan-1-yl, bi - cycle [2.2.1]heptan-2-yl, or bicycle [2.2.1]heptan-7-yl), bicycle [3.1.1]heptyl (bicycle [3.1.1]heptan-1-yl, bicycle [3.1.1]heptan-2-yl, bicycle [3.1.1]heptan-3-yl, or bicycle [3.1.1]heptan-6-yl), adamantyl (adamantan-1-yl or adamantan-2 -ila), etc.; and specifically include bridged C4-C12 cycloalkyl, etc.

[00127] In the present specification, examples of "aralkyl" include benzyl, phenethyl, naphthylmethyl, fluorenylmethyl, etc.; and specifically include C7-C14 aralkyl, etc.

[00128] In the present specification, "alkenyl" can be linear or branched, and refers to an unsaturated aliphatic hydrocarbon having at least one (e.g., 1 or 2, or 1) double bond. Examples include vinyl, allyl, 1-propenyl, 2-methyl-2-propenyl, isopropenyl, 1-, 2- or 3-butenyl, 2-, 3-, or 4-pentenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl , 5-hexenyl, 1-cyclopentenyl, 1-cyclohexenyl, 3-methyl-3-butenyl, etc.; and specifically include C2-C6 alkenyl, C2-C4 alkenyl, etc.

[00129] In the present specification, "cycloalkenyl" refers to an unsaturated alicyclic hydrocarbon having at least one (e.g., 1 or 2, or 1) double bond. Examples include cyclopropenyl (e.g., 2-cyclopropen-1- yl), cyclobutenyl (e.g. 2-cyclobuten-1-yl), cyclopentenyl (e.g. 2-cyclopenten-1-yl and 3-cyclopenten-1-yl), cyclopentadienyl (e.g. 2,4-cyclopentadienyl 1-yl), cyclohexenyl (e.g. 3-cyclohexen-1-yl), cycloheptenyl (e.g. 3-cyclohexenyl-1-yl), etc.; and specifically include C3-C7 cycloalkenyl, C3-C5 cycloalkenyl, C3-C4 cycloalkenyl, etc.

[00130] In the present specification, "alkynyl" may be linear, branched, or cyclic, and refers to an unsaturated hydrocarbon having at least one triple bond. Examples include ethynyl, 1- or 2-propynyl, 1-, 2 - or 3-butynyl, 1-methyl-2-propynyl, etc.; and specifically include C2-C6 alkynyl, C2-C4 alkynyl, etc.

[00131] In the present specification, "alkoxy” can be linear or branched. Examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, hexyloxy, etc.; and specifically include C1-C6 alkoxy, C1-C4 alkoxy, etc.

[00132] In the present specification, "haloalkoxy" refers to linear or branched C1-C6 alkoxy having one or more (e.g., 1 to 10, 1 to 7, or 1 to 5) halogen atoms (C1 halogen -C6 alkoxy). Examples include fluoromethoxy, difluoromethoxy, trifluoromethoxy, trichloromethoxy, fluoroethoxy, 1,1,1-trifluoroethoxy, monofluoro-n-propoxy, perfluoro-n-propoxy, perfluoro-isopropoxy, etc.; and specifically include halogen C1-C6 alkoxy, halogen C1-C4 alkoxy, etc.

[00133] In the present specification, specific examples of "cycloalkoxy" include cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, etc.; and specifically include C3-C7 cycloalkoxy.

[00134] In the present specification, examples of "cycloalkyl-alkoxy" include cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, cycloheptylmethoxy, etc.; and specifically include C1-C4 alkoxy substituted by C3-C7 cycloalkyl, etc.

[00135] In the present specification, examples of "aralkyloxy" include benzyloxy, phenethyloxy, naphthylmethyloxy, fluorenylmethyloxy, etc.; and specifically include C7-C14 aralkyloxy, etc.

[00136] In the present specification, "alkylthio” can be linear or branched. Examples include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio, isopentylthio, hexylthio, etc. ; and specifically include C1-C6 alkylthio, C1-C4 alkylthio, etc.

[00137] In the present specification, examples of "cycloalkyl-alkylthio" include cyclopropylmethylthio, cyclobutylmethylthio, cyclopentylmethylthio, cyclohexylmethylthio, cycloheptylmethylthio, etc.; and specifically include C1-C4 alkylthio substituted by C3-C7 cycloalkyl, etc.

[00138] In the present specification, examples of "monoalkylamino" include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, tert-butylamino, n-pentylamino, isopentylamino, hexylamino, etc.; and specifically include amino monosubstituted with linear or branched C1-C6 alkyl.

[00139] In the present specification, examples of "dialkylamino" include dimethylamino, ethylmethylamino, diethylamino, di(n-propyl)amino, diisopropylamino, di(n-butyl)amino, diisobutylamino, di(tert- butyl)amino, di(n-pentyl)amino, diisopentylamino, dihexylamino, etc.; and specifically include amino disubstituted with linear or branched C1-C6 alkyl.

[00140] In the present specification, examples of "cycloalkyl-alkylamino" include cyclopropylmethylamino, cyclobutylmethylamino, cyclopentylmethylamino, cyclohexylmethylamino, cycloheptylmethylamino, etc.; and specifically include C1-C4 alkylamino substituted by C3-C7 cycloalkyl , etc.

[00141] In this specification, "acyl" refers to alkylcarbonyl or arylcarbonyl.

[00142] In the present specification, examples of "alkylcarbonyl" include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, hexylcarbonyl, etc.; and specifically include linear or branched (C1-C6 alkyl)carbonyl, etc.

[00143] In the present specification, examples of "arylcarbonyl" include phenylcarbonyl, naphthylcarbonyl, fluorenylcarbonyl, anthrylcarbonyl, biphenylylcarbonyl, tetrahydronaphthylcarbonyl, cromanylcarbonyl, 2,3-dihydro-1,4-dioxanaphthalenylcarbonyl, indanylcarbonyl, phenantrylcarbonyl, etc. ; and specifically include (C6-C14 aryl)carbonyl, etc.

[00144] In this specification, "acyloxy" refers to alkylcarbonyloxy or arylcarbonyloxy.

[00145] In this specification, examples of "alkylcarbonyloxy" include methylcarbonyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, isopropylcarbonyloxy, n-butylcarbonyloxy, isobutylcarbonyloxy, tert-butylcarbonyloxy, n-pentylcarbonyloxy, isopentylcarbonyloxy, hexylcarbonyloxy, etc. ; and specifically include linear or branched (C1-C6 alkyl)carbonyloxy, etc.

[00146] In the present specification, examples of "arylcarbonyloxy" include phenylcarbonyloxy, naphthylcarbonyloxy, fluorenylcarbonyloxy, anthrylcarbonyloxy, biphenylylcarbonyloxy, tetrahydronaphthylcarbonyloxy, chromanylcarbonyloxy, 2,3-dihydro-1,4-dioxanaphthalenylcarbonyloxy, indanylcarbonyloxy, phenantrylcarbonyloxy, etc.; and specifically include (C6-C14 aryl)carbonyloxy, etc.

[00147] In the present specification, "alkoxycarbonyl" can be linear or branched. Examples include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, hexyloxycarbonyl, etc.; and specifically include (C1-C6 alkoxy)carbonyl, etc.

[00148] In the present specification, examples of "aralkyloxycarbonyl" include benzyloxycarbonyl, phenethyloxycarbonyl, naphthylmethyloxycarbonyl, fluorenylmethyloxycarbonyl, etc.; and specifically include (C7-C14 aralkyl)oxycarbonyl, etc.

[00149] In the present specification, the "saturated heterocyclic group" refers to a monocyclic or polycyclic saturated heterocyclic group having a heteroatom selected from nitrogen, oxygen, and sulfur. Specific examples include morpholino, 1-pyrrolidinyl, pipe- ridino, piperazinyl, 4-methyl-1-piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, thiazolidinyl, oxazolidinyl, 7-azabicyclo [2.2.1]hept-2-yl, 2,6-dioxabicyclo [3.2. 1]oct-7-yl, etc. In the present invention, examples of the saturated heterocyclic group include a "monocyclic or polycyclic C3-C10 saturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, ” a “monocyclic saturated C3-C6 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur,” and a “monocyclic C4-C5 saturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen."

[00150] In the present specification, the "unsaturated heterocyclic group" refers to a completely or partially unsaturated, monocyclic or polycyclic heterocyclic group having a heteroatom selected from nitrogen, oxygen, and sulfur. Specific examples include imidazolyl, thienyl , furanyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridyl, pyrazyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, indazolyl, triazolopyridyl, benzoimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl , purinyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, methylenedioxyphenyl, ethylenedioxyphenyl, dihydrobenzofuranyl, etc. In the present invention, examples of the unsaturated heterocyclic group include a "monocyclic or polycyclic C3-C10 unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms a "monocyclic unsaturated heterocyclic C3-C6 group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur," a "monocyclic unsaturated heterocyclic C4-C5 group containing 1 or 2 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur,” a “monocyclic unsaturated heterocyclic C4-C5 group containing a nitrogen atom, an oxygen atom, or a sulfur atom,” a “C4- C5 monocyclic unsaturated heterocyclic group containing one oxygen atom or one sulfur atom,” and a “monocyclic unsaturated heterocyclic C3-C6 group containing 1 to 3 nitrogen atoms.”

[00151] In the present specification, the "aromatic hydrocarbon" (aryl) includes phenyl, tolyl, xylyl, naphthyl, anthracenyl, phenantryl, fluorenyl, tetrahydronaphthyl, etc.; and specifically includes C6-C14 hydrocar- aromatic boneto, etc.

[00152] In the present specification, the "saturated heterocyclic oxy" refers to the oxy to which a saturated heterocyclic ring having a heteroatom selected from nitrogen, oxygen, and sulfur is attached. Specific examples include morpholinyloxy, 1-pyrrolidinyloxy, piperi- dinooxy, piperazinyloxy, 4-methyl-1-piperazinyloxy, tetrahydrofuranyloxy, tetrahydropyranyloxy, tetrahydrothiophenyloxy, thiazolidinyloxy, and oxazolidinyloxy.

[00153] The term "Ca-Cb” in the description regarding the substituent in the present specification indicates that the substituent has a- to b- number carbon atoms. For example, "C1-C6 alkyl” refers to the alkyl having 1 to 6 carbon atoms, and “C6-C14 aromatic oxy hydrocarbon” refers to the oxy to which C6-C14 aromatic hydrocarbon is bonded. Furthermore, the term “a- to b-members” indicates that the number of atoms (number of ring members) that make up the ring is “a” to “b”. For example, a “4- to 10-membered saturated heterocyclic group” refers to a saturated heterocyclic group with a 4- to 10-membered ring.

[00154] In Formulas (I) and (I'), A is pyrazolyl substituted by number n of R1. Examples of the pyrazolyl represented by A include pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, and pyrazol-5-yl. Pyrazol-3-yl is preferred in the present invention.

[00155] In Formulas (I) and (I'), examples of the "halogen" represented by R1 include those mentioned above, preferably chlorine and bromine, and more preferably bromine.

[00156] In Formulas (I) and (I'), examples of the "C1-C6 alkyl" in the "C1C6 substituted or unsubstituted alkyl" represented by R1 include those mentioned above, and preferably C1-C4 alkyl. Specific examples include methyl, ethyl, n-propyl, isopropyl, etc.; more preferably methyl and ethyl; and even more preferably methyl.

[00157] Examples of the "substituent" in the "substituted or unsubstituted C1-C6 alkyl" represented by R1 include those mentioned above, and preferably halogen and C1-C4 alkoxy. Specific examples include fluorine, methoxy, etc.; more preferably halogen; and even more preferably fluorine.

[00158] When the C1-C6 alkyl is substituted, the number of substituents will not be particularly limited, but will preferably be 1 to 3. When the substituent is halogen, the number of substituents will preferably be 2 or 3. When the substituent is C1-C4 alkoxy, the number of substituents will preferably be 1.

[00159] The “substituted or unsubstituted C1-C6 alkyl” represented by R1 is preferably C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy. Specific examples include methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, difluoromethyl, methoxymethyl, etc.; more preferably C1-C6 alkyl that can be substituted with halogen; even more preferably C1-C4 alkyl that can be substituted with halogen; even more preferably C1-C4 alkyl that can be substituted with fluorine; even more preferably C1-C4 alkyl; and even more preferably methyl.

[00160] In Formulas (I) and (I'), examples of the "C3-C7 cycloalkyl" in the "C3-C7 substituted or unsubstituted cycloalkyl" represented by R1 include those mentioned above; preferably cyclopropyl, cyclobutyl, and cyclopentyl; and more preferably cyclopropyl.

[00161] Examples of the "substituent” in the “substituted or unsubstituted C3-C7 cycloalkyl” represented by R1 include those mentioned above.

[00162] The "substituted or unsubstituted C3-C7 cycloalkyl" represented by R1 is preferably C3-C7 cycloalkyl. Specific examples include cyclopropyl, cyclobutyl, cyclopentyl, etc.; more preferably C3-C5 cycloalkyl; and even more preferably cyclopropyl .

[00163] In Formulas (I) and (I'), examples of the "C6-C14 aromatic hydrocarbon" in the "C6-C14 substituted or unsubstituted aromatic hydrocarbon" represented by R1 include those mentioned above, and preferably phenyl.

[00164] Examples of the "substituent” in the “C6-C14 substituted or unsubstituted aromatic hydrocarbon” represented by R1 include those mentioned above.

[00165] The “C6-C14 substituted or unsubstituted aromatic hydrocarbon” represented by R1 is preferably phenyl.

[00166] In Formulas (I) and (I'), the "saturated or unsaturated C3-C10 monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" in the "heterocyclic group saturated or unsaturated substituted or unsubstituted, monocyclic or polycyclic C3-C10 containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur” represented by R1 is preferably a monocyclic unsaturated heterocyclic C3-C6 group containing a oxygen or a sulfur atom; more preferably a monocyclic unsaturated C4-C5 heterocyclic group containing an oxygen atom or a sulfur atom; even more preferably thienyl and furanyl; even more preferably the following:

[00167] where * represents a connection position (hereinafter the same)

[00168] and even more preferably the following: , *

[00169] Examples of the "substituent" in the "saturated or unsaturated, C3-C10 monocyclic or polycyclic, substituted or unsubstituted heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R1 include those mentioned above.

[00170] The "saturated or unsaturated, C3-C10 monocyclic or polycyclic, substituted or unsubstituted heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R1 is preferably a hemigroup. unsaturated terocyclic, C3-C6 monocyclic group containing an oxygen atom or a sulfur atom; more preferably an unsaturated heterocyclic group, C4-C5 monocyclic containing an oxygen atom or a sulfur atom; even more preferably thienyl or furanyl; further more preferably the following:

[00171] and even more preferably the following:

[00172] [Formula 6] * . *

[00173] In Formulas (I) and (I'), R1 is preferably

[00174] halogen, cyano, substituted or unsubstituted C1-C6 alkyl,

[00175] C3-C7 substituted or unsubstituted cycloalkyl, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted or unsubstituted C3-C10 monocyclic or polycyclic saturated or unsaturated heterocyclic group containing 1 to 3 selected identical or different heteroatoms of nitrogen, oxygen, and sulfur.

[00176] R1 is more preferably halogen; cyan; C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy; C3-C7 cycloalkyl; phenyl; or an unsaturated heterocyclic group, C3-C6 monocyclic containing an oxygen atom or a sulfur atom.

[00177] R1 is even more preferably halogen; cyan;

[00178] C1-C6 alkyl that can be substituted with halogen; C3 C7 cycloalkyl; phenyl; or a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom.

[00179] R1 is even more preferably halogen, cyano, or C1-C4 alkyl that can be substituted with halogen.

[00180] R1 is even more preferably halogen or C1-C4 alkyl.

[00181] R1 is even more preferably methyl.

[00182] In Formulas (I) and (I'), examples of the "C1-C10 alkyl" in the "C1-C10 substituted or unsubstituted alkyl" represented by R2 include those mentioned above; preferably C1-C6 linear alkyl or C3-C8 branched alkyl; more preferably C1-C4 linear alkyl or C3-C8 branched alkyl; even more preferably C1-C4 linear alkyl or C3-C6 branched alkyl; and even more preferably C3-C6 branched alkyl.

[00183] The C1-C4 linear alkyl is preferably methyl, ethyl, or n-propyl; and more preferably methyl.

[00184] The C3-C8 branched alkyl is preferably isobutyl, isopropyl, sec-butyl, tert-butyl, tert-pentyl, 1,1,2,2,-tetramethylpropyl, 1,1,2,2,-tetramethylethyl , or 1,1-diethylmethyl; and more preferably iso-propyl or tert-butyl.

[00185] In Formulas (I) and (I'), examples of the "substituent" in the "substituted or unsubstituted C1C10 alkyl" represented by R2 include those mentioned above. The substituent is preferably halogen, C3-C7 cycloalkyl which may be substituted with C1-C4 alkyl, phenyl, C1-C6 alkoxy, or one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups containing 1 to 3 identical heteroatoms or different selected nitrogen, oxygen, and sulfur;

[00186] more preferably halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom; It is

[00187] even more preferably fluorine, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, methoxy, or one or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom.

[00188] Specific examples include fluorine, cyclopropyl, methyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, phenyl, methoxy, thienyl, etc.; more preferably fluorine, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, and the following:

[00189] and even more preferably fluorine and cyclopropyl.

[00190] When the C1-C10 alkyl is substituted, the number of substituents will not be particularly limited, but is preferably 1 to 3.

[00191] When the C1-C10 alkyl is substituted with "halogen," the number of substituents is preferably 1 to 3; when the C1-C10 alkyl is substituted with "C3-C7 cycloalkyl which can be substituted with C1-C4 alkyl, ” the number of substituents is preferably 1; when the C1-C10 alkyl is substituted with "phenyl," the number of substituents is preferably 1; when the C1-C10 alkyl is substituted with "C1-C6 alkoxy," the number of substituents is preferably 1; and when the C1-C10 alkyl is substituted with a "monocyclic or polycyclic C3-C10 unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur," the number of substituents is preferably 1 .

[00192] The "substituted or unsubstituted C1-C10 alkyl" represented by R2 is preferably C1-C10 alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1C4 alkyl, phenyl, C1-C6 alkoxy, or one or more monocyclic or polycyclic C3-C10 unsaturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00193] more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more heterocyclic groups unsaturated C3-C6 monocyclics containing one oxygen atom or one sulfur atom;

[00194] even more preferably linear C1-C4 alkyl that is substituted with fluorine or C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl; or

[00195] C3-C8 branched alkyl that can be substituted with fluor, C3-C7 cycloalkyl, one or more unsaturated C3-C6 monocyclic heterocyclic groups containing an oxygen atom or a sulfur atom, phenyl, or C1-C4 alkoxy.

[00196] Specific examples include the following:

[00197] and the like.

[00198] The “substituted or unsubstituted C1-C10 alkyl” represented by R2 is more preferably linear C1-C4 alkyl that is substituted with C3-C7 cycloalkyl, or

[00199] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy; It is

[00200] even more preferably C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl, or

[00201] C3-C6 branched alkyl that can be substituted with fluorine, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy.

[00202] Specific examples include the following:

[00203] and the like.

[00204] The “substituted or unsubstituted C1-C10 alkyl” represented by R2 is more preferably C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl;

[00205] even more preferably branched C3-C6 alkyl that can be substituted with fluorine or C3-C5 cycloalkyl; It is

[00206] even more preferably isopropyl or tert-butyl which can be replaced with fluorine or cyclopropyl.

[00207] Specific examples include the following:

[00208] and the like.

[00209] In Formula (I), examples of the "C3-C7 cycloalkyl" in the "C3-C7 substituted or unsubstituted cycloalkyl" represented by R2 include those mentioned above.

[00210] Specific examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.; preferably C3-C5 cycloalkyl; more preferably C3-C4 cycloalkyl; and even more preferably cyclopropyl.

[00211] In Formula (I'), examples of the "C3-C4 cycloalkyl" in the "C3C4 substituted or unsubstituted cycloalkyl" represented by R2 include those mentioned above.

[00212] Specific examples include cyclopropyl, cyclobutyl, etc.; and preferably cyclopropyl.

[00213] In Formulas (I) and (I'), examples of the "substituent" in the "substituted or unsubstituted C3C7 cycloalkyl" represented by R2 include those mentioned above; and preferably halogen, C1C4 alkyl, halogen C1-C4 alkyl, and C3-C5 cycloalkyl.

[00214] Specific examples include fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, cyclopropyl, etc.; and more preferably halogen, C1-C4 alkyl, and C3-C5 cycloalkyl.

[00215] Specific examples include fluorine, methyl, and cyclopropyl; and more preferably methyl.

[00216] When the above C3-C7 cycloalkyl or C3-C4 cycloalkyl is substituted, the number of substituents will not be particularly limited, but is preferably 1 or 2.

[00217] When the C3-C7 cycloalkyl is substituted with "halogen," the number of substituents is preferably 1 or 2.

[00218] When C3-C7 cycloalkyl is substituted with "C1-C4 alkyl," the number of substituents is preferably 1 or 2.

[00219] When the C3-C7 cycloalkyl is substituted with "halogen C1-C4 alkyl," the number of substituents is preferably 1.

[00220] When C3-C7 cycloalkyl is substituted with "C3-C5 cycloalkyl," the number of substituents is preferably 1.

[00221] In Formula (I), the "substituted or unsubstituted C3-C7 cycloalkyl" represented by R2 is preferably C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1C4 alkyl, or C3-C5 cycloalkyl .

[00222] Specific examples include the following:

[00223] and the like.

[00224] The "substituted or unsubstituted C3-C7 cycloalkyl" represented by R2 is more preferably C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl; and

[00225] even more preferably C3-C7 cycloalkyl that can be substituted with fluorine, C1-C4 alkyl, or C3-C5 cycloalkyl.

[00226] Specific examples include the following:

[00227] and the like.

[00228] The “substituted or unsubstituted C3-C7 cycloalkyl” represented by R2 is more preferably C3-C5 cycloalkyl that can be substituted with C1-C4 alkyl;

[00229] even more preferably C3-C5 cycloalkyl that can be substituted with methyl;

[00230] even more preferably cyclopropyl which can be substituted with methyl; It is

[00231] even more preferably the following:

[00232] In Formula (I'), the "substituted or unsubstituted C3-C4 cycloalkyl" represented by R2 is preferably C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1C4 alkyl, or C3-C5 cycloalkyl.

[00233] Specific examples include the following:

[00234] and the like.

[00235] The "substituted or unsubstituted C3-C4 cycloalkyl" represented by R2 is more preferably C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl; and

[00236] even more preferably C3-C4 cycloalkyl that can be substituted with fluorine, C1-C4 alkyl, or C3-C5 cycloalkyl.

[00237] Specific examples include the following:

[00238] and the like.

[00239] The “substituted or unsubstituted C3-C4 cycloalkyl” represented by R2 is more preferably C3-C4 cycloalkyl which can be substituted with C1-C4 alkyl,

[00240] even more preferably C3-C4 cycloalkyl that can be substituted with methyl,

[00241] even more preferably cyclopropyl which can be substituted with methyl, and

[00242] even more preferably the following:

[00243] In Formulas (I) and (I'), examples of the "C2-C6 alkenyl" in the "C2-C6 substituted or unsubstituted alkenyl" represented by R2 include those mentioned above, preferably C2-C4 alkenyl, and more preferably isopropenyl.

[00244] In Formulas (I) and (I'), examples of the "substituent" in the "substituted or unsubstituted C2C6 alkenyl" represented by R2 include those mentioned above, preferably halogen, and more preferably fluorine.

[00245] When the C2-C6 alkenyl is substituted, the number of substituents will not be particularly limited, but is preferably 1 to 3. When the substituent is halogen, the number of substituents is preferably 1.

[00246] In Formulas (I) and (I'), the "substituted or unsubstituted C2-C6 alkenyl" represented by R2 is preferably C2-C6 alkenyl that can be substituted with halogen;

[00247] more preferably C2-C6 alkenyl that can be substituted with fluorine; It is

[00248] even more preferably the following:

[00249] In Formulas (I) and (I'), examples of "C3-C7 cycloalkenyl" and "C3-C4 cycloalkenyl" in "C3-C7 substituted or unsubstituted cycloalkenyl" and "C3-C4 substituted or unsubstituted cycloalkenyl ” represented by R2 include those mentioned above, preferably C3-C4 cycloalkenyl, and more preferably cyclobutenyl.

[00250] In Formulas (I) and (I'), examples of the "substituent" in "C3C7 substituted or unsubstituted cycloalkenyl" and "C3-C4 substituted or unsubstituted cycloalkenyl" represented by R2 include those mentioned above, preferably halogen, and more preferably fluorine.

[00251] When C3-C7 cycloalkenyl or C3-C4 cycloalkenyl is substituted, the number of substituents will not be particularly limited, but is preferably 1 to 3. When the substituent is halogen, the number of substituents is preferably 1.

[00252] In Formula (I), the "substituted or unsubstituted C3-C7 cycloalkenyl" represented by R2 is preferably C3-C7 cycloalkenyl that can be substituted with halogen, and

[00253] more preferably C3-C4 cycloalkenyl that can be substituted with halogen.

[00254] In Formula (I'), the "substituted or unsubstituted C3-C4 cycloalkenyl" represented by R2 is preferably C3-C4 cycloalkenyl that can be substituted with halogen.

[00255] In Formulas (I) and (I'), examples of the "bridged C4-C12 cycloalkyl" in the "substituted or unsubstituted bridged C4-C12 cycloalkyl" represented by R2 include those mentioned above;

[00256] preferably bicyclo [1.1.1]pentan-1-yl, bicyclo [2.2.1]heptan-2-yl, adamantan-2-yl, and bicyclo [3.1.1]heptan-3-yl;

[00257] more preferably bicyclo [1.1.1]pentan-1-yl, bicyclo[2.2.1]heptan-2-yl, and adamantan-2-yl;

[00258] even more preferably bicyclo [1.1.1]pentan-1-yl and bicyclo[2.2.1]heptan-2-yl; It is

[00259] even more preferably bicyclo [2.2.1]heptan-2-yl.

[00260] In Formulas (I) and (I'), examples of the "substituent" in the "substituted or unsubstituted C4C12 bridged cycloalkyl" represented by R2 include those mentioned above, preferably C1-C4 alkyl, and more preferably methyl.

[00261] When the bridged C4-C12 cycloalkyl is substituted, the number of substituents is not particularly limited, but is preferably 1 to 3. When the substituent is C1-C4 alkyl, the number of substituents is preferably 1 to 3, and more preferably 3.

[00262] In Formulas (I) and (I'), the "substituted or unsubstituted C4-C12 bridged cycloalkyl" represented by R2 is preferably C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl; and

[00263] more preferably C4-C12 bridged cycloalkyl that can be substituted with methyl and is selected from bicyclo [1.1.1]pentan-1-yl, bicyclo [2.2.1]heptan-2-yl, adamantan-2-yl , and bicyclo [3.1.1]heptan- 3-yl.

[00264] Specific examples include bicyclo [1.1.1]pentan-1-yl, bicyclo[2.2.1]heptan-2-yl, adamantan-2-yl, 2,6,6-trimethylbicyclo [3.1.1] heptan-3-yl, etc.

[00265] The “substituted or unsubstituted C4-C12 bridged cycloalkyl” represented by R2 is more preferably C4-C12 bridged cycloalkyl;

[00266] even more preferably bicyclo [1.1.1]pentan-1-yl or bicyclo[2.2.1]heptan-2-yl; It is

[00267] even more preferably bicyclo [2.2.1]heptan-2-yl.

[00268] In Formulas (I) and (I'), examples of the "C6-C14 aromatic hydrocarbon" in the "C6-C14 substituted or unsubstituted aromatic hydrocarbon" represented by R2 include those mentioned above, and preferably phenyl.

[00269] Examples of the "substituent” in the “C6-C14 substituted or unsubstituted aromatic hydrocarbon” represented by R2 include those mentioned above.

[00270] The “C6-C14 substituted or unsubstituted aromatic hydrocarbon” represented by R2 is preferably phenyl.

[00271] In Formulas (I) and (I'), the "saturated or unsaturated C3-C10 monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" in the "heterocyclic group saturated or unsaturated C3-C10 monocyclic or polycyclic, substituted or unsubstituted containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur” represented by R2 is preferably an unsaturated heterocyclic group, C3-C6 monocyclic containing a nitrogen atom, an oxygen atom, or a sulfur atom;

[00272] more preferably an unsaturated heterocyclic group, C4-C5 monocyclic containing a nitrogen atom, an oxygen atom, or a sulfur atom; It is

[00273] even more preferably thienyl or furanyl.

[00274] Examples of the "substituent" in the "saturated or unsaturated C3-C10 monocyclic or polycyclic, substituted or unsubstituted heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R2 include those mentioned above .

[00275] The "saturated or unsaturated, C3-C10 monocyclic or polycyclic, substituted or unsubstituted heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R2 is preferably a heterocyclic group unsaturated terocyclic, C3-C6 monocyclic containing one nitrogen atom, one oxygen atom, or one sulfur atom;

[00276] more preferably an unsaturated heterocyclic group, C4-C5 monocyclic containing a nitrogen atom, an oxygen atom, or a sulfur atom; It is

[00277] even more preferably thienyl or furanyl.

[00278] R2 in Formula (I) is preferably,

[00279] C1-C10 substituted or unsubstituted alkyl,

[00280] C3-C7 substituted or unsubstituted cycloalkyl,

[00281] C2-C6 substituted or unsubstituted alkenyl, or

[00282] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[00283] R2 is more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or a or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00284] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00285] C2-C6 alkenyl that can be substituted with halogen; or

[00286] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl.

[00287] R2 is even more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more plus monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00288] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00289] C2-C6 alkenyl that can be substituted with halogen; or

[00290] C4-C12 bridged cycloalkyl.

[00291] R2 is even more preferably

[00292] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[00293] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[00294] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[00295] C2-C6 alkenyl that can be substituted with halogen; or

[00296] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl.

[00297] R2 is even more preferably

[00298] C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl;

[00299] C3-C5 cycloalkyl that can be substituted with C1-C4 alkyl, or

[00300] bicycle [2.2.1]heptan-2-yl.

[00301] R2 is even more preferably isopropyl or tert-butyl which can be substituted with fluorine or cyclopropyl, or

[00302] cyclopropyl that can be replaced with methyl.

[00303] Furthermore, R2 in Formula (I') is preferably

[00304] C1-C10 substituted or unsubstituted alkyl,

[00305] C3-C4 substituted or unsubstituted cycloalkyl,

[00306] C2-C6 substituted or unsubstituted alkenyl, or

[00307] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[00308] R2 is more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or a or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00309] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00310] C2-C6 alkenyl that can be substituted with halogen; or

[00311] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl.

[00312] R2 is even more preferably C1-C6 linear alkyl or C3 C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00313] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00314] C2-C6 alkenyl that can be substituted with halogen; or

[00315] C4-C12 bridged cycloalkyl.

[00316] R2 is even more preferably C1-C4 linear alkyl which is substituted with C3-C7 cycloalkyl;

[00317] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[00318] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[00319] C2-C6 alkenyl that can be substituted with halogen; or

[00320] C4-C12 cycloalkyl bridge selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl.

[00321] R2 is even more preferably C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl;

[00322] C3-C4 cycloalkyl that can be substituted with C1-C4 alkyl; or

[00323] bicycle [2.2.1]heptan-2-yl.

[00324] R2 is even more preferably isopropyl or tert-butyl which can be substituted with fluorine or cyclopropyl, or cyclopropyl which can be substituted with methyl.

[00325] In Formulas (I) and (I'), X is N or CR3, and preferably CR3.

[00326] In Formulas (I) and (I'), examples of the "halogen" represented by R3 include those mentioned above, and preferably bromine and chlorine.

[00327] In Formulas (I) and (I'), examples of the "C1-C6 alkyl" in the "C1C6 substituted or unsubstituted alkyl" represented by R3 include those mentioned above, preferably C1-C4 alkyl, and more preferably methyl.

[00328] Examples of the "substituent” in the “substituted or unsubstituted C1-C6 alkyl” represented by R3 include those mentioned above.

[00329] The "substituted or unsubstituted C1-C6 alkyl" represented by R3 is preferably C1-C6 alkyl, more preferably C1C4 alkyl, and even more preferably methyl.

[00330] In Formulas (I) and (I'), examples of the "C2-C6 alkenyl" in the "C2-C6 substituted or unsubstituted alkenyl" represented by R3 include those mentioned above, and preferably vinyl and isopropenyl.

[00331] Examples of the "substituent” in the “substituted or unsubstituted C2-C6 alkenyl” represented by R3 include those mentioned above.

[00332] In Formulas (I) and (I'), the "substituted or unsubstituted C2-C6 alkenyl" represented by R3 is preferably vinyl or isopropenyl.

[00333] Examples of the "C2-C6 alkynyl" in the "C2-C6 substituted or unsubstituted alkynyl" represented by R3 include those mentioned above, preferably C2-C4 alkynyl, and more preferably ethynyl or propynyl.

[00334] The number of triple bonds in the "C2-C6 alkynyl" is preferably 1, and the triple bond is preferably positioned between a carbon atom bonded to a 7H-pyrrole [2,3-d]pyrimidine skeleton and a carbon adjacent to the cabone atom.

[00335] Examples of the "substituent” in the “substituted or unsubstituted C2-C6 alkynyl” represented by R3 include those mentioned above; It is

[00336] preferably

[00337] C1-C6 alkyl that can be substituted with hydroxy,

[00338] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00339] one or more monocyclic C3-C10 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00340] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contains 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00341] Specific examples include hydroxyisopropyl, hydroxycyclopentyl, hydroxycyclobutyl, morpholino, tetrahydropyranyl, pyrazolyl that can be substituted with methyl, imidazo [1,2-b]pyridazinyl,

[00342] imidazolyl, which can be substituted with methyl, and pyridinyl.

[00343] The “substituent” is more preferably

[00344] C1-C6 alkyl that can be substituted with hydroxy,

[00345] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00346] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic or polycyclic C3-C10 unsaturated heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00347] The "substituent” is even more preferably

[00348] C1-C6 alkyl that can be substituted with hydroxy,

[00349] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00350] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00351] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00352] The "substituent" is even more preferably C1-C4 alkyl that can be substituted with hydroxy, C3-C5 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected nitrogen and oxygen groups, or one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00353] The "substituent" is even more preferably isopropyl which can be substituted with hydroxy, C3-C5 cycloalkyl which can be substituted with hydroxy, one or more monocyclic C4-C5 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or

[00354] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00355] The "substituted or unsubstituted C2-C6 alkynyl" represented by R3 is preferably C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more saturated monocyclic C3-C10 heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00356] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00357] Specific examples include the following:

[00358] The "substituted or unsubstituted C2-C6 alkynyl" represented by R3 is more preferably C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy,

[00359] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00360] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00361] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00362] The "substituted or unsubstituted C2-C6 alkynyl" represented by R3 is even more preferably C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy,

[00363] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00364] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00365] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00366] The "substituted or unsubstituted C2-C6 alkynyl" represented by R3 is even more preferably ethynyl or propynyl which is substituted with

[00367] C1-C4 alkyl that can be substituted with hydroxy,

[00368] C3-C5 cycloalkyl that can be substituted with hydroxy,

[00369] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or

[00370] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00371] The "substituted or unsubstituted C2-C6 alkynyl" represented by R3 is even more preferably ethynyl or propynyl which is substituted with

[00372] isopropyl that can be replaced with hydroxy,

[00373] C3-C5 cycloalkyl that can be substituted with hydroxy,

[00374] one or more monocyclic C4-C5 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or

[00375] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00376] Examples of the "C1-C6 alkoxy" in the "C1-C6 substituted or unsubstituted alkoxy" represented by R3 include those mentioned above, preferably C1-C4 alkoxy, and more preferably methoxy.

[00377] Examples of the "substituent” in the “substituted or unsubstituted C1-C6 alkoxy” represented by R3 include those mentioned above;

[00378] preferably one or more monocyclic C3-C10 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00379] more preferably one or more monocyclic C3-C6 saturated heterocyclic groups containing an oxygen atom.

[00380] The “substituted or unsubstituted C1-C6 alkoxy” represented by R3 is C1-C4 alkoxy that may be substituted with one or more monocyclic C3-C10 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen , and sulfur, or

[00381] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing an oxygen atom;

[00382] more preferably C1-C4 alkoxy; It is

[00383] even more preferably methoxy.

[00384] In Formulas (I) and (I'), examples of the "substituent" in the "substituted or unsubstituted amino" represented by R3 include those mentioned above.

[00385] In Formulas (I) and (I'), the "C6-C14 aromatic hydrocarbon" in the "C6-C14 substituted or unsubstituted aromatic hydrocarbon" represented by R3 include those mentioned above, and preferably phenyl.

[00386] Examples of the "substituent” in the “C6-C14 substituted or unsubstituted aromatic hydrocarbon” represented by R3 include those mentioned above.

[00387] In Formulas (I) and (I'), the "C6-C14 substituted or unsubstituted aromatic hydrocarbon" represented by R3 is preferably phenyl.

[00388] In Formulas (I) and (I'), the "saturated or unsaturated C3-C10 monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" in the "heterocyclic group saturated or unsaturated C3-C10 substituted or unsubstituted monocyclic or polycyclic containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur” represented by R3 is preferably an unsaturated heterocyclic group, C3-C6 monocyclic containing a oxygen atom or a sulfur atom, and more preferably thienyl or furanyl.

[00389] Examples of the "substituent" in the "saturated or unsaturated C3-C10 monocyclic or polycyclic substituted or unsubstituted heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R3 include those mentioned above.

[00390] The "substituted or unsubstituted C3-C10 monocyclic or polycyclic saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur" represented by R3 is preferably an unsaturated heterocyclic group , C3-C6 monocyclic containing an oxygen atom or a sulfur atom, and more preferably thienyl or furanyl.

[00391] R3 is preferably hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, or substituted or unsubstituted C1-C6 alkoxy.

[00392] R3 is more preferably

[00393] hydrogen;

[00394] halogen;

[00395] C1-C6 alkyl;

[00396] C2-C4 alkynyl that can be substituted with

[00397] C1-C6 alkyl that can be substituted with hydroxy,

[00398] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00399] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00400] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00401] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00402] R3 is even more preferably

[00403] hydrogen;

[00404] halogen;

[00405] C1-C4 alkyl;

[00406] C2-C4 alkynyl that can be replaced with

[00407] C1-C6 alkyl that can be substituted with hydroxy,

[00408] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00409] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00410] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00411] C1-C4 alkoxy.

[00412] R3 is even more preferably

[00413] hydrogen; or

[00414] C2-C4 alkynyl that is substituted with

[00415] C1-C6 alkyl that can be substituted with hydroxy,

[00416] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00417] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00418] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00419] R3 is even more preferably

[00420] hydrogen; or

[00421] ethynyl or propynyl that is substituted with

[00422] C1-C4 alkyl that can be substituted with hydroxy,

[00423] C3-C5 cycloalkyl that can be substituted with hydroxy,

[00424] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or

[00425] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00426] R3 is even more preferably hydrogen.

[00427] In Formulas (I) and (I'), n is an integer from 0 to 3, preferably 0 to 2, more preferably 1 or 2, and even more preferably 1.

[00428] When n is 2 or 3, R1 can be identical or different from each other, and is preferably identical.

[00429] In Formulas (I) and (I'), the bonding position between the amide structure and the pyrazolyl group is preferably as shown in Formulas (II) and (II') below.

[00430] Furthermore, when n is 1, the bonding position between the substituent R1 and the pyrazolyl group is preferably as shown in Formulas (VIII) and (VIII') below.

[00431] When n is 1, the bond position between the substituent R1 and the pyrazolyl group is more preferably as shown in Formulas (IX) and (IX') below:

[00432] [1] The present invention provides a compound represented by formula (I) below or a salt thereof:

[00433] where A is pyrazolyl substituted by number n of R1;

[00434] R1 is

[00435] halogen,

[00436] cyan,

[00437] C1-C6 substituted or unsubstituted alkyl,

[00438] C3-C7 substituted or unsubstituted cycloalkyl,

[00439] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00440] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00441] R2 is

[00442] C1-C10 substituted or unsubstituted alkyl,

[00443] C3-C7 substituted or unsubstituted cycloalkyl,

[00444] C2-C6 substituted or unsubstituted alkenyl,

[00445] C3-C7 substituted or unsubstituted cycloalkenyl,

[00446] C4-C12 substituted or unsubstituted bridged cycloalkyl,

[00447] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00448] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00449] X is

[00450] N or

[00451] CR3, where R3 is

[00452] hydrogen,

[00453] halogen,

[00454] cyan,

[00455] C1-C6 substituted or unsubstituted alkyl,

[00456] C2-C6 substituted or unsubstituted alkenyl,

[00457] C2-C6 substituted or unsubstituted alkynyl,

[00458] C1-C6 substituted or unsubstituted alkoxy,

[00459] substituted or unsubstituted amino,

[00460] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00461] a substituted or unsubstituted C3-C10 monocyclic or polycyclic unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00462] n is an integer from 0 to 3,

[00463] where when n is 2 or 3, R1 can be identical or different from each other.

[00464] [2] In Formula (I),

[00465] A is preferably pyrazolyl substituted with number n of R1;

[00466] R1 is preferably

[00467] halogen,

[00468] cyan,

[00469] C1-C6 substituted or unsubstituted alkyl,

[00470] C3-C7 substituted or unsubstituted cycloalkyl,

[00471] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00472] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00473] R2 is preferably

[00474] C1-C10 substituted or unsubstituted alkyl,

[00475] C3-C7 substituted or unsubstituted cycloalkyl,

[00476] C2-C6 substituted or unsubstituted alkenyl, or

[00477] C4-C12 substituted or unsubstituted bridged cycloalkyl;

[00478] X is preferably

[00479] N or

[00480] CR3, where R3 is

[00481] hydrogen,

[00482] halogen,

[00483] C1-C6 substituted or unsubstituted alkyl,

[00484] C2-C6 substituted or unsubstituted alkynyl, or

[00485] substituted or unsubstituted C1-C6 alkoxy; It is

[00486] n is preferably an integer from 1 to 3,

[00487] where when n is 2 or 3, R1 can be identical or different from each other.

[00488] [3] In Formula (I),

[00489] A is more preferably pyrazolyl substituted with number n of R1;

[00490] R1 is more preferably

[00491] halogen;

[00492] cyan;

[00493] C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy;

[00494] C3-C7 cycloalkyl;

[00495] phenyl; or

[00496] a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom;

[00497] R2 is more preferably

[00498] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3 unsaturated heterocyclic groups -C6 monocyclics containing one oxygen atom or one sulfur atom;

[00499] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00500] C2-C6 alkenyl that can be substituted with halogen; or

[00501] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl;

[00502] X is more preferably

[00503] N or

[00504] CR3, where R3 is

[00505] hydrogen;

[00506] halogen;

[00507] C1-C6 alkyl;

[00508] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy,

[00509] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00510] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00511] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00512] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00513] n is more preferably 1 or 2,

[00514] where when n is 2, R1 can be identical or different from each other.

[00515] In another embodiment of the present invention, a compound of Formula (I) in which pyrazolyl is linked to an amide structure in position 3 is preferred. Furthermore, a preferred embodiment of the compound of Formula (I) in which pyrazolyl is attached to an amide structure at position 3 in the present invention is

[00516] [4] a compound represented by formula (II) below or a salt thereof:

[00517] where R1 is

[00518] halogen,

[00519] cyan,

[00520] C1-C6 substituted or unsubstituted alkyl,

[00521] C3-C7 substituted or unsubstituted cycloalkyl,

[00522] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00523] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00524] R2 is

[00525] C1-C10 substituted or unsubstituted alkyl,

[00526] C3-C7 substituted or unsubstituted cycloalkyl,

[00527] C2-C6 substituted or unsubstituted alkenyl, or

[00528] C4-C12 substituted or unsubstituted bridged cycloalkyl;

[00529] X is

[00530] N or

[00531] CR3, where R3 is

[00532] hydrogen,

[00533] halogen,

[00534] C1-C6 substituted or unsubstituted alkyl,

[00535] C2-C6 substituted or unsubstituted alkenyl, or

[00536] substituted or unsubstituted C1-C6 alkoxy; It is

[00537] n is an integer from 1 to 3,

[00538] where when n is 2 or 3, R1 can be identical or different from each other.

[00539] In the present invention, the compound represented by Formula (II) above is also referred to simply as Compound (II).

[00540] [5] In Formula (II),

[00541] R1 is more preferably

[00542] halogen;

[00543] cyan;

[00544] C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy;

[00545] C3-C7 cycloalkyl;

[00546] phenyl; or

[00547] a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom;

[00548] R2 is more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or a or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00549] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00550] C2-C6 alkenyl that can be substituted with halogen; or

[00551] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl;

[00552] X is more preferably

[00553] N or

[00554] CR3, where R3 is

[00555] hydrogen;

[00556] halogen;

[00557] C1-C6 alkyl;

[00558] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy,

[00559] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00560] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00561] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00562] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00563] n is more preferably 1 or 2,

[00564] where when n is 2, R1 can be identical or different from each other.

[00565] [6] In Formula (II),

[00566] R1 is more preferably

[00567] halogen;

[00568] cyan;

[00569] C1-C6 alkyl that can be substituted with halogen;

[00570] C3-C7 cycloalkyl;

[00571] phenyl; or

[00572] a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom;

[00573] R2 is more preferably

[00574] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3 unsaturated heterocyclic groups -C6 monocyclics containing one oxygen atom or one sulfur atom;

[00575] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00576] C2-C6 alkenyl that can be substituted with halogen; or

[00577] C4-C12 bridged cycloalkyl;

[00578] X is more preferably

[00579] N or

[00580] CR3, where R3 is

[00581] hydrogen;

[00582] halogen;

[00583] C1-C4 alkyl;

[00584] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy,

[00585] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00586] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00587] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00588] C1-C4 alkoxy; It is

[00589] n is more preferably 1 or 2,

[00590] where when n is 2, R1 can be identical or different from each other.

[00591] [7] In Formula (II),

[00592] R1 is more preferably

[00593] halogen,

[00594] cyan, or

[00595] C1-C4 alkyl that can be substituted with halogen;

[00596] R2 is more preferably

[00597] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[00598] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[00599] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[00600] C2-C6 alkenyl that can be substituted with halogen; or

[00601] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl;

[00602] X is more preferably

[00603] N or

[00604] CR3, where R3 is

[00605] hydrogen; or

[00606] C2-C4 alkynyl that is substituted with

[00607] C1-C6 alkyl that can be substituted with hydroxy,

[00608] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00609] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00610] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00611] n is more preferably an integer of 1.

[00612] Preferred in another embodiment of the present invention is

[00613] [8] a compound represented by formula (IX) below or a salt thereof:

[00614] where R1 is

[00615] halogen;

[00616] cyan;

[00617] C1-C6 alkyl that can be substituted with halogen;

[00618] C3-C7 cycloalkyl;

[00619] phenyl; or

[00620] a monocyclic unsaturated C3-C6 heterocyclic group containing an oxygen atom or a sulfur atom;

[00621] R2 is

[00622] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more heterocyclic groups unsaturated C3-C6 monocyclics containing one oxygen atom or one sulfur atom;

[00623] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00624] C2-C6 alkenyl that can be substituted with halogen; or

[00625] C4-C12 bridged cycloalkyl;

[00626] X is

[00627] N or

[00628] CR3, where R3 is

[00629] hydrogen;

[00630] halogen;

[00631] C1-C4 alkyl;

[00632] C2-C4 alkynyl that can be replaced with

[00633] C1-C6 alkyl that can be substituted with hydroxy,

[00634] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00635] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00636] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00637] C1-C4 alkoxy.

[00638] In the present invention, the compound represented by Formula (IX) above is also referred to simply as Compound (IX).

[00639] [9] In Formula (IX),

[00640] R1 is more preferably

[00641] halogen,

[00642] cyan, or

[00643] C1-C4 alkyl that can be substituted with halogen;

[00644] R2 is more preferably

[00645] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[00646] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[00647] C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[00648] C2-C6 alkenyl that can be substituted with halogen; or

[00649] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl; It is

[00650] X is more preferably

[00651] N or

[00652] CR3, where R3 is

[00653] hydrogen; or

[00654] C2-C4 alkynyl that can be replaced with

[00655] C1-C6 alkyl that can be substituted with hydroxy,

[00656] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00657] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00658] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00659] [10] In Formula (IX),

[00660] R1 is more preferably

[00661] bromine,

[00662] cyan, or

[00663] C1-C4 alkyl that can be substituted with fluorine;

[00664] R2 is more preferably

[00665] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[00666] C3-C6 branched alkyl that can be substituted with fluorine, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[00667] C3-C7 cycloalkyl that can be substituted with fluorine, C1 C4 alkyl, or C3-C5 cycloalkyl;

[00668] C2-C6 alkenyl that can be substituted with fluorine; or

[00669] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl; It is

[00670] X is more preferably

[00671] N or

[00672] CR3, where R3 is

[00673] hydrogen; or

[00674] C2-C4 alkynyl that is substituted with

[00675] C1-C6 alkyl that can be substituted with hydroxy,

[00676] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00677] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00678] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[00679] Furthermore, in another embodiment of the present invention, [11] in Formula (IX), R1 is more preferably halogen or C1-C4 alkyl;

[00680] R2 is more preferably C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl, C3-C5 cycloalkyl that can be substituted with C1-C4 alkyl, or bicyclo [2.2.1] heptan-2-yl; It is

[00681] X is more preferably

[00682] N or

[00683] CR3, where R3 is

[00684] hydrogen; or

[00685] ethynyl or propynyl that is substituted with C1-C4 alkyl that can be substituted with hydroxy, C3-C5 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or

[00686] one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[00687] [12] In Formula (IX),

[00688] R1 is more preferably bromine or methyl;

[00689] R2 is more preferably

[00690] C3-C6 branched alkyl that can be substituted with fluorine or C3-C5 cycloalkyl, or

[00691] C3-C5 cycloalkyl that can be substituted with methyl; It is

[00692] X is more preferably

[00693] N or

[00694] CR3, where R3 is hydrogen.

[00695] [13] In Formula (IX),

[00696] R1 is more preferably methyl;

[00697] R2 is more preferably isopropyl or tert-butyl which can be substituted with fluorine or cyclopropyl, or

[00698] cyclopropyl that can be substituted with methyl; It is

[00699] X is more preferably

[00700] N or

[00701] CR3, where R3 is hydrogen.

[00702] Furthermore, [14] in Formulas (I), (II), and (IX) of the present invention, when X is N,

[00703] R1 is preferably

[00704] halogen,

[00705] cyan,

[00706] C1-C6 substituted or unsubstituted alkyl,

[00707] C3-C7 substituted or unsubstituted cycloalkyl,

[00708] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00709] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00710] R2 is preferably

[00711] C1-C10 substituted or unsubstituted alkyl,

[00712] C3-C7 substituted or unsubstituted cycloalkyl,

[00713] C2-C6 substituted or unsubstituted alkenyl, or

[00714] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[00715] Furthermore, [15] in Formulas (I), (II), and (IX) of the present invention, when X is CR3 (R3 is as defined above),

[00716] R1 is preferably

[00717] halogen,

[00718] C1-C6 substituted or unsubstituted alkyl, or

[00719] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00720] R2 is preferably

[00721] C1-C10 substituted or unsubstituted alkyl,

[00722] C3-C7 substituted or unsubstituted cycloalkyl, or

[00723] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[00724] Specific examples of the compound of the present invention include, but are not limited to, compounds produced in the Examples described below.

[00725] Specific preferred examples of Compound (I) are as follows:

[00726] [16]

[00727] (1) 4-amino-1-cyclopentyl-N-(5-ethyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 1 );

[00728] (2) 4-amino-1-cyclopentyl-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 2);

[00729] (3) 4-amino-1-cyclopentyl-N-(5-(furan-3-yl)-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 3);

[00730] (4) 4-amino-1-cyclopentyl-N-(5-(thiophen-2-yl)-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 4);

[00731] (5) 4-amino-1-cyclopentyl-N-(5-phenyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 5 );

[00732] (6) 4-amino-1-cyclopentyl-N-(5-cyclopentyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 6 );

[00733] (7) 4-amino-1-cyclopentyl-N-(5-cyclopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 7 );

[00734] (8) 4-amino-1-cyclopentyl-N-(3-propyl-1H-pyrazol-5-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 8 );

[00735] (9) 4-amino-1-cyclopentyl-N-(1,3-dimethyl-1H-pyrazol-5-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 9);

[00736] (10) 4-amino-1-cyclopentyl-N-(5-isopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 10 );

[00737] (11) 4-amino-1-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 11 );

[00738] (12) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-((1-methylcyclopropyl)methyl)-1H-pyrazolo [3,4-d]pyrimidine-3 -carboxamide (example compound 12);

[00739] (13) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-(2,2,2-trifluoroethyl)- 1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 13);

[00740] (14) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-(3,3,3-trifluoropropyl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 14);

[00741] (15) 4-amino-1-(sec-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 15);

[00742] (16) 4-amino-1-(cyclobutylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 16);

[00743] (17) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclobutylmethyl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 17);

[00744] (18) 4-amino-1-(cyclopropylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 18);

[00745] (19) 4-amino-1-(cyclopentylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 19);

[00746] (20) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclopentylmethyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 20);

[00747] (21) 4-amino-1-isopropyl-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 21);

[00748] (22) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 22 );

[00749] (23) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-((1R,2R)-2-methylcyclohexyl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 23);

[00750] (24) 4-amino-1-(4,4-dimethylcyclohexyl)-N-(5-methyl-1H-pyrazol- 3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 24);

[00751] (25) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 25);

[00752] (26) 4-amino-1-(3,3-dimethylcyclobutyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 26);

[00753] (27) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 27);

[00754] (28) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-bromo-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 28);

[00755] (29) 1-(adamantan-2-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 29);

[00756] (30) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-((2S,3R)-2,6,6-trimethylbicyclo [3.1.1]heptan-3 -yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide (example compound 30);

[00757] (31) 4-amino-1-(3-fluoroprop-1-en-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 31);

[00758] (32) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-cyclohexyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 32);

[00759] (33) 4-amino-1-cyclohexyl-N-(5-(difluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 33);

[00760] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[00761] (35) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 35);

[00762] (36) 4-amino-1-(tert-butyl)-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 36);

[00763] (37) 4-amino-1-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)- 1H-pyrazole [3,4-d] pyrimidine-3-carboxamide (example compound 37);

[00764] (38) 4-amino-1-(tert-butyl)-N-(5-cyano-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 38);

[00765] (39) 4-amino-1-(tert-butyl)-N-(5-ethyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 39);

[00766] (40) 4-amino-1-(tert-butyl)-N-(5-isopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 40);

[00767] (41) 4-amino-1-(tert-butyl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 41);

[00768] (42) 4-amino-1-(tert-butyl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 42);

[00769] (43) 4-amino-1-(4,4-difluorocyclohexyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 43);

[00770] (44) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(4,4-difluorocyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 44);

[00771] (45) 4-amino-7-isopropyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 45 );

[00772] (46) 4-amino-7-(1-fluoropropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 46);

[00773] (47) 4-amino-7-(4,4-dimethylcyclohexyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 47);

[00774] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[00775] (49) 4-amino-7-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)- 7H-pyrrole [2,3-d] pyrimidine-5-carboxamide (example compound 49);

[00776] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[00777] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51);

[00778] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 52);

[00779] (53) 4-amino-7-(1-methoxy-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 53);

[00780] (54) 4-amino-7-(1-(fluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide (example compound 54);

[00781] (55) 4-amino-7-(1-(difluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide (example compound 55);

[00782] (56) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2-(thiophen-2-yl)propan-2-yl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 56);

[00783] (57) 4-amino-7-(3,3-difluorocyclopentyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5- carboxamide (example compound 57);

[00784] (58) 4-amino-7-(bicyclo [1.1.1]pentan-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 58);

[00785] (59) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopentyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 59);

[00786] (60) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2-phenylpropan-2-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 60);

[00787] (61) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2,3,3-trimethylbutan-2-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 61);

[00788] (62) 4-amino-7-(2,3-dimethylbutan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide (example compound 62);

[00789] (63) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(tert-butyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 63);

[00790] (64) 4-amino-7-(tert-butyl)-N-(5-(methoxymethyl)-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5- carboxamide (example compound 64);

[00791] (65) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 65 );

[00792] (66) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-fluoro-2-methylpropan-2-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 66);

[00793] (67) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 67);

[00794] (68) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclobutyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 68);

[00795] (69) 4-amino-7-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 69 );

[00796] (70) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(tert-pentyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 70);

[00797] (71) 4-amino-7-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 71);

[00798] (72) 4-amino-7-cyclopentyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 72 );

[00799] (73) 4-amino-7-(tert-butyl)-6-methyl-N-(3-methyl-1H-pyrazol-5-yl)- 7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 73);

[00800] (74) 7-([1,1'-bi(cyclopropan)]-1-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [ 2,3-d]pyrimidine-5-carboxamide (example compound 74);

[00801] (75) 4-amino-6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 75);

[00802] (76) 4-amino-6-bromo-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 76);

[00803] (77) 4-amino-6-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 77);

[00804] (78) 4-amino-6-chloro-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [ 2,3-d]pyrimidine-5-carboxamide (example compound 78);

[00805] (79) 4-amino-6-(3-hydroxy-3-methyl-1-butyn-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1 -methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 79);

[00806] (80) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(pyridin-3-ylethynyl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide (example compound 80);

[00807] (81) 4-amino-6-((1-hydroxycyclopentyl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 81);

[00808] (82) 4-amino-6-((1-methyl-1H-pyrazol-4-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 82);

[00809] (83) 4-amino-6-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 83);

[00810] (84) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(3-morpholino-1-propyn-1-yl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 84);

[00811] (85) 4-amino-6-(3-(1-hydroxycyclobutyl)-1-propyne)-N-(5-methyl- 1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 85);

[00812] (86) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-((tetrahydro-2H-pyran-4-yl) ethynyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 86);

[00813] (87) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-6-((1-methyl-1H-pyrazol-3-yl)ethynyl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 87);

[00814] (88) 4-amino-6-(imidazo [1,2-b]pyridazin-3-ylethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl )-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 88);

[00815] (89) 4-amino-6-ethoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 89); It is

[00816] (90) (R)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2-yl) methoxy)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 90).

[00817] More preferred examples of Compound (I) are as follows:

[00818] [17]

[00819] (27) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 27);

[00820] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[00821] (45) 4-amino-7-isopropyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 45 );

[00822] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[00823] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[00824] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51);

[00825] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 52);

[00826] (65) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 65 );

[00827] (68) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclobutyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 68);

[00828] (71) 4-amino-7-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 71);

[00829] (72) 4-amino-7-cyclopentyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 72 );

[00830] (79) 4-amino-6-(3-hydroxy-3-methyl-1-butyn-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1 -methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 79);

[00831] (80) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(pyridin-3-ylethynyl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide (example compound 80);

[00832] (81) 4-amino-6-((1-hydroxycyclopentyl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 81);

[00833] (82) 4-amino-6-((1-methyl-1H-pyrazol-4-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 82);

[00834] (83) 4-amino-6-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 83);

[00835] (84) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(3-morpholino-1-propyn-1-yl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 84); It is

[00836] (85) 4-amino-6-(3-(1-hydroxycyclobutyl)-1-propyne)-N-(5-methyl- 1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 85).

[00837] Even more preferred examples of Compound (I) are as follows:

[00838] [18]

[00839] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[00840] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[00841] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[00842] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51); It is

[00843] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 52).

[00844] Furthermore, the present invention provides a RET inhibitor comprising the compound or a salt thereof according to any one of [1] to [18] as an active ingredient.

[00845] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [1] to [18].

[00846] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [1] to [18], wherein the pharmaceutical composition prevents or treats a disease that can be treated by RET inhibition.

[00847] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [1] to [18].

[00848] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [1] to [18], wherein the antitumor agent treats a malignant tumor with enhanced RET activation.

[00849] Furthermore, the present invention provides the compound or a salt thereof according to any one of [1] to [18] for use in preventing or treating a malignant tumor.

[00850] Furthermore, the present invention provides the compound or a salt thereof according to any one of [1] to [18] for use in preventing or treating a malignant tumor, wherein the malignant tumor is a malignant tumor with enhanced activation of RET.

[00851] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [1] to [18] to produce an antitumor agent.

[00852] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [1] to [18] to produce an antitumor agent, wherein the antitumor agent is an antitumor agent for treating a tumor malignant disease with enhanced RET activation.

[00853] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [1] to [18] to produce a RET inhibitor.

[00854] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [1] to [18] to a mammal.

[00855] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [1] to [18] to a mammal, wherein Malignant tumor is a malignant tumor with enhanced RET activation.

[00856] Furthermore, the present invention provides a method of inhibiting RET comprising administering the compound or a salt thereof according to any one of [1] to [18] to a mammal.

[00857] Furthermore, the present invention provides

[00858] [19] a compound represented by formula (I') below or a salt thereof:

[00859] where A is pyrazolyl substituted by number n of R1;

[00860] R1 is

[00861] halogen,

[00862] cyan,

[00863] C1-C6 substituted or unsubstituted alkyl,

[00864] C3-C7 substituted or unsubstituted cycloalkyl,

[00865] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00866] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00867] R2 is

[00868] C1-C10 substituted or unsubstituted alkyl,

[00869] C3-C4 substituted or unsubstituted cycloalkyl,

[00870] C2-C6 substituted or unsubstituted alkenyl,

[00871] C3-C4 substituted or unsubstituted cycloalkenyl,

[00872] C4-C12 substituted or unsubstituted bridged cycloalkyl,

[00873] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00874] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00875] X is

[00876] N or

[00877] CR3, where R3 is

[00878] hydrogen,

[00879] halogen,

[00880] cyan,

[00881] C1-C6 substituted or unsubstituted alkyl,

[00882] C2-C6 substituted or unsubstituted alkenyl,

[00883] C2-C6 substituted or unsubstituted alkynyl,

[00884] C1-C6 substituted or unsubstituted alkoxy,

[00885] substituted or unsubstituted amino,

[00886] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00887] a substituted or unsubstituted monocyclic or polycyclic C3-C10 unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00888] n is an integer from 0 to 3,

[00889] where when n is 2 or 3, R1 can be identical or different from each other.

[00890] [20] In Formula (I’),

[00891] A is preferably pyrazolyl substituted with number n of R1;

[00892] R1 is preferably

[00893] halogen,

[00894] cyan,

[00895] C1-C6 substituted or unsubstituted alkyl,

[00896] C3-C7 substituted or unsubstituted cycloalkyl,

[00897] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00898] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00899] R2 is preferably

[00900] C1-C10 substituted or unsubstituted alkyl,

[00901] C3-C4 substituted or unsubstituted cycloalkyl,

[00902] C2-C6 substituted or unsubstituted alkenyl, or

[00903] C4-C12 substituted or unsubstituted bridged cycloalkyl,

[00904] X is preferably

[00905] N or

[00906] CR3, where R3 is

[00907] hydrogen,

[00908] halogen,

[00909] C1-C6 substituted or unsubstituted alkyl,

[00910] C2-C6 substituted or unsubstituted alkenyl, or

[00911] substituted or unsubstituted C1-C6 alkoxy; It is

[00912] n is preferably an integer from 1 to 3, where when n is 2 or 3, R1 can be identical or different from each other.

[00913] [21] In Formula (I’),

[00914] A is pyrazolyl substituted by number n of R1;

[00915] R1 is more preferably

[00916] halogen;

[00917] cyan;

[00918] C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy;

[00919] C3-C7 cycloalkyl;

[00920] phenyl; or

[00921] a monocyclic unsaturated C3-C6 heterocyclic group containing an oxygen atom or a sulfur atom;

[00922] R2 is more preferably

[00923] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more heterocyclic groups unsaturated C3-C6 monocyclics containing one oxygen atom or one sulfur atom;

[00924] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00925] C2-C6 alkenyl that can be substituted with halogen; or

[00926] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl;

[00927] X is more preferably

[00928] N or

[00929] CR3, where R3 is

[00930] hydrogen;

[00931] halogen;

[00932] C1-C6 alkyl;

[00933] C2-C4 alkynyl that can be replaced with

[00934] C1-C6 alkyl that can be substituted with hydroxy,

[00935] C3-C7 cycloalkyl that can be substituted with hydroxy,

[00936] one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[00937] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00938] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00939] n is more preferably 1 or 2,

[00940] where when n is 2, R1 can be identical or different from each other.

[00941] In another embodiment of the present invention, a compound of Formula (I') in which pyrazolyl is linked to an amide structure in position 3 is preferred. Furthermore, a preferred embodiment of the compound of Formula (I') in which pyrazolyl is attached to an amide structure at position 3 in the present invention is

[00942] [22] a compound represented by formula (II') below or a salt thereof:

[00943] where R1 is

[00944] halogen,

[00945] cyan,

[00946] C1-C6 substituted or unsubstituted alkyl,

[00947] C3-C7 substituted or unsubstituted cycloalkyl,

[00948] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[00949] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur;

[00950] R2 is

[00951] C1-C10 substituted or unsubstituted alkyl,

[00952] C3-C4 substituted or unsubstituted cycloalkyl,

[00953] C2-C6 substituted or unsubstituted alkenyl, or

[00954] C4-C12 substituted or unsubstituted bridged cycloalkyl;

[00955] X is

[00956] N or

[00957] CR3, where R3 is

[00958] hydrogen,

[00959] halogen,

[00960] C1-C6 substituted or unsubstituted alkyl,

[00961] C2-C6 substituted or unsubstituted alkynyl, or

[00962] substituted or unsubstituted C1-C6 alkoxy; It is

[00963] n is an integer from 1 to 3, where when n is 2 or 3, R1 can be identical or different from each other.

[00964] In the present invention, the compound represented by Formula (II') above is also referred to simply as Compound (II').

[00965] [23] In Formula (II’),

[00966] R1 is more preferably

[00967] halogen;

[00968] cyan;

[00969] C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy;

[00970] C3-C7 cycloalkyl;

[00971] phenyl; or

[00972] a monocyclic unsaturated C3-C6 heterocyclic group containing an oxygen atom or a sulfur atom;

[00973] R2 is more preferably

[00974] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more heterocyclic groups unsaturated C3-C6 monocyclics containing one oxygen atom or one sulfur atom;

[00975] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00976] C2-C6 alkenyl that can be substituted with halogen; or

[00977] C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl;

[00978] X is more preferably

[00979] N or

[00980] CR3, where R3 is

[00981] hydrogen;

[00982] halogen;

[00983] C1-C6 alkyl;

[00984] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected nitrogen, oxygen, and sulfur, or

[00985] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[00986] C1-C4 alkoxy that can be replaced with one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[00987] n is more preferably 1 or 2,

[00988] where when n is 2, R1 can be identical or different from each other.

[00989] [24] In Formula (II’),

[00990] R1 is more preferably

[00991] halogen;

[00992] cyan;

[00993] C1-C6 alkyl that can be substituted with halogen;

[00994] C3-C7 cycloalkyl;

[00995] phenyl; or

[00996] a monocyclic unsaturated C3-C6 heterocyclic group containing an oxygen atom or a sulfur atom;

[00997] R2 is more preferably C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or a or more monocyclic C3-C6 unsaturated heterocyclic groups containing an oxygen atom or a sulfur atom;

[00998] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[00999] C2-C6 alkenyl that can be substituted with halogen; or

[001000] C4-C12 bridged cycloalkyl; It is

[001001] X is more preferably

[001002] N or

[001003] CR3, where R3 is

[001004] hydrogen;

[001005] halogen;

[001006] C1-C4 alkyl,

[001007] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy;

[001008] C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or

[001009] one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that can be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or

[001010] C1-C4 alkoxy; It is

[001011] n is more preferably 1 or 2, where when n is 2, R1 can be identical or different from each other.

[001012] [25] In Formula (II’),

[001013] R1 is more preferably

[001014] halogen,

[001015] cyan, or

[001016] C1-C4 alkyl that can be substituted with halogen;

[001017] R2 is more preferably

[001018] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[001019] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[001020] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[001021] C2-C6 alkenyl that can be substituted with halogen; or

[001022] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl;

[001023] X is more preferably

[001024] N or

[001025] CR3, where R3 is

[001026] hydrogen; or

[001027] C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected from nitrogen, oxygen, and sulfur, or one or more unsaturated C3-C6 monocyclic heterocyclic groups that may be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is more preferably an integer of 1.

[001028] Preferred in another embodiment of the present invention is

[001029] [26] a compound represented by formula (IX') below or a salt thereof:

[001030] where R1 is

[001031] halogen;

[001032] cyan;

[001033] C1-C6 alkyl that can be substituted with halogen;

[001034] C3-C7 cycloalkyl;

[001035] phenyl; or

[001036] a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom;

[001037] R2 is

[001038] C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more heterocyclic groups unsaturated C3-C6 monocyclics containing one oxygen atom or one sulfur atom;

[001039] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl;

[001040] C2-C6 alkenyl that can be substituted with halogen; or

[001041] C4-C12 bridged cycloalkyl; It is

[001042] X is

[001043] N or

[001044] CR3, where R3 is

[001045] hydrogen;

[001046] halogen;

[001047] C1-C4 alkyl;

[001048] C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected from nitrogen, oxygen, and sulfur, or one or more unsaturated C3-C10 monocyclic or polycyclic heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different hetero-atoms selected from nitrogen, oxygen, and sulfur; or C1-C4 alkoxy.

[001049] In the present invention, the compound represented by Formula (IX') above is also referred to simply as Compound (IX').

[001050] [27] In Formula (IX’),

[001051] R1 is more preferably

[001052] halogen,

[001053] cyan, or

[001054] C1-C4 alkyl that can be substituted with halogen;

[001055] R2 is more preferably

[001056] C1-C4 linear alkyl that is substituted with C3-C7 cycloalkyl;

[001057] C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[001058] C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;

[001059] C2-C6 alkenyl that can be substituted with halogen; or

[001060] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl; It is

[001061] X is more preferably

[001062] N or

[001063] CR3, where R3 is

[001064] hydrogen; or

[001065] C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected from nitrogen, oxygen, and sulfur, or one or more unsaturated C3-C6 monocyclic heterocyclic groups that may be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[001066] [28] In Formula (IX’),

[001067] R1 is more preferably

[001068] bromine,

[001069] cyan, or

[001070] C1-C4 alkyl that can be substituted with fluorine;

[001071] R2 is more preferably C1-C4 linear alkyl which is substituted with C3-C7 cycloalkyl;

[001072] C3-C6 branched alkyl that can be substituted with fluorine, C3-C7 cycloalkyl, one or more monocyclic C3-C6 unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy;

[001073] C3-C4 cycloalkyl that can be substituted with fluorine, C1 C4 alkyl, or C3-C5 cycloalkyl;

[001074] C2-C6 alkenyl that can be substituted with fluorine; or

[001075] C4-C12 bridged cycloalkyl selected from bicyclo [1.1.1]pentan-1-yl and bicyclo [2.2.1]heptan-2-yl; It is

[001076] X is more preferably

[001077] N or

[001078] CR3, where R3 is

[001079] hydrogen; or

[001080] C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical heteroatoms or different selected from nitrogen, oxygen, and sulfur, or one or more unsaturated C3-C6 monocyclic heterocyclic groups that may be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur.

[001081] Furthermore, in another embodiment of the present invention, [29] in Formula (IX'),

[001082] R1 is more preferably halogen or C1-C4 alkyl;

[001083] R2 is more preferably C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl, C3-C4 cycloalkyl that can be substituted with C1-C4 alkyl, or

[001084] bicyclo [2.2.1]heptan-2-yl; It is

[001085] X is more preferably

[001086] N or

[001087] CR3, where R3 is

[001088] hydrogen; or

[001089] ethynyl or propynyl that is substituted with C1-C4 alkyl that can be substituted with hydroxy, C3-C5 cycloalkyl that can be substituted with hydroxy, one or more monocyclic C3-C6 saturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen and oxygen, or one or more unsaturated C3-C6 monocyclic heterocyclic groups that can be substituted with methyl and contain 1 to 3 nitrogen atoms.

[001090] [30] In Formula (IX’),

[001091] R1 is more preferably bromine or methyl;

[001092] R2 is more preferably C3-C6 branched alkyl that can be substituted with fluorine or C3-C5 cycloalkyl, or

[001093] C3-C4 cycloalkyl that can be substituted with methyl; It is

[001094] X is more preferably

[001095] N or

[001096] CR3, where R3 is hydrogen.

[001097] [31] In Formula (IX’),

[001098] R1 is more preferably methyl;

[001099] R2 is more preferably isopropyl or tert-butyl which can be substituted with fluorine or cyclopropyl, or

[001100] cyclopropyl that can be substituted with methyl; It is

[001101] X is more preferably

[001102] N or

[001103] CR3, where R3 is hydrogen.

[001104] Furthermore, [32] in Formulas (I'), (II'), and (IX') of the present invention, when X is N,

[001105] R1 is preferably

[001106] halogen,

[001107] cyan,

[001108] C1-C6 substituted or unsubstituted alkyl,

[001109] C3-C7 substituted or unsubstituted cycloalkyl,

[001110] substituted or unsubstituted C6-C14 aromatic hydrocarbon, or

[001111] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[001112] R2 is preferably

[001113] C1-C10 substituted or unsubstituted alkyl,

[001114] C3-C4 substituted or unsubstituted cycloalkyl,

[001115] C2-C6 substituted or unsubstituted alkenyl, or

[001116] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[001117] Furthermore, in Formulas (I'), (II'), and (IX') of the present invention, when X is CR3 (R3 is as defined above),

[001118] R1 is preferably

[001119] halogen,

[001120] C1-C6 substituted or unsubstituted alkyl, or

[001121] a substituted or unsubstituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; It is

[001122] R2 is preferably

[001123] C1-C10 substituted or unsubstituted alkyl,

[001124] C3-C4 substituted or unsubstituted cycloalkyl, or

[001125] C4-C12 substituted or unsubstituted bridged cycloalkyl.

[001126] Specific examples of the compound of the present invention include, but are not limited to, compounds produced in the Examples described below.

[001127] Specific preferred examples of Compound (I') are as follows:

[001128] (11) 4-amino-1-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 11 );

[001129] (12) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-((1-methylcyclopropyl)methyl)-1H-pyrazolo [3,4-d]pyrimidine-3 -carboxamide (example compound 12);

[001130] (13) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-(2,2,2-trifluoroethyl)- 1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 13);

[001131] (14) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-(3,3,3-trifluoropropyl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide (example compound 14);

[001132] (15) 4-amino-1-(sec-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 15);

[001133] (16) 4-amino-1-(cyclobutylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 16);

[001134] (17) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclobutylmethyl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 17);

[001135] (18) 4-amino-1-(cyclopropylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 18);

[001136] (19) 4-amino-1-(cyclopentylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 19);

[001137] (20) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclopentylmethyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 20);

[001138] (21) 4-amino-1-isopropyl-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (compound of example 21);

[001139] (22) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide (example compound 22 );

[001140] (26) 4-amino-1-(3,3-dimethylcyclobutyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 26);

[001141] (27) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 27);

[001142] (28) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-bromo-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 28);

[001143] (29) 1-(adamantan-2-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 29);

[001144] (30) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1-((2S,3R)-2,6,6-trimethylbicyclo [3.1.1]heptan-3 -yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide (example compound 30);

[001145] (31) 4-amino-1-(3-fluoroprop-1-en-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 31);

[001146] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[001147] (35) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 35);

[001148] (36) 4-amino-1-(tert-butyl)-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide (example compound 36);

[001149] (37) 4-amino-1-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)- 1H-pyrazole [3,4-d] pyrimidine-3-carboxamide (example compound 37);

[001150] (38) 4-amino-1-(tert-butyl)-N-(5-cyano-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 38);

[001151] (39) 4-amino-1-(tert-butyl)-N-(5-ethyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 39);

[001152] (40) 4-amino-1-(tert-butyl)-N-(5-isopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 40);

[001153] (41) 4-amino-1-(tert-butyl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 41);

[001154] (42) 4-amino-1-(tert-butyl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 42);

[001155] (45) 4-amino-7-isopropyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 45 );

[001156] (46) 4-amino-7-(1-fluoropropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide (example compound 46);

[001157] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[001158] (49) 4-amino-7-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)- 7H-pyrrole [2,3-d] pyrimidine-5-carboxamide (example compound 49);

[001159] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[001160] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51);

[001161] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 52);

[001162] (53) 4-amino-7-(1-methoxy-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 53);

[001163] (54) 4-amino-7-(1-(fluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide (example compound 54);

[001164] (55) 4-amino-7-(1-(difluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide (example compound 55);

[001165] (56) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2-(thiophen-2-yl)propan-2-yl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 56);

[001166] (58) 4-amino-7-(bicyclo [1.1.1]pentan-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 58);

[001167] (60) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2-phenylpropan-2-yl))-7H-pyrrolo [2,3-d]pyrimidine -5-carboxamide (example compound 60);

[001168] (61) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2,3,3-trimethylbutan-2-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 61);

[001169] (62) 4-amino-7-(2,3-dimethylbutan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide (example compound 62);

[001170] (63) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(tert-butyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 63);

[001171] (64) 4-amino-7-(tert-butyl)-N-(5-(methoxymethyl)-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5- carboxamide (example compound 64);

[001172] (65) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 65 );

[001173] (66) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-fluoro-2-methylpropan-2-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 66);

[001174] (67) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 67);

[001175] (68) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclobutyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 68);

[001176] (69) 4-amino-7-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 69 );

[001177] (70) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(tert-pentyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 70);

[001178] (71) 4-amino-7-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 71);

[001179] (73) 4-amino-7-(tert-butyl)-6-methyl-N-(3-methyl-1H-pyrazol-5-yl)- 7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 73);

[001180] (74) 7-([1,1'-bi(cyclopropan)]-1-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [ 2,3-d]pyrimidine-5-carboxamide (example compound 74);

[001181] (75) 4-amino-6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 75);

[001182] (76) 4-amino-6-bromo-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 76);

[001183] (77) 4-amino-6-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 77);

[001184] (78) 4-amino-6-chloro-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [ 2,3-d]pyrimidine-5-carboxamide (example compound 78);

[001185] (79) 4-amino-6-(3-hydroxy-3-methyl-1-butyn-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1 -methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 79);

[001186] (80) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(pyridin-3-ylethynyl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide (example compound 80);

[001187] (81) 4-amino-6-((1-hydroxycyclopentyl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 81);

[001188] (82) 4-amino-6-((1-methyl-1H-pyrazol-4-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 82);

[001189] (83) 4-amino-6-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 83);

[001190] (84) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(3-morpholino-1-propyn-1-yl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 84);

[001191] (85) 4-amino-6-(3-(1-hydroxycyclobutyl)-1-propyne)-N-(5-methyl- 1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 85);

[001192] (86) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-((tetrahydro-2H-pyran-4-yl) ethynyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 86);

[001193] (87) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-6-((1-methyl-1H-pyrazol-3-yl)ethynyl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 87);

[001194] (88) 4-amino-6-(imidazo [1,2-b]pyridazin-3-ylethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl )-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 88);

[001195] (89) 4-amino-6-ethoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 89); It is

[001196] (90) (R)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2-yl) methoxy)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 90).

[001197] More preferred examples of Compound (I') are as follows:

[001198] [35]

[001199] (27) 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4- d]pyrimidine-3-carboxamide (example compound 27);

[001200] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[001201] (45) 4-amino-7-isopropyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 45 );

[001202] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[001203] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[001204] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51);

[001205] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 52);

[001206] (65) 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 65 );

[001207] (68) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclobutyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 68);

[001208] (71) 4-amino-7-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 71);

[001209] (79) 4-amino-6-(3-hydroxy-3-methyl-1-butyn-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1 -methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 79);

[001210] (80) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(pyridin-3-ylethynyl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide (example compound 80);

[001211] (81) 4-amino-6-((1-hydroxycyclopentyl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2 ,3-d]pyrimidine-5-carboxamide (example compound 81);

[001212] (82) 4-amino-6-((1-methyl-1H-pyrazol-4-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 82);

[001213] (83) 4-amino-6-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1- methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 83);

[001214] (84) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(3-morpholino-1-propyn-1-yl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 84); It is

[001215] (85) 4-amino-6-(3-(1-hydroxycyclobutyl)-1-propyne)-N-(5-methyl- 1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)- 7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (example compound 85).

[001216] Even more preferred examples of Compound (I') are as follows:

[001217] [36] [001218] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide (example compound 34); [001219] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide ( example compound 48); [001220] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3- d]pyrimidine-5-carboxamide (example compound 50); [001221] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51); and [001222] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine -5-carboxamide (example compound 52). [001223] Furthermore, the present invention provides a RET inhibitor comprising the compound or a salt thereof according to any one of [19] to [36] as an active ingredient. [001224] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [19] to [36]. [001225] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [19] to [36], wherein the pharmaceutical composition prevents or treats a disease that can be treated by RET inhibition. [001226] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [19] to [36]. [001227] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [19] to [36], wherein the antitumor agent treats a malignant tumor with enhanced RET activation. [001228] Furthermore, the present invention provides the compound or a salt thereof according to any one of [19] to [36] for use in preventing or treating a malignant tumor. [001229] Furthermore, the present invention provides the compound or a salt thereof according to any one of [19] to [36] for use in preventing or treating a malignant tumor, wherein the malignant tumor is a malignant tumor with enhanced activation of RET. [001230] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce an antitumor agent. [001231] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce an antitumor agent, wherein the antitumor agent is an antitumor agent for treating a tumor malignant disease with enhanced RET activation. [001232] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce a RET inhibitor. [001233] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal. [001234] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal, wherein the malignant tumor is a malignant tumor with enhanced RET activation. [001235] Furthermore, the present invention provides a method of inhibiting RET comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal.

[01218] (34) 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide ( example compound 34);

[01219] (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 48);

[01220] (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide (example compound 50);

[01221] (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide ( example compound 51); It is

[01222] (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide (example compound 52).

[01223] Furthermore, the present invention provides a RET inhibitor comprising the compound or a salt thereof according to any one of [19] to [36] as an active ingredient.

[01224] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [19] to [36].

[01225] Furthermore, the present invention provides a pharmaceutical composition comprising the compound or a salt thereof according to any one of [19] to [36], wherein the pharmaceutical composition prevents or treats a disease that can be treated by RET inhibition.

[01226] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [19] to [36].

[01227] Furthermore, the present invention provides an antitumor agent comprising the compound or a salt thereof according to any one of [19] to [36], wherein the antitumor agent treats a malignant tumor with enhanced RET activation.

[01228] Furthermore, the present invention provides the compound or a salt thereof according to any one of [19] to [36] for use in preventing or treating a malignant tumor.

[01229] Furthermore, the present invention provides the compound or a salt thereof according to any one of [19] to [36] for use in preventing or treating a malignant tumor, wherein the malignant tumor is a malignant tumor with enhanced activation of RET.

[01230] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce an antitumor agent.

[01231] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce an antitumor agent, wherein the antitumor agent is an antitumor agent for treating a tumor malignant disease with enhanced RET activation.

[01232] Furthermore, the present invention provides use of the compound or a salt thereof according to any one of [19] to [36] to produce a RET inhibitor.

[01233] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal.

[01234] Furthermore, the present invention provides a method for preventing or treating a malignant tumor, the method comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal, wherein the malignant tumor is a malignant tumor with enhanced RET activation.

[01235] Furthermore, the present invention provides a method of inhibiting RET comprising administering the compound or a salt thereof according to any one of [19] to [36] to a mammal.

[001236] Next, the method for producing the compound of the present invention is described.

[001237] Compound (I) of the present invention can be produced, for example, by means of production methods below or the methods described in the Examples. Compound (I') of the present invention can also be produced by the same production method as Compound (I). However, the method for producing Compounds (I) and (I') is not limited to these reaction examples. Production method 1

[001238] where L1 is a leaving group, and R2 and R3 are as defined above.

Step 1

[001239] This step synthesizes a compound represented by formula (BB) from a compound represented by formula (AA).

[001240] Step 1 is carried out using an amino compound represented by Formula (RE1) or a salt thereof in an amount of 0.5 to 5 mols, preferably 0.9 to 1.5 mols, per mol of the compound represented by Formula (AA).

[001241] Examples of bases include inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium hydroxide, sodium hydride, and potassium hydride; and organic amines, such as trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, lutidine, and collidine. The amount of base used is 1 to 100 moles, preferably 1 to 10 moles, per mole of the compound represented by Formula (AA). The amino compound can be obtained from commercial suppliers, or can be produced by a known method. Furthermore, the reaction can be promoted by adding acid during the reaction if necessary. Examples of acids include formic acid, acetic acid, hydrochloric acid, phosphoric acid, and the like. The amount of acid used is 1 to 100 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (AA).

[001242] As the solvent used in the reaction, any solvent that does not negatively affect the reaction can be used. Examples of the solvent include alcohols (e.g., methanol and ethanol), hydrocarbons (e.g., benzene, toluene, and xylene), halogenated hydrogenated hydrocarbons (e.g., methylene chloride, chloroform, and 1,2-dichloroethane ), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane and tetrahydrofuran), polar aprotic solvents (e.g., N,N-dimethylformamide, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof.

[001243] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 48 hours. The reaction temperature ranges from 0 to 120°C, preferably 50 to 120°C.

[001244] The compound thus obtained represented by Formula (BB) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography.

Step 2

[001245] This step synthesizes a compound represented by formula (CC) from the compound represented by Formula (BB).

[001246] Step 2 is carried out using a halogenation reagent in an amount of 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (BB).

[001247] Examples of halogenation reagents include N-iodosuccinimide, N-bromosuccinimide, N-chlorosuccinimide, iodine, bromine, and the like. The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include toluene, benzene, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and mixtures thereof.

[001248] Examples of the leaving group represented by L1 include chlorine, bromine, iodine, and the like.

[001249] The reaction temperature generally ranges from -78 to 200°C, preferably 0 to 50°C. Reaction time generally ranges from 5 minutes to 6 days, preferably 10 minutes to 3 days.

[001250] The compound thus obtained represented by Formula (CC) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography.

Step 3

[001251] This step produces a compound represented by formula (DD) by reacting the compound represented by Formula (CC) with ammonia or a salt thereof. The amount of ammonia or a salt thereof used in this step is generally equimolar to the excess molar amount per mole of the compound represented by Formula (CC).

[001252] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include water, methanol, ethanol, isopropanol, tert-butyl alcohol, tetrahydrofuran, 1,4-dioxane, dimethylformamide, N-methylpyrrolidone, 1,2-dimethoxyethane, dimethyl sulfoxide, and mixtures thereof.

[001253] The reaction temperature generally ranges from 0 to 200°C, preferably room temperature to 150°C. Reaction time generally ranges from 5 minutes to 7 days, preferably 30 minutes to 48 hours.

[001254] The compound thus obtained represented by Formula (DD) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 2

[001255] wherein L1 and L2 are each a leaving group, and R2 is as defined above.

Step 4

[001256] This step produces a compound represented by formula (FF) using a compound represented by formula (EE) and a compound represented by formula (III) or (IV).

[001257] When the compound represented by Formula (III) is used as an alkylating reagent, the compound represented by Formula (FF) can be produced in the presence of a base. In Formula (III), L2 is a leaving group such as chlorine, bromine, iodine, methanesulfonic acid ester, or p-toluenesulfonic acid ester; and may be obtained from commercial suppliers, or may be produced using a known method. The amount of the compound represented by Formula (III) used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (EE).

[001258] Examples of bases include inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium hydroxide, sodium hydride, and potassium hydride; and organic amines, such as trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, lutidine, and collidine. The amount of base used is 1 to 100 moles, preferably 2 to 10 moles, per mole of the compound represented by Formula (EE).

[001259] Examples of the solvent include N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, 1,4-dioxane, N-methylpyrrolidin-2-one, acetonitrile, and the like. These solvents can be used alone or in a mixture.

[001260] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 100°C.

[001261] When the compound of Formula (IV) is used as an alkylating reagent, the compound represented by Formula (FF) can be produced through a Mitsunobu reaction. This step can generally be carried out by a known method, for example, the method disclosed in Chemical Reviews, Vol. 109, p. 2551 (2009). For example, this step can be carried out in the presence of a Mitsunobu reagent and a phosphine reagent in a solvent that does not negatively affect the reaction. This step is generally carried out using the compound represented by Formula (IV) in an amount of 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (EE).

[001262] Examples of Mitsunobu reagents include diethyl azodicarboxylate, diisopropyl azodicarboxylate, and the like. The amount of Mitsunobu reagent used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (EE).

[001263] Examples of phosphine reagents include triphenylphosphine and tributylphosphine. The amount of phosphine reagent used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (EE).

[001264] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include toluene, benzene, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and mixtures thereof.

[001265] The reaction temperature generally ranges from -78 to 200°C, preferably 0 to 50°C. Reaction time generally ranges from 5 minutes to 3 days, preferably 10 minutes to 10 hours.

[001266] The compound thus obtained represented by Formula (FF) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography.

Step 5

[001267] This step produces a compound represented by formula (GG) by reacting the compound represented by Formula (FF) with ammonia or a salt thereof. The amount of ammonia or a salt thereof used in this step is generally equimolar to the excess molar amount per mole of the compound represented by Formula (FF).

[001268] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include water, methanol, ethanol, isopropanol, tert-butyl alcohol, tetrahydrofuran, 1,4-dioxane, dimethylformamide, 1,2-dimethoxyethane, N-methylpyrrolidone, dimethylsulfoxide, and mixtures thereof.

[001269] The reaction temperature generally ranges from 0 to 200°C, preferably room temperature to 150°C. Reaction time generally ranges from 5 minutes to 7 days, preferably 30 minutes to 24 hours.

[001270] The compound thus obtained represented by Formula (GG) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 3

[001271] wherein L1 and L2 are each a leaving group, and R2 is as defined above.

Step 6

[001272] This step produces a compound represented by formula (WW) using a compound represented by formula (QQ) and a compound represented by formula (III) or (IV).

[001273] When the compound represented by Formula (III) is used as an alkylating reagent, the compound represented by Formula (WW) can be produced in the presence of a base. In Formula (III), L2 is a leaving group such as chlorine, bromine, iodine, methanesulfonic acid ester, or p-toluenesulfonic acid ester; and may be obtained from commercial suppliers, or may be produced using a known method. The amount of the compound represented by Formula (III) used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (QQ).

[001274] Examples of bases include inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium hydroxide, sodium hydride, and potassium hydride; and organic amines, such as trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, lutidine, and collidine. The amount of base used is 1 to 100 moles, preferably 2 to 10 moles, per mole of the compound represented by Formula (QQ). Examples of the solvent include N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, 1,4-dioxane, N-methylpyrrolidin-2-one, acetonitrile, and the like. These solvents can be used alone or in a mixture.

[001275] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 100°C.

[001276] When the compound of Formula (IV) is used as an alkylating reagent, the compound represented by Formula (WW) can be produced through a Mitsunobu reaction. This step can generally be carried out by a known method, for example, the method disclosed in Chemical Reviews, Vol. 109, p. 2551 (2009). For example, this step can be carried out in the presence of a Mitsunobu reagent and a phosphine reagent in a solvent that does not negatively affect the reaction. This step is generally carried out using the compound represented by Formula (IV) in an amount of 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (QQ).

[001277] Examples of Mitsunobu reagents include diethyl azodicarboxylate, diisopropyl azodicarboxylate, and the like. The amount of Mitsunobu reagent used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (QQ). Examples of phosphine reagents include triphenylphosphine and tributylphosphine. The amount of phosphine reagent used is 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (QQ).

[001278] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include toluene, benzene, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and mixtures thereof.

[001279] The reaction temperature generally ranges from -78 to 200°C, preferably 0 to 50°C. Reaction time generally ranges from 5 minutes to 3 days, preferably 10 minutes to 10 hours.

[001280] The compound thus obtained represented by Formula (WW) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 4

[001281] where L1 is a leaving group, and R2 and X are as defined above.

Step 7

[001282] This step produces a compound represented by the formula (JJ) by reacting a compound represented by the formula (HH) in a carbon monoxide atmosphere in the presence of an alcohol using, for example, a transition metal and optionally a base in a solvent that does not negatively affect the reaction.

[001283] The compound represented by Formula (HH) can be produced by steps 1 to 3, steps 4 and 5, or step 6 of the production method of the present application.

[001284] In this step, the carbon monoxide pressure is generally 1 atm to 10 atms, preferably 1 atm to 7 atms.

[001285] The amount of alcohol compound used is 1 to an excessive molar amount, preferably 1 to 200 moles, per mole of the compound represented by Formula (HH). Examples of compound compounds include methanol, ethanol, propanol, isopropyl alcohol, diethylaminoethanol, isobutanol, 4-(2-hydroxyethyl)morpholine, 3-morpholinopropanol, diethylaminopropanol, and the like.

[001286] Examples of transition metal catalysts usable in this step include palladium catalysts (e.g., palladium acetate, tris(benzylideneacetone)dipalladium, bis(triphenylphosphine)palladium(II) dichloride, dichloromethane complex of 1, 1-bis(diphenylphosphine)ferrocene-palladium(II), carbon-supported palladium, etc.). If necessary, a ligand (e.g. triphenylphosphine, xantphos, tri-tert-butylphosphine, etc.) is added. The amount of transition metal catalyst varies depending on the type of catalyst. For example, the amount of transition metal catalyst used is generally 0.0001 to 1 mol, preferably 0.001 to 0.5 mol, per mole of the compound represented by Formula (HH). The amount of ligand used is generally 0.000 1 to 4 moles, preferably 0.01 to 2 moles, per mole of the compound represented by Formula (HH).

[001287] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, colidine, 4-dimethylaminopyridine, N-methylmorpholine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and butyllithium; and inorganic bases, such as sodium hydrogencarbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, and sodium hydride. The amount of base used is generally 0.1 to 50 moles, preferably 1 to 20 moles, per mole of the compound represented by Formula (HH).

[001288] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol and ethanol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof. The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature is 0°C to 200°C, preferably 0 to 150°C.

[001289] When a mixture of an ester form corresponding to the alcohol used and a carboxylic acid compound (JJ) is obtained after this reaction, a hydrolysis reaction can be carried out to convert the mixture into a compound represented by the formula (JJ) . Hydrolysis is carried out using a base. Examples of bases include organic bases such as diethylamine, diisopropylamine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and butyllithium; and inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, and calcium hydroxide.

[001290] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol and ethanol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof.

[001291] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 150°C.

[001292] The compound thus obtained represented by Formula (JJ) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 5

[001293] where L1 is a leaving group; E is ester, cyano, or equivalent carboxylic acid, such as carboxamide; Z is halogen; and R2 and R3 are as defined above.

Step 8

[001294] This step produces an ester derivative or cyano derivative represented by Formula (KK) by reacting the compound represented by Formula (GG), in a carbon monoxide atmosphere in the presence of an alcohol, or using a carbon monoxide compound. cyano, such as copper cyanide or zinc cyanide, using, for example, a transition metal catalyst and optionally a base in a solvent that does not negatively affect the reaction.

[001295] The compound represented by Formula (GG) can be produced by steps 1 to 3, steps 4 and 5 of the production method of the present application.

[001296] In the production of the ester derivative, the carbon monoxide pressure is generally 1 atm to 10 atms, preferably 1 atm to 7 atms. The amount of the alcohol compound used as a reaction agent is 1 to an excessive molar amount, preferably 1 to 200 moles, per mole of the compound represented by Formula (GG). Examples of alcohol compounds include methanol, ethanol, propanol, isopropyl alcohol, diethylaminoethanol, isobutanol, 4-(2-hydroxyethyl)morpholine, 3-morpholinopropanol, diethylaminopropanol, and the like.

[001297] In the production of the cyano derivative, examples of the cyano compound used as a reaction agent include copper cyanide, zinc cyanide, tri-n-butylcyanotine, and the like. The amount of the cyano compound used as an agent is generally 1 to 100 moles, preferably 1 to 10 moles, per mole of the compound represented by Formula (GG).

[001298] Examples of transition metal catalysts usable in this step for both the production of the ester derivative and the production of the cyano derivative include palladium catalysts (e.g., palladium acetate, tetracys triphenylphosphine palladium, tris(benzylideneacetone)dipalladium, bis(triphenylphosphine)palladium(II) dichloride, 1,1-bis(diphenylphosphine)ferrocene-palladium(II) dichloromethane complex, carbon-supported palladium, etc.). If necessary, a ligand (e.g. triphenylphosphine, xantphos, tri-tert-butylphosphine, etc.) is added. The amount of transition metal catalyst varies depending on the type of catalyst. For example, the amount of transition metal catalyst used is generally 0.0001 to 1 mol, preferably 0.001 to 0.5 mol, per mol of the compound represented by Formula (GG). The amount of ligand used is generally 0.0001 to 4 moles, preferably 0.01 to 2 moles, per mole of the compound represented by Formula (GG).

[001299] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, collidine, 4-dimethylaminopyridine, N-methylmorpholine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, hexamethyl - lithium disilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and butyllithium; and inorganic bases, such as sodium hydrogencarbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, and sodium hydride. The amount of base used is generally 0.1 to 50 moles, preferably 1 to 20 moles, per mole of the compound represented by Formula (GG).

[001300] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol and ethanol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof. The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature is 0°C to 200°C, preferably 0 to 150°C. The compound thus obtained represented by Formula (KK) can be subjected to the subsequent step after, or without, isolation and purification by known means of separation and purification, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation, and chromatography. .

Step 9

[001301] This step produces a halogen compound (LL) by treating the compound represented by Formula (KK) with a halogenating agent.

[001302] This step is generally carried out using a halogenated reagent in an amount of 1 to 10 moles, preferably 1 to 5 moles, per mole of the compound represented by Formula (KK).

[001303] Examples of halogenating reagents include 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), N-iodosuccinimide, N-bromosuccinimide, N-chlorosuccinimide, iodine, bromine, and similar. The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include dichloromethane, chloroform, toluene, benzene, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and mixtures thereof.

[001304] Examples of the halogen represented by Z include fluorine, chlorine, bromine, iodine, and the like.

[001305] The reaction temperature generally ranges from -78 to 200°C, preferably 0 to 50°C. Reaction time generally ranges from 5 minutes to 6 days, preferably 10 minutes to 3 days.

[001306] The compound thus obtained represented by Formula (LL) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography.

[001307] Furthermore, E can be converted to another E, if necessary, by a known method, such as hydrolysis or solvolysis. For example, cyano can be converted to carboxamide by hydrolysis, and cyano or carboxamide can be converted to ester by solvolysis.

Step 10

[001308] This step produces a compound represented by formula (MM) by subjecting the compound represented by Formula (LL) to a coupling reaction with a borate derivative, boric acid derivative, tin derivative, acetylene derivative, or derivative of alkoxide having R3 using, for example, a transition metal and optionally a base in a solvent that does not negatively affect the reaction.

[001309] The amount of the borate derivative, boric acid derivative, tin derivative, acetylene derivative, or alkoxide derivative that has R3 used is 1 to 100 mol, preferably 1 to 20 mol. Examples of transition metal catalysts usable in this step include palladium catalysts (e.g., palladium acetate, tetracys triphenylphosphine palladium, tris(benzylideneacetone)dipalladium, bis(triphenylphosphine)palladium(II) dichloride, dichloromethane dichloride complex of 1,1-bis(diphenylphosphine)ferrocene-palladium(II), etc.). If necessary, a ligand (e.g., triphenylphosphine, xantphos, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, tricyclohexylphosphine, tri-tert-butylphosphine, etc.) is added. Examples of copper catalysts include copper iodide, copper bromide, and copper chloride. The amount of transition metal catalyst varies depending on the type of catalyst. For example, the amount of transition metal catalyst used is generally 0.0001 to 1 mol, preferably 0.001 to 0.5 mol, per mol of the compound represented by Formula (LL). Transition metal catalysts can be used in combination if necessary. The amount of ligand used is generally 0.000 1 to 4 moles, preferably 0.01 to 2 moles, per mole of the compound represented by Formula (LL).

[001310] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, collidine, 4-dimethylaminopyridine, N-methylmorpholine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, hexamethyl - lithium disilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and butyllithium; and inorganic bases, such as sodium hydrogencarbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium hydroxide, and sodium hydride. The amount of base used is generally 0.1 to 50 moles, preferably 1 to 20 moles, per mole of the compound represented by Formula (LL).

[001311] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol , ethanol, and ethylene glycol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof.

[001312] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 160°C. Furthermore, the reaction can be carried out while appropriately protecting the compound represented by Formula (LL) with a protecting group, such as Boc (tert-butoxycarbonyl), and then the protecting group can be removed.

[001313] The compound thus obtained represented by Formula (MM) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 6

[001314] wherein E, R2, and R3 are as defined above.

Step 11

[001315] This step produces a carboxylic acid compound represented by Formula (NN) by hydrolyzing the compound represented by Formula (MM).

[001316] Hydrolysis is carried out using a base or an acid. Examples of bases include organic bases such as diethylamine, diisopropylamine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide , and butyllithium; and inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, and calcium hydroxide. Examples of acids include hydrochloric acid, sulfuric acid, phosphoric acid, and the like.

[001317] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol , ethanol, and ethylene glycol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof.

[001318] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 160°C.

[001319] The compound thus obtained represented by Formula (NN) can be subjected to the subsequent step after, or without, isolation and purification by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation , and chromatography. Production method 7

[001320] wherein A, R2, and X are as defined above.

Step 12

[001321] This step produces a compound represented by formula (I) by carrying out an amidation reaction using the compound represented by Formula (JJ) and a compound represented by formula (VII). This step is carried out in the presence of a suitable condensing agent or activating agent such as an amidating reagent, using the compound of Formula (VII) in an amount of 0.5 to 10 mol, preferably 1 to 3 mol, per mol of the compound represented by Formula (JJ).

[001322] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include isopropanol, tert-butyl alcohol, toluene, benzene, methylene chloride, chloroform, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, acetonitrile, and mixtures thereof.

[001323] The reaction temperature generally ranges from -78 to 200°C, preferably 0 to 100°C. The reaction time generally ranges from 5 minutes to 7 days, preferably 5 minutes to 3 days, more preferably 5 minutes to 1 day.

[001324] Examples of condensing agents and activating agents include diphenylphosphoryl azide, N,N'-dicyclohexylcarbodiimide, benzotriazol-1-yloxy-trisdimethylaminophosphonium salt, 4-(4,6-dimethoxy-1,3 ,5-triazin-2-yl)-4-methylmorpholinium, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, combination of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole, 2- chloro-1,3-dimethylimidazolinium, (dimethylamino)-N,N-dimethyl(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methaniminium hexafluorophosphate, 1,1-carbonyldiimidazole , N-hydroxysuccinic acid imide, and the like.

[001325] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, collidine, 4-dimethylaminopyridine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, lithium hexamethyldisilazide, hexamethyldisilazide sodium, potassium hexamethyldisilazide, diazabicycloundecene, diazabicyclononene, and butyllithium; and inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, and sodium hydride. The amount of base added is 1 to 100 moles, preferably 1 to 10 moles, per mole of the compound represented by Formula (JJ).

[001326] After completion of the reaction, a base, such as a sodium hydroxide solution, can be added to perform post-treatment.

[001327] The compound thus obtained represented by Formula (I) can be isolated and purified by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation, and chromatography. Production method 8

[001328] wherein L1 is a leaving group, and A, R2, and X are as defined above.

Step 13

[001329] This step produces a compound represented by formula (I) by reacting the compound represented by Formula (HH) in the presence of Compound (VII) in a carbon monoxide atmosphere using, for example, a transition metal and optionally a base in a solvent that does not negatively affect the reaction.

[001330] In this step, the carbon monoxide pressure is 1 atm to 10 atms, preferably 1 atm to 7 atms.

[001331] Examples of transition metal catalysts usable in this step include palladium catalysts (e.g., palladium acetate, tris(dibenzylideneacetone)dipalladium, bis(triphenylphosphine)palladium(II) dichloride, dichloromethane complex of 1, 1-bis(diphenylphosphine)ferrocene-palladium(II), carbon-supported palladium, etc.). If necessary, a ligand (e.g. triphenylphosphine, xantphos, tri-tert-butylphosphine, etc.) is added. The amount of transition metal catalyst varies depending on the type of catalyst. For example, the amount of transition metal catalyst used is generally 0.0001 to 1 mol, preferably 0.001 to 0.5 mol, per mole of the compound represented by Formula (HH). The amount of ligand used is generally 0.000 1 to 4 moles, preferably 0.01 to 2 moles, per mole of the compound represented by Formula (HH).

[001332] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, collidine, 4-dimethylaminopyridine, N-methylmorpholine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, hexamethyl - lithium disilazide, sodium hexamethyldisilazide, 1,8-diazabicyclo [5.4.0]undec-7-ene, potassium hexamethyldisilazide, and butylithium; and inorganic bases, such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, and sodium hydride. The amount of base used is generally 0.1 to 50 moles, preferably 1 to 20 moles, per mole of the compound represented by Formula (HH).

[001333] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol and ethanol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof. The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature is 0°C to 250°C, preferably 0 to 200°C.

[001334] The compound thus obtained represented by Formula (I) can be isolated and purified by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation, and chromatography. Production method 9

[001335] wherein A, R2, and R3 are as defined above.

[001336] This step produces a compound represented by the formula (SS) by subjecting a compound represented by the formula (RR) to a coupling reaction with a borate derivative, boric acid derivative, tin derivative, or acetylene derivative having R3 using, for example, a transition metal and optionally a base in a solvent that does not negatively affect the reaction.

[001337] The amount of the borate derivative, boric acid derivative, tin derivative, or acetylene derivative that has R3 used is 1 to 100 mol, preferably 1 to 20 mol. Examples of transition metal catalysts usable in this step include palladium catalysts (e.g., palladium acetate, tetracys triphenylphosphine palladium, tris(benzylideneacetone)dipalladium, bis(triphenylphosphine)palladium(II) dichloride, dichloromethane complex of 1 ,1-bis(diphenylphosphine)ferrocene-palladium(II), etc.). If necessary, a ligand (e.g., triphenylphosphine, xanthos, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, tricyclohexylphosphine, tri-tert-butylphosphine, etc.) is added. Examples of copper catalysts include copper iodide, copper bromide, and copper chloride. The amount of transition metal catalyst varies depending on the type of catalyst. For example, the amount of transition metal catalyst used is generally 0.0001 to 1 mol, preferably 0.001 to 0.5 mol, per mole of the compound represented by Formula (RR). Transition metal catalysts can be used in combination if necessary. The amount of ligand used is generally 0.000 1 to 4 moles, preferably 0.01 to 2 moles, per mole of the compound represented by Formula (RR).

[001338] Furthermore, a base can be added during the above reaction if necessary. Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, lutidine, collidine, 4-dimethylaminopyridine, N-methylmorpholine, potassium tert-butyrate, sodium tert-butyrate, sodium methoxide, sodium ethoxide, hexamethyl - lithium disilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and butyllithium; and inorganic bases, such as sodium hydrogencarbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium hydroxide, and sodium hydride. The amount of base used is generally 0.1 to 50 moles, preferably 1 to 20 moles, per mole of the compound represented by Formula (RR).

[001339] The reaction solvent is not particularly limited, and any solvent that does not negatively affect the reaction can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, and xylene), nitriles (e.g., acetonitrile), ethers (e.g., dimethoxyethane, tetrahydrofuran, and 1,4-dioxane), alcohols (e.g., methanol , ethanol, and ethylene glycol), polar aprotic solvents (e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethylsulfoxide, and hexamethylphosphoramide), water, and mixtures thereof.

[001340] The reaction time varies from 0.1 to 100 hours, preferably 0.5 to 24 hours. The reaction temperature varies from 0°C to the boiling temperature of the solvent, preferably 0 to 160°C.

[001341] The compound thus obtained represented by Formula (SS) can be isolated and purified by known separation and purification means, such as concentration, vacuum concentration, crystallization, solvent extraction, reprecipitation, and chromatography.

[001342] When the compound of the present invention has isomers, such as optical isomers, stereoisomers, regioisomers, and rotational isomers, mixtures of any of the isomers are included within the scope of the compound of the present invention. For example, when the compound of the present invention has optical isomers, the optical isomer separated from a racemic mixture is also included within the scope of the compound of the present invention. Each of such isomers can be obtained as a simple compound by known means of synthesis and separation (e.g. concentration, solvent extraction, column chromatography, recrystallization, etc.).

[001343] The compound or a salt thereof of the present invention may be in the form of crystals. Single crystals and polymorphic mixtures are included within the scope of the compound or a salt thereof of the present invention. Such crystals can be produced by crystallization in accordance with a crystallization method known per se in the art. The compound or a salt thereof of the present invention may be a solvate (e.g., a hydrate) or a non-solvate. Any such form is included within the scope of the compound or a salt thereof of the present invention. Compounds labeled with an isotope (e.g., 2H, 3H, 13C, 14C, 35S, 125I, etc.) are also included within the scope of the compound or a salt thereof of the present invention.

[001344] A prodrug of the compound or a salt thereof of the present invention refers to a compound that can be converted to the compound or a salt thereof of the present invention through a reaction with an enzyme, gastric acid, or the like , under in vivo physiological conditions, for example, a compound that can be converted to the compound or a salt thereof of the present invention by enzymatic oxidation, reduction, hydrolysis, or the like; or a compound that can be converted to the compound or a salt thereof of the present invention by hydrolysis with gastric acid or the like. Furthermore, the prodrug of the compound or a salt thereof of the present invention may be compounds that can be converted to the compound or a salt thereof of the present invention under physiological conditions, such as those described in "Iyakuhin no Kaihatsu [Deve-lopment of Pharmaceuticals],” Vol. 7, Molecular Design, published 1990 by Hirokawa Shoten Co., pp. 163-198.

[001345] The salt of the compound of the present invention refers to a common salt used in the field of organic chemistry. Examples of such salts include base addition salts to a carboxyl group when the compound has a carboxyl group, and acid addition salts to a basic amino or heterocyclic group when the compound has a basic amino or heterocyclic group.

[001346] Examples of base addition salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; ammonium salts; and organic amine salts such as trimethylamine salts, triethylamine salts, dicyclohexylamine salts, ethanolamine salts, diethanolamine salts, triethanolamine salts, procaine salts, and N,N'-dibenzylethylenediamine salts.

[001347] Examples of acid addition salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, and perchlorate; organic acid salts such as acetate, formate, maleate, fumarate, tartrate, citrate, ascorbate, and trifluoroacetate; and sulfonates such as methanesulfonate, isethionate, benzenesulfonate, and p-toluenesulfonate.

[001348] The compound or a salt thereof of the present invention has superior RET inhibitory activity and is useful as an antitumor agent. Preferable antitumor agents are antitumor agents to treat malignant tumors with enhanced RET activation. The compound or a salt thereof of the present invention has excellent RET selectivity and has the advantage that there are few side effects caused by inhibition of other kinases.

[001349] In the present specification, "RET” means RET (rearranged during transfection) tyrosine kinase, and includes human RET and non-human mammalian RET, preferably human RET. Furthermore, the term "RET” includes isoforms.

[001350] Furthermore, due to its excellent RET inhibitory activity, the compound or a salt thereof of the present invention is useful as a pharmaceutical preparation for the prevention and treatment of RET-related diseases. Examples of "RET-related diseases" include diseases whose incidence can be reduced, and whose symptoms can be alleviated, alleviated, and/or completely cured by deletion, suppression, and/or inhibition of RET function. RET-related diseases” are preferably diseases that can be treated by RET inhibition. Examples of such diseases include, but are not limited to, malignant tumors, etc. Examples of malignant tumor include those with enhanced RET activation. Malignant tumor with enhanced RET activation refers to a malignant tumor with enhanced RET activation due to translocation, mutation (including point mutation and gene fusion mutation), and overexpression (including states in which the copy number of the RET gene increases, RET messenger RNA is overexpressed, the number of RET proteins increases, and RET proteins are constantly activated) of the RET gene.

[001351] The type of malignant tumor to be treated by the compound or a salt thereof of the present invention is not particularly limited. Examples of malignant tumors include epithelial cancers (cancers of the respiratory system, cancers of the digestive system, cancers of the reproductive system, cancers of the secretory system, etc.), sarcomas, hematopoietic tumors, tumors of the central nervous system, and tumors of the peripheral nerve .

[001352] Specific examples of the type of cancer include head and neck cancer, thyroid cancer, esophageal cancer, gastric cancer, duodenal cancer, liver cancer, biliary tract cancer (gallbladder, cholangiocarcinoma, etc.), breast cancer pancreas, colorectal cancer (colonic cancer, rectal cancer, etc.), lung cancer (non-small cell lung cancer, small cell lung cancer, mesothelioma, etc.), breast cancer, ovarian cancer , uterine cancer (cervical cancer, endometrial cancer, etc.), kidney cancer, renal pelvis ureteral cancer, bladder cancer, prostate cancer, testicular tumor, leukemia, malignant lymphoma, multiple myeloma, osteosarcoma, soft tissue sarcoma, cancer skin tumor, brain tumor, adrenal tumor, neuroblastoma, and the like.

[001353] The target cancer is preferably lung cancer (non-small cell lung cancer, small cell lung cancer, mesothelioma, etc.), colorectal cancer (colorectal cancer, rectal cancer, etc.), thyroid cancer , breast cancer, brain tumor, and leukemia; more preferably non-small cell lung cancer and thyroid cancer; and more preferably non-small cell lung cancer and thyroid cancer with enhanced RET activation. The meaning of the phrase "enhanced activation of RET" is as defined above.

[001354] The pharmaceutical composition comprising the compound or a salt thereof of the present invention is preferably a pharmaceutical composition for preventing or treating diseases that can be treated by RET inhibition. Preferred pharmaceutical compositions are antitumor agents. When the compound or a salt thereof of the present invention is used as a pharmaceutical preparation, a pharmaceutical carrier may be added, if required, thereby forming a suitable dosage form in accordance with prevention and treatment purposes. Examples of the dosage form include oral preparations, injections, suppositories, ointments, plasters, and the like. Such dosage forms may be formed by methods conventionally known to those skilled in the art.

[001355] As the pharmaceutical carrier, various conventional inorganic or organic carrier materials used as preparation materials can be mixed as an excipient, binder, disintegrant, lubricant, or coating agent in solid preparations; or as a solvent, solubilizing agent, suspending agent, isotonizing agent, pH adjuster/buffer, or calming agent in liquid preparations. Furthermore, pharmaceutical preparation additives, such as antiseptics, antioxidants, colorants, sweeteners, and stabilizers, can be used if necessary.

[001356] Examples of excipients include lactose, sucrose, D-mannitol, starch, crystalline cellulose, calcium silicate, and the like.

[001357] Examples of binders include hydroxypropyl cellulose, methyl cellulose, polyvinylpyrrolidone, candy powder, hypromellose, and the like.

[001358] Examples of disintegrants include sodium starch glycolate, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxy propyl cellulose, partially pregelatinized starch, and the like.

[001359] Examples of lubricants include talc, magnesium stearate, sucrose fatty acid ester, stearic acid, sodium stearyl fumarate, and the like.

[001360] Examples of coating agents include ethyl cellulose, RS aminoalkyl methacrylate copolymer, hypromellose, sucrose, and the like.

[001361] Examples of solvents include water, propylene glycol, physiological saline, and the like.

[001362] Examples of solubilizing agents include polyethylene glycol, ethanol, α-cyclodextrin, macrogol 400, polysorbate 80, and the like.

[001363] Examples of suspending agents include carrageenan, crystalline cellulose/sodium carmellose, polyoxyethylene hydrogenated castor oil, and the like.

[001364] Examples of isotonizing agents include sodium chloride, glycerin, potassium chloride, and the like.

[001365] Examples of pH adjusters/buffers include sodium citrate, hydrochloric acid, lactic acid, phosphoric acid, sodium dihydrogen phosphate, and the like.

[001366] Examples of calming agents include procaine hydrochloride, lidocaine, and the like.

[001367] Examples of antiseptics include ethyl parahydroxybenzoate, cresol, benzalkonium chloride, and the like.

[001368] Examples of antioxidants include sodium sulfite, ascorbic acid, natural vitamin E, and the like.

[001369] Examples of colorants include titanium oxide, iron sesquioxide, Food Blue No. 1, copper chlorophyll, and the like.

[001370] Examples of sweeteners include aspartame, saccharin, sucralose, l-menthol, mint flavor, and the like.

[001371] Examples of stabilizers include sodium pyrosulfite, disodium edetate, erythorbic acid, magnesium oxide, dibutylhydroxytoluene, and the like.

[001372] When a solid preparation for oral administration is prepared, an excipient, optionally an excipient, a binder, a disintegrant, a lubricant, a colorant, a sweetener, and the like, can be added to the compound of the present invention; and the resulting mixture can be formulated into tablets, coated tablets, granules, powders, capsules, etc., according to a common method.

[001373] When an injection is prepared, a pH adjuster, a buffer, a stabilizer, an isotonizing agent, a local anesthetic, and the like can be added to the compound of the present invention; and the resulting mixture can be formulated into subcutaneous, intramuscular, and intravenous injections according to a common method.

[001374] The amount of the compound of the present invention to be incorporated into each of the unit dosage forms depends on the condition of the patient to whom the compound is administered, the dosage form, etc. In general, in the case of an oral agent, an injection, and a suppository, the amount of the compound of the present invention is preferably 0.05 to 1000 mg, 0.01 to 500 mg, and 1 to 1000 mg, respectively. valy, per unit dosage form.

[001375] The daily dose of medicine in such a dosage form depends on the patient's condition, body weight, age, gender, etc., and cannot be generalized. For example, the daily dose of the compound of the present invention for an adult (body weight: 50 kg) may generally be 0.05 to 5000 mg, and preferably 0.1 to 1000 mg; and is preferably administered in one dose, or in two to three divided doses, per day.

[001376] In the present invention, examples of mammals to which compound (I) or a salt thereof is administered include humans, monkeys, mice, rats, rabbits, dogs, cats, cows, horses, pigs, sheep, and the like.

Examples

[001377] The following describes the present invention in more detail with reference to the Examples. However, the present invention is not limited to the Examples.

[001378] Commercially available reagents were used in the Examples, unless otherwise specified. For silica gel column chromatography, the following columns were used: SI Purif-Pack (trademark) produced by Moritex Corp., silica prepacked column KP-Sil (trademark) produced by Biotage, prepackaged column -packed with HP-Sphere silica (registered trademark) produced by Biotage, or column pre-packed with HP-Sil silica (registered trademark) produced by Biotage. For basic silica gel column chromatography, an NH Purif-Pack (trademark) produced by Moritex Corp. or prepackaged KP-NH (trademark) column produced by Biotage was used. For preparative thin layer chromatography, Kieselgel TM 60F 254, Art. 5744 produced by Merck or an NH2 Silica Gel 60F254 plate produced by Wako was used. NMR spectra were measured using an AL400 (400 MHz; produced by JEOL), model Mercury 400 spectrometer (400 MHz; produced by Agilent Technologies, Inc.), or model Inova 400 spectrometer (400 MHz; produced by Agilent Technologies, Inc. ) equipped with an OMNMR probe (Protasis). The measurement was performed using tetramethylsilane as an internal standard when tetramethylsilane was contained in a deuterated solvent; otherwise, an NMR solvent was used as an internal standard. All d values are shown in ppm. Microwave reaction was carried out using an Initiator produced by Biotage.

[001379] LCMS spectra were measured using an Acquity SQD (quadrupole) produced by Waters Corporation under the following conditions.

[001380] Column: Acquity UPLC (registered trademark) BEH C18, 2.1 x 50 mm, 1.7 µm (produced by Waters Corporation)

[001381] MS detection: ESI positive

[001382] UV detection: 254 and 210 nm

[001383] Column flow rate: 0.5 mL/min

[001384] Mobile phase: Water/acetonitrile (0.1% formic acid)

[001385] Column flow rate: 0.5 mL/min Mobile phase: Water/acetonitrile (0.1% formic acid) Injection volume: gradient 1 µL

[001386] Purification by preparative reversed phase HPLC was carried out using a preparative separation system available from Gilson, Inc.

[001387] Column: CombiPrep Pro C18, 50 X 30 mml.D., S-5 µm (produced by YMC)

[001388] UV detection: 254 nm

[001389] Column flow rate: 40 mL/min

[001390] Mobile phase: Water/acetonitrile (0.1% formic acid)

[001391] Injection volume: 0.1 to 1 mL

[001392] UV detection: 254 nm Column flow rate: 40 mL/min Mobile phase: Water/acetonitrile (0.1% formic acid) Injection volume: 0.1 to 1 mL The following are the abbreviations used and the meaning of each one.

[001393] s: singlet

[001394] d: doublet

[001395] t: triplet

[001396] q: quartet

[001397] dd: double doublet

[001398] dt: double triplet

[001399] td: triple doublet

[001400] tt: triplet triplet

[001401] ddd: double double doublet

[001402] ddt: double double triplet

[001403] s: singlet d: doublet t: triplet q: quartet dd: double doublet dt: double triplet td: triple doublet tt: triple triplet ddd: double double doublet ddt: double double triplet dtd: double triple doublet

[001404] tdd: double triple doublet

[001405] m: multiplet

[001406] br: wide

[001407] brs: broad singlet

[001408] CDI: carbonyldiimidazole

[001409] DMSO-d6: deuterated dimethyl sulfoxide

[001410] CDCl3: deuterated chloroform

[001411] CD3OD: deuterated methanol

[001412] THF: tetrahydrofuran

[001413] DMF: N,N-dimethylformamide

[001414] DMA: N,N-dimethylacetamide

[001415] NMP: 1-methyl-2-pyrrolidinone

[001416] DMSO: dimethyl sulfoxide

[001417] HATU: (dimethylamino)-N,N-dimethyl(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methane iminium hexafluorophosphate

[001418] DIAD: diisopropyl azodicarboxylate

[001419] DIPEA: diisopropylethylamine

[001420] DME: 1,2-dimethoxyethane

[001421] Reference Example 1: Synthesis of 4-amino-1-cyclopentyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[001422] Step 1: Synthesis of 1-cyclopentyl-3-iodo-1H-pyrazolo [3,4- d]pyrimidin-4-amine

[001423] A suspension of 3.0 g of 3-iodo-1H-pyrazole [3,4-d]pyrimidin-4-amine synthesized according to the procedure described in International Publication No. WO2007/126841, 3.4 g of iodocyclopentane, and 4.8 g of potassium carbonate in 30 ml of DMF was heated to 80°C and stirred for 18 hours. After the resulting mixture was cooled to room temperature, 200 mL of water was added to it, followed by filtration of the solid formed. The solid was washed with water and dried, thereby obtaining 3.7 g of the title compound as a yellow solid.

[001424] Physical Properties: m/z [M+H]+ 330.1.

[001425] Step 2: Synthesis of 4-amino-1-cyclopentyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[001426] 21 g of 1-cyclopentyl-3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine obtained in step 1, 42 ml of 2-diethylaminoethanol, and 2.24 g of Pd(PPh3 )2Cl2 were dissolved in 120 ml of NMP, and the interior of the system was replaced with carbon monoxide, followed by heating to 120°C. After stirring for 2 hours, the resulting mixture was cooled to room temperature, and 50 ml of methanol was added thereto. 19 ml of a 5N aqueous sodium hydroxide solution was again added thereto and stirred for 30 minutes. After adding water, the aqueous layer was washed with ethyl acetate, and the washed aqueous layer was adjusted with hydrochloric acid to a pH of 3. The precipitated solid was collected by filtration, washed with water, and dried, thereby obtaining 9 .8 g of the title compound as a pale yellow solid.

[001427] Physical Properties: m/z [M+H]+ 248.3.

[001428] Reference Example 2: Synthesis of 4-amino-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[001429] Step 1: Synthesis of 1-(4,4-dimethylcyclohexyl)-3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine

[001430] 6.08 ml of diisopropyl azodicarboxylate were added to a solution of 4 g of 3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine, 5.89 g of 4, 4-dimethylcyclohexanol, and 8.0 g of triphenylphosphine in 30 mL of THF at room temperature, followed by stirring overnight. After concentration, the residue was purified by silica gel chromatography (hexane -> hexane/ethyl acetate = 1/1), thereby obtaining 3.9 g of the title compound as a white solid.

[001431] Physical Properties: m/z [M+H]+ 373.1.

[001432] Step 2: Synthesis of 4-amino-1-(4,4-dimethylcyclohexyl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[001433] 3.14 g of 1-(4,4-dimethylcyclohexyl)-3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine obtained in step 1, 5.61 mL of 2 -diethylaminoethanol, and 297 mg of Pd(PPh3)2Cl2 were dissolved in 15 mL of NMP, and the interior of the system was replaced with carbon monoxide, followed by heating to 120°C. After stirring for 2 hours, the resulting mixture was cooled to room temperature, and 15 mL of methanol was added thereto. 6.9 mL of a 5N aqueous sodium hydroxide solution was again added thereto and stirred for 30 minutes. After adding water, the aqueous layer was washed with ethyl acetate, and the washed aqueous layer was adjusted with hydrochloric acid to a pH of 3. The precipitated solid was collected by filtration, washed with water, and dried, thereby obtaining 2 .2 g of the title compound as a pale yellow solid.

[001434] Physical Properties: m/z [M+H]+ 290.3.

[001435] Reference Example 3: Synthesis of 4-amino-1-(tert-butyl)-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid

[001436] Step 1: Synthesis of methyl 4-amino-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylate

[001437] 3.33 g of triethylamine and 1.35 g of a dichloromethane complex of 1,1'-bis(diphenylphosphine)ferrocene-palladium(II) dichloride were added to a suspension of 4.45 g of 3-bromo-1-(tert-butyl)- 1H-pyrazolo [3,4-d]pyrimidin-4-amine in 45 mL of methanol. The mixture was stirred in a carbon monoxide atmosphere in an autoclave at 0.5 MPa and 100°C for 3 hours. After cooling, the mixture was dissolved in chloroform, washed with water, and dried over anhydrous sodium sulfate. The dried mixture was then filtered and concentrated. The residue obtained was purified by silica gel column chromatography (hexane-ethyl acetate), and the solid obtained was suspended and washed with hexane-ethyl acetate. After filtration, the solid was dried at 70°C under reduced pressure, thereby obtaining 2.37 g of the title compound as a pale orange solid.

[001438] Physical Properties: m/z [M+H]+ 250.1.

[001439] Step 2: Synthesis of 4-amino-1-(tert-butyl)-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid

[001440] 2.23 g of methyl 4-amino-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylate obtained in step 1 of Reference Example 3 were suspended in 33 ml of methanol, and 3.58 mL of a 5 M aqueous sodium hydroxide solution was added thereto. The mixture was heated under reflux with stirring for 30 minutes. After cooling, the reaction solution was neutralized with a 5 M aqueous hydrochloric acid solution and diluted with water to collect the precipitated solid by filtration. The solid obtained was dried at 60°C under reduced pressure, thereby obtaining 2.05 g of the title compound as a colorless solid.

[001441] Physical Properties: m/z [M+H]+ 236.3.

[001442] Reference Example 4: Synthesis of 4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[001443] Step 1: Synthesis of 1-(4,4-difluorocyclohexyl)-3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine

[001444] 1.6 mL of diisopropyl azodicarboxylate was added to a solution of 1.6 g of 3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine, 1.0 g of 4 ,4-difluorocyclohexanol, and 2.1 g of triphenylphosphine in 50 mL of THF at room temperature, followed by stirring overnight. After concentration, the mixture was suspended and washed with methanol and filtered. The solid obtained was dried at 60°C under reduced pressure, thereby obtaining 1.5 g of the title compound as a colorless solid.

[001445] Physical Properties: m/z [M+H]+ 380.2.

[001446] Step 2: Synthesis of methyl 4-amino-1-(4,4-difluorocyclohexyl)- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxylate

[001447] A mixture solution of 1.5 g of 1-(4,4-difluorocyclohexyl)-3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine obtained in step 1 of Example Reference 4, 330 mg of a dichloromethane complex of 1,1'-bis(diphenylphosphine)ferrocene-palladium(II) dichloride, and 3 mL of N,N-diisopropylethylamine in 30 mL of methanol was stirred in a carbon monoxide atmosphere in an autoclave at 0.45 MPa and 100°C for 2 hours. After cooling, the mixture was concentrated and purified by silica gel column chromatography (hexane-ethyl acetate). After concentration, the crude product obtained was repurified by basic silica gel chromatography (hexane-ethyl acetate), and the solid obtained was suspended and washed with hexane-ethyl acetate, followed by filtration and drying under reduced pressure, thereby obtaining 650 mg of the title compound as a colorless solid.

[001448] Physical Properties: m/z [M+H]+ 312.1.

[01449] Step 3: Synthesis of 4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid

[01450] According to the step 2 synthesis procedure in Reference Example 3, using 653 mg of methyl-4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazole [3,4-d ]pyrimidine-3-carboxylate obtained in step 2 above, in place of methyl 4-amino-1-(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate used in step 2 of Example Reference 3.605 mg of the title compound was obtained as a colorless solid.

[01451] Physical Properties: m/z [M+H]+ 298.1.

[01452] Reference Example 5: Synthesis of tert-butyl 5-amino-3-methyl-1H-pyrazol-1-carboxylate

[01453] 75 g of 5-methyl-1H-pyrazol-3-amine were dissolved in 800 ml of dichloromethane, and 750 ml of a 5N aqueous NaOH solution were added thereto. 184.5 g of di-tert-butyl dicarbonate were added to the solution, and the mixture was stirred at room temperature for 3 days. Water was added to the solution, followed by chloroform extraction. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The organic solution was concentrated under reduced pressure, and the solid obtained was washed with hexane, thereby obtaining 68 g of the title compound as a white solid.

[01454] Physical Properties: m/z [M+H]+ 198.1 NMR (DMSO-d6) dppm 1.51(s,9H),1.98(s,3H),5.13(s,1H),6.23(s, 2H).

[01455] Reference Example 6: Synthesis of 4-amino-7-isopropyl-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid

[01456] Step 1: Synthesis of 4-chloro-5-iodo-7-isopropyl-7H-pyrrole [2,3-d]pyrimidine

[01457] 5.79 mL of DIAD was added to a solution of 4.0 g of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine, 2.58 g of propan-2-ol , and 7.51 g of triphenylphosphine in 30 mL of tetrahydrofuran. The reaction solution was stirred for 18 hours. The reaction solution was concentrated, and the residue obtained was purified by silica gel chromatography (hexane -> hexane/ethyl acetate = 1/1), thereby obtaining 4.0 g of the title compound as a pale yellow solid .

[01458] Physical Properties: m/z [M+H]+ 322.0.

[01459] Step 2: Synthesis of 5-iodo-7-isopropyl-7H-pyrrole [2,3- d]pyrimidin-4-amine

[01460] 30 mL of 1,2-dimethoxyethane and 30 mL of 28% ammonia water were added to 3 g of 4-chloro-5-iodo-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine obtained in step 1 above, and the mixture was stirred in a pressure-resistant stainless tube at 115°C for 18 hours. 300 mL of water was added to a reaction solution, and the solid obtained was washed with water, thereby obtaining 2.0 g of the title compound as a white solid.

[01461] Physical Properties: m/z [M+H]+ 303.1.

[01462] Step 3: Synthesis of 4-amino-7-isopropyl-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid

[01463] 3.8 g of 5-iodo-7-isopropyl-7H-pyrrolo [2,3-d]pyrimidin-4-amine obtained in step 2 above, 8.3 mL of 2-diethylamino ethanol, and 0. 44 g of Pd(PPh3)2Cl2 were dissolved in 10 mL of NMP, and the interior of the system was replaced with carbon monoxide, followed by heating to 120°C. After stirring for 2 hours, the reaction mixture was cooled to room temperature, and 7 mL of methanol was added thereto. 3.5 mL of a 5N aqueous sodium hydroxide solution was added again, and the mixture was stirred for 30 minutes. After adding water, the aqueous layer was washed with ethyl acetate and adjusted with hydrochloric acid to a pH of 3, followed by filtration of the precipitated solid. The solid obtained was washed with water and dried, thereby obtaining 0.670 g of the title compound as a pale yellow solid.

[01464] Physical Properties: m/z [M+H]+ 221.2.

[01465] Reference Example 7: Synthesis of 4-amino-7-(tert-butyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid

[01466] Step 1: Synthesis of 7-(tert-butyl)-4-chloro-7H-pyrrole [2,3- d]pyrimidine

[01467] A mixture solution of 29.3 g of 2-(4,6-dichloropyrimidin-5-yl)acetaldehyde, 13.4 g of tert-butylamine, and 29.7 g of N,N-diisopropylethylamine in 200 mL of ethanol was stirred with heating under reflux for 2 hours. After cooling, the reaction mixture was concentrated. The residue was diluted with ethyl acetate, washed with water and subsequently with saturated aqueous sodium chloride solution. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel chromatography, thereby obtaining 21.5 g of the title compound as a colorless solid.

[01468] Physical Properties: m/z [M+H]+ 210.0.

[01469] Step 2: Synthesis of 7-(tert-butyl)-4-chloro-5-iodo-7H-pyrrole [2,3-d]pyrimidine

[01470] 46.7 g of N-iodosuccinimide were added to a solution of 36 g of 7-(tert-butyl)-4-chloro-7H-pyrrolo [2,3-d]pyrimidine obtained in step 1 in 360 mL of DMF, and the mixture was stirred at room temperature for 3 days. The mixture was diluted with ethyl acetate and washed with water 3 times, followed by washing with saturated aqueous sodium chloride solution. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated. The solid obtained was suspended and washed with hexane-ethyl acetate, and filtered, followed by drying under reduced pressure, thereby obtaining 45.5 g of the title compound as a pale orange solid.

[01471] Physical Properties: m/z [M+H]+ 335.9.

[01472] Step 3: Synthesis of 7-(tert-butyl)-5-iodo-7H-pyrrole [2,3- d]pyrimidin-4-amine

[01473] A suspension of 52 g of 7-(tert-butyl)-4-chloro-5-iodo-7H-pyrrole [2,3-d]pyrimidine obtained in step 2 in 180 mL of THF and 180 mL of water of 28% ammonia was stirred at 120°C for 14 hours in an autoclave. After cooling, the mixture was diluted with water to collect the precipitated solid by filtration, followed by drying at 60°C under reduced pressure, thereby obtaining 52 g of the title compound as a colorless solid.

[01474] Physical Properties: m/z [M+H]+ 317.3.

[01475] Step 4: Synthesis of methyl 4-amino-7-(tert-butyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylate

[01476] A suspension of 15 g of 7-(tert-butyl)-5-iodo-7H-pyrrole [2,3-d]pyrimidin-4-amine obtained in step 3, 1.94 g of a complex of 1 ,1'-bis(diphenylphosphine)ferrocene-palladium(II) dichloride-dichloromethane, and 13.2 mL of triethylamine in 150 mL of methanol was stirred in a carbon monoxide atmosphere in an autoclave at 100°C and 0 .45 MPa for 1.5 hours. After cooling, the reaction solution was concentrated and purified by silica gel chromatography (hexane-ethyl acetate). The solid obtained was suspended and washed with hexane-ethyl acetate, filtered, and dried under reduced pressure, thereby obtaining 9.70 g of the title compound as a dark red solid.

[01477] Physical Properties: m/z [M+H]+ 249.3.

[01478] Step 5: 4-amino-7-(tert-butyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid

[01479] 23.4 mL of a 5 M aqueous sodium hydroxide solution was added to a suspension of 9.70 g of methyl 4-amino-7-(tert-butyl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxylate obtained in step 4 in 97 mL of methanol. The mixture was stirred with heating under reflux for 2 hours. After cooling, the mixture was neutralized with a 5 M aqueous hydrochloric acid solution to precipitate a brown solid. After dilution with water, the solid was filtered and dried at 60°C under reduced pressure, thereby obtaining 8.0 g of the title compound as a brown solid.

[01480] Physical Properties: m/z [M+H]+ 235.2.

[01481] Reference Example 8: Synthesis of 7-(tert-butyl)-5-iodo-6-methyl-7H-pyrrole [2,3-d]pyrimidin-4-amine

[01482] Step 1: Synthesis of 1-(4,6-dichloropyrimidin-5-yl)propan-2-ol

[01483] 1 g of 2-(4,6-dichloropyrimidin-5-yl) acetaldehyde was dissolved in 20 mL of THF, and the reactor was cooled to -78°C. 4.36 mL of a methylmagnesium bromide diethyl ether solution (3 mol/L) was slowly added dropwise to this. At the same temperature, the mixture was stirred for 1 hour, and a saturated aqueous ammonium chloride solution was slowly added to it to terminate the reaction. The reaction mixture was stirred at room temperature for 10 minutes and placed in a separatory funnel, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and then dried over sodium sulfate to remove the solvent. The residue was purified by basic silica gel chromatography (hexane/ethyl acetate = 1/0 -> 3/1), thereby obtaining 446 mg of the title compound as a colorless oil.

[01484] Physical Properties: m/z [M+H]+ 207.0.

[01485] Step 2: Synthesis of 1-(4,6-dichloropyrimidin-5-yl)propan-2-one

[01486] 246 mg of 1-(4,6-dichloropyrimidin-5-yl)propan-2-ol obtained in step 1 were dissolved in 2.5 mL of dichloromethane, and 1.0 g of a Dess-Martin reagent was added to this, followed by stirring at room temperature for 1 hour. A 10% aqueous solution of sodium thiosulfate and saturated sodium bicarbonate water were added to a reaction solution, and the mixture was stirred again for 30 minutes. The reaction mixture was extracted with chloroform, and the organic layer was washed with water and saturated aqueous sodium chloride solution, followed by addition of sodium sulfate while drying. After removing the solvent, the residue was purified by silica gel chromatography (hexane/ethyl acetate = 1/0 -> 3/1), thereby obtaining 198 mg of the title compound as a yellow solid.

[01487] Physical Properties: m/z [M+H]+ 205.0.

[01488] Step 3: Synthesis of 1-(4-(tert-butylamino)-6-chloropyrimidin-5-yl)propan-2-one

[01489] 198 mg of 1-(4,6-dichloropyrimidin-5-yl)propan-2-one obtained in step 2, 122 µL of tert-butylamine, and 252 µL of diisopropylethylamine were dissolved in 2 mL of ethanol , and the solution was stirred at 90°C overnight.

[01490] After the reaction mixture was concentrated, the residue was purified by silica gel chromatography (hexane/ethyl acetate = 1/0 -> 3/1), thereby obtaining 64 mg of the title compound as an oil colorless.

[01491] Physical Properties: m/z [M+H]+ 242.1.

[01492] Step 4: Synthesis of 7-(tert-butyl)-4-chloro-6-methyl-7H-pyrrole [2,3-d]pyrimidine

[01493] 64 mg of 1-(4-(tert-butylamino)-6-chloropyrimidin-5-yl)propan-2-one obtained in step 3 and 42 µL of acetic acid were dissolved in 5.5 mL of ethanol, and the solution was reacted in a microwave reactor at 120°C for 1 hour. After removing the solvent, the residue was purified by silica gel chromatography (hexane/ethyl acetate =1/0 -> 4/1), thereby obtaining 54 mg of the title compound as a colorless oil.

[01494] Physical Properties: m/z [M+H]+ 224.1.

[01495] Step 5: Synthesis of 7-(tert-butyl)-4-chloro-5-iodo-6-methyl-7H-pyrrole [2,3-d]pyrimidine

[01496] 7-(tert-butyl)-4-chloro-6-methyl-7H-pyrrole [2,3-d]pyrimidine obtained in step 4 was dissolved in 1.5 mL of DMF. 64 mg of N-iodosuccinimide was added thereto, and the mixture was stirred at room temperature for. A 10% aqueous sodium thiosulfate solution was added to a reaction solution to terminate the reaction, and the reaction solution was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution, and dried over sodium sulfate, followed by removal of the solvent. The residue was purified by silica gel chromatography (hexane/ethyl acetate = 1/0 -> 4/1), thereby obtaining 69 mg of the title compound as a white solid.

[01497] Physical Properties: m/z [M+H]+ 349.9.

[01498] Step 6: 7-(tert-butyl)-5-iodo-6-methyl-7H-pyrrole [2,3-d]pyrimidin-4-amine

[01499] 60 mg of 7-(tert-butyl)-4-chloro-5-iodo-6-methyl-7H-pyrrole [2,3-d]pyrimidine obtained in step 5 were reacted with 600 µL of DME and 600 µL of ammonia water in a pressure-resistant stainless tube at 115°C for 12 hours. After air cooling, water was added to the reaction mixture. The white solid obtained was filtered and dried, thereby obtaining 45 mg of the title compound.

[01500] Physical Properties: m/z [M+H]+ 331.0.

[01501] Example 1: Synthesis of 4-amino-1-cyclopentyl-N-(5-ethyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01502] 30 mg of 4-amino-1-cyclopentyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid obtained in step 2 of Reference Example 1, 16 mg of 5-ethyl-1H-pyrazole -3-amine, and 55 mg of HATU were dissolved in 1 mL of DMF, and 62 µL of diisopropylethylamine were added to it. The mixture was stirred at room temperature for 18 hours, and water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water, and dried over anhydrous magnesium sulfate, followed by concentration of the organic solution under reduced pressure. The residue was purified by silica gel chromatography (chloroform -> chloroform/methanol = 10/1), thereby obtaining 29 mg of the title compound as a white solid.

[01503] Example 2: Synthesis of 4-amino-1-cyclopentyl-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide

[01504] According to the synthesis procedure of Example 1, using 5-(furan-2-yl)-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (55%) was obtained as a brownish solid.

[01505] Example 3: Synthesis of 4-amino-1-cyclopentyl-N-(5-(furan-3-yl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide

[01506] According to the synthesis procedure of Example 1, using 5-(furan-3-yl)-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the compound of titer (76%) was obtained as a brownish solid.

[01507] Example 4: Synthesis of 4-amino-1-cyclopentyl-N-(5-(thiophen-2-yl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide

[01508] According to the synthesis procedure of Example 1, using 5-(thiophen-2-yl)-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the compound of titer (60%) was obtained as a brownish solid.

[01509] [453]

[01510] Example 5: Synthesis of 4-amino-1-cyclopentyl-N-(5-phenyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01511] According to the synthesis procedure of Example 1, using 5-phenyl-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (77%) was obtained as a brownish solid.

[01512] Example 6: Synthesis of 4-amino-1-cyclopentyl-N-(5-cyclopentyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01513] According to the synthesis procedure of Example 1, using 5-cyclopentyl-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (63%) was obtained as a brownish solid.

[01514] Example 7: Synthesis of 4-amino-1-cyclopentyl-N-(5-cyclopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01515] According to the synthesis procedure of Example 1, using 5-cyclopropyl-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (68%) was obtained as a brownish solid.

[01516] Example 8: Synthesis of 4-amino-1-cyclopentyl-N-(3-propyl-1H-pyrazol-5-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01517] According to the synthesis procedure of Example 1, using 5-propyl-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (70%) was obtained as a brownish solid.

[01518] Example 9: Synthesis of 4-amino-1-cyclopentyl-N-(1,3-dimethyl-1H-pyrazol-5-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01519] According to the synthesis procedure of Example 1, using 1,3-dimethyl-1H-pyrazol-5-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (28%) was obtained as a white solid.

[01520] [458]

[01521] Example 10: Synthesis of 4-amino-1-cyclopentyl-N-(5-isopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01522] According to the synthesis procedure of Example 1, using 5-isopropyl-1H-pyrazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (89%) was obtained as a brownish solid.

[01523] [459]

[01524] Example 11: Synthesis of 4-amino-1-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01525] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using bromocyclobutane instead of iodocyclopentane, 4-amino-1-cyclobutyl-1H-pyrazolo[3,4-d]pyrimidine acid -3-carboxylic acid was obtained as a brownish solid. According to example procedure 1, using 4-amino-1-cyclobutyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazole acid [3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound (50%) was obtained as a brownish solid.

[01526] Example 12: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1-((1-methylcyclopropyl)methyl)-1H-pyrazolo [3,4-d]pyrimidine -3-carboxamide

[01527] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (1-methylcyclopropyl)methyl methanesulfonate instead of iodocyclopentane, 4-amino-7-((1-methylcyclopropyl)methyl) acid -7H-pyrazole [3,4-d]pyrimidine-5-carboxylic acid was obtained as a brownish solid. According to example procedure 1, using 4-amino-7-((1-methylcyclopropyl)methyl)-7H-pyrazolo[3,4-d]pyrimidine-5-carboxylic acid in place of 4-amino- 1-cyclopentyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the compound of titer (38%) was obtained as a brownish solid.

[01528] Example 13: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1-(2,2,2-trifluoroethyl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01529] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using 2,2,2-trifluoroethyl methanesulfonate instead of iodocyclopentane, 4-amino-1-(2,2,2- trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to example procedure 1, using 4-amino-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino acid -1-cyclopentyl-1H- pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound (51%) was obtained as a white solid.

[01530] Example 14: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1-(3,3,3-trifluoropropyl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01531] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using 3-bromo-1,1,1-trifluoropropane instead of iodocyclopentane, 4-amino-1-(3,3,3 -trifluoropropyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a white solid. According to Example Procedure 1, using 4-amino-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino- 1-cyclopentyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the compound of the title (84%) was obtained as a white solid.

[01532] Example 15: Synthesis of 4-amino-1-(sec-butyl)-N-(5-methyl- 1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01533] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using 2-bromobutane instead of iodocyclopentane, 4-amino-7-(sec-butyl)-7H-pyrazole acid [2 ,3-d]pyrimidine-5-carboxylic acid was obtained as a white solid. According to example procedure 1, using 4-amino-7-(sec-butyl)-7H-pyrazolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-1-cyclopentyl acid -1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound ( 62%) was obtained as a brownish solid.

[01534] Example 16: Synthesis of 4-amino-1-(cyclobutylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01535] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (bromomethyl)cyclobutane instead of iodocyclopentane, 4-amino-1-(cyclobutylmethyl)-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a white solid. According to example procedure 1, using 4-amino-1-(cyclobutylmethyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H -pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound was obtained as a brownish solid (63%).

[01536] Example 17: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclobutylmethyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01537] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (bromomethyl)cyclobutane instead of iodocyclopentane, 4-amino-1-(cyclobutylmethyl)-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a white solid. According to example procedure 1, using 5-bromo-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, and using 4-amino-1-(cyclobutylmethyl)- 1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound was obtained as a brownish solid (42%).

[01538] [466]

[01539] Example 18: Synthesis of 4-amino-1-(cyclopropylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01540] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (bromomethyl)cyclopropane instead of iodocyclopentane, 4-amino-1-(cyclopropylmethyl)-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a white solid. According to example procedure 1, using 4-amino-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H -pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound was obtained as a brownish solid (71%).

[01541] Example 19: Synthesis of 4-amino-1-(cyclopentylmethyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01542] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (bromomethyl)cyclopentane instead of iodocyclopentane, 4-amino-1-(cyclopentylmethyl)-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to Example Procedure 1, using 4-amino-1-(cyclopentylmethyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H -pyrazolo [3,4-d]pyrimidine-3-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound (53% ) was obtained as a white solid.

[01543] Example 20: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(cyclopentylmethyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01544] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using (bromomethyl)cyclopentane instead of iodocyclopentane, 4-amino-1-(cyclopentylmethyl)-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to example procedure 1, using 5-bromo-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, and using 4-amino-1-(cyclopentylmethyl)- 1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound (61% ) was obtained as a brownish solid.

[01545] Example 21: Synthesis of 4-amino-1-isopropyl-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01546] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using 2-bromopropane instead of iodocyclopentane, 4-amino-1-isopropyl-1H-pyrazole acid [3,4- d ]pyrimidine-3-carboxylic acid was obtained as a white solid. According to Example Procedure 1, using 5-(trifluoromethyl)-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, and using 4-amino-1-isopropyl- 1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid, the title compound (22% ) was obtained as a brownish solid.

[01547] Example 22: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01548] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using 2-bromopropane instead of iodocyclopentane, 4-amino-1-isopropyl-1H-pyrazole acid [3,4-d ]pyrimidine-3-carboxylic acid was obtained as a white solid. According to example procedure 1, using 5-bromo-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3-amine, and using 4-amino-1-isopropyl- 1H- pyrazole [3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, the title compound (50% ) was obtained as a brownish solid.

[01549] Example 23: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1-((1R,2R)-2-methylcyclohexyl)-1H-pyrazole [3, 4-d]pyrimidine-3-carboxamide

[01550] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using [(1S,2R)-2-methylcyclohexyl]methanesulfonate instead of iodocyclopentane, 4-amino-1-(( 1R,2R)-2-methylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to Example Procedure 1, using 4-amino-1-((1R, 2R)-2-methylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid and using 5-methyl-1H-pyrazol-3-amine in place of 5-ethyl-1H-pyrazol-3- amine, the title compound (35%) was obtained as a white solid.

[01551] Example 24: Synthesis of 4-amino-1-(4,4-dimethylcyclohexyl)- N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01552] 35 mg of 4-amino-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid obtained in step 2 in Reference Example 2, 14 mg of 5-methyl-1H-pyrazol-3-amine, and 55 mg of HATU were dissolved in 1 mL of DMF, and 63 µL of diisopropylethylamine were added to it. After stirring at room temperature for 18 hours, water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration of the organic solution under reduced pressure. The residue was purified by silica gel chromatography (chloroform -> chloroform/methanol = 10/1), thereby obtaining 27 mg of the title compound as a white solid.

[01553] Example 25: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(4,4-dimethylcyclohexyl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01554] According to the procedure of example 24, using 5-bromo-1H-pyrazol-3-amine instead of 5-methyl-1H-pyrazol-3-amine, the title compound (53%) was obtained as a brownish solid.

[01555] Example 26: Synthesis of 4-amino-1-(3,3-dimethylcyclobutyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide

[01556] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using 3,3-dimethylcyclobutanol instead of 4,4-dimethylcyclohexanol, the acid 4-amino-1-(3,3- dimethylcyclobutyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a white solid. According to the procedure of example 24, using 4-amino-1-(3,3-dimethylcyclobutyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1 -(4,4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound (47%) was obtained as a brownish solid.

[01557] Example 27: Synthesis of 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazole [3, 4-d]pyrimidine-3-carboxamide

[01558] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using bicyclo [2.2.1]heptan-2-ol instead of 4,4-dimethylcyclohexanol, the acid 4-amino-1 -(bicyclo[2.2.1]heptane)- 1H-pyrazole[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to example procedure 24, using 4-amino-1-(bicyclo[2.2.1]heptane)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino acid -1-(4,4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound (57%) was obtained as a brownish solid.

[01559] Example 28: Synthesis of 4-amino-1-(bicyclo [2.2.1]heptan-2-yl)-N-(5-bromo-1H-pyrazol-3-yl)-1H-pyrazole [3, 4-d]pyrimidine-3-carboxamide

[01560] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using bicyclo [2.2.1]heptan-2-ol instead of 4,4-dimethylcyclohexanol, the acid 4-amino-1 -(bicyclo[2.2.1]heptane)- 1H-pyrazole[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to example procedure 24, using 4-amino-1-(bicyclo[2.2.1]heptane)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino acid -1-(4,4-dimethylcyclohexyl)-1H- pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 3-bromo-1H-pyrazol-5-amine in place of 5-methyl-1H -pyrazol-3-amine, the title compound (61%) was obtained as a brownish solid.

[01561] Example 29: Synthesis of 1-(adamantan-2-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3-carboxamide

[01562] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using adamantan-2-ol instead of 4,4-dimethylcyclohexanol, the acid 1-(adamantan-2-yl)-4 -amino-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to the procedure of example 24, using 1-(adamantan-2-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo acid [3,4- d]pyrimidine-3-carboxylic acid in place of 4-amino-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound (69% ) was obtained as a brownish solid.

[01563] Example 30: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 1-((2S,3R)-2,6,6-trimethylbicyclo [3.1.1]heptan -3-yl)-1H-pyrazolo[3,4- d]pyrimidine-3-carboxamide

[01564] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using (2S,3S)-2,6,6-trimethylnorpinan-3-ol instead of 4,4-dimethylcyclohexanol, the 4-amino-1-((2S,3R)- 2,6,6-trimethylbicyclo [3.1.1]heptan-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to the procedure of example 24, using 4-amino-1-((2S,3R)-2,6,6-trimethylbicyclo [3.1.1]heptan-3-yl)-1H-pyrazole acid [3, 4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound ( 61%) was obtained as a brownish solid.

[01565] Example 31: Synthesis of 4-amino-1-(3-fluoroprop-1-en-2-yl)- N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazole [3, 4-d]pyrimidine-3-carboxamide

[01566] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using 1,3-difluoropropan-2-ol instead of 4,4-dimethylcyclohexanol, 4-amino-1-( 3-fluoroprop-1-en-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to the procedure of example 24, using 4-amino-1-(3-fluoroprop-1-en-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-(4,4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid, the title compound (65%) was obtained as a brownish solid.

[01567] Example 32: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-cyclohexyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01568] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using cyclohexanol instead of 4,4-dimethylcyclohexanol, 4-amino-1-cyclohexyl-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to the procedure of example 24, using 4-amino-1-cyclohexyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-(4, 4-dimethylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid and using 3-bromo-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, the title compound (23%) was obtained as a brownish solid.

[01569] Example 33: Synthesis of 4-amino-1-cyclohexyl-N-(5-(difluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01570] According to the synthetic procedures of steps 1 and 2 in Reference Example 2, using cyclohexanol instead of 4,4-dimethylcyclohexanol, 4-amino-1-cyclohexyl-1H-pyrazole acid [3,4- d]pyrimidine-3-carboxylic acid was obtained as a brownish solid. According to the procedure of example 24, using 4-amino-1-cyclohexyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-(4, 4-dimethylcyclohexyl)-1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 5-(difluoromethyl)-1H-pyrazol-3-amine in place of 5-methyl-1H-pyrazol-3 -amine, the title compound (41%) was obtained as a brownish solid.

[01571] Example 34: Synthesis of 4-amino-1-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01572] 429 mg of HATU were added to a suspension of 177 mg of 4-amino-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid obtained in step 2 of Example of Reference 3, 109 mg of 5-methyl-1H-pyrazol-3-amine, and 0.393 mL of N,N-diisopropylethylamine in 4 mL of DMF, and the mixture was stirred at room temperature overnight. 100 µL of 5M aqueous sodium hydroxide solution was added to the reaction solution, and stirred for 1 hour. Subsequently, the mixture was neutralized with a 5M aqueous hydrochloric acid solution. After extraction with chloroform, the extract was dried over anhydrous sodium sulfate, filtered and concentrated. The residue obtained was suspended and washed with methanol, filtered and dried at 60°C under reduced pressure, thereby obtaining 97 mg of the title compound as a colorless solid.

[01573] Example 35: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(tert-butyl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01574] According to the procedure of example 34, using 3-bromo-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, the title compound was obtained as a light brownish solid (25%).

[01575] Example 36: Synthesis of 4-amino-1-(tert-butyl)-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine- 3- carboxamide

[01576] According to the procedure of example 34, using 5-(trifluoromethyl)-1H-pyrazol-3-amine instead of 5-methyl-1H-pyrazol-3-amine, the title compound (72%) was obtained as a light brownish solid.

[01577] Example 37: Synthesis of 4-amino-1-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)-1H-pyrazole [3,4- d]pyrimidine-3-carboxamide

[01578] According to example procedure 34, using 3-(furan-2-yl)-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, the title compound ( 32%) was obtained as a light brownish solid.

[01579] Example 38: Synthesis of 4-amino-1-(tert-butyl)-N-(5-cyano- 1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01580] According to the procedure of example 34, using 5-amino-1H-pyrazol-3-carbonitrile instead of 5-methyl-1H-pyrazol-3-amine, the title compound (22%) was obtained as a brownish solid.

[01581] Example 39: Synthesis of 4-amino-1-(tert-butyl)-N-(5-ethyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01582] According to the synthesis procedure of Example 34, using 3-ethyl-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, followed by purification with preparative reverse phase HPLC , the title compound (55%) was obtained as a brownish solid.

[01583] Example 40: Synthesis of 4-amino-1-(tert-butyl)-N-(5-isopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01584] According to the synthesis procedure of Example 34, using 3-isopropyl-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, followed by purification with preparative reverse phase HPLC , the title compound (81%) was obtained as a brownish solid.

[01585] Example 41: Synthesis of 4-amino-1-(tert-butyl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01586] According to the synthesis procedure of Example 34, using 3-cyclopropyl-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, followed by purification with preparative reverse phase HPLC , the title compound (69%) was obtained as a brownish solid.

[01587] Example 42: Synthesis of 4-amino-1-(tert-butyl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3- carboxamide

[01588] According to example procedure 34, using 3-cyclobutyl-1H-pyrazol-5-amine in place of 5-methyl-1H-pyrazol-3-amine, followed by purification with preparative reverse phase HPLC, the title compound (33%) was obtained as a brownish solid.

[01589] Example 43: Synthesis of 4-amino-1-(4,4-difluorocyclohexyl)- N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01590] According to the synthesis procedure of Example 34, using 4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid obtained in step 3 of Reference Example 4 in place of 4-amino-1-(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid of Example 34, the title compound (21%) was obtained as a colorless solid.

[01591] Example 44: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-1-(4,4-difluorocyclohexyl)-1H-pyrazole [3,4-d] pyrimidine-3-carboxamide

[01592] According to the synthesis procedure of Example 34, using 4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid obtained in step 3 of Reference Example 4 in place of 4-amino-1-(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid of Example 34, and using 3-bromo-1H- pyrazol-5-amine instead of 5-methyl-1H-pyrazol-3-amine, the title compound (33%) was obtained as a colorless solid.

[01593] Example 45: Synthesis of 4-amino-7-isopropyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide

[01594] 121 mg of 5-iodo-7-isopropyl-7H-pyrrole [2,3-d]pyrimidin-4-amine obtained in step 2 of Reference Example 6, 197 mg of 5-amino-3-methyl- Tert-butyl 1H-pyrazol-1-carboxylate obtained in Reference Example 5, and 120 µL of 1,8-diazabicyclo [5.4.0]undec-7-ene were dissolved in 2 mL of DMA. 33 mg of 1,1'-bis(diphenylphosphine)ferrocene-palladium(II)-dichloromethane dichloride was also added thereto, and the mixture was stirred in a carbon monoxide atmosphere at 110°C for 4 hours. The residue obtained by concentrating the reaction mixture was purified by silica gel chromatography (hexane/ethyl acetate = 1/1 -> ethyl acetate/methanol = 10/1), thus obtaining 52 mg of the title compound as a light brown solid.

[01595] Example 46: Synthesis of 4-amino-7-(1-fluoropropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01596] According to the synthetic procedures of steps 1 and 2 in Reference Example 6, using 1-fluoropropan-2-ol instead of propan-2-ol, 7-(1-fluoropropan-2-yl)-5 -iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to example procedure 45, using 7-(1-fluoropropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 5-iodo- 7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound was obtained as a brownish solid (90%).

[01597] Example 47: Synthesis of 4-amino-7-(4,4-dimethylcyclohexyl)- N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01598] According to the synthetic procedures of steps 1 and 2 in Reference Example 6, using 4,4-dimethylcyclohexanol instead of propan-2-ol, 7-(4,4-dimethylcyclohexyl)-5 -iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a yellow solid. According to Example Procedure 45, using 7-(4,4-dimethylcyclohexyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 5-iodo-7- isopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (31%) was obtained as a brownish solid.

[01599] [496]

[01600] Example 48: Synthesis of 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d]pyrimidine-5- carboxamide

[01601] A solution of 6.0 g of 7-(tert-butyl)-5-iodo-7H-pyrrole [2,3-d]pyrimidin-4-amine obtained in step 3 of Reference Example 7, 7, 48 g of tert-butyl 5-amino-3-methyl-pyrazol-1-carboxylate obtained in Reference Example 5, 5.67 ml of 1,8-diazabicyclo [5.4.0]undec-7-ene, and 1 .55 g of a 1,1'-bis(diphenylphosphine)ferrocene-palladium(II)-dichloromethane dichloride complex in 200 mL of DMA was stirred in a carbon monoxide atmosphere at 100°C for 3 hours. The reaction solution was concentrated and then purified by silica gel chromatography (hexane-ethyl acetate-methanol), followed by purification by basic silica gel chromatography, thereby obtaining 3.24 g of the title compound as a brownish solid.

[01602] Example 49: Synthesis of 4-amino-7-(tert-butyl)-N-(5-(furan-2-yl)-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide

[01603] According to example procedure 48, using 5-(furan-2-yl)-1H-pyrazol-3-amine instead of tert-butyl 5-amino-3-methyl-pyrazol-1-carboxylate used in Example 48, the title compound (42%) was obtained as a light brownish solid.

[01604] Example 50: Synthesis of 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01605] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-fluoro-2-methylpropane-2-amine hydrochloride instead of tert-butylamine, 7-(1-fluoro -2-methylpropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to Example Procedure 48, using 7-(1-fluoro-2-methylpropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7- (tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (70%) was obtained as a brownish solid.

[01606] Example 51: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5- carboxamide

[01607] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-methylcyclopropane amine hydrochloride instead of tert-butylamine, 5-iodo-7-(1-methylcyclopropyl)-7H -pyrrole[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to Example Procedure 48, using 5-iodo-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl)-5- iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (37%) was obtained as a brownish solid.

[01608] Example 52: Synthesis of 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01609] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2-cyclopropylpropane-2-amine hydrochloride instead of tert-butylamine, 7-(2-cyclopropylpropan-2-yl )-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to the procedure of example 48, using 7-(2-cyclopropylpropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl )-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (60%) was obtained as a brownish solid.

[01610] Example 53: Synthesis of 4-amino-7-(1-methoxy-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01611] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2-methoxy-2-methylpropan-2-amine instead of tert-butylamine, 5-iodo-7-(1 -methoxy-2-methylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to Example Procedure 48, using 5-iodo-7-(1-methoxy-2-methylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7- (tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (50%) was obtained as a brownish solid.

[01612] Example 54: Synthesis of 4-amino-7-(1-(fluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine -5-carboxamide.

[01613] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-(fluoromethyl)cyclopropane amine hydrochloride instead of tert-butylamine, 7-(1-(fluoromethyl)cyclopropyl) -5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to Example Procedure 48, using 7-(1-(fluoromethyl)cyclopropyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl) -5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (60%) was obtained as a brownish solid.

[01614] Example 55: Synthesis of 4-amino-7-(1-(difluoromethyl)cyclopropyl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine -5-carboxamide

[01615] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-(difluoromethyl)cyclopropane amine hydrochloride instead of tert-butylamine, 7-(1-(difluoromethyl)cyclopropyl) -5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a yellow solid. According to Example Procedure 48, using 7-(1-(difluoromethyl)cyclopropyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl) -5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (40%) was obtained as a brownish solid.

[01616] Example 56: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(2-(thiophen-2-yl)propan-2-yl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxamide

[01617] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2-(thiophen-2-yl)propan-2-amine instead of tert-butylamine, 5-iodo-7 -(2-(thiophen-2-yl)propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a yellow solid. According to example procedure 48, using 5-iodo-7-(2-(thiophen-2-yl)propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine instead of 7-(tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (70%) was obtained as a brownish solid.

[01618] Example 57: Synthesis of 4-amino-7-(3,3-difluorocyclopentyl)- N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide

[01619] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 3,3-difluorocyclopentane amine hydrochloride in place of tert-butylamine, 7-(3,3-difluorocyclopentyl)-5 -iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a yellow solid. According to Example Procedure 48, using 7-(3,3-difluorocyclopentyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl)- 5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (50%) was obtained as a brownish solid.

[01620] Example 58: Synthesis of 4-amino-7-(bicyclo [1.1.1]pentan-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01621] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using bicyclo [1.1.1]pentane-1-amine hydrochloride instead of tert-butylamine, 7- (bicyclo [1.1.1]pentan-1-yl)-4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine was obtained. According to example procedure 48, using 7-(bicyclo[1.1.1]pentan-1-yl)-4-chloro-5-iodo-7H-pyrrole[2,3-d]pyrimidine in place of 7- (tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (36%) was obtained as a colorless solid.

[01622] Example 59: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclopentyl)-7H-pyrrolo [2,3-d]pyrimidine-5- carboxamide

[01623] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-methylcyclopentane amine hydrochloride instead of tert-butylamine, 5-iodo-7-(1-methylcyclopentyl)-7H -pyrrole[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to Example Procedure 48, using 5-iodo-7-(1-methylcyclopentyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl)-5- iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (20%) was obtained as a brownish solid.

[01624] Example 60: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(2-phenylpropan-2-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01625] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2-phenylpropan-2-amine instead of tert-butylamine, 5-iodo-7-(2-phenylpropan-2 -yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a yellow solid. According to the procedure of example 48, using 5-iodo-7-(2-phenylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert-butyl )-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (41%) was obtained as a brownish solid.

[01626] Example 61: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(2,3,3-trimethylbutan-2-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01627] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2,3,3-trimethylbutan-2-amine instead of tert-butylamine, 5-iodo-7-(2 ,3,3-trimethylbutan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to example procedure 48, using 5-iodo-7-(2,3,3-trimethylbutan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7- (tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (60%) was obtained as a brownish solid.

[01628] Example 62: Synthesis of 4-amino-7-(2,3-dimethylbutan-2-yl)-N- (5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide

[01629] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 2,3-dimethylbutane-2-amine hydrochloride instead of tert-butylamine, 7-(2,3-dimethylbutan - 2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a white solid. According to the procedure of example 48, using 7-(2,3-dimethylbutan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in place of 7-(tert -butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (50%) was obtained as a brownish solid.

[01630] Example 63: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(tert-butyl)-7H-pyrrole [2,3-d]pyrimidine-5- carboxamide

[01631] 40 mg of 4-amino-7-(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid obtained in step 5 of Reference Example 7 was suspended in 2 mL of DMF , and 33 mg of 3-bromo-1H-pyrazol-5-amine, 89 µL of diisopropylethylamine, and 78 mg of HATU were added to it, followed by stirring at room temperature overnight. 2 mL of an aqueous sodium hydroxide solution (1 mol/L) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Subsequently, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and saturated aqueous sodium chloride solution, and dried over sodium sulfate. After concentration, the residue was purified by silica gel chromatography (ethyl acetate/methanol = 1/0 - > 10/1), thereby obtaining 6.5 mg of the title compound as a white solid.

[01632] Example 64: Synthesis of 4-amino-7-(tert-butyl)-N-(5-(methoxymethyl)-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide

[01633] According to the procedure of example 63, using 5-(methoxymethyl)-1H-pyrazol-3-amine instead of 3-bromo-1H-pyrazol-5-amine, the title compound (24%) was obtained as a white solid.

[01634] Example 65: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-isopropyl-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide

[01635] According to the procedure of example 63, using 4-amino-7-isopropyl-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid obtained in step 3 of Reference Example 6 instead of the 4-amino-7-(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, the title compound (20%) was obtained as a brownish solid.

[01636] Example 66: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-fluoro-2-methylpropan-2-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01637] According to the procedure of step 3 in Reference Example 6, using 7-(1-fluoro-2-methylpropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin- 4-amine used in Example 50 in place of 7-(tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 4-amino-7-(1-fluoro- 2-methylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid was obtained. According to the procedure of example 63, using 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, the title compound (29%) was obtained as a white solid.

[01638] Example 67: Synthesis of 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5- carboxamide

[01639] According to the procedure of step 3 in Reference Example 6, using 5-iodo-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidin-4-amine used in Example 51 in instead of 7-(tert-butyl)-5-iodo-7H-pyrrolo [2,3-d]pyrimidin-4-amine, 4-amino-7-(1-methylcyclopropyl)-7H-pyrrolo acid [2, 3-d]pyrimidine-5-carboxylic acid was obtained. According to the procedure of example 63, using 4-amino-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-( tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, the title compound (19%) was obtained as a white solid.

[01640] Example 68: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclobutyl)-7H-pyrrolo [2,3-d]pyrimidine-5- carboxamide

[01641] According to the synthetic procedures of steps 1 to 5 in Reference Example 7, using 1-methylcyclobutane-amine hydrochloride instead of tert-butylamine, 4-amino-7-(methylcyclobutyl)-7H-pyrrole acid [2,3-d]pyrimidine-5-carboxylic acid was obtained as a white solid. According to the procedure of example 63, using 4-amino-7-(methylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-(tert- butyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 3-bromo-1H-pyrazol-5-amine, the compound of titer (15%) was obtained as a brownish solid.

[01642] Example 69: Synthesis of 4-amino-7-cyclobutyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide

[01643] According to the synthetic procedures of steps 1 to 5 in Reference Example 7, using cyclobutane amine instead of tert-butylamine, 4-amino-7-cyclobutyl-7H-pyrrole [2,3-d] acid pyrimidine-5-carboxylic acid was obtained. According to Example Procedure 63, using 4-amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-(tert-butyl) acid -7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 3-bromo-1H-pyrazol-5-amine, the title compound ( 8%) was obtained as a brownish solid.

[01644] Example 70: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(tert-pentyl)-7H-pyrrole [2,3-d]pyrimidine-5- carboxamide

[01645] According to the synthetic procedures of steps 1 to 5 in Reference Example 7, using 2-methylbutan-2-amine instead of tert-butylamine, the acid 4-amino-7-(tert-pentyl)-7H -pyrrole[2,3-d]pyrimidine-5-carboxylic acid was obtained as a white solid. According to the procedure of example 63, using 4-amino-7-(tert-pentyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-( tert-butyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 3-bromo-1H-pyrazol-5-amine, the title compound (16%) was obtained as a brownish solid.

[01646] Example 71: Synthesis of 4-amino-7-(bicyclo [2.2.1]heptan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrole [2, 3-d]pyrimidine-5-carboxamide

[01647] According to the synthetic procedures of steps 1 to 5 in Reference Example 7, using bicyclo[2.2.1]heptan-2-amine instead of tert-butylamine, 4-amino-7-(bicyclo[ 2.2.1]heptan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid was obtained as a white solid. According to the procedure of example 63, using 4-amino-7-(bicyclo[2.2.1]heptan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 3-bromo- 1H-pyrazol-5-amine, the title compound (8%) was obtained as a brownish solid.

[01648] Example 72: Synthesis of 4-amino-7-cyclopentyl-N-(5-methyl-1H-pyrazol-3-yl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxamide

[01649] According to the synthetic procedures of steps 1 to 3 in Reference Example 6, using cyclopentanol instead of propan-2-ol, 4-amino-7-cyclopentyl-7H-pyrrole acid [2,3 -d]pyrimidine-5-carboxylic acid was obtained as a white solid. According to Example Procedure 63, using 4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid in place of 4-amino-7-(tert-butyl) acid -7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid, and using 5-methyl-1H-pyrazol-3-amine in place of 3-bromo-1H-pyrazol-5-amine, the title compound ( 15%) was obtained as a white solid.

[01650] Example 73: Synthesis of 4-amino-7-(tert-butyl)-6-methyl-N-(3-methyl-1H-pyrazol-5-yl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01651] According to example procedure 48, using 7-(tert-butyl)-5-iodo-6-methyl-7H-pyrrole [2,3-d]pyrimidin-4-amine obtained in step 6 of Example of Reference 8 instead of 7-(tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine to carry out the reaction, the title compound (6.7%) was obtained as a white solid.

[01652] Example 74: Synthesis of 7-([1,1'-bi(cyclopropan)]-1-yl)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7H- pyrrole [2,3-d]pyrimidine-5-carboxamide

[01653] According to the synthetic procedures of steps 1, 2, and 3 in Reference Example 7, using 1-cyclopropyl cyclopropane amine hydrochloride instead of tert-butylamine, 7-([1,1'-bi (cyclopropan)]-1-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine was obtained as a brownish solid. According to Example Procedure 48, using 7-([1,1'-bi(cyclopropan)]-1-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine in Instead of 7-(tert-butyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine, the title compound (59%) was obtained as a brownish solid.

[01654] Example 75: Synthesis of 4-amino-6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01655] Step 1: Synthesis of methyl 4-amino-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

[01656] 12.1 g of triethylamine and 2.25 g of a complex of [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane were added to a suspension of 18.85 g of 5 -iodo-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine obtained as an intermediate in Example 51 in 180 ml of methanol. The mixture was stirred in a carbon monoxide atmosphere in an autoclave at 0.5 MPa and 100°C for 1.5 hours. After stirring, the solvent was removed, and the residue was dissolved in 300 mL of chloroform. 20 g of Celita was added to it, followed by stirring at room temperature for 1 hour. Insoluble matter was removed by filtration, and the filtrate was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered, followed by concentration. The residue obtained was purified by silica gel column chromatography (chloroform/methanol = 100/1 -> 20/1), and the solvent was removed. The solid obtained was suspended and washed with ethyl acetate, thereby obtaining 11.6 g of the title compound.

[01657] Step 2: Synthesis of methyl 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylate

[01658] 1.71 g of methyl 4-amino-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 1 was dissolved in 17 mL of DMF, and 1.39 g of N-chlorosuccinimide was added thereto, followed by stirring at 50°C for 2 hours. 80 mL of a 10% aqueous sodium thiosulfate solution and 120 mL of water were added to the reaction solution, and the mixture was stirred with ice-cooling for 3 hours, followed by stirring at room temperature overnight. The precipitate was collected by filtration and washed with water, thereby obtaining 1.13 g of the title compound.

[01659] Step 3: Synthesis of 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid

[01660] 272 mg of methyl 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 2 were dissolved in 2.7 mL of THF and 2.7 mL of methanol, and 1.45 mL of an aqueous solution of lithium hydroxide (4 mol/L) was added to it, followed by stirring at room temperature overnight. 20 mL of water and a 2N aqueous hydrochloric acid solution were added to the reaction solution to acidify the solution, thereby obtaining a precipitate. The organic solvent was removed, and the residue was stirred with ice-cooling for 1 hour, followed by filtration, thereby obtaining 248 mg of the title compound.

[01661] Step 4: Synthesis of 4-amino-6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01662] 2.5 mL of DMF were added to 48 mg of 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid obtained in step 3, and 33 mg of 1-hydroxybenztriazole and 38 mg of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride were also added thereto, followed by stirring at room temperature for 1.5 hours. 106 mg of tert-butyl 5-amino-3-methyl-1H-pyrazol-1-carboxylate synthesized in Reference Example 5 was added to the reaction solution, and the mixture was cooled to 0 ° C. Subsequently, 0.45 mL of a lithium hexamethyldisilazide (1M THF) solution was added to it, followed by stirring at 0°C for 30 minutes. 5 mL of a 1N aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with water three times and washed with a saturated aqueous sodium chloride solution, followed by drying over anhydrous sodium sulfate. After filtration, the resulting solution was concentrated. The residue was purified by silica gel column (ethyl acetate/methanol = 1/0 -> 8/1), thus obtaining 15 mg of the title compound.

[01663] Example 76: Synthesis of 4-amino-6-bromo-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01664] Step 1: Synthesis of methyl 4-amino-6-bromo-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylate.

[01665] 2.3 g of methyl 4-amino-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 1 of Example 75 were dissolved in 47 ml of chloroform, and 3.3 g of N-bromosuccinimide were added to it, followed by stirring at room temperature for 3 days. The reaction solution was divided between chloroform and a 10% aqueous solution of sodium thiosulfate. The organic layer was washed with water and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated. Methanol and water were added to the residue to form a suspension, and the methanol was removed. The residue was stirred at 0°C for 1 hour, and the solid was collected by filtration, thereby obtaining 2.50 g of the title compound.

[01666] Step 2: Synthesis of 4-amino-6-bromo-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid

[01667] According to the procedure of step 3 in Example 75, using 1.10 g of 4-amino-6-bromo-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5 -methyl carboxylate obtained in step 1, the title compound (97%) was obtained.

[01668] Step 3: Synthesis of 4-amino-6-bromo-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01669] According to the procedure of step 4 in Example 75, using 238 mg of 4-amino-6-bromo-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5- acid carboxylic acid obtained in step 2, the title compound (26%) was obtained.

[01670] Example 77: Synthesis of 4-amino-6-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01671] Step 1: Synthesis of 4-amino-6-methoxy-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid

[01672] 560 mg of methyl 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 2 of Example 75 were suspended in 10 mL of THF, and 121 mg of 4-dimethylamino pyridine and 1.52 g of di-tert-butyl dicarbonate were added to the suspension with stirring. The mixture was stirred at 50°C for 1 hour. After cooling, the reaction solution was concentrated and partitioned between ethyl acetate and water. The organic layer was washed with water and saturated aqueous sodium chloride solution. Anhydrous sodium sulfate was added, and the mixture was filtered, and concentrated. 10 mL of methanol was added to the residue, and 1 mL of sodium methoxide (about 5 mol/L methanol solution) was added to it with stirring, followed by stirring at 50°C for 1 hour. After cooling, the mixture was concentrated, and the residue was partitioned between chloroform and saturated ammonium chloride. The organic layer was washed with water and saturated aqueous sodium chloride solution. Anhydrous sodium sulfate was added, and the mixture was filtered and concentrated. 1 ml of dichloromethane and 2 ml of trifluoroacetic acid were added to the residue, and the mixture was stirred at room temperature for 1 hour. After concentration, the residue was partitioned between chloroform and a saturated aqueous sodium bicarbonate solution. The organic layer was washed with water and saturated aqueous sodium chloride solution. Anhydrous sodium sulfate was added, and the mixture was filtered and concentrated. The residue was dissolved in 20 mL of methanol, and 2.3 mL of an aqueous sodium hydroxide solution (4 mol/L) was added to it, and the mixture was stirred at 50°C for 1 hour, followed by another stirring at 80°C for 1 hour. After cooling, 20 mL of water and a 2N aqueous hydrochloric acid solution were added to the reaction solution to acidify the solution, thereby obtaining a precipitate. After the organic solvent was removed, the residue was stirred with ice-cooling for 1 hour and filtered, thereby obtaining 417 mg of the title compound.

[01673] Step 2: Synthesis of 4-amino-6-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01674] According to the procedure of step 4 in Example 75, using 30 mg of 4-amino-6-methoxy-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d]pyrimidine-5- acid carboxylic acid obtained in step 1, the title compound (36%) was obtained.

[01675] Example 78: Synthesis of 4-amino-6-chloro-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7H- pyrrole [2,3-d]pyrimidine- 5-carboxamide

[01676] According to the procedure of step 4 in Example 75, using 30 mg of 4-amino-6-chloro-7-(1-fluoro-2-methylpropan-2-yl)-7H-pyrrole acid [2, 3-d]pyrimidine-5-carboxylic acid which was synthesized using 7-(1-fluoro-2-methylpropan-2-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine obtained as an intermediate in Example 50 according to the procedures of steps 1 to 3 in Example 75, the title compound (16%) was obtained.

[01677] Example 79: Synthesis of 4-amino-6-(3-hydroxy-3-methyl-1-butyn-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-7- (1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01678] 35 mg of 4-amino-6-bromo-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine- 5-carboxamide obtained in Example 76 were dissolved in 1 ml of DMF. 1.7 mg of copper iodide, 87 µL of 2-methyl-3-butyn-1-ol, 31 µL of triethylamine, and 10 mg of tetracys triphenylphosphine palladium were added to it and degassed, followed by stirring at 100 °C for 2 hours. The reaction solution was divided between chloroform and water. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and filtered, followed by concentration. The residue was purified by silica gel column (ethyl acetate/methanol = 1/0 -> 4/1), thus obtaining 14 mg of the title compound.

[01679] Example 80: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-(pyridin-3-ylethynyl)-7H-pyrrole [ 2,3-d]pyrimidine-5-carboxamide

[01680] According to the procedure of example 79, using 3-ethynylpyridine instead of 2-methyl-3-butyn-1-ol, the title compound (72%) was obtained.

[01681] Example 81: Synthesis of 4-amino-6-((1-hydroxycyclopentyl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)- 7H-pyrrole [2,3-d]pyrimidine-5-carboxamide

[01682] According to the procedure of example 79, using 1-ethynylcyclopentan-1-ol instead of 2-methyl-3-butyn-1-ol, the title compound (18%) was obtained.

[01683] Example 82: Synthesis of 4-amino-6-((1-methyl-1H-pyrazol-4-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-( 1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01684] According to the procedure of example 79, using 4-ethynyl-1-methyl-1H-pyrazole instead of 2-methyl-3-butyn-1-ol, the title compound (43%) was obtained.

[01685] Example 83: Synthesis of 4-amino-6-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-( 1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01686] According to the procedure of example 79, using 5-ethynyl-1-methyl-1H-imidazole instead of 2-methyl-3-butyn-1-ol, the title compound (57%) was obtained.

[01687] Example 84: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclopropyl)-6-(3-morpholino-1-propyn-1-yl )-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide

[01688] According to example procedure 79, using 4-(2-propyn-1-yl)morpholine instead of 2-methyl-3-butyn-1-ol, the title compound (39%) was obtained .

[01689] Example 85: Synthesis of 4-amino-6-(3-(1-hydroxycyclobutyl)-1-propine)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl )-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide

[01690] According to example procedure 79, using 1-(2-propyn-1-yl)cyclobutan-1-ol in place of 2-methyl-3-butyn-1-ol, the title compound (58 %) It was obtained.

[01691] Example 86: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclopropyl)-6-((tetrahydro-2H-pyran-4- yl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01692] According to the procedure of example 79, using 4-ethynyltetrahydro-2H-pyran instead of 2-methyl-3-butyn-1-ol, the title compound (56%) was obtained.

[01693] Example 87: Synthesis of 4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 6-((1-methyl-1H-pyrazol-3-yl)ethynyl)-7-( 1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01694] According to the procedure of example 79, using 3-ethynyl-1-methyl-pyrazole instead of 2-methyl-3-butyn-1-ol, the title compound (28%) was obtained.

[01695] Example 88: Synthesis of 4-amino-6-(imidazo [1,2-b]pyridazin-3-ylethynyl)-N-(5-methyl-1H-pyrazol-3-yl)-7-(1 -methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

[01696] According to the procedure of example 79, using 1-ethynimidazo [1,2-b]pyridazine instead of 2-methyl-3-butyn-1-ol, the title compound (19%) was obtained.

[01697] Example 89: Synthesis of 4-amino-6-ethoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01698] Step 1: Synthesis of 4-amino-6-ethoxy-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid

[01699] 630 mg of methyl 4-amino-6-bromo-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 1 of Example 76 were suspended in 10 mL of THF. 119 mg of 4-dimethylamino pyridine and 1.27 g of di-tert-butyl dicarbonate were added thereto with stirring, and the solution was stirred at 50°C for 1 hour. After cooling, the reaction solution was concentrated and partitioned between ethyl acetate and water. The organic layer was washed with water and saturated aqueous sodium chloride solution. Anhydrous sodium sulfate was added to it, and the mixture was filtered and concentrated. 15 mL of ethanol was added to the residue, and 2.28 mL of sodium ethoxide (28% ethanol solution) was also added with stirring, followed by stirring at room temperature overnight. The reaction solution was neutralized with a 2N aqueous hydrochloric acid solution, and then concentrated. The residue was partitioned between chloroform and water. The organic layer was washed with a saturated aqueous sodium chloride solution, and anhydrous sodium sulfate was added thereto. After filtration, the resulting solution was concentrated. 3 ml of dichloromethane and 6 ml of trifluoroacetic acid were added to the residue, and the mixture was stirred at room temperature for 1.5 hours. After concentration, the residue was divided between chloroform and a saturated aqueous sodium bicarbonate solution. The organic layer was washed with water and a saturated aqueous sodium chloride solution, and anhydrous sodium sulfate were added to it, followed by filtration and concentration. The residue was dissolved in 20 mL of methanol, and 3.88 mL of an aqueous sodium hydroxide solution (4 mol/L) was added to it, followed by stirring at 60°C for 3 hours. After cooling, 50 mL of water and a 2N aqueous hydrochloric acid solution were added to the reaction solution to acidify the solution, thereby obtaining a precipitate. The organic solvent was removed, and the residue was stirred with ice-cooling for 1 hour, followed by filtration, thereby obtaining 432 mg of the title compound.

[01700] Step 2: Synthesis of 4-amino-6-ethoxy-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d] pyrimidine-5-carboxamide

[01701] 1.2 mL of DMF was added to 67 mg of 4-amino-6-ethoxy-7-(1-methylcyclopropyl)-7H-pyrrolo [2,3-d]pyrimidine-5-carboxylic acid obtained in step 1, and 41 mg of 1-hydroxybenzotriazole and 51 mg of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride were also added thereto, followed by stirring at room temperature for 2 hours. 143 mg of tert-butyl 5-amino-3-methyl-1H-pyrazol-1-carboxylate synthesized in Reference Example 5 were added to the reaction solution, and 0.60 mL of a sodium tert-butoxide solution ( 2M THF) was added to it at room temperature. After stirring for 30 minutes, 5 mL of a 1N aqueous sodium hydroxide solution was added to the reaction solution, followed by stirring at room temperature for 1 hour. The reaction solution was partitioned between ethyl acetate and water, and the organic layer was washed with water three times, and washed with saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the resulting solution was filtered and concentrated. The residue was purified by silica gel column (ethyl acetate/methanol = 1/0 -> 5/1), thus obtaining 33 mg of the title compound.

[01702] Example 90: Synthesis of (R)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2- il)methoxy)-7H- pyrrole [2,3-d]pyrimidine-5-carboxamide

[01703] Step 1: Synthesis of methyl 4-(bis(tert-butoxycarbonyl)amino)-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrole [2,3-d]pyrimidine-5-carboxylate

[01704] 351 mg of methyl 4-amino-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 2 of Example 75 were suspended in 6 .3 mL of THF, and 76 mg of 4-dimethylamino pyridine and 818 mg of di-tert-butyl dicarbonate were added thereto with stirring. The solution was then stirred at 60°C for 1 hour. After cooling, the reaction solution was concentrated, and the residue was purified by a silica gel column (hexane/ethyl acetate = 4/1 -> 2/3), thus obtaining 523 mg of the title compound. .

[01705] Step 2: Synthesis of 4-(bis(tert-butoxycarbonyl)amino)-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2-yl)methoxy)-7H-pyrrole [2,3 - (R)-methyl d]pyrimidine-5-carboxylate

[01706] 86 µL of (R)-(-)-tetrahydrofurfuryl alcohol was added to a suspension of 35 mg of sodium hydride (60%) in 1 mL of DMF with ice cooling, and the mixture was stirred at room temperature for 30 minutes. A solution of 212 mg of methyl 4-(bis(tert-butoxycarbonyl)amino)-6-chloro-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 1 in 1 mL of DMF was added to this solution, and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was partitioned between chloroform and water, and the organic layer was washed with a saturated aqueous sodium chloride solution. Anhydrous sodium sulfate was added to it, and the mixture was filtered and then concentrated. The residue was purified by a silica gel column (hexane/ethyl acetate = 4/1 -> 2/3), thus obtaining 141 mg of the title compound.

[01707] Step 3: Synthesis of (R)-4-amino-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2-yl)methoxy)-7H-pyrrole [2,3-d] acid pyrimidine-5-carboxylic acid

[01708] 1.5 mL of chloroform and 2 mL of trifluoroacetic acid were added to 141 mg of 4-(bis(tert-butoxycarbonyl)amino)-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2 (R)-methyl-yl)methoxy)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate obtained in step 2, and the mixture was stirred at room temperature for 1.5 hours. After concentration, 2 mL of methanol and 2 mL of tetrahydrofuran were added to the residue, and 1.29 mL of an aqueous sodium hydroxide solution (4 mol/L) was also added to it, followed by stirring at 60 °C for 3 hours. After cooling, 10 mL of water and a 2N aqueous hydrochloric acid solution were added to the reaction solution to acidify the solution, thereby obtaining a precipitate. After the organic solvent was removed, the residue was stirred with ice-cooling for 1 hour, followed by filtration, thereby obtaining 52 mg of the title compound.

[01709] Step 4: Synthesis of (R)-4-amino-N-(5-methyl-1H-pyrazol-3-yl)- 7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2- il)methoxy)-7H-pyrrole [2,3- d]pyrimidine-5-carboxamide

[01710] According to the procedure of step 2 in Example 89, using 52 mg of (R)-4-amino-7-(1-methylcyclopropyl)-6-((tetrahydrofuran-2-yl)methoxy acid) -7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid obtained in step 1, the title compound (39%) was obtained.

[01711] Comparative Example 1: Synthesis of 4-amino-1-cyclopentyl- N-(4-fluoro-1H-indazol-3-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01712] According to the synthesis procedure of Example 1, using 4-fluoro-1H-indazol-3-amine instead of 5-ethyl-1H-pyrazol-3-amine, the title compound (48%) was obtained as a brownish solid.

[01713] Comparative Example 2: Synthesis of 4-amino-1-cyclobutyl-N- (4-methylthiazol-2-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01714] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using bromocyclobutane instead of iodocyclopentane, 4-amino-1-cyclobutyl-1H-pyrazolo[3,4-d]pyrimidine-acid 3-carboxylic acid was obtained as a brownish solid. According to the synthesis procedure of Example 1, using 4-amino-1-cyclobutyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid instead of 4-amino-1-cyclopentyl acid -1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 4-methylthiazol-2-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound (83%) was obtained as a brownish solid.

[01715] Comparative Example 3: Synthesis of 4-amino-1-cyclobutyl-N- (4-methyl-1H-imidazol-2-yl)-1H-pyrazolo [3,4-d]pyrimidine-3-carboxamide

[01716] According to the synthetic procedures of steps 1 and 2 in Reference Example 1, using bromocyclobutane instead of iodocyclopentane, 4-amino-1-cyclobutyl-1H-pyrazole [2,3-d]pyrimidine acid -3- carboxylic acid was obtained as a brownish solid. According to the synthesis procedure of Example 1, using 4-amino-1-cyclobutyl-1H-pyrazolo [3,4-d]pyrimidine-3-carboxylic acid in place of 4-amino-1-cyclopentyl acid -1H-pyrazole [3,4-d]pyrimidine-3-carboxylic acid, and using 4-methyl-1H-imidazol-2-amine in place of 5-ethyl-1H-pyrazol-3-amine, the title compound ( 58%) was obtained as a brownish solid.

[01717] Comparative Example 4: Synthesis of 1-(tert-butyl)-3-(p-tolyl)pyrazolo [3,4-d]pyrimidin-4-amine

[001718] According to the synthesis procedure described in Tetrahedron Letters, 52(44), 5761-5763; 2011, the title compound (30%) was obtained as a white solid.

[001719] Tables 1 to 14 show the formulas and physical properties of the compounds obtained in the Examples and Comparative Examples. Table 1 Note: In tables and figures, “Comp.” denotes compounds, and “Ex.” denotes Examples. Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table Legend: Compound "x” from the Comparative Example. Test Example 1: Assessment of RET Inhibitory Activity (in vitro)

[001720] Regarding the conditions for evaluating the in vitro inhibitory activity of compounds against RET kinase activity, the AnaSpec website establishes that Srctide (GEEPLYWSFPAKKK) corresponds to the substrate peptide for the reaction to measure RET kinase activity . Therefore, the amino acid sequence was partially modified and biotinylated to prepare biotinylated peptides (biotin-EEPLYWSFPAKKK). Purified human recombinant RET protein used in the assay was purchased from Carna Biosciences, Inc.

[001721] To measure inhibitory activity, first, the compounds of the present invention were individually diluted with dimethyl sulfoxide (DMSO) in stages. Subsequently, the RET protein, the substrate peptide (final concentration: 250 nM), magnesium chloride (final concentration: 10 mM), ATP (final concentration: 10 µM), and a solution of the compound of the present invention in DMSO (final DMSO concentration: 2.5%) were added to a buffer for the kinase reaction (13.5 mM Tris, pH 7.5, 2 mM dithiothreitol, 0.009% Tween-20). Each of the mixtures was incubated at 25°C for 100 minutes to perform the kinase reaction. EDTA was then added to provide a final concentration of 24 mM for the reaction to be terminated. A detection solution containing Eu-labeled PT66 antiphosphotyrosine antibody (PerkinElmer) and SureLight APC-SA (PerkinElmer) was added thereto, and each mixture was allowed to sit at room temperature for 2 hours or more. Finally, the fluorescence intensity under the excitation light with a wavelength of 337 nm was measured with a PHERAstar FS (BMG Labtech) at the two wavelengths of 620 nm and 665 nm. The phosphorylation level was calculated from the relationship of the fluorescence intensity at the two wavelengths, and the compound concentration at which phosphorylation was inhibited by 50% was defined as the IC50 value (nM).

[001722] Table 15 shows IC50 (nM) of the RET inhibitory activity (WT) of the compounds of Examples and compounds 1 to 3 of Comparative Examples.

[001723] Vandetanib is known to have high inhibitory activity against RET and exhibits a high antitumor effect (e.g. Carlomagno F. Cancer Res. 2002 Dec 15; 62(24): 7284-90). The compounds of the present invention have been found to inhibit RET inhibitory activity in vitro at a level equivalent to or greater than Vandetanib.

[001724] Compounds 1 to 3 of Comparative Examples, which do not have a pyrazolyl group continuous with an amide group, respectively have an IC50 (nM) of 451, 752, and 486, exhibiting weak inhibitory activity. On the contrary, the compounds of the present invention have an IC50 (nM) of about 40 times, or more than 40 times, the IC50 (nM) of compounds 1 to 3 of the Comparative Examples, revealing that the compounds of the present invention have a elevated RET inhibitory activity. Table 15 Caption of Table 15: Compound “x” from the Comparative Examples.

[001725] Example Test 2: Inhibitory selectivity of RET (in vitro) over other kinase inhibitory activity

[001726] Assessment of RET Inhibitory Activity

[001727] RET inhibitory activity was measured in the same way as in Test Example 1.

[001728] 2) Assessment of SRC Inhibitory Activity

[001729] Regarding the conditions for evaluating the in vitro inhibitory activity of compounds against the kinase activity of SRC, the price list of consumable reagents from PerkinElmer's LabChip series shows that FL-Peptide 4 corresponds to the substrate peptide for the reaction to measure the kinase activity of SRC. Therefore, FL-Peptide 4 was used as a substrate. The purified human recombinant SRC protein used in the test was purchased from Carna Biosciences, Inc.

[001730] To evaluate the inhibitory activity, first, the compounds of the present invention were individually diluted with dimethyl sulfoxide (DMSO) step by step. Subsequently, the SRC protein, FL-Peptide 4 (final concentration: 1.5 µM), magnesium chloride (final concentration: 10 mM), ATP (final concentration: 15 µM), and a solution of the compound of the present invention in DMSO (final DMSO concentration: 5%) were added to a reaction buffer (100 mM HEPES, pH 7.0, 1 mM dithiothreitol, 0.003% Brij35, 0.04% Tween-20) containing a phosphatase inhibitor cocktail (PhosSTOP, Roche) and a protease inhibitor cocktail (cOmplete Mini, EDTA-free, Roche) at recommended concentrations. Each mixture was incubated at 30°C for 90 minutes to perform the kinase reaction. EDTA diluted with a separation buffer available from PerkinElmer (final concentration: 30 mM) was then added to terminate the kinase reaction. Finally, unphosphorylated substrate (S) peptides and phosphorylated (P) peptides were separated and detected by microchannel capillary electrophoresis using a II La bChip EZ Reader (PerkinElmer). The phosphorylation level was calculated from the height of the S and P peaks, and the compound concentration at which phosphorylation was inhibited by 50% was defined as the IC50 value (nM).

[001731] 3) Assessment of LCK Inhibitory Activity

[001732] Regarding the conditions for evaluating the in vitro inhibitory activity of compounds against the kinase activity of LCK, the AnaSpec website establishes that Srctide (GEEPLYWSFPAKKK) corresponds to the substrate peptide for the reaction to measure the kinase activity of LCK. In this way, the amino acid sequence was partially modified and biotinylated to prepare biotinylated peptides (biotin-EEPLYWSFPAKKK). The purified human recombinant LCK protein used in the test was purchased from Carna Biosciences, Inc.

[001733] To measure the inhibitory activity, first, the compounds of the present invention were individually diluted with dimethyl sulfoxide (DMSO) step by step. Subsequently, LCK protein, the substrate peptides (final concentration: 250 nM), magnesium chloride (final concentration: 10 mM), ATP (final concentration: 50 µM), and a solution of the compound of the present invention in DMSO (final concentration of DMSO: 5%) were added to a kinase reaction buffer (13.5 mM Tris, pH 7.5, 2 mM dithiothreitol, 0.009% Tween-20). Each mixture was incubated at 25°C for 60 minutes to perform the kinase reaction. EDTA was then added to provide a final concentration of 40 mM so that the reaction was terminated. A detection solution containing Eu-labeled PT66 antiphosphotyrosine antibody (PerkinElmer) and SureLight APC-SA (PerkinElmer) was added thereto, and each mixture was allowed to sit at room temperature for 2 hours or more. Finally, the fluorescence intensity under excitation light with a wavelength of 337 nm was measured with a PHERAstar FS (BMG Labtech) at the two wavelengths of 620 nm and 665 nm. The phosphorylation level was calculated from the relationship of the fluorescence intensity at the two wavelengths, and the concentration of compound at which phosphorylation was inhibited by 50% was defined as the IC50 value (nM).

[001734] 4) RET inhibitory selectivity

[001735] From the values obtained in sections 1) and 3) above, SRC inhibitory activity IC50 (nM)/RET inhibitory activity IC50 (nM) and LCK inhibitory activity IC50 (nM)/RET inhibitory activity IC50 ( nM) were calculated, and the RET inhibitory selectivity of the tested compounds was examined. Table 16 Table Legend: Example compounds; and Compound “x” from the Comparative Examples.

[001736] As shown in Table 16, compound 4 of the Comparative Examples exhibited about 15 times greater inhibitory selectivity for RET over SRC or LCK.

[001737] In comparison, the compounds of the present invention exhibited several hundred times to several thousand times greater inhibitory selectivity for RET over SRC or LCK, revealing their excellent inhibitory selectivity for RET. The results also suggest that the compounds of the present invention have a low probability of involving side effects caused by the inhibition of kinases other than RET.

[001738] Test Example 3: Evaluation of the Cell Growth Inhibitory Effect on Tumor Cell Carrying RET Gene Defect (1)

[001739] A cell death test was performed on TT cells (human thyroid cancer line carrying RET activating mutation (C634W)).

[001740] A suspension of TT cells in Ham's F12K medium (Kaighn's) containing 10% FBS (produced by Life Technologies Japan) was inoculated into each well of a 96-well flat-bottom microplate in an amount of 5x103 (0 .15 mL) for each well, and cultured in an incubator containing 5% carbon dioxide at 37°C overnight (day 0). The compounds of the present invention were individually dissolved in dimethyl sulfoxide to provide a concentration of 10 mM, and also diluted with RPMI1640 medium containing 10% FBS (produced by Wako Pure Chemical Industries, Ltd.) so that the compounds of the present invention respectively have a final concentration of 40, 12, 4, 1.2, 0.4, 0.12, 0.04, and 0.012 µM. Compounds of different concentrations were individually added to the wells of the TT cell-containing culture plate described above in an amount of 0.05 mL for each well (day 1), and cultured in an incubator containing 5% carbon dioxide at 37° C for 7 days. After culture (day 8), 0.1 mL of medium was removed from each well, and 0.1 mL of CellTiter Glo 2.0 reagent (Promega Corporation), which is an intracellular ATP luminescence detection reagent, was added to it, followed by stirring for 1 minute. After shaking, each culture was allowed to rest at room temperature for 15 minutes, and chemiluminescence was measured with a luminometer to use it as an index of the number of viable cells. The day 1 growth rate of compounds with different concentrations was calculated from the following equations, depending on the value of Tday 8 and Cday 1, to determine the concentration (GI50 (µM)) of the tested compounds capable of suppressing cell growth by 50% . 1) Day 8—Day 1

[001741] Growth rate (%)=(Tday 8-Cday i)/(Tday 8-Cday i)x100

[001742] T: Absorbency of the cavity to which a tested compound was added.

[001743] C: Absorbency of the cavity to which a tested compound was not added.

[001744] Day 1: Day on which a tested compound was added.

[001745] Day 8: Day on which the assessment was carried out.

[001746] 2) Day 8<Day 1

[001747] Growth rate (%)=(Tday 8-Cday 1)/(Tday 1)*100

[001748] T: Absorbency of the cavity to which a tested compound was added.

[001749] C: Absorbency of the cavity to which a tested compound was not added.

[001750] Day 1: Day on which a tested compound was added.

[001751] Day 8: Day on which the assessment was carried out.

[001752] Table 17 shows the results. The compounds of the present invention exhibited a greater growth inhibitory effect on TT cells than compound 4 of the Comparative Examples or Vandetanib. Table 17

[001753] Test Example 4: Evaluation of the cell growth inhibitory effect on the tumor cell carrying the RET gene defect (2).

[001754] An in vitro cell death test was performed on LC-2/ad cells (human lung adenocarcinoma line carrying the CCDC6-RET fusion gene).

[001755] A suspension of LC-2/ad cells in an RPMI1640 medium containing 10% FBS was inoculated into each well of a 96-well micro flat base plate in an amount of 5x103 for each well (0.15 mL ), and cultured in an incubator containing 5% carbon dioxide at 37°C overnight (day 0). The compounds of the present invention were individually dissolved in dimethyl sulfoxide to provide a concentration of 10 mM, and also diluted with RPMI1640 medium containing 10% FBS such that the compounds of the present invention respectively had a final concentration of 40, 12 , 4, 1.2, 0.4, 0.12, 0.04, and 0.012 µM. Compounds of different concentrations were individually added to each well of the LC-2/ad cell-containing culture plate described above in an amount of 0.05 mL for each well (day 1), and cultured in an incubator containing 5% carbon dioxide. carbon at 37°C for 7 days. After culture (day 8), 0.1 mL of medium was removed from each well, and 0.1 mL of CellTiter Glo 2.0 reagent (Promega Corporation), which is an intracellular ATP luminescence detection reagent, was added, followed by stirring for 5 minutes. After shaking, each culture was allowed to rest at room temperature for 15 minutes, and chemiluminescence was measured with a luminometer to use it as an index of the number of viable cells. The day 1 growth rate of compounds with different concentrations was calculated from the following equations, depending on the value of Tday 8 and Cday 1, to determine the concentration (GI50 (µM)) of the tested compounds capable of suppressing cell growth by 50% . 1) Day 8—Day 1

[001756] Growth rate (%)=(Tday 8-Cday 1)/(Tday 8-Cday 1)x100

[001757] T: Absorbency of the cavity to which a tested compound was added.

[001758] C: Absorbency of the cavity to which a tested compound was not added.

[001759] Day 1: Day on which a tested compound was added.

[001760] Day 8: Day on which the assessment was carried out.

[001761] Tday 8<Cday 1

[001762] Growth rate (%)=(Tday 8-Cday i)/(Cday i)x100

[001763] T: Absorbency of the cavity to which a tested compound was added.

[001764] C: Absorbency of the cavity to which a tested compound was not added.

[001765] Day 1: Day on which a tested compound was added.

[001766] Day 8: Day on which the assessment was carried out.

[001767] Table 18 shows the results. The compounds of the present invention exhibited a greater growth inhibitory effect on LC-2/ad cells than compound 4 of Comparative Examples or Vandetanib. Table 18

[001768] Test Example 5: Evaluation of the Antitumor Effect on an In Vivo Model Having TT Cells (Human Thyroid Cancer Cell Line Carrying the RET Activation Mutation) Subcutaneously Implanted

[001769] Human thyroid cancer (TT) cell lines were subcutaneously implanted into the right breast of 6- to 7-week-old male BALB/cA Jcl-nu/nu mice. About 3 weeks after cell implantation, length (mm) and width (mm) of tumors found in the bodies of the mice were measured. After their tumor volume (tumor volume: TV) was calculated, the mice were divided into groups (n = 5 or 6) so that the groups had a substantially equal average tumor volume. The day the mice were divided into groups was determined to be the “grouping day” (day 0 or 1).

[001770] Test solutions containing the compounds of the present invention were prepared at a dose of 100 mg/kg/day, and orally administered to mice for 14 days (the first day of administration is day 1). A control group was administered a solvent (0.5% HPMC/0.1N HCl).

[001771] To determine the index of antitumor effect, TV of each group administered drug was measured on day 15, and the tumor volume on day 15 in relation to the tumor volume on the grouping day (day 0 or 1) (volume of relative tumor: RTV) and T/C (%) were calculated from the following equations to evaluate the antitumor effect. When a group administered any of the compounds of the present invention (group administered the test solution) exhibited a statistically significantly lower mean RTV (Dunnett's test or Student's t-test, p<0.05) than the mean RTV of the test solution group. control, an antitumor effect was determined to be present. Figures 1 and 2 and Tables 19 and 20 show the results. In the figures, the symbol "*” indicates a statistically significant difference.

[001772] TV (mm3) = (length x width2)/2

[001773] RTV = (TV on day 15)/(TV on day 0 or day 1)

[001774] T/C(%) = (the average RTV of a group administered test solution)/(the average RTV of the control group)x100

[001775] To determine the toxicity index, the body weight (body weight: BW) of the mice was measured over time, and the average body weight change (body weight change: BWC (%)) from the day of grouping (day 0 or day 1) to day 15 was calculated from the following equation (n: day on which body weight was measured 2 times/week, and the day of the final assessment is day 15 on which the final assessment was carried out ). Figures 3 and 4 show the results.

[001776] BWC (%)= [(BW on day n)-(BW on day 0 or day 1)]/(BW on day 0 or day 1)x100

[001777] As is clear from Figures 1 and 2 and Tables 19 and 20, the compounds of the present invention exhibited a remarkable antitumor effect on human thyroid cancer TT lines carrying the RET activating mutation that were subcutaneously implanted into mice nudes. As shown in Figures 3 and 4, toxicity, such as weight loss, was not observed. Table 19 Table 20

[001778] Test example 6: Assessment of stability in liver microsome

[001779] Solutions of the tested compounds in DMSO/acetonitrile (the final concentration of each tested compound was 1 µM, the final concentration of DMSO was 0.01%, and the final concentration of acetonitrile was 1%) were individually added to a liver microsome mixture solution (mouse liver microsome with a final concentration of 0.25 mg/mL, a potassium phosphate buffer with a final concentration of 100 mM, and magnesium chloride with a final concentration of 3 mM), and each mixture was pre-incubated at 37°C for 5 minutes. A system for generating NADPH (glucose-6-phosphate with a final concentration of 10 mM, oxidized nicotinamide adenine dinucleotide phosphate with a final concentration of 1 mM, and glucose-6-phosphate dehydrogenase with a final concentration of 1 unit /mL) was added to a portion of each mixture solution, and the metabolic reaction was started. After incubation at 37°C for 30 minutes, a double amount of ethanol was added to terminate the reaction, thereby obtaining post-reaction samples. A double amount of ethanol was added to each of the remaining mixture solutions, and a NADPH generation system was also added, thereby obtaining pre-reaction samples. The pre-reaction samples and post-reaction samples were centrifuged at 2000xg, and their supernatant was filtered through a glass filter. Each filtrate was then introduced into LC-MS/MS, and MS/MS peaks of the tested compounds were detected. From the ratio of the post-reaction MS/MS peak to the pre-reaction MS/MS peak of the tested compounds, the percentage of the tested compounds remaining (% remaining) was calculated.

[001780] The results showed that while compound 4 of the Comparative Examples had a remaining percentage of 0% in any case, the compounds of the present invention or salts thereof described in the Examples had a high remaining percentage. This indicates that the compounds of the present invention or salts thereof are significantly more stable in mouse liver microsomes than the compound of the Comparative Examples.

[001781] Example Test 7: Assessment of oral absorption

[001782] The compounds of the present invention were suspended or dissolved in 0.5% HPMC and 0.1N hydrochloric acid, and orally administered to BALB/cA mice. At a time point of 0.5, 1, 2, 4, and 6 hours after oral administration, the mice's blood was collected from their ocular fundus or facial vein, and centrifuged to obtain plasma. The concentration of compounds in the obtained plasma was measured by LC-MS/MS, and oral absorption was evaluated.

[001783] The results reveal that the plasma concentration of the compounds of the present invention was sufficient, indicating excellent oral absorption.

Claims (24)

1. RET inhibitor, characterized by the fact that it comprises a compound represented by formula (I) below or a salt thereof as an active ingredient: wherein A is pyrazolyl substituted by number n of R1; R1 is halogen, cyano, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted or unsubstituted C3-C10 saturated or unsaturated monocyclic or polycyclic heterocyclic group substituted containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; R2 is C1-C10 alkyl, which is unsubstituted or is substituted with at least one substituent selected from the group consisting of the group of substituents defined below: - halogen, - C3-C7 cycloalkyl which can be substituted with C1-C4 alkyl, - phenyl , - C1-C6 alkoxy, and - one or more C3-C10 unsaturated monocyclic or polycyclic heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, C3-C7 substituted or unsubstituted cycloalkyl, C2-C6 substituted or unsubstituted alkenyl, substituted or unsubstituted C3-C7 cycloalkenyl, substituted or unsubstituted C4-C12 bridged cycloalkyl, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group or unsubstituted containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; " at least one substituent selected from the group consisting of the group of substituents defined below: - C1-C6 alkyl or hydroxyl C1-C6 alkyl, - C3-C7 cycloalkyl which can be substituted with hydroxy, - one or more C3-C6 monocyclic saturated heterocyclic groups - cyclic containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, and - one or more C3-C10 monocyclic or polycyclic unsaturated heterocyclic groups that may be substituted with C1-C6 alkyl containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted or unsubstituted monocyclic or polycyclic unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer from 0 to 3, where when n is 2 or 3, R1 can be identical or different from each other, where when at least one of these groups is substituted, the group is replaced with at least one selected substituent from the group consisting of halogen, hydroxy, cyano, nitro, C1-C10 alkyl, halo C1-C10 alkyl; hydroxyl C1-C10 alkyl, C1-C6 alkoxy C1-C10 alkyl; C3-C7 cycloalkyl; C3-C7 cycloalkyl-substituted C1-C10 alkyl; C4-C12 substituted cycloalkyl; C7-C14 aralkyl; C2-C6 alkenyl; C2-C6 alkynyl; C1-C6 alkoxy; halogen C1-C6 alkoxy; C3-C7 cycloalkoxy; C3-C7 cycloalkyl-substituted C1-C4alkoxy; C7-C14 aralkyloxy; C1-C6 alkylthio; C3-C7 cycloalkyl C1-C4 alkylthio; amino; mono-substituted amino with linear or branched C1-C6 alkyl; amino disubstituted with linear or branched C1-C6 alkyl; C3-C7 cycloalkyl C1-C4 alkylamine; linear or branched alkylamine (C1-C6 alkyl)carbonyl; (C6-C14 aryl)carbonyl; linear or branched carbonyl (C1-C6 alkyl)carbonyl; (C6-C14 aryl)carbonyloxy; oxo; carboxyl; (C1- C6 alkoxy)carbonyl; (C7-C14 aralkyl)oxycarbonyl; carbamoyl; C3-C10 saturated monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur; C3-C10 unsaturated monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur; C6-C14 aromatic hydrocarbon, oxy to which C3-C10 monocyclic or polycyclic saturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur is attached. 2. RET inhibitor, according to claim 1, characterized by the fact that in Formula (I), A is pyrazolyl substituted by number n of R1; R1 is halogen; cyan; C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy; C3-C7 cycloalkyl; phenyl; or a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom; R2 is C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3-C6 heterocyclic groups monocyclic unsaturated substances containing one oxygen atom or one sulfur atom; C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl; C2-C6 alkenyl that can be substituted with halogen; or C4-C12 bridged cycloalkyl that can be substituted with C1-C4 alkyl; X is N or CR3, where R3 is hydrogen; halogen; C1-C6 alkyl; C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic or polycyclic unsaturated C3-C10 heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or C1-C4 alkoxy which may be substituted with one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer of 1 or 2, where when n is 2, R1 can be identical or different from each other. 3. RET inhibitor, according to claim 1 or 2, characterized by the fact that the compound represented by Formula (I) or a salt thereof is a compound represented by formula (II) below or a salt thereof: where R1 is halogen; cyan; C1-C6 alkyl that can be substituted with halogen; C3-C7 cycloalkyl; phenyl; or a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom; R2 is C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3-C6 heterocyclic groups monocyclic unsaturated substances containing one oxygen atom or one sulfur atom; C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl; C2-C6 alkenyl that can be substituted with halogen; or C4-C12 bridged cycloalkyl; X is N or CR3, where R3 is hydrogen; halogen; C1-C4 alkyl; C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic or polycyclic unsaturated C3-C10 heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or C1-C4 alkoxy; n is an integer of 1 or 2, where when n is 2, R1 can be identical or different from each other. 4. RET inhibitor, according to claim 3, characterized by the fact that in Formula (II), R1 is halogen, cyano, or C1-C4 alkyl that can be substituted with halogen; R2 is C1-C4 linear alkyl which is substituted with C3-C7 cycloalkyl; C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more C3-C6 monocyclic unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy; C3-C7 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl;C2-C6 alkenyl that can be substituted with halogen; or C4-C12 bridged cycloalkyl selected from bicyclo[1.1.1]pentan-1-yl and bicyclo[2.2.1]heptan-2-yl; X is N or CR3, where R3 is hydrogen; or C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic unsaturated C3-C6 heterocyclic groups that may be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer of 1. 5. RET inhibitor according to any one of claims 1 to 4, characterized in that the compound represented by Formula (I) or a salt thereof is a compound represented by Formula (IX) below or a salt thereof : wherein R1 is halogen or C1-C4 alkyl; R2 is C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl; C3-C5 cycloalkyl that can be substituted with C1-C4 alkyl; or bicyclo[2.2.1]heptan-2-yl; and X is N or CR3, where R3 is hydrogen; or ethynyl or propynyl that is substituted with C1-C4 alkyl that can be substituted with hydroxy, C3-C5 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 selected identical or different heteroatoms of nitrogen and oxygen, or one or more monocyclic unsaturated heterocyclic C3-C6 groups that may be substituted with methyl and contain 1 to 3 nitrogen atoms. 6. RET inhibitor, according to claim 5, characterized by the fact that in Formula (IX), R1 is bromine or methyl; R2 is C3-C6 branched alkyl which can be substituted with fluorine or C3-C5 cycloalkyl, or C3-C5 cycloalkyl which can be substituted with methyl; and X is N or CR3, where R3 is hydrogen. 7. RET inhibitor according to any one of claims 1 to 6, characterized in that it is at least one member selected from the group consisting of: (34) 4-amino-1-(tert-butyl)- N-(5-methyl-1H-pyrazol-3-yl)-1Hpyrazolo[3,4-d]pyrimidine-3-carboxamide; (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1Hpyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide; (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide; (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1Hpyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide; and salts of these compounds. 8. Pharmaceutical composition, characterized by the fact that it comprises the compound or a salt thereof that is an active ingredient of the RET inhibitor, as defined in any one of claims 1 to 7, for preventing or treating a disease that can be treated by RET inhibition. 9. Antitumor agent, characterized in that it comprises a compound or a salt thereof that is an active ingredient of the RET inhibitor, as defined in any one of claims 1 to 7. 10. Antitumor agent according to claim 9, characterized by the fact that it is for treating a malignant tumor with enhanced RET activation. 11. Use of the compound or a salt thereof which is an active ingredient of the RET inhibitor, as defined in any one of claims 1 to 7, characterized by the fact that it is for the production of an antitumor agent or a RET inhibitor for the treatment of a malignant tumor with enhanced RET activation. 12. Compound, characterized by the fact that it is represented by Formula (I') below or a salt thereof: wherein A is pyrazolyl substituted by number n of R1; R1 is halogen, cyano, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted or unsubstituted C3-C10 saturated or unsaturated monocyclic or polycyclic heterocyclic group substituted containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; R2 is C1-C10 alkyl, which is unsubstituted or is substituted with at least one substituent selected from the group consisting of the group of substituents defined below: - halogen, - C3-C7 cycloalkyl which can be substituted with C1-C4 alkyl, - phenyl , - C1-C6 alkoxy, and - one or more C3-C10 monocyclic or polycyclic unsaturated heterocyclic groups containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, C3-C4 substituted or unsubstituted cycloalkyl, C2-C6 substituted or unsubstituted alkenyl, substituted or unsubstituted C3-C4 cycloalkenyl, substituted or unsubstituted C4-C12 bridged cycloalkyl, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted monocyclic or polycyclic C3-C10 saturated or unsaturated heterocyclic group or unsubstituted containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; " with at least one substituent selected from the group consisting of the group of substituents defined below: - C1-C6 alkyl or hydroxyl C1-C6 alkyl, - C3-C7 cycloalkyl which can be substituted with hydroxy, - one or more C3-C6 saturated monocyclic groups heterocyclic containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, and - one or more C3-C10 monocyclic or polycyclic unsaturated heterocyclic groups that may be substituted with C1-C6 alkyl containing 1 to 3 identical heteroatoms or different selected from nitrogen, oxygen, and sulfur, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted C6-C14 aromatic hydrocarbon, or a substituted or unsubstituted monocyclic or polycyclic unsaturated C3-C10 heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer from 0 to 3, where when n is 2 or 3, R1 can be identical or different from each other, where when at least one of these groups is substituted, the group is replaced with at least one selected substituent from the group consisting of halogen, hydroxy, cyano, nitro, C1-C10 alkyl, halo C1-C10 alkyl; hydroxyl C1-C10 alkyl, C1-C6 alkoxy C1-C10 alkyl; C3-C7 cycloalkyl; C3-C7 cycloalkyl-substituted C1-C10 alkyl; C4-C12 substituted cycloalkyl; C7-C14 aralkyl; C2-C6 alkenyl; C2-C6 alkynyl; C1-C6 alkoxy; halogen C1-C6 alkoxy; C3-C7 cycloalkoxy; C3-C7 cycloalkyl-substituted C1-C4alkoxy; C7-C14 aralkyloxy; C1-C6 alkylthio; C3-C7 cycloalkyl C1-C4 alkylthio; amino; mono-substituted amino with linear or branched C1-C6 alkyl; amino disubstituted with linear or branched C1-C6 alkyl; C3-C7 cycloalkyl C1-C4 alkylamine; linear or branched alkylamine (C1-C6 alkyl)carbonyl; (C6-C14 aryl)carbonyl; linear or branched carbonyl (C1-C6 alkyl)carbonyl; (C6-C14 aryl)carbonyloxy; oxo; carboxyl; (C1- C6 alkoxy)carbonyl; (C7-C14 aralkyl)oxycarbonyl; carbamoyl; C3-C10 saturated monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur; C3-C10 unsaturated monocyclic or polycyclic heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur; C6-C14 aromatic hydrocarbon, oxy to which C3-C10 monocyclic or polycyclic saturated heterocyclic group containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen and sulfur is attached. 13. Compound or a salt thereof, according to claim 12, characterized by the fact that in Formula (I'), A is pyrazolyl substituted by number n of R1; R1 is halogen; cyan; C1-C6 alkyl that can be substituted with halogen or C1-C4 alkoxy; C3-C7 cycloalkyl; phenyl; or a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom; R2 is C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3-C6 heterocyclic groups monocyclic unsaturated substances containing one oxygen atom or one sulfur atom; C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl; C2-C6 alkenyl that can be substituted with halogen; or bridged C4-C12 cycloalkyl that can be substituted with C1-C4 alkyl; X is N or CR3, where R3 is hydrogen; halogen; C1-C6 alkyl; C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic or polycyclic unsaturated C3-C10 heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or C1-C4 alkoxy which may be substituted with one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer of 1 or 2, where when n is 2, R1 can be identical or different from each other. 14. Compound or a salt thereof, according to claim 12 or 13, characterized by the fact that it is represented by Formula (II') below: where R1 is halogen; cyan; C1-C6 alkyl that can be substituted with halogen; C3-C7 cycloalkyl; phenyl; or a C3-C6 monocyclic unsaturated heterocyclic group containing an oxygen atom or a sulfur atom; R2 is C1-C6 linear alkyl or C3-C8 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl that can be substituted with C1-C4 alkyl, phenyl, C1-C4 alkoxy, or one or more C3-C6 heterocyclic groups monocyclic unsaturated substances containing one oxygen atom or one sulfur atom; C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, halogen C1-C4 alkyl, or C3-C5 cycloalkyl; C2-C6 alkenyl that can be substituted with halogen; or C4-C12 bridged cycloalkyl; X is N or CR3, where R3 is hydrogen; halogen; C1-C4 alkyl; C2-C4 alkynyl that can be substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic or polycyclic unsaturated C3-C10 heterocyclic groups that may be substituted with C1-C6 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; or C1-C4 alkoxy; n is an integer of 1 or 2, where when n is 2, R1 can be identical or different from each other. 15. Compound or a salt thereof, according to claim 14, characterized by the fact that in Formula (II'), R1 is halogen, cyano, or C1-C4 alkyl that can be substituted with halogen; R2 is C1-C4 linear alkyl which is substituted with C3-C7 cycloalkyl; C3-C6 branched alkyl that can be substituted with halogen, C3-C7 cycloalkyl, one or more C3-C6 monocyclic unsaturated heterocyclic groups containing a sulfur atom, or C1-C4 alkoxy; C3-C4 cycloalkyl that can be substituted with halogen, C1-C4 alkyl, or C3-C5 cycloalkyl; C2-C6 alkenyl that can be substituted with halogen; or C4-C12 bridged cycloalkyl selected from bicyclo[1.1.1]pentan-1-yl and bicyclo[2.2.1]heptan-2-yl; X is N or CR3, where R3 is hydrogen; or C2-C4 alkynyl that is substituted with C1-C6 alkyl that can be substituted with hydroxy, C3-C7 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur, or one or more monocyclic unsaturated C3-C6 heterocyclic groups that may be substituted with C1-C4 alkyl and contain 1 to 3 identical or different heteroatoms selected from nitrogen, oxygen, and sulfur; and n is an integer of 1. 16. Compound or a salt thereof, according to any one of claims 12 to 15, characterized by the fact that it is represented by Formula (IX') below: wherein R1 is halogen or C1-C4 alkyl; R2 is C3-C6 branched alkyl that can be substituted with halogen or C3-C5 cycloalkyl; C3-C4 cycloalkyl that can be substituted with C1-C4 alkyl; or bicyclo[2.2.1]heptan-2-yl; and X is N or CR3, where R3 is hydrogen; or ethynyl or propynyl that is substituted with C1-C4 alkyl that can be substituted with hydroxy, C3-C5 cycloalkyl that can be substituted with hydroxy, one or more monocyclic saturated C3-C6 heterocyclic groups, containing 1 to 3 selected identical or different heteroatoms of nitrogen and oxygen, or one or more monocyclic unsaturated heterocyclic C3-C6 groups that may be substituted with methyl and contain 1 to 3 nitrogen atoms. 17. Compound or a salt thereof, according to claim 16, characterized by the fact that in Formula (IX'), R1 is bromine or methyl; R2 is C3-C6 branched alkyl which can be substituted with fluorine or C3-C5 cycloalkyl, or C3-C4 cycloalkyl which can be substituted with methyl; and X is N or CR3, where R3 is hydrogen. 18. Compound or a salt thereof, according to any one of claims 12 to 17, characterized by the fact that it is at least one member selected from the group consisting of: (34) 4-amino-1-(tert-butyl )-N-(5-methyl-1H-pyrazol-3-yl)-1Hpyrazolo[3,4-d]pyrimidine-3-carboxamide; (48) 4-amino-7-(tert-butyl)-N-(5-methyl-1H-pyrazol-3-yl)-7Hpyrrolo[2,3-d]pyrimidine-5-carboxamide; (50) 4-amino-7-(1-fluoro-2-methylpropan-2-yl)-N-(5-methyl-1Hpyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5 -carboxamide; (51) 4-amino-N-(5-methyl-1H-pyrazol-3-yl)-7-(1-methylcyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide; (52) 4-amino-7-(2-cyclopropylpropan-2-yl)-N-(5-methyl-1Hpyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide; and salts of these compounds. 19. RET inhibitor, characterized by the fact that it comprises a compound or a salt thereof, as defined in any one of claims 12 to 18, as an active ingredient. 20. Pharmaceutical composition, characterized by the fact that it comprises the compound or a salt thereof, as defined in any one of claims 12 to 18 and a pharmaceutical carrier. 21. Pharmaceutical composition according to claim 20, characterized by the fact that it prevents or treats a disease that can be treated by RET inhibition. 22. Compound or salt thereof, according to any one of claims 12 to 18, characterized by the fact that it is for use in the prevention or treatment of a malignant tumor. 23. Compound or salt thereof, according to claim 22, characterized by the fact that the malignant tumor is a malignant tumor with enhanced RET activation. 24. Use of a compound or a salt thereof, as defined in any one of claims 12 to 18, characterized in that it is for the production of an antitumor agent or a RET inhibitor for the treatment of a malignant tumor with activation highlighted from RET.