EA041852B1 - 4-AZAINDOL COMPOUNDS - Google Patents

Description

Link to related application

This application claims priority under U.S. Provisional Application No. 62/599,875, filed Dec. 18, 2017, which is incorporated herein in its entirety.

Background of the present invention

The present invention relates generally to 4-azaindole compounds useful as inhibitors of Toll-like receptor 7, 8 or 9 (TLR7, TLR8, TLR9) signaling or combinations thereof. The present invention relates to 4-azaindole compounds, compositions containing such compounds, and methods of using them. The present invention further relates to pharmaceutical compositions containing at least one compound of the present invention that can be used to treat pathological conditions associated with TLR modulation, such as inflammatory and autoimmune diseases, and to methods of inhibiting TLR activity in a mammal.

Members of the Toll/IL-1 receptor family are important regulators of inflammation and host resistance. The Toll-like receptor family recognizes the molecular patterns of infectious organisms, including bacteria, fungi, parasites, and viruses (for a review, see Kawai T. et al., Nature Immunol, 11:373-384 (2010)). Ligand binding to the receptor induces dimerization and recruitment of adapter molecules to a conserved cytoplasmic motif in the receptor called the Toll/IL-1 receptor (TIR) domain, with the exception of TLR3, all TLRs recruit the adapter molecule MyD88. Members of the IL-1 receptor family also contain a cytoplasmic TIR motif and recruit MyD88 when bound to a ligand (for a review, see Sims J. E. et al., Nature Rev. Immunol, 10:89-102 (2010)).

Toll-like receptors (TLRs) are a family of evolutionarily conserved transmembrane innate immune receptors that are involved in the first line of defense. As pattern recognition receptors, TLRs protect against foreign molecules activated by pathogen-associated molecular patterns (PAMP) or damaged tissue activated by hazard-associated molecular patterns (DAMP). A total of 13 members of the TLR family were identified, 10 of which are in humans, covering either the cell surface or the endosomal compartment. TLR7-9 are among the receptors that are located in the endosomal compartment and are responsible for the response to single-stranded RNA (TLR7 and TLR8) or unmethylated single-stranded DNA containing cytosine phosphate guanine (CpG) motifs (TLR9).

Activation of TLR7/8/9 can initiate a number of inflammatory responses (cytokine production, B cell activation and IgG production, type I interferon response). In the case of autoimmune disorders, aberrant long-term activation of TLR7/8/9 leads to worsening disease states. While TLR7 overexpression in mice has been shown to exacerbate autoimmune disease, TLR7 knockout in mice has been found to protect lupus-prone MRL/lpr mice from developing disease. At double knockout, TLR7 and 9 saw additional enhanced protection.

Since treatments involving the modulation of cytokines, IFN production, and B cell activity may be beneficial in many pathological conditions, it is immediately apparent that novel compounds capable of modulating TLR7 and/or TLR8 and/or TLR9 and methods of using such compounds may provide significant therapeutic benefits for a wide range of patients.

The present invention relates to a new class of 4-azaindole compounds which have been found to be effective inhibitors of TLR7/8/9 signaling. These compounds are envisaged as being useful as pharmaceuticals with the required stability, bioavailability, therapeutic index and toxicity values which are important for their suitability as drugs.

Brief summary of the invention

The present invention relates to compounds of formula (I) which are useful as inhibitors of signaling through Toll-like receptor 7, 8 or 9 and are useful in the treatment of proliferative diseases, allergic diseases, autoimmune diseases and inflammatory diseases, or their pharmaceutically acceptable salts.

The present invention also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier and at least one of the compounds of the present invention or their pharmaceutically acceptable salts.

The present invention also relates to a method for the treatment of proliferative, metabolic, allergic, autoimmune and inflammatory diseases, comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or their pharmaceutically acceptable salts.

The present invention also relates to processes and intermediates for the preparation of compounds of formula (I), including their salts.

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The present invention also relates to at least one of the compounds of formula (I), or salts thereof, for use in the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease.

These and other features of the present invention will be set forth in an expanded form as the disclosure is presented below.

Detailed description of the invention

The first aspect of the present invention relates to at least one compound of formula (I):

Ri (R ₅ )n ^H (I), or a pharmaceutically acceptable salt thereof, wherein G is

DOS ₃

I - { y - main ₃ (O ^? \=/ ;

A represents:

(i) -OR6 or -O(CR _x R _x )i-2-R6;

(ii) -NR7R8;

(iii) - C(O)NR9R _w ;

(iv) -CH2CH2R11;

(v) -CR _x R ₁₂ R ₁₃ where R ₁₂ and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from azetidinyl, C _3-6 cycloalkyl, morpholinyl or piperidinyl, each substituted from zero to 3 R _12a ;

(vi) pyrazolyl substituted with zero to 1 R _14a ;

R1 is -CH ₃ or -CH(CH ₃ ) ₂ ;

each R2 is independently Cl, -CH ₃ , -CH ₂ CH ₃ , -CH2OH, -CH2CH2OH, -CH2CN, -OCH3, -CH2OCH3 or -CH2CH2S(O)2CH3;

R _2a is C _1-6 alkyl;

R _2b is H, halo or C _1-6 alkyl;

R5 is F or C _1-3 alkyl;

R ₆ is (i) -CH ₃ ; or (ii) azetidinyl, cyclohexyl or piperidinyl, each substituted with zero to 2 R _6a ;

each R _6a is independently -CH ₃ , -CH ₂ CH ₂ CH ₃ , -C(CH ₃ ) ₂ , -CH ₂ C(CH ₃ ) ₂ OH, -N(CH ₃ ) ₂ , -N(CH2CH2CH3) 2, -CH2CH2S(O)2CH3, -CH2C(O)N(CH3)2 or tetrahydropyranyl;

R ₇ and R ₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from azetidinyl, diazepanil, diazaspiro[3.5]nonanyl, piperazinonyl, piperazinyl, piperidinyl and pyrrolidinyl, said heterocyclic ring being substituted from zero to 1 R _7b and from zero to 2 R _7c ;

R _7b is:

(a) -NR _x R _x , C _1-6 alkyl, C _2-3 fluoroalkyl, C _1-4 hydroxyalkyl, C _1-2 cyanoalkyl, -CHR _x CH ₂ OCH ₃ , -CH ₂ C(O)NR _x R _x , -CH ₂ CH ₂ C(O)NR _x R _x , -(CH ₂ ) _2-3 S(O) ₂ CH ₃ , -CH ₂ CH ₂ NHS(O) ₂ CH ₃ , -N(CH ₃ )(CH ₂ CH ₃ ), -N(CH ₂ CH ₃ ) ₂ , -NH(CH ₂ CN), -N(CH ₂ CN) ₂ , -NR _x CH ₂ C(O)N(CH ₃ ) ₂ , -NR _x C(O)CH ₂ N(CH ₃ ) ₂ ,

-NH(CH2CH2S(O)2CH3), -N(CH2C(O)N(CH3)2)2, -S(O)2CH2CH2N(CH3)2, -C(O)CH2CH2N(CH3)2,

-C(O)CH ₂ NR _x R _x , -C(O)CH ₂ N(CD ₃ ) ₂ , -C(O)CD ₂ N(CH ₃ ) ₂ , -C(O)CD ₂ N(CD ₃ ) ₂ , -C(O)CH ₂ NH(CH(CH ₃ ) ₂ ), -C(O)CH2NH(CH2CH2OCH3), -C(O)CH2NH(CH2CH2OH), -CH2(cyclopropyl), -CH methyloxetanyl) , -CH ₂ (tetrahydrofuranyl), -CH ₂ (methyltriazolyl), -CH ₂ CH ₂ (morpholinyl), -NR _x (cyclobutyl), -NR _x (oxetanyl), -NR _x (pyrimidinyl),

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-NR _x (tetrahydrohydroxranil), -NHCH ₂ (methylsulfonylcyclopropyl), -NHCH ₂ (methyloxetanyl), -NHCH ₂ (methoxypyrimidinyl), -C(O)CH ₂ NH (cyclobutyl), -N (CH ₂ (dimethoxypyrimidinyl)) ₂ ,

-N (CH ₂ (methoxypyrimidinyl)) ₂ , -N (CH ₂ (triazolyl)) ₂ , -N (CH ₂ (methyltriazolyl)) ₂ , -N (CH ₃ ) CH ₂ (cyclopropyl), -N (CH ₃ ) CH ₂ (methylpyrazolyl), -N (CH ₃ ) CH ₂ (pyrimidinyl), -N (CH ₃ ) CH ₂ (methylpyrimidinyl), -N (CH ₃ ) CH ₂ (dimethoxypyrimidinyl), -N (CH ₃ ) CH ₂ (methoxypyrimidinyl), -N (CH ₃ ) CH ₂ (thiadiazolyl), -N (CH ₃ ) CH ₂ (methyltriazolyl), -NH (CH ₂ (methylpyrimidinyl)) ₂ , -NH (CH ₂ (thiadiazolyl), - C(O)CH ₂ (azetidinyl), -C(O)CH ₂ (morpholinyl), -C(O)CH ₂ (hydroxypiperidinyl), -C(O)CH ₂ (pyrrolidinyl) or -C(O)CH ₂ NHCH ₂ (cyclopropyl) or (b) cyclobutyl, cyclohexyl, dioxothiomorpholinyl, oxetanyl, piperazinyl, piperidinyl, tetrahydrofuranyl or tetrahydropyranyl, each substituted with zero to 1 R _8a and zero to 3 R _8b ;

each R7 _c is independently -CH ₃ or -CH2CN;

R8a is -OH, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2CH(CH3)2, -CH2CH2OCH3, -CH2CH2CF3, -C(O) _CH3 , -C( O) OCH ₃ , -CH ₂ (cyclopropyl), -CH ₂ (methylphenyl), -(CH ₂ ) ₂ . ₃ (pyrrolidinyl), -CH2 (methylpyrazolyl), -CH2 (thiophenyl), -NRxRx, cyclopentyl, methylpiperidinyl or pyridinyl;

each R _8b is independently —CH ₃ ;

R9 is -CH2CH2CF3 or -CH ₂ CH ₂ N(CH ₃ ) ₂ ;

R ₁₀ is H or C ₁ . ₂ alkyl;

or R9 and _R10 together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperidinyl substituted with -C(O)CH3 or -CH(CH3)2;

R11 is azetidinyl or piperidinyl, each substituted with zero to 1 substituents selected from halo, -CH2(methyloxetanyl), -CH2(triazolyl), -C(O)CH2N(CH3)2, -CH2C(CH3)2OH , -CH2C(O)N(CH3)2, -CH2CH2S(O)2CH3 and oxetanyl;

each R _12a is independently -OH, -CH ₃ , -CH2CH2CH3, -CH(CH ₃ ) ₂ , -CH ₂ CH(CH ₃ ) ₂ , CH2CN, -CH2C(CH3)2OH, -CH2C(O)NH( CH3), -CH2C(O)N(CH3)2, -CH2C(O)NH2, -C(CH3)2CH2C(O)N(CH3)2, CH2CH2SO2CH3, -NRxRy, -NRxCHNRxRx, -NRx(CH2CHF2), -N(Rx)(CH2CH2CF3), ^(C^C^OCH3), -NRx(C _b 2cyanoalkyl), -NRx(CH2CH2OH), -N(CH2CH2OH)(CH2C(O)N(CH3)2), - N(CH2CH2OH)(CH2CH2S(O)2CH3), -N(CH2CH2S(O)2CH3)2, -NRxCH2CRxRxS(O)2CH3, -NRxCH2CH2S(O)2CF3, -NRxCH2CH2S(O)2NH2, -NRxC(O)CH3 , -NRxC(O)CH2N(CH3)2, -NRx(CRxRxC(O)NRxRx), -NHCH2C(O)NRx(C(CH3)3), -NRx(CRxRxC(O)CH2NRxRx), -NH(CH2C (O)N(CH3)CH2CH2OCH3), -N(CH2CH3)2, -N(CH2CH3)(CH2C(O)N(CH3)2),

-N(CH2CH3)(CH2CH2S(O)2CH3), -N(CH2CN)2, -N(CH2CN)(CH2C(O)N(CH3)2), -N(CH2CN)(CH2CH2S(O)2CH3), -N(CH2C(O)NRxRx)2, , -C(O)CHN(CH3)2, -C(O)CH2CH2N(CH3)2, R _nb -CHR^, -NRxR^b, -N(cyclopropyl) R12b, -NRxCHRxR12b, -NHC(O)R12b, -NHCRxRxC(O)R12b, -N(CH2CH3)(CH2R12b), -NCCHCHOHRi",

-N(CH2CH2OH)(CH2R12b), -NCCHCNRub -N(CH2CN)(CH2R12b) or -N(CH2(methyl oxetanyl))2; or two R _12a and the carbon atom to which they are attached form C=O;

R _12b is azaspiro[3.5]nonanyl, azetidinyl, cyclopropyl, cyclopentyl, dioxotetrahydrothiofuranyl, dioxytetrahydrothiopyranyl, dioxothiaazaspiro[3.3]heptanyl, morpholinyl, oxaazaspiro[3.3]heptanyl, oxazolyl, oxetanyl, phenyl, piperazinonyl, pyridinyl, pyridinyl, pyridinyl, pyrrolidinyl, pyrrolidinonyl, tetrahydrofuranyl, tetrahydropyranyl or triazolyl, each substituted with zero to 4 substituents independently selected from F, -CN, -CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH , C^cyanoalkyl, -OCH3, -CH2C(O)NH(CH3), -C(O)NRxRx, -S(O)2CH3 and -CH2S(O)2CH3;

R _14a is piperidinyl or —CH ₂ CH ₂ (morpholinyl);

each R _x is independently H or -CH ₃ ;

R _y is H or C ₁ . ₆ alkyl;

n is zero or 1; and p is zero, 1, 2, or 3.

The second embodiment relates to a compound of formula (I) or a salt thereof, wherein

G represents

And

A represents -CR _x R ₁₂ R ₁₃ where R ₁₂ and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from azetidinyl, C ₄ . ₆ cycloalkyl or piperidinyl, each substituted with zero to 3 R _12a ;

where R _2a , R _2b , R2, R _12a and p have the meanings specified in claim 1.

The third embodiment relates to a compound of formula (I) or a salt thereof, wherein

G represents

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A represents -CRxR ₁₂ R ₁₃ where R12 and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl and cyclohexyl, each substituted with zero to 1 R12a;

R1 is -CH(CH ₃ ) ₂ ;

R _12a is -NRxRy, -NRx(CH ₂ CHF ₂ ), -N(Rx)(CH ₂ CH ₂ CF ₃ ), -NRx(CH ₂ CH ₂ OCH ₃ ), -NRx(C1_2cyanoalkyl), -NRxCHNRxRx , -NRx(CH2CH2OH), -NRx(CH2C(O)NRxRx), -CHRub, -NRxR12b or -NRxCHRxR12b; And

R _12b is cyclopropyl, cyclopentyl, dioxotetrahydrothiofuranyl, dioxytetrahydrothiofuranyl, morpholinyl, oxazaspiro[3.3]heptanyl, oxazolyl, oxetanyl, phenyl, piperidinyl, pyrazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, tetrahydrofuranyl, tetrahydropyranyl, or triazolyl, each substituted with from zero to 4 independently selected from F, -CN, -CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH, C1_2cyanoalkyl, -OCH3, -CH2C(O)NH( _CH3 ) , -C(O)NR _x R _x , -S(O) ₂ CH ₃ and -CH ₂ S(O) ₂ CH ₃ ;

where R2, R _x , R ₁₂ , R ₁₃ and R _y have the meanings specified in claim 1.

The fourth embodiment relates to a compound of formula (I) or a salt thereof, wherein

G represents:

And

And represents -NR7R8, where R2, R ₇ , Rg and p have the meanings specified in claim 1.

The fifth embodiment relates to a compound of formula (I) or a salt thereof, wherein G is

R1 is -CH(CH ₃ ) ₂ and

A is piperazinil; where R2 and p have the values specified in claim 1.

One embodiment relates to a compound of formula (I)

One embodiment relates to is either a salt thereof, where the compound is to a compound of formula (I) or a salt thereof, where the compound

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refers to a compound of formula (I) or a salt thereof, wherein said compound is

One embodiment relates to a compound of formula (I), its N-oxide or salt, wherein said compound is selected from the compounds of Examples 1-1078.

One embodiment relates to a pharmaceutical composition for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

One embodiment relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease. Moreover, the specified autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS) and Sjögren's syndrome.

One embodiment relates to the use of a compound or a pharmaceutically acceptable salt thereof for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease, wherein said compound is selected from

The present invention may be embodied in other specific forms without departing from

- 5 041852 its essence or main features. The present invention covers all noted combinations of aspects and/or embodiments of the present invention. It is to be understood that any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe further embodiments. It is also to be understood that each individual element of the embodiments is intended to be combined with any or all of the other elements of any embodiment to describe a further embodiment.

Definitions

The features and advantages of the present invention may be better understood by those skilled in the art upon reading the following detailed description. It was contemplated that certain features of the present invention, which for purposes of clarity are described above and below in the context of separate embodiments, may also be combined to form one embodiment. In turn, the various features of the present invention, which are described for brevity in the context of one embodiment, may also be combined to form subcombinations thereof. Embodiments defined herein as exemplary or preferred are intended to be illustrative and non-limiting.

Unless otherwise specifically noted herein, references made in the singular may also include the plural. For example, the singular forms can refer either to one or to one or more.

Used in the present description, the expression connection refers to at least one connection. For example, a compound of formula (I) includes a compound of formula (I) and two or more compounds of formula (I).

Unless otherwise noted, any heteroatom with an unsaturated valence is assumed to contain sufficient hydrogen atoms to saturate the valences.

The definitions set forth herein take precedence over the definitions set forth in any patent, patent application and/or published patent application, which are incorporated herein by reference.

The following are definitions of various terms used to describe the present invention. These definitions apply to terms as they are used throughout the description (unless they are otherwise limited in specific cases) either alone or as part of a larger group.

Throughout the description, the groups and their substituents can be selected by a person skilled in the art to obtain stable fragments and compounds.

According to the symbol used in the present field of technology

used in the structural formulas of the present description to denote a connection, which is the point of attachment of a fragment or substituent to the core or main structure.

As used herein, the terms halo and halogen refer to F, Cl, Br, and I.

The term cyano refers to the -CN group.

The term amino refers to the -NH ₂ group.

The term oxo refers to the =O group.

As used herein, the term alkyl refers to both branched and straight chain saturated aliphatic hydrocarbon groups containing, for example, 1 to 12 carbon atoms, 1 to 6 carbon atoms, and 1 to 4 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, sec-butyl, and t-butyl), and pentyl ( for example, n-pentyl, isopentyl, neopentyl), n-hexyl, 2-methylpentyl, 2-ethylbutyl, 3-methylpentyl and 4-methylpentyl. If the numbers are in a subscript after the symbol C, the subscript more specifically means the number of carbon atoms that a particular group can contain. For example, _C1 . ₆ alkyl means straight chain and branched alkyl groups with one to six carbon atoms.

As used herein, the term fluoroalkyl is intended to include both branched and straight chain saturated aliphatic hydrocarbon groups substituted with one or more fluorine atoms. For example, C ₁ .4fluoroalkyl is meant to include C 1 , C 2 , C ₃ and C ₄ alkyl groups substituted with one or more fluorine atoms. Illustrative examples of fluoroalkyl groups include, without limitation, -CF3 and -CH2CF3.

The term cyanoalkyl includes saturated branched and straight chain alkyl groups substituted with one or more cyano groups. For example, cyanoalkyl includes -CH2CN, -CH2CH2CN, and C ₁ .4 cyanoalkyl.

The term aminoalkyl includes both branched and straight chain saturated alkyl groups substituted with one or more amine groups. For example, aminoalkyl includes -CH2NH2, -CH2CH2NH2 and C ₁ .4 aminoalkyl.

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The term hydroxyalkyl includes both branched and straight chain saturated alkyl groups substituted with one or more hydroxyl groups. For example, hydroxyalkyl includes -CH2OH, -CH2CH2OH and C _1-4 hydroxyalkyl.

The term hydroxyfluoroalkyl includes saturated branched and straight chain alkyl groups with one or more hydroxyl groups and one or more fluorine atoms. For example, hydroxyfluoroalkyl includes -CHFCH2OH, -CH ₂ CHFC(CH ₃ ) ₂ OH, and C ₁ . ₄ hydroxyfluoroalkyl.

As used herein, the term cycloalkyl refers to a group derived from a non-aromatic monocyclic or polycyclic hydrocarbon molecule by removing one hydrogen atom from a carbon atom of a saturated ring. Illustrative examples of cycloalkyl groups include, without limitation, cyclopropyl, cyclopentyl, and cyclohexyl. If the numbers in the index are after the symbol C, then the index means more specifically the number of carbon atoms that a particular cycloalkyl group can contain. For example, C ₃ -C ₆ -cycloalkyl means cycloalkyl groups with three to six carbon atoms.

As used herein, the term alkoxy refers to an alkyl group attached to the parent molecular moiety through an oxygen atom, such as a methoxy group (-OCH3). For example, _C1 . ₃ α alkoxy means alkoxy groups with one to three carbon atoms.

As used herein, the term alkoxyalkyl refers to an alkoxy group attached via its oxygen atom to an alkyl group that is attached to the parent molecular moiety, such as a methoxymethoxy group (-CH2OCH3). For example, C _{2 -4} alkoxyalkyl means alkoxyalkyl groups with two to four carbon atoms, such as -CH2OCH3, -CH2CH2OCH3, -CH2OCH2CH3 and -CH2CH2OCH2CH3.

As used herein, the term pharmaceutically acceptable refers to those compounds, substances, compositions and/or dosage forms that, based on careful medical evaluation, are suitable for use in contact with human and animal tissues without undue toxicity, irritation, allergic reaction, or other problems or complications. according to an acceptable benefit/risk ratio.

The compounds of formula (I) may be provided as amorphous solids or crystalline solids. Lyophilization can be used to obtain compounds of formula (I) as amorphous solids.

In addition, it should be understood that solvates (eg hydrates) of the compounds of formula (I) are also within the scope of the present invention. The term solvate means the physical association of a compound of formula (I) with one or more solvent molecules, organic or inorganic. Such a physical association includes a hydrogen bond. In certain cases, the solvate can be isolated, for example, if one or more solvent molecules are included in the crystal lattice of a crystalline solid. Solvate encompasses both liquid phase and separable solvates. Exemplary solvates include hydrates, ethanolates, methanolates, isopropanolates, acetonitrile solvates, and ethyl acetate solvates.

Solvation methods are known in the art.

Various forms of prodrugs are well known in the art and are described in:

a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al., Ch 31, (Academic Press, 1996);

b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985);

c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson and H. Bundgaard, eds. Ch 5, pgs 113-191 (Harwood Academic Publishers, 1991); And

d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and Joachim M. Mayer, (Wiley-VCH, 2003).

In addition, the compounds of formula (I) after their preparation can be isolated and purified to obtain a composition containing an amount equivalent to or more than 99% by weight of the compound of formula (I) (essentially pure), which is then used or formulated as described in the present invention. Such essentially pure compounds of formula (I) are also considered in the present description as part of the present invention.

A stable compound and a stable structure are meant to mean a compound that is stable enough to persist after isolation to an acceptable degree of purity from a reaction mixture and subsequent incorporation into an effective therapeutic agent. The present invention is intended to provide stable compounds.

A therapeutically effective amount is intended to include an amount of a single compound of the present invention, or an amount of a combination of the claimed compounds, or an amount of a compound of the present invention in combination with other active ingredients that are effective as an inhibitor of TLR7/8/9, or are effective for the treatment or prevention of autoimmune and/or inflammatory disease conditions such as SLE, IBD, multiple sclerosis (MS), Sjögren's syndrome and rheumatoid arthritis.

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As used herein, the term treatment process or treatment means the treatment of a disease state in a mammal, in particular a human, and is intended to: (a) prevent the occurrence of the disease state in a mammal, in particular if such mammal is predisposed to the disease state but has not yet been diagnosed its presence; (b) inhibiting the disease state, ie, stopping its development; and/or (c) alleviating the disease state, ie, causing regression of the disease state.

It is envisaged that the compounds of the present invention include all isotopes of atoms occurring in these compounds. Isotopes include those atoms that have the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium (D) and tritium (T). Isotopes of carbon include ¹³ C and ¹⁴ C. The isotopically labeled compounds of the present invention can generally be prepared by conventional procedures known to those skilled in the art, or by methods similar to those described herein, using a suitable isotopically labeled reagent instead of an unlabeled reagent used otherwise. For example, methyl (-CH3) also includes deuterated methyl groups such as -CD ₃ .

Utility

The human immune system evolves to protect the body from microorganisms, viruses, and parasites that can cause infection, disease, or death. Complex regulatory mechanisms ensure that the various cellular components of the immune system purposefully neutralize foreign substances or organisms without causing irreversible or significant damage to the individual. Although the initiating factors are currently not fully understood, in autoimmune disease states, the immune system directs its inflammatory response to target organs in the affected individual. Various autoimmune diseases are usually characterized by predominant or initial involvement of the target organ or tissues, such as the joint in rheumatoid arthritis, the thyroid in autoimmune thyroiditis, the central nervous system in multiple sclerosis, the pancreas in type I diabetes mellitus, and the gut in inflammatory bowel disease.

The compounds of the present invention inhibit signaling involving Toll-like receptor 7 or 8 or 9 (TLR7, TLR8, TLR9) or combinations thereof. Accordingly, the compounds of formula (I) are useful in the treatment of pathological conditions associated with inhibition of signaling involving one or more of TLR7, TLR8 or TLR9. Such pathological conditions include diseases associated with TLR7, TLR8 or TLR9 receptors, in which cytokine levels are modulated due to intracellular signaling.

As used herein, the terms administering treatment or treatment encompasses the treatment of a disease state in a mammal, especially a human, and includes: (a) preventing or delaying the onset of the disease state in the mammal, particularly where such mammal is predisposed to developing such disease state, but still has not been diagnosed as having it; (b) suppression of the disease state, ie. stop its development; and/or (c) achieving total or partial reduction of the symptoms or disease state and/or mitigation, alleviation, amelioration or cure of the disease or disorder and/or its symptoms.

In view of their activity as selective inhibitors of TLR7, TLR8, or TLR9, the compounds of formula (I) are useful in the treatment of diseases associated with the TLR7, TLR8, or TLR9 family of receptors, including, but not limited to, inflammatory diseases such as Crohn's disease, ulcerative colitis, asthma, graft-versus-host disease, allograft rejection, chronic obstructive pulmonary disease; autoimmune diseases such as Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, cutaneous lupus, psoriasis; autoinflammatory diseases, including cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS), familial Mediterranean fever (FMF), adult-onset Still's disease, systemic-onset juvenile idiopathic arthritis, gout, gouty arthritis ; metabolic disorders, including type 2 diabetes mellitus, atherosclerosis, myocardial infarction; bone-breaking disorders such as bone resorption disease, osteoarthritis, osteoporosis, multiple myeloma-associated bone disease; proliferative disorders such as acute myelogenous leukemia, chronic myelogenous leukemia; angiogenic disorders such as angiogenic disorders including solid tumors, ocular neovascularization and childhood hemangiomas; infectious diseases such as sepsis, septic shock and shigellosis; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, cerebral ischemia or neurodegenerative disease caused by traumatic injury, cancer and viral diseases such as metastatic melanoma, Kaposi's sarcoma, multiple myeloma and HIV infection and CMV retinitis, AIDS, respectively.

More specifically, specific pathological conditions or diseases that can be treated using the compounds of the present invention include, without limitation, pancreatitis (acute or chronic), asthma, allergies, adult respiratory distress syndrome, chronic

- 8 041852 structural lung disease, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Graves' disease, autoimmune gastritis, diabetes mellitus, autoimmune hemolytic anemia, autoimmune neutropenia, thrombocytopenia, atopic dermatitis, chronic active hepatitis, myasthenia gravis sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, psoriasis, graft-versus-host disease, endotoxin-induced inflammatory response, tuberculosis, atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis, Reiter's syndrome, gout, traumatic arthritis, rubella measles, acute synovitis , a disease associated with P-cells of the pancreas; diseases characterized by massive infiltration of neutrophils; rheumatoid spondylitis, gouty arthritis and other arthritic conditions, cerebral malaria, chronic inflammatory lung disease, silicosis, pulmonary sarcoidosis, disease leading to bone resorption, allograft rejection, fever and myalgia due to infection, cachexia due to infection, keloid formation , scar tissue formation, ulcerative colitis, fever, influenza, osteoporosis, osteoarthritis, acute myelogenous leukemia, chronic myelogenous leukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma, sepsis, septic shock and shigellosis; Alzheimer's disease, Parkinson's disease, cerebral ischemia or neurodegenerative disease caused by traumatic injury; angiogenic disorders including solid tumors, ocular neovascularization, and childhood hemangiomas; viral diseases including acute hepatitis (including hepatitis A, hepatitis B and hepatitis C), HIV infection and CMV retinitis, AIDS, ARC or malignancy and herpes; stroke, myocardial ischemia, stroke ischemia, heart attacks, organ hypoxia, vascular hyperplasia, reperfusion injury of the heart and kidneys, thrombosis, cardiac hypertrophy, thrombin-induced platelet aggregation, endotoxemia and/or toxic shock syndrome, pathological conditions associated with prostaglandin- endoperoxide synthase-2, and pemphigus vulgaris. Included in this embodiment are treatments wherein the condition is selected from lupus, including lupus nephritis and systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, allograft rejection, rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis, and pemphigus ordinary. Also included are methods of treatment in which the pathological condition is selected from ischemia-reperfusion injury, including ischemia-reperfusion injury of the brain resulting from a stroke, and ischemia-reperfusion injury of the heart resulting from myocardial infarction. Another treatment method is one in which the pathological condition is multiple myeloma.

In one embodiment, the compounds of formula (I) are useful in the treatment of cancer, including Waldenström macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), cutaneous diffuse large B-cell lymphoma, and primary CNS lymphoma. .

In addition, the TLR7, TLR8 or TLR9 inhibitors of the present invention inhibit the expression of inducible pro-inflammatory proteins such as prostaglandin endoperoxide synthase-2 (PGHS-2), also called cyclooxygenase-2 (COX-2), IL-1, IL- 6, IL-18, chemokines. Accordingly, additional TLR7/8/9 associated pathological conditions include edema, analgesia, fever, and pain such as neuromuscular pain, headache, pain caused by cancer, toothache, and arthritis pain. The compounds of the present invention may also be used to treat veterinary viral infections such as lentiviral infections, including, but not limited to, equine infectious anemia virus infections; or retroviral infections, including those caused by feline immunodeficiency virus, bovine immunodeficiency virus, and canine immunodeficiency virus.

Thus, the present invention relates to methods for treating such pathological conditions, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound of formula (I) or a salt thereof. A therapeutically effective amount is meant to include an amount of a compound of the present invention which, when administered alone or in combination, is effective in inhibiting an autoimmune disease or a chronic inflammatory disease.

Methods for treating pathological conditions associated with TLR7, TLR8 or TLR9 may include the administration of compounds of formula (I) alone or in combination with each other and/or other suitable therapeutic agents useful in the treatment of such pathological conditions. Accordingly, a therapeutically effective amount is also meant to include an amount of the combination of the claimed compounds that is effective to inhibit TLR7, TLR8 or TLR9 and/or treat diseases associated with TLR7, TLR8 or TLR9.

Examples of such other therapeutic agents include corticosteroids, rolipram, calfostin, cytokine suppressive anti-inflammatory drugs (CSAIDs), interleukin 10, glucocorticoids, salicylates, nitric oxide, and other immunosuppressants; nuclear translocation inhibitors such as deoxyspergualine (DSG); non-steroidal anti-inflammatory drugs

- 9 041852 NSAIDs such as ibuprofen, celecoxib and rofecoxib; steroids such as prednisone or dexamethasone; antivirals such as abacavir; antiproliferatives such as methotrexate, leflunomide, FK506 (tacrolimus, PROGRAF®); antimalarials such as hydroxychloroquine; cytotoxic drugs such as azatiprine and cyclophosphamide; TNF-α inhibitors such as tenidap, anti-TNF antibodies or soluble TNF receptor and rapamycin (sirolimus or RAPAMUNE®) or derivatives thereof.

The aforementioned other therapeutic agents, when used in combination with the compounds of the present invention, may be used, for example, in the amounts indicated in the Physicians' Desk Reference (PDR) or in the amounts otherwise determined by one of ordinary skill in the art. In the methods of the present invention, such other one or more therapeutic agents may be administered before, simultaneously with, or after administration of the compounds of the present invention. The present invention also relates to pharmaceutical compositions that can be used to treat pathological conditions associated with the TLR7/8/9 receptor, including the above-described diseases mediated by the IL-1 family receptor.

Compositions of the present invention may contain other therapeutic agents as described above and may be formulated, for example, using conventional solid or liquid carriers or diluents, as well as pharmaceutical excipients of the type that is appropriate for the desired route of administration (for example , excipients, binders, preservatives, stabilizers, flavoring agents, etc.) according to such techniques as are well known in the art of pharmaceutical formulations.

Accordingly, the present invention further includes compositions containing one or more compounds of formula (I) and a pharmaceutically acceptable carrier.

A pharmaceutically acceptable carrier refers to a medium generally accepted in the art for the delivery of biologically active agents to animals, in particular mammals. Pharmaceutically acceptable carriers have been formulated according to a variety of factors well known to those skilled in the art. These include, without limitation, the type and nature of the active agent formulated; a subject who has been administered a composition containing the agent; the intended route of administration of the composition; and the therapeutic symptom being treated. Pharmaceutically acceptable carriers include both aqueous and non-aqueous liquid media, as well as various solid and semi-solid dosage forms. Such carriers may include a number of different ingredients and additives in addition to the active agent, such additional ingredients have been included for a number of reasons, such as to stabilize the active agent, binders, and the like, well known to those skilled in the art. Descriptions of suitable pharmaceutically acceptable carriers and factors included in their selection are provided in various readily available sources such as, for example, Remington's Pharmaceutical Sciences, 17th Edition (1985), which are incorporated herein by reference in their entirety.

Compounds of formula (I) may be administered by any route suitable for the condition being treated, which may depend on the need for site-specific treatment or the amount of compound of formula (I) delivered.

The present invention also encompasses a class of pharmaceutical compositions comprising a compound of formula (I) and one or more non-toxic, pharmaceutically acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as carrier materials) and, if necessary, other active Ingredients. The compounds of formula (I) may be administered by any suitable route, preferably in the form of a pharmaceutical composition capable of such a route and at a dose effective for the intended treatment. The compounds and compositions of the present invention may, for example, be administered orally, transmucosally, or parenterally, including intravascularly, intravenously, intraperitoneally, subcutaneously, intramuscularly, and intrasternally, in unit dosage formulations containing conventional pharmaceutically acceptable carriers, auxiliaries, and media. . For example, the pharmaceutical carrier may contain a mixture of mannitol or lactose and microcrystalline cellulose. The mixture may contain additional ingredients such as a lubricant such as magnesium stearate and a disintegrant such as crospovidone. The carrier mixture may be filled into a gelatin capsule or compressed into a tablet. The pharmaceutical composition may be administered as an oral dosage form or infusion, for example.

For oral administration, the pharmaceutical composition may take the form of, for example, tablets, capsules, liquid capsules, suspensions or liquids. The pharmaceutical composition is preferably in the form of a dosage unit containing a certain amount of the active ingredient. For example, the pharmaceutical composition may be presented as a tablet or capsule containing an amount of the active ingredient in the range of from about 0.1 to 1000 mg, preferably from about 0.25 to 250 mg, and more preferably from about 0.5 to 100 mg. A suitable daily dose for a human or other mammal may vary widely.

- 10 041852 depends on the condition of the patient and other factors, and can be determined using routine methods.

Any pharmaceutical composition provided herein, for example, can be delivered orally using any acceptable and suitable oral preparations. Exemplary oral preparations include, but are not limited to, tablets, lozenges, lozenges, aqueous and oily suspensions, dispersible powders or granules, emulsions, hard and soft capsules, liquid capsules, syrups, and elixirs. Pharmaceutical compositions intended for oral administration can be prepared according to any methods known in the art for the manufacture of pharmaceutical compositions intended for oral administration. In order to provide pharmaceutical preparations with an acceptable taste, the pharmaceutical composition in accordance with the present invention may contain at least one agent selected from sweeteners, flavors, colors, coating agents, antioxidants and preservatives.

A tablet, for example, can be obtained by mixing at least one compound of formula (I) with at least one non-toxic pharmaceutically acceptable excipient suitable for the manufacture of tablets. Exemplary excipients include, without limitation, for example, inert diluents such as, for example, calcium carbonate, sodium carbonate, lactose, calcium phosphate, and sodium phosphate; granulating agents and disintegrators such as, for example, microcrystalline cellulose, croscarmellose sodium, corn starch and alginic acid; binders such as, for example, starch, gelatin, polyvinylpyrrolidone and gum arabic; and lubricants such as, for example, magnesium stearate, stearic acid and talc. In addition, the tablet may be either uncoated or coated by known techniques, either to mask the bad taste of the off-tasting drug, or to delay disintegration and absorption of the active ingredient in the gastrointestinal tract, thereby allowing the active ingredient to act for a longer period. Exemplary water-soluble taste-masking agents include, but are not limited to, hydroxypropyl methylcellulose and hydroxypropyl cellulose. Exemplary time delay agents include, but are not limited to, ethylcellulose and cellulose acetate butyrate.

Hard gelatin capsules, for example, can be prepared by mixing at least one compound of formula (I) with at least one inert solid diluent such as, for example, calcium carbonate, calcium phosphate and kaolin.

Soft gelatin capsules, for example, can be obtained by mixing at least one compound of formula (I) with at least one water-soluble carrier, such as, for example, polyethylene glycol; and at least one oil medium such as, for example, walnut oil, liquid paraffin and olive oil.

An aqueous suspension can be obtained, for example, by mixing at least one compound of formula (I) with at least one excipient suitable for making an aqueous suspension. Exemplary excipients suitable for making an aqueous suspension include, but are not limited to, for example, suspending agents such as, for example, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, alginic acid, polyvinylpyrrolidone, gum tragacanth, and gum arabic; dispersing or wetting agents, such as, for example, a naturally occurring phosphatide, for example, lecithin; condensation products of alkylene oxide with fatty acids, such as, for example, polyoxyethylene stearate; condensation products of ethylene oxide with long chain aliphatic alcohols such as, for example, heptadecaethyleneoxycetanol; condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol, such as, for example, polyoxyethylene sorbitol monooleate; and condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, such as, for example, polyethylene sorbitan monooleate. The aqueous suspension may also contain at least one preservative such as, for example, ethyl and npropyl para-hydroxybenzoate; at least one dye; at least one flavor and/or at least one sweetener, including but not limited to, for example, sucrose, saccharin, and aspartame.

Oil suspensions, for example, can be prepared by suspending at least one compound of formula (I) either in a vegetable oil such as, for example, peanut oil, olive oil, sesame oil and coconut oil; or in a mineral oil such as, for example, liquid paraffin. The oil suspension may also contain at least one thickening agent such as, for example, beeswax, hard paraffin and cetyl alcohol. In order to provide an edible oil suspension, at least one of the sweeteners already described above and/or at least one flavor can be added to the oil suspension. The oil suspension may further contain at least one preservative, including, but not limited to, for example, an antioxidant such as, for example, butylated hydroxyanisole and alpha tocopherol.

- 11 041852

Dispersible powders and granules, for example, may be prepared by mixing at least one compound of formula (I) with at least one dispersing and/or wetting agent, at least one suspending agent and/or at least one preservative. Suitable dispersing agents, wetting agents and suspending agents have already been described above. Exemplary preservatives include, without limitation, for example, antioxidants such as ascorbic acid. In addition, dispersible powders and granules may also contain at least one excipient, including, but not limited to, sweeteners, flavors, and colors.

An emulsion of at least one compound of formula (I), for example, can be prepared as an oil-in-water emulsion. The oil phase of emulsions containing compounds of formula (I) may be formulated from known ingredients in a known manner. The oil phase can be provided with, but not limited to, vegetable oil such as, for example, olive oil and peanut oil; mineral oil, such as, for example, liquid paraffin; and their mixtures. While the phase may contain only an emulsifier, it may contain a mixture of at least one emulsifier with fat or oil, or both fat and oil. Suitable emulsifying agents include, without limitation, for example, naturally occurring phosphatides, such as soy lecithin; esters or partial esters derived from fatty acids and hexitol anhydrides, such as, for example, sorbitan monooleate; and condensation products of partial esters with ethylene oxide, such as, for example, polyoxyethylene sorbitan monooleate. Preferably, a hydrophilic emulsifier is included along with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both oil and fat. The emulsifier(s), with or without stabilizer(s), constitute(s) the so-called emulsifying wax, and the wax, together with oil and fat, constitutes the so-called emulsifying ointment base, which forms the oily dispersible phase of cream formulations. The emulsion may also contain a sweetener, flavor, preservative and/or antioxidant. Emulsifiers and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, glyceryl distearate alone or with wax, or other substances well known from the art technology.

The compounds of formula (I), for example, can also be delivered intravenously, subcutaneously and/or intramuscularly in any pharmaceutically acceptable and suitable injectable form. Exemplary injectable forms include, without limitation, for example, sterile aqueous solutions containing acceptable vehicles and solvents such as, for example, water, Ringer's solution, and isotonic sodium chloride solution; sterile oil-in-water microemulsions; and aqueous or oily suspensions.

Compositions for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injectable solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules using one or more of the carriers or diluents mentioned for use in oral formulations or other suitable dispersing or wetting agents and suspending agents. The compounds can be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, nut oil, sesame oil, benzyl alcohol, sodium chloride solution, gum tragacanth and/or various buffers. Other adjuvants and routes of administration are well and widely known in the pharmaceutical industry. The active ingredient may also be administered by injection as a composition with suitable vehicles, including saline, dextrose, or water, or cyclodextrin (i.e., Captisol), solubilization with co-solvent (i.e., propylene glycol) or micellar solubilization (ie, Tween 80).

The sterile injectable may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or vehicle, such as a solution in 1,3-butanediol. Acceptable vehicles and solvents that may be used are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils have traditionally been used as a solvent or suspending medium. Any bland fixed oil may be used for this purpose, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Sterile injectable oil-in-water microemulsion, for example, can be obtained by 1) dissolving at least one compound of formula (I) in an oil phase, such as, for example, a mixture of soybean oil and lecithin; 2) combining the oil phase containing the compounds of formula (I) with a mixture of water and glycerol; and 3) processing the combination to form a microemulsion.

Sterile aqueous or oily suspension can be obtained according to methods already known from the prior art. For example, a sterile aqueous solution or suspension can be prepared with a non-toxic, parenterally acceptable diluent or vehicle such as, for example, 1,3-butanediol; and a sterile oil suspension can be obtained with a sterile non-toxic reception

- 12 041852 a suitable solvent or suspending medium, such as, for example, sterile fixed oils, for example, synthetic mono- or diglycerides; and fatty acids such as, for example, oleic acid.

Pharmaceutically acceptable carriers, adjuvants and media that may be used in the pharmaceutical compositions of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d polyethylene glycol alpha-tocopherol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tweens, polyethoxylated castor oil such as CREMOPHOR surfactant (BASF), or other similar polymeric delivery matrices, whey proteins such as human serum albumin, buffering agents such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of vegetable saturated fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc ols, colloidal silicon oxide, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, block polymers of polyethylene and polyoxypropylene, polyethylene glycol and wool grease. Cyclodextrins such as alpha-, beta- and gamma-cyclodextrin, or chemically modified derivatives such as hydroxyalkylcyclodextrins, including 2- and 3-hydroxypropylcyclodextrins, or other solubilized derivatives, can also be successfully used to improve the delivery of compounds of the formulas described in this document.

Pharmaceutically active compounds of the present invention may be processed according to conventional pharmaceutical methods to provide medical agents for administration to patients, including humans and other mammals. The pharmaceutical compositions may be subjected to conventional pharmaceutical procedures such as sterilization and/or may contain conventional adjuvants such as preservatives, stabilizers, wetting agents, emulsifiers, buffers, and the like. Tablets and pills can also be prepared with enteric coatings. Such compositions may also contain adjuvants such as moisturizers, sweeteners, flavorings and fragrances.

The amounts of compounds administered and the dosage regimen for treating a disease state with compounds and/or compositions in accordance with the present invention depend on a number of factors, including age, weight, sex, health status of the subject, type of disease, severity of the disease, route and frequency of administration, and also the specific compound used. Thus, the dosage regimen can vary widely and can be determined by standard procedures using standard methods. A daily dose of from about 0.001 to 100 mg/kg of body weight may be acceptable, preferably from about 0.0025 to about 50 mg/kg of body weight, and most preferably from about 0.005 to 10 mg/kg of body weight. The daily dose may be administered in one to four doses per day. Other dosing regimens include one dose per week and one dose per two day cycle.

For therapeutic purposes, the active compounds of the present invention are usually combined with one or more adjuvants suitable for the indicated route of administration. When administered orally, the compounds can be mixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, arabic gum, sodium alginate, polyvinylpyrrolidone and/or polyvinyl alcohol and then tableted or encapsulated for easy administration. Such capsules or tablets may contain a controlled release formulation which may be provided in a dispersion of the active compound in hydroxypropyl methylcellulose.

Pharmaceutical compositions in accordance with the present invention contain at least one compound of formula (I) and optionally an additional agent selected from any pharmaceutically acceptable carrier, adjuvant and environment. Alternative compositions according to the present invention comprise a compound of formula (I) as described herein, or a prodrug thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

The present invention also covers the finished product. As used herein, the finished product is intended to include, without limitation, kits and packages. The finished product of the present invention includes: (a) a first container; (b) a pharmaceutical composition contained in a first container, the composition comprising a first therapeutic agent comprising a compound of the present invention or a pharmaceutically acceptable salt form thereof; and (c) instructions for use stating that the pharmaceutical composition may be used to treatment of an inflammatory disorder and/or an autoimmune disease

- 13 041852 (as defined above). According to another embodiment, the instructions for use indicate that the pharmaceutical composition can be used in combination (as defined above) with a second therapeutic agent for the treatment of an inflammatory disorder and/or an autoimmune disease. The finished product may further include: (d) a second container, wherein components (a) and (b) are in the second container and component (c) is in or outside of the second container. Being in the first and second containers means that the corresponding container contains the product within its limits.

The first container is a receptacle used to contain the pharmaceutical composition. This container may be for manufacture, storage, transport and/or individual/bulk sale. The first container is designed to protect a vial, jar, vessel, flask, syringe, tube (for example, for making a cream) or any other container used to manufacture, contain, store or distribute a pharmaceutical product.

The second container was used to contain the first container and optionally instructions for use. Examples of the second container include, but are not limited to, boxes (eg, cardboard or plastic), trays, cartons, pouches (eg, paper or plastic bags), pouches, and pouches. The instructions for use may be physically attached to the outside of the first container by tape, adhesive, staple, or other attachment method, or it may be located within the second container without means of being physically attached to the first container. Alternatively, instructions for use are placed on the outside of the second container. If placed on the outside of the second container, it is preferred that the instructions for use be physically attached by tape, adhesive, staple, or other attachment method. Alternatively, it may abut or touch the outside of the second container without being physically attached.

Instructions for use is a label, label, marking, etc., which contains information that relates to the pharmaceutical composition in the first container. This information is usually set by the regulatory authority that regulates the area in which the finished product is sold (for example, the US Food and Drug Administration). In one embodiment, the instructions for use specifically indicate the indications for which the pharmaceutical composition has been approved. Instructions for use may be made of any material on which the user can read the information contained in it or on it. For example, an instruction manual is made from a printable material (eg, paper, plastic, cardboard, foil, adhesive-coated paper or plastic, etc.) on which the required information has been drawn up (eg, printed or applied).

How to get

The compounds of the present invention may be prepared in a variety of ways well known to those skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of organic synthesis chemistry, or variations thereof, as noted by those skilled in the art. Preferred methods include, without limitation, the methods described below. All references cited in the present description are incorporated herein in their entirety by reference.

Compounds of the present invention can be obtained using the reactions and procedures described in this section. The reactions were carried out in solvents suitable for the reagents and materials used, and they are suitable for the transformations being carried out. Also, in describing the synthesis methods below, it is understood that all proposed reaction conditions, including the choice of solvent, the reaction atmosphere, the reaction temperature, the duration of the experiment, and the research methodology, are chosen to be standard conditions for such interaction, which should be easily confirmed by a person skilled in the art. the field of technology. A person skilled in the field of organic synthesis will understand that the functional group present in various parts of the molecule must match the proposed reagents and reactions. Such restrictions on substituents that are compatible with the reaction conditions will be readily apparent to those skilled in the art, and alternative methods should then be used. Sometimes it will be necessary to modify the order of the synthetic steps, or to select one particular process scheme over another, in order to obtain the desired compound of the present invention. It will also be noted that another important principle in planning any synthetic route in this area is the rational choice of the protecting group used to protect the reactive functional groups present in the compounds described in the present invention. An authoritative source that describes many alternatives for the skilled practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Third Edition, Wiley and Sons, 1999).

Examples

Preparations of compounds of formula (I) and intermediates used in the preparation

- 14 041852 compounds of formula (I), can be obtained using the procedures shown in the following examples, and related procedures. The methods and conditions used in these examples, and the actual compounds obtained in these examples, are not intended to be limiting, but are intended to show how the compounds of formula (I) can be obtained. The starting materials and reagents used in these examples, when not obtained by the procedure described in the present invention, are usually either commercially available or described in the chemical literature, or can be obtained using the procedures described in the chemical literature.

Abbreviations Ac acetyl

ACN acetonitrile

AsOH acetic acid anhydrous. anhydrous water. water

Vp benzyl

Wee butyl

Vos tert-butoxycarbonyl ob.kol. Column volumes

DCE dichloroethane

DCM dichloromethane

DMAP dimethylaminopyridine

DMF dimethylformamide

DMSO dimethyl sulfoxide

EtOAc ethyl acetate

Et ethyl

EtOH ethanol

H or Ng hydrogen h, h or hour. watch)

hex hexane i iso IPA isopropyl alcohol HC1 hydrochloric acid HPLC high performance liquid chromatography LC liquid chromatography M molar mm millimolar Me methyl Meon methanol

- 15 041852

MHz megahertz min. minute(s) min minute(s) M ⁺¹ (M+H) ⁺ MS mass spectrometry n or n normal NBS n-bromosuccinimide nm nanometer nM nanomolar NMP N-methylpyrrolidine Pd/C palladium on carbon Ph phenyl PPh ₃ triphenylphosphine Pr propyl PSI pounds per square inch bp. hold retention time sat. saturated SFH supercritical fluid chromatography TBAF tetrabutylammonium fluoride TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran T3P 2,4,6-tripropyl-1,3,5,2,4,6-trioxatrypyo8pyoppape-2,4,6-trioxide

2nd generation RuPhos precatalyst: chlorine(2-dicyclohexylphosphino-2',6'diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,G-biphenyl)]palladium(II) 2- th generation of XPhos: chloro(2-dicyclohexylphosphino-2',4',6'triisopropyl-1,1'-biphenyl) [2-(2'-amino-1,1'-biphenyl)]palladium(II)

Analytical and preparative HPLC conditions:

QC-ACN-AA-XB: Column: Waters Acquity UPLC VEN C18, 2.1x50 mm, 1.7 µm particles;

Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate;

Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min;

Detection: UV at 220 nm.

QC-ACN-TFA-XB: Column: Waters Acquity UPLC VEN C18, 2.1x50 mm, 1.7 µm particles;

Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid;

Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; temperature: 50°C;

Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B;

Elution: 1.0 ml/min; Detection: UV at 220 nm.

Method Al: L3 Acquity: Column: (LCMS) UPLC WEEN C18, 2.1x50 mm, 1.7 µm particles;

Mobile phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA; Gradient interval: 2%-98% B (0-1 min) 98% B (up to 1.5 min) 98%-2% B (up to 1.6 min); Gradient time: 1.6 min; Elution rate: 0.8 ml/min; Analysis time: 2.2 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ESI+).

Method Bl: L2 Aquity(4); Column: (LCMS) UPLC WEEN C18, 2.1x50 mm, 1.7 µm particles; Mobile phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA; Gradient interval: 2% - 98% B (0 - 1 min) 98% B (up to 1.5 min) 98% - 2% B (up to 1.5 min); Gradient time: 1.8 min; Elution rate: 0.8 ml/min; Analysis time: 2.2 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ESI+).

Method Dl SCP: Column: Waters Acquity UPLC VEN C18, 2.1x50 mm, 1.7 µm particles;

Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C;

Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B;

Elution: 1.11 ml/min; Detection: UV at 220 nm.

Method D2 SCP: Column: XBridge C18, 19x200 mM, 5 µm particles;

Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 ace

- 16 041852 tonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 5 minutes at 100% B; Elution: 20 ml/min. Detection: UV at 220 nm.

Method D3 SCP: Column: XBridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 6-46% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. Detection: UV at 220 nm.

El iPAC Method: Column: Waters Xbridge C18 4.6x50 mm 5 um particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate. Temperature: 50°C; Gradient: 0-100% B over 1 minute; Elution: 4 ml/min; Detection: UV at 220 nm.

Fl iPAC Method: Column: Waters Acquity VEN C18 2.1 x 50 mM 1.7 µm particles;

Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid;

Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C;

Gradient: 0-100% B over 2.20 min; Elution: 0.800 ml/min; Detection: UV at 220 nm.

Method Gl: Column: SyMMetry C8, (250x4.6 mM), 5 µm particles;

Mobile phase A: 1:1 acetonitrile:TFE with 10 mM ammonium acetate;

Mobile phase B: 1:1 acetonitrile:TFE with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0-100% B over 25 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min; Detection: UV at 220 nm. Method Hl (SFC): Column: Luxcellulose-4 (250x4.6 mm), 5 µm particles; %CO ₂ : 50%, % Co-solvent: 50% 0.4% isopropylamine in methanol; Temperature 30°C; Elution: 120 g/min; Detection: UV at 230 nm.

(A): Column-Ascentis Express C18 (50x2.1 mM-2.7 µm) Sus. phase A: 10 mM NH4COOH in water: ACN (98:02); Suspended phase B: 10 mM NH ₄ cOoH in water: ACN (02:98), Gradient: 0-100% B over 3 min, Elution = 1 ml/min.

(D): Kinetex XB-C18 (75x3 mM) 2.6 µm; Solvent A: 10 mM ammonium formate in water: acetonitrile (98:02); Mobile phase B: 10 mM ammonium formate in water: acetonitrile (02:98); Temperature: 50°C; Gradient: 0-100% B over 3 min; Elution rate: 1.1 ml/min; Detection: UV at 220 nm.

(E): Column: Ascentis Express C18 (50x2.1) mm, 2.7 µm; Mobile phase A: 5:95 acetonitrile: water with 10 mM NH ₄ OAc; Mobile phase B: 95:5 acetonitrile: water with 10 mM NH ₄ OAc; Temperature: 50°C; Gradient: 0-100% B over 3 minutes; Elution: 1.1 ml/min. (F): Column: Ascentis Express C18 (50x2.1) mm, 2.7 µm; Mobile phase A: 5:95 acetonitrile: water with 0.1% TFA; Mobile phase B: 95:5 acetonitrile: water with 0.1% TFA; Temperature: 50°C; Gradient: 0-100%V for 3 minutes; Elution: 1.1 ml/min. (G): Column: Waters Acquity UPLC WEN C18 (2.1x50 mm), 1.7 µm; Solvent A = 100% water with 0.05% TFA; Solvent B = 100% acetonitrile with 0.05% TFA; gradient = 2-98% B over 1 minute, then 0.5 minute hold at 98% B; Elution rate: 0.8 ml/min; Detection: UV at 220 nm.

(H): Column: Acentis Express C18 (50x2.1 mM) 1.7 µm, Acentis C8 NH ₄ COOH 5 min. M, Mobile phase A: 10 mM ammonium formate: ACN (98:2), Mobile phase B: 10 mM ammonium formate: ACN (2:98), gradient: 20%-100% B (0-4 min); 100% B (4-4.6 min); Elution: 1 ml/min (I) Column: Sunfire C18 (4.6x150) mM, 3.5 µm; Mobile phase A: 5:95 acetonitrile: water with 0.05% TFA; Mobile phase B: 95:5 acetonitrile: water with 0.05% TFA; Temperature: 50°C; Gradient: 10-100%B over 12 min; Elution: 1 ml/min.

(J) Column: Sunfire C18 (4.6x150) mm, 3.5 µm; Mobile phase A: 5:95 acetonitrile: water with 0.05% TFA; Mobile phase B: 95:5 acetonitrile: water with 0.05% TFA.

(K) Waters Acquity SDS Mobile phase: A: water B: ACN; 5%-95%B for 1 min;

Gradient interval: 50%-98% B (0-0.5 min); 98%B (0.5 min-1 min); 98%-2% B (1-1.1 min);

Elution time: 1.2 min; Elution rate: 0.7 ml/min; Analysis time: 1.7 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ES+).

(L) Acquity UPLC VEN C18 (3.0x50 mm) 1.7 µm. Buffer: 5 mM ammonium acetate;

Mobile phase A: Buffer: ACM (95:5);

Mobile phase B: Buffer: ACM (5:95) Procedure: % B: 0 min-20%: 1.1 min-90%: 1.7 min-90%. Elution time: 2.25 min; Elution rate: 0.7 ml/min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ES+).

(M) : Kinetex SBC18 (4.6x50 mm) 5 µm; Solvent A: 10 mM ammonium formate in water: acetonitrile (98:02);

Mobile phase B: 10 mM ammonium formate in water: acetonitrile (02:98); Temperature: 50°C; Gradient: 30-100% B (0-4 min), 100% B (4-4.6 min), 100-30% B (4.6-4.7 min), 30% B (4.7- 5.0 min); Elution rate: 1.5 ml/min; Detection: UV at 220 nm.

(N): Column-Ascentis Express C18 (50x2.1 mM 2.7 µm) Sus. phase A: 10 mM NH4COOH in water: ACN (98:02); Suspended phase B: 10 mM NH4COOH in water: ACN (02:98), Gradient: 0-100% B (0-1.7 min); 100% B (1.7-3.4 min). Elution = 1 ml/min.

(O) Waters Acquity SDS Column BEN C18 (2.1x50 mm) 1.7 µm. Phase A: buffer in water; Suspended phase B:

- 17 041852 buffer in ACN, Gradient: 20-98% B (0-1.25 min); 98% B (1.25-1.70 min); 98%-2% B (1.70-1.75 min); Elution = 0.8 ml/min.

(P): Column: XBridge VEN XP C18 (50x2.1) mm, 2.5 µm; Mobile phase A: 5:95 acetonitrile: water with 10 mM NH ₄ OAc; Mobile phase B: 95:5 acetonitrile: water with 10 mM NH ₄ OAc; Temperature: 50°C; Gradient: 0-100% B over 3 min; Elution: 1.1 ml/min.

(Q): Column: XBridge VEN XP C18 (50x2.1) mm, 2.5 µm; Mobile phase A: 5:95 acetonitrile: water with 0.1% TFA; Mobile phase B: 95:5 acetonitrile: water with 0.1% TFA; Temperature: 50°C; Gradient: 0100% B over 3 min; Elution: 1.1 ml/min.

(R): Column-ZORBAX SB-C18 (50x4.6 mM - 5.0 µm) Susp. phase A: 10 mM NH4COOH in water: ACM (98:02) Susp. phase B: 10 mM NH4COOH in water: ACM (02:98). Gradient: 0 min-30%, 4.0 min-100%, 4.6 min-100%, 4.7 min-30%. Elution/min. 1.5 ml.

(TS): Column: Waters Acquity UPLC WEN C18 (2.1x50 mm), 1.7 µm; Solvent A = 100% water with 0.05% TFA; Solvent B = 100% acetonitrile with 0.05% TFA; gradient = 2-98% B over 1 minute, then 0.5 minute hold at 98% B; Elution rate: 0.8 ml/min; Detection: UV at 254 nm.

(DDS) Aquity: Column: (LCMS) UPLC WEEN C18, 3.0x50 mm, 1.7 µm particles; Mobile phase: (A) 10 mM NH ₄ OAc: acetonitrile (95:5) Phase B) 10 mM NH ₄ OAc: acetonitrile (5:95): Method: %B: 0 min20:2 min-100:2.3 min-1001.8 min; Elution rate: 0.7 ml/min;

Detection: Detector 1: UV at 220nm; Detector 2: MS (ESI+).

(DDS2) Acquity: Column: (LCMS) UPLC WEEN C18, 3.2x50 mm, 1.7 µm particles; Buffer: 10 mM Ammonium acetate Mobile phase A: Buffer: ACN (95:5) Mobile phase B: Buffer: ACM (5:95); Method %B: 0 min-20%:2 min-100%:2.2 min-100%; Elution rate = 0.7 ml/min, Detection: Detector 1: UV at 220 nm; Detector 2: MS (ESI+).

Example 1

1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N-(tetrahydro-2H-pyran-4-yl)azetidine-3-amine ^H H ₃ C CH _{3 (1)}

Intermediate 1A: 2-bromo-5-hydrazinylpyridine

ΎΊ

V%nh ₂ ^N (1A)

A solution of 6-bromopyridine-3-amine (10.0 g, 57.8 mmol) in 6 M aqueous HCl (111 ml) was cooled to 0°C. A solution of sodium nitrite (3.99 g, 57.8 mmol) in water (148 ml), pre-cooled to 0°C, was added over 5 min and the reaction mixture was stirred for 45 min at 0°C. Tin(II) chloride dihydrate (32.6 g, 144 mmol) was suspended in 6 M aqueous HCl (111 mL), precooled to 0°C, and added to the reaction mixture over 5 min. The reaction mixture was stirred for 60 min more at 0°C. Upon completion, the reaction was quenched by adding a 40 wt.% solution of KOH in water until the solution was alkalized by the color of the pH paper. The mixture was diluted with water and DCM. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give 2-bromo-5-hydrazinylpyridine (8.08 g, 43.0 mmol, 74.3% yield). LCMS retention time 0.41 min [Al]. MS (E ⁺ ) m/z: 190.1 [(M+2)+H ⁺ ].

1H NMR (499 MHz, chloroform-d) δ 7.98 (d, J=3.0 Hz, 1H), 7.28 (app d, J=8.5 Hz, 1H), 7.10 (dd, J=8.7, 3.0 Hz, 1H), 5.25 (br app s, 1H), 3.62 (br app s, 2H).

Intermediate 1B: 5-6rom-3-isopropyl-1H-pyrrolo[3,2-b]pyridine

2-bromo-5-hydrazinylpyridine (8.08 g, 43.0 mmol) was suspended in 5% vol. H ₂ SO ₄ in water (215 ml) to obtain a thick suspension. 3-Methylbutanal (5.19 ml, 47.3 mmol) was added and the suspension was stirred for 20 minutes at room temperature, then heated under reflux at 110° C. for 20 hours. Upon completion, the mixture was cooled in an ice bath. The reaction was quenched by adding a 40 wt.% solution of KOH in water until alkalized by the color of the pH paper. Water and DCM were added until all solids were dissolved. The organic layer was separated and the aqueous layer was extracted twice with DCM. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give a crude orange solid, which was purified by silica gel column chromatography (Hex/EtOAc 0-50%) to give 5-bromo-3-isopropyl-1Hpyrrolo[3.2 -b]pyridine (6.19 g, 25.9 mmol, 60% yield). LCMS retention time 0.90 min [Al].

- 18 041852

MS (E ⁺ ) m/z: 239.1 (M+H).

¹ H NMR (499 MHz, chloroform-d) δ 8.71-8.43 (m, 1H), 7.48 (d, J=8.4 Hz, 1H), 7.22-7.17 (m , 2H), 3.37 (spt, J=6.8 Hz, 1H), 1.35 (d, J=6.8 Hz, 6H).

Intermediate 1C: tert-Butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1carboxylate

Vos (IQ

To a solution of 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine (5.0 g, 20.9 mmol) in THF (84 ml) was added Et ₃ N (4.37 ml, 4 mmol) and DMAP (0.255 g, 2.09 mmol). The mixture was cooled to 0°C. BOC anhydride 30% in toluene (16.73 g, 23.0 mmol) was added in one portion and the reaction mixture was stirred for 1 hour. Another aliquot of BOC anhydride 30% in toluene (2.0 g, 2.75 mmol) was added and the reaction mixture was stirred for 10 min. Upon completion, the reaction mixture was concentrated and the crude material was purified by silica gel column chromatography (Hex/EtOAc 0-40%) to give t-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1 -carboxylate (6.98 g, 20.6 mmol, 98% yield). LCMS retention time 1.14 min [TS]. MS (E ⁺ ) m/z: 339.1 (M+H).

Intermediate 1D: tert-Butyl-5-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-3isopropyl-1H-pyrrolo[3,2-b]picidin-1-carboxylate

Suspension of tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylateα (1.05 g, 3.10 mmol), tert-butyl azetidin-3-ylcarbamate (0.693 g, 4.02 mmol), 2nd generation precatalyst RuPhos (0.120 g, 0.155 mmol) and Cs ₂ CO ₃ (3.03 g, 9.29 mmol) were prepared in 1,4-dioxane (21 ml). The suspension was degassed with nitrogen for 5 min, sealed, and placed in a heating block at 130°C for 4 h 20 min. Upon completion, the reaction mixture was filtered, concentrated and purified by silica gel column chromatography (Hex/EtOAc 0-50%) to give t-butyl-5-(3((t-butoxycarbonyl)amino)azetidin-1-yl)-3 -isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (970 mg, 2.253 mmol, 72.8% yield). LCMS retention time 0.86 min [TS]. MS (E ⁺ ) m/z: 431.2 (M+H).

¹ H NMR (499 MHz, chloroform-d) δ 8.19-7.98 (m, 1H), 7.45-7.29 (m, 1H), 6.26 (d, J=8.8 Hz , 1H), 5.074.88 (m, 1H), 4.68-4.51 (m, 1H), 4.35 (br t, J=7.6 Hz, 2H), 3.78 (dd, J = 8.6, 5.4 Hz, 2H), 3.24-3.15 (m, 1H), 1.65 (s, 9H), 1.46 (s, 9H), 1.35 (d, J=7.0Hz, 6H).

Intermediate 1E: tert-Butyl-5-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-3isopropyl-2-(4,4,5,5-teρamethyl-1,3,2-dioxaborolane -2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Vos CH ₃

Solution containing tert-butyl 5-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-1-carboxylate (802 mg, 1 86 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2dioxaborolane (0.49 ml, 2.42 mmol) in dry THF (9.3 ml), cooled under nitrogen to - 78°C and treated with LDA (2M in THF) (2.33 ml, 4.66 mmol). The mixture was heated to -30°C for 30 min and stirred at -30°C for 30 min, then left to slowly warm to 0°C. The reaction mixture was treated with saturated aqueous ammonium chloride, water and DCM. The organic layer was dried over sodium sulfate, filtered and concentrated.

The crude material was purified by silica gel column chromatography (Hex/EtOAc 050%) to give t-butyl-5-(3-((t-butoxycarbonyl)amino)azetidin-1-yl)-3-isopropyl-2(4.4 ,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (830 mg, 1.49 mmol, 80% yield). LCMS retention time 1.05 min [TS]. MS (E ⁺ ) m/z: 557.7 (M+H).

1H NMR (499 MHz, chloroform-d) δ 7.84 (d, J=8.8 Hz, 1H), 6.21 (d, J=8.8 Hz, 1H), 5.05-4.86 (m, 1H), 4.70-4.53 (m, 1H), 4.34 (br t, J=7.5 Hz, 2H), 3.77 (dd, J=8.5, 5, 3 Hz, 2H), 3.29-3.14 (m, 1H), 1.64 (s, 9H), 1.46 (s, 9H), 1.44-1.41 (m, 18H).

Intermediate 1F: (1-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrrolo[3,2-b]pyridine-5 -yl)azetidin-3-yl)carbamate

- 19 041852

tert-Butyl-5-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-3-isopropyl-2-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl )-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (830 mg, 1.49 mmol) was heated neat under nitrogen with slow stirring at 165°C for 100 min. Upon completion, the material was dissolved in DCM and concentrated to give tert-butyl-(1-(3-isopropyl-2-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)azetidin-3-yl)carbamate as an off-white foam. LCMS retention time 0.92 min [TS]. MS (E+) m/z: 457.7 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.06 (br s, 1H), 7.42 (d, J=8.8 Hz, 1H), 6.29 (d, J=8.7 Hz, 1H), 5.074.85 (m, 1H), 4.66-4.54 (m, 1H), 4.39-4.29 (m, 2H), 3.77 (dd, J=8.7, 5.5 Hz, 2H), 3.68-3.59 (m, 1H), 1.48 (d, J=7.0 Hz, 6H), 1.46 (s, 9H), 1.34 ( s, 12H).

Intermediate 1G: tert-Butyl-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)3-isopropyl-1H-pyrrolo[ 3,2-b]pyridin-5-yl)azetidin-3-yl)carbamate

BocHN^ ^H3C usN _{3 N} y T _y \=N

N /=\ ^H H ₃ C CH _{3 (1G)}

To a suspension of tert-butyl-(1-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1Hpyrrolo[3,2-b]pyridin- 5-yl)azetidin-3-yl)carbamate (227 mg, 0.497 mmol), 6-bromo-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (124 mg, 0.547 mmol ), and 2nd generation precatalyst Xphos (19.6 mg, 0.025 mmol) in dioxane (3.3 ml) was added 2M aqueous tribasic potassium phosphate (0.75 ml, 1.49 mmol). The biphasic mixture was degassed with nitrogen for 10 min. The vial was sealed and stirred at 70° C. for 2 hours. Upon completion, the reaction mixture was cooled to room temperature and concentrated. The crude material was taken up in DCM and purified by silica gel column chromatography (0-100% Hex/EtOAc) to give t-butyl-(1-(2-(7,8-dimethyl[1,2,4]triazolo[1, 5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)azetidin-3-yl)carbamate (170 mg, 0.357 mmol, 72% yield). LCMS retention time 0.77 min [TS]. MS (E ⁺ ) m/z: 476.6 (M+H).

Example 1

To a suspension of tert-butyl-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2 -b]pyridin-5-yl)azetidin-3-yl)carbamate (170 mg, 0.357 mmol) in DCM (14 mL) TFA (3.6 mL) was added at room temperature. The reaction mixture was stirred at room temperature for 30 minutes. Upon completion, the reaction mixture was concentrated. The crude material was taken up in DMF (3.6 ml) and Et ₃ N (0.15 ml, 1.07 mmol), tetrahydro-4H-pyran-4-one (71.5 mg, 0.714 mmol) and sodium triacetoxyborohydride (151 mg, 0.714 mmol) were added sequentially. After stirring for 3 hours, additional DMF (3.6 ml) and Et ₃ N (0.15 ml, 1.07 mmol), tetrahydro-4Hpyran-4-one (71.5 mg, 0.714 mmol) and sodium triacetoxyborohydride (151 mg, 0.714 mmol) were added sequentially. After stirring for another 2 hours at room temperature, the reaction was quenched by the addition of water, an aqueous K2HPO4 dibasic solution 1.5M and DCM. The organic layer was separated, dried over sodium sulfate, concentrated and the crude material was purified by SFC chromatography using the following conditions: CHIRAL IC 25x3.0 cm ID, 5 μm column; 85.0 ml/min elution rate; 60/40 CO ₂ /methanol with 0.1% diethylamine mobile phase; detector at a wavelength of 260 nm to obtain 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3, 2-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)azetidine-3-amine (95 mg, 0.203 mmol, 57% yield). LCMS retention time 0.53 min [TS]. MS (E ⁺ ) m/z: 460.7 (M+H).

1H NMR (499 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.75 (s, 1H), 8.46 (s, 1H), 7.50 (d, J=8.7 Hz , 1H), 6.27 (d, J=8.7 Hz, 1H), 4.11 (t, J=7.3 Hz, 2H), 3.86-3.73 (m, 3H), 3 .57 (t, J=6.8 Hz, 2H), 3.32-3.25 (m, 3H), 2.84-2.75 (m, 1H), 2.58 (s, 3H), 2.15 (s, 3H), 1.75-1.66 (m, 2H), 1.36 (br d, J=6.8 Hz, 6H), 1.31-1.21 (m, 2H ).

Example 2 6-(3-Isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo [1,5-a]pyridine ^Η 3\ GN ην η Y-cHz _Ν y φ __V \=Ν ^Η H ₃ C CH ₃ (2)

Intermediate 2A: tert-Butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

- 20 041852

NoS BocN η ^ό -CH ₃

ΙΧ>

Vos (2Α)

Suspension of tert-butyl-5-bromo-3-isopropyl-III-pyrrolo[3,2-b]pyridine-1-carboxylate (2.0 g, 5.90 mmol), tert-butylpiperazine-1-carboxylate (1, 32 g, 7.07 mmol), 2nd generation RuPhos precatalyst (0.114 g, 0.147 mmol) and Cs ₂ CO ₃ (4.80 g, 14.7 mmol) in 1,4-dioxane (20 ml) in a reaction a vessel with a lid with a safety diaphragm and a magnetic stirrer was degassed with nitrogen gas for 5 min. The reaction vessel was sealed and placed in a heating block with stirring at 100° C. for 3 hours. In parallel, an identical reaction was run according to the same protocol and the two reactions were combined during processing and purification. Upon completion, the combined reactions were filtered and concentrated. The crude material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-60% to give t-butyl-5-(4-(t-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1H -pyrrolo[3,2b]pyridine-1-carboxylate (4.64 g total) as an off-white foam. LCMS retention time 1.13 [TS]. MS (E ⁺ ) 445.3 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.13 (br s, 1H), 7.39 (br s, 1H), 6.65 (br d, J=9.0 Hz, 1H), 3, 64-3.57(m, 4H), 3.57-3.50(m, 4H), 3.28-3.14(m, 1H), 1.65(s, 9H), 1.49( s, 9H), 1.36 (d, J=6.9 Hz, 6H).

Intermediate 2B: tert-Butyl-5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Solution containing tert-butyl-5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-1-carboxylate (4.64 g, 10.4 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2dioxaborolane (3.19 ml, 15.66 mmol) in dry THF (52 ml), cooled under nitrogen in a dry ice/ acetone to -78°C and treated with LDA (2M in THF, 10.4 ml, 20.8 mmol). The mixture was left to warm to 0°C for 5 hours. Upon completion, the reaction was quenched by adding a saturated aqueous solution of NH ₄ Cl, water and EtOAc. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated. The crude material was purified by silica gel column chromatography eluting with Hex/EtOAc 0-50% to give t-butyl-5-(4-(t-butoxycarbonyl)piperazin-1-yl)-3isopropyl-2-(4,4,5 ,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (5.29 g, 9.27 mmol, 89% yield). LCMS retention time 1.23 [TS]. MS (E ⁺ ) m/z: 571.2.

1H NMR (499 MHz, chloroform-d) δ 7.86 (d, J=9.1 Hz, 1H), 6.59 (d, J=9.1 Hz, 1H), 3.62-3.55 (m, 4H), 3.55-3.49 (m, 4H), 3.20 (spt, J=7.0 Hz, 1H), 1.64 (s, 9H), 1.49 (s, 9H), 1.44 (d, J=6.9 Hz, 6H), 1.42 (s, 12H).

Intermediate 2C: tert-Butyl-4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperazine-1-carboxylate

BocN η ^J y-CH ₃

N.^7 O-^ ^CH s 1Γ X/ ⁱⁿ 1 DX X ^CH 3 ^{H n} sC ³ (2C) tert-Butyl-5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl- 2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (5.29 g, 9.27 mmol) heated neat at 170° C. under nitrogen with stirring for 6 hours. The reaction mixture was cooled to room temperature and left at room temperature for 3 days. The reaction mixture was then reheated to 170°C under nitrogen with stirring for another 4 hours. Upon completion, the material was dissolved in DCM and concentrated to give t-butyl-4-(3-isopropyl-2-(4.4, 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-carboxylate (4.02 g, 8.55 mmol, 92 % yield) as a light brown foam. The material was carried on without further purification. Significant conversion to boronic acid was observed on LCMS, although NMR indicated that the product was a pure compound. The retention time of boronic acid in LCMS is 0.74 [TS]. Boronic acid MS (E ⁺ ) m/z: 389.1 (M+H). Product Characteristics: LCMS retention time 0.93 [TS]. MS (E+) m/z: 471.2 (M+H).

1H NMR (499 MHz, CHLOROFORM-d) δ 8.07 (s, 1H), 7.46 (d, J=8.9 Hz, 1H), 6.69 (d, J=9.l Hz, 1H ), 3.683.55 (m, 5H), 3.55-3.47 (m, 4H), 1.51-1.48 (m, 15H), 1.34 (s, 12H).

Intermediate 2D: tert-Butyl-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)3-isopropyl-1H-pyrrolo[ 3,2-b] pyridin-5-yl)piperazine-1-carboxylate

- 21 041852

To a mixture of tert-butyl-4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1Hpyrrolo[3,2-b]pyridin-5 -yl)piperazine-1-carboxylate (2.5 g, 5.31 mmol), 6-bromo-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (1.44 g , 6.38 mmol) and Xphos of the 2nd generation precatalyst (0.209 g, 0.266 mmol) in 1,4-dioxane (27 ml) was added an aqueous solution of K ₃ PO ₄ (2M, 7.97 ml, 15.9 mmol) . The biphasic mixture was degassed with nitrogen gas for 10 minutes. The reaction vessel was sealed, a nitrogen gas feed was connected, and the reaction mixture was stirred at 70° C. for 3 hours. Upon completion, the reaction mixture was cooled to room temperature and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layer was dried over MgSO ₄ and concentrated to give a crude brown oil. This material was column chromatographed on silica gel using a Teledyne Isco instrument eluting with 0-100% Hex/EtOAc to give tert-butyl-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1, 5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-carboxylate (2.31 g, 4.72 mmol, 89% yield). LCMS retention time 0.77 [TS]. MS (E+) m/z: 490.2 (M+H).

1H NMR (499 MHz, DMSO-d6) δ 10.89 (s, 1H), 8.77 (s, 1H), 8.47 (s, 1H), 7.56 (d, J=8.9 Hz , 1H), 6.77 (d, J=8.9 Hz, 1H), 3.54-3.40 (m, 8H), 2.79 (spt, J=6.8 Hz, 1H), 2 .58 (s, 3H), 2.16 (s, 3H), 1.43 (s, 9H), 1.38 (d, J=6.9 Hz, 6H).

Example 2

To a suspension of tert-butyl-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b]pyridin-5-yl)piperazine-1-carboxylate (223 mg, 0.455 mmol) in DCM (5 ml) TFA (1 ml) was added at room temperature. The reaction mixture was stirred at room temperature for 90 minutes and then concentrated to give the crude material 6-(3-isopropyl-5(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)- 7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine. A portion (10%) of this material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 5% B, 5-45% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl- [1,2,4]triazolo[1,5-a]pyridine (15.9 mg, 0.040 mmol). LCMS retention time 0.77 min [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 390.3 (M+H).

1H NMR (500 MHz, DMSO-d6) δ 10.70 (s, 1H), 8.69 (s, 1H), 8.42 (s, 1H), 7.53 (d, J=8.8 Hz , 1H), 6.71 (d, J=8.9 Hz, 1H), 3.46-3.36 (m, 4H), 2.94-2.85 (m, 4H), 2.85- 2.77 (m, 1H), 2.59 (s, 3H), 2.17 (s, 3H), 1.37 (br d, J=6.6 Hz, 6H).

Example 3 1-(4-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3 ,2b]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one

6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo[1] solution ,5-a]pyridine, TFA (18.9 mg, 0.0376 mmol) in methanol was converted to the HCl salt form by adding 1 ml of 4N HCl in dioxane and concentrating to dryness. The material was taken up again in methanol, 1 ml of 4N HCl in dioxane was added and the material was concentrated to dryness. The material was then suspended in DMF (1 ml) and dimethylglycine (28 mg, 0.272 mmol), Et ₃ N (0.10 ml, 0.717 mmol) and T3P 50% in DMF (0.110 ml, 0.188 mmol) were added. The reaction mixture was stirred for 1 hour at room temperature. Upon completion, the reaction was quenched by the addition of water, aqueous 1.5M K2HPO4, and DCM. The organic layer was separated, concentrated, taken up in methanol and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 13% B, 13-53% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl- 1 H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethane-1

- 22 041852 she (12.8 mg, 0.026 mmol, 69.4% yield). LCMS retention time 0.86 min [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 475.3 (M+H).

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.87 (s, 1H), 8.70 (s, 1H), 8.44 (s, 1H), 7.57 (d, J=8, 9 Hz, 1H), 6.78 (d, J=8.9 Hz, 1H), 3.16 (s, 2H), 2.84-2.73 (m, 1H), 2.56 (s, 3H), 2.14 (s, 3H), 1.35 (br d, J=6.7 Hz, 6H).

Example 4 4-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b] pyridin-5-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine

Intermediate 4A: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate

Vos (4A)

To a solution of tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (19.00 g, 56.0 mmol), 4,4,5,5-tetramethyl -2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (16.40 g, 61.6 mmol) and 2 M tribasic potassium phosphate aqueous solution ( 84 ml, 168 mmol) in THF (300 ml) was added PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (1.372 g, 1.680 mmol). The biphasic mixture was degassed with nitrogen gas for 10 minutes and the vessel sealed and stirred at 70° C. for 2 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The mixture was transferred to a separating funnel and the layers were separated. The combined organic fractions were washed with saturated sodium sulfate solution, filtered and concentrated to dryness. Further purification was carried out by chromatography on silica gel, which made it possible to obtain tert-butyl-3-isopropyl-5-(1,4dioxaspiro[4.5]dec-7-en-8-yl)-1H-pyrrolo[3,2-b]pyridine -1-carboxylate (18.00 g, 45.0 mmol, 86% yield) as a light yellow solid. LCMS retention time 1.09 min [Al]. MS m/z: 399.5 (M+H).

Intermediate 4B: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate ⁿ = Basic cP 1 y- SNz to A (20

Vos (4B)

To tert-butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1 H-pyrrolo[3,2-b]pyridine-1 carboxylate (18.00 g, 45.0 mmol) MeOH (15 ml) and 10 wt% Pd/C (1.490 g, 1.400 mmol) were added in a Parr apparatus. The vessel was placed on a high pressure Parr hydrogenator and nitrogen gas was sparged three times with a pump. After evacuation, the vessel was backfilled with hydrogen gas to approximately 40 psi and the reaction mixture was left to shake for 2 hours. The contents of the vessel were diluted with MeOH (200 ml) and ethyl acetate (200 ml) and the contents were filtered through tightly packed celite. After concentration, 3-isopropyl 5-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-indole (19.00 g, 47.0 mmol, 100% yield) was collected as a dark oil. LCMS retention time 0.95 min [Al]. MS m/z: 401.6 (M+H).

Intermediate 4C: 3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-pyrrolo[3,2-b]pyridine ⁰ 1 m/sn ₃ ^ιί Ti°1 ^CH3 oA-CH3 n sn ₃ 0Q

Solution containing tert-butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-pyrrolo[3,2b]pyridine-1-carboxylate (1.600 g, 3.99 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.467 ml, 7.19 mmol) in dry THF (9.99 ml), cooled in a dry bath under nitrogen atmosphere ice/acetone at -78°C. After stirring at -78°C for 20 min, LDA (2M in THF) (5.99 ml, 11.98 mmol) was added. The mixture was stirred at -78°C for 30 minutes and allowed to warm to -30°C for 1 hour and stirred at -30°C for 30 minutes. The reaction mixture was treated with 1.5 M aqueous KH2PO4 solution. Water and ethyl acetate were added and the mixture was transferred to a separating funnel. The layers were separated and the combined organic fractions were washed with brine, dried over anhydrous

- 23 041852 sodium sulfate, filtered and concentrated. The crude product was further purified by silica gel chromatography to afford tert-butyl-3-isopropyl-5-(1,4dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1.7 g, 3.22 mmol, 81% yield). LCMS retention time 1.00 min [A1]. MS m/z: 527.3 (M+H).

tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl )-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1.7 g, 3.22 mmol) was added to the tall vessel and the vessel was closed. The vessel was pumped three times with nitrogen gas and left to heat at 165° C. under nitrogen for 1.5 h. 8-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine (1.4 g, 3, 28 mmol, 100% yield) was obtained and used unchanged. LCMS retention time 0.61 min [Al]. MS m/z: 345.8 (M+H) (the mass of the corresponding boronic acid was observed).

Intermediate 4D: 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexan-1-one

3-Isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 -yl)-1H-pyrrolo[3,2-b]pyridine (0.500 g, 1.173 mmol), 1,1'-bis(di-tert-butylphosphino)ferrocenepalladium dichloride (0.023 g, 0.035 mmol), 6-bromo- 7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (0.265 g, 1.173 mmol) and THF (20 ml). The reaction vessel was sealed and nitrogen gas was sparged three times with a pump. To this was added 2 M aqueous potassium phosphate tribasic (1.759 ml, 3.52 mmol) and the reaction mixture was heated to 65°C for 1 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with water, then with brine and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated. The residue was further purified by silica gel chromatography. After concentrating the 6-(3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[ 1,2,4]triazolo[1,5-a]pyridine was collected as a tan solid. DCM (0.5 ml), TFA (5 ml) and water (0.02 ml) were added to this intermediate. The reaction vessel was closed and stirred at room temperature for 4 h, then concentrated in a stream of nitrogen. To this was added 1.5 M potassium phosphate solution, water and DCM. The mixture was poured into a separating funnel and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl )-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-one (0.22 g, 0.548 mmol, 47% yield). LCMS retention time 0.61 min [A1]. MS m/z: 402.2 (M+H).

Example 4

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)cyclohexan-1-one (0.500 g, 1.245 mmol), (1-(methylsulfonyl)cyclopropyl) methanamine hydrochloride (0.347 g, 1.868 mmol) and TEA (0.694 ml, 4.98 mmol) were mixed in DCM (5 ml). The reaction vessel was closed and the reaction mixture was stirred under nitrogen atmosphere overnight at room temperature. The volatiles were removed under a stream of nitrogen and the residue was placed under nitrogen and diluted with MeOH (5 ml). This was cooled to -78°C and lithium borohydride (0.081 g, 3.74 mmol) was added. The reaction mixture was allowed to warm to room temperature in a dry ice bath overnight. The reaction was quenched by adding 1.5M K2HPO4 solution. Ethyl acetate was added and the mixture was extracted three times. The organic layer was washed with saturated NaCl solution, dried over sodium sulfate, filtered and concentrated. The material was further purified by silica gel chromatography followed by SFC. The main and first eluted isolate was collected to give 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3 ,2-b]pyridin-5-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (0.300 g, 0.555 mmol, 45% yield) as an off-white solid. HPLC retention time 1.44 min [Method C]. MS m/z: 535.4 (M+H). HPLC retention time 0.845 min [Method D].

1H NMR (499 MHz, DMSO-d ₆ ) δ 11.14-11.02 (m, 1H), 8.80 (s, 1H), 8.49 (s, 1H), 7.66-7.55 (m, 1H), 7.076.94 (m, 1H), 3.41-3.29 (m, 2H), 3.17 (d, J=2.9 Hz, 1H), 3.14-3, 12 (m, 1H), 3.14 (s, 1H), 3.02 (br d, J=7.0 Hz, 2H), 2.96-2.84 (m, 1H), 2.71 ( tt, J=12.0, 3.5 Hz, 1H), 2.45 (br d, J=2.0 Hz, 1H), 2.18(s, 3H), 2.08-1.99 ( m, 2H), 1.94 (br d, J=11.8 Hz, 2H), 1.89-1.76 (m, 1H), 1.75-1.56 (m, 2H), 1, 40 (d, J=6.8 Hz, 6H), 1.29-1.13 (m, 5H), 1.08-0.94 (m, 2H).

- 24 041852

Example 5 Rolo[3,2-b]pyridine

2-(3,4-Dimethoxyphenyl)-5-(1'-isobutyl-[1,4'-bipiperidin]-4-yl)-3-methyl-1H-pyr-

Intermediates 5A-1 and 5A-1: 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2b]pyridine and 5-bromo-3-(3,4-dimethoxyphenyl) )-2-methyl-1H-pyrrolo[3,2-b]pyridine n ₃ c _x o

To a mixture of 6-bromo-2-iodopyridin-3-amine (100 mg, 0.34 mmol), 1,2-dimethoxy-4-(prop-1-yn-1yl)benzene (74 mg, 0.42 mmol) , lithium chloride (18 mg, 0.42 mmol), sodium carbonate (180 mg, 1.68 mmol) and Pd(dppf)Cl ₂ (12.5 mg, 0.017 mmol) DMF (2 ml ). The vessel was equipped with a lid with a Teflon-coated diaphragm. The system was evacuated (using a nitrogen line/vacuum line needle) and refilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vessel was heated at 100° C. for 16 hours. LCMS analysis indicated the formation of two isomers, approximately in a ratio of 3:1. ¹ H NMR analysis suggested that the main product was 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2b]pyridine (5A-1). The reaction mixture was diluted with EtOAc (50 ml), poured into a separating funnel and washed with aqueous 10% LiCl solution (2x10 ml) and saturated aqueous NaCl solution (10 ml), dried (Na ₂ SO ₄ ), filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM and purified by silica gel column chromatography from 15 min over a 0%-100% DCM/EtOAc gradient to give 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo [3,2b]pyridine (Intermediate 5A-1) contaminated with intermediate 5A-2,5bromo-3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridine, m /z (303, M+1), 80 mg (67%).

Intermediate 5B: tert-Butyl-4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,6-dihydropyridine-1 ( 2H)-carboxylate

To a mixture containing 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) and Intermediate 5A-2 (100 mg, 0.29 mmol), tert-butyl-4(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (111 mg , 0.36 mmol), and Pd(dppf)Cl ₂ (10.5 mg, 0.014 mmol) THF (2.5 ml) was added in a screw cap vial followed by the addition of a 3M aqueous solution of tripotassium phosphate (0.10 ml, 0.3 mmol). The vessel was equipped with a Teflon-coated lid with a diaphragm. The system was evacuated (using a nitrogen line/vacuum line needle) and refilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vessel was heated at 75°C for 3 hours, the Reaction mixture was cooled to room temperature and treated with saturated aqueous NaCl (5 ml) and was extracted with the addition of ethyl acetate (3x10 ml). The extracts were combined, dried (Na ₂ SO ₄ ), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified by silica gel column chromatography eluting 10 min with a 5%-100% DCM/EtOAc gradient. Separation was not observed. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and the regioisomer tert-butyl-4(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine- 1(2H)carboxylate was isolated (100 mg, 77% yield), m/z (550, M+1) and used unchanged in the next step.

Intermediate 5C: tert-Butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-1-carboxylate

A mixture of tert-butyl-4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydro-25 041852 ropyridine-1 (2H)-carboxylate (Intermediate 5B) and tert-butyl-4-(3-(3,4dimethoxyphenyl)-2-methyl-III-pyrrolo[3,2-b]pyridin-5-yl)-5 regioisomer, 6-dihydropyridine-1(2H)-carboxylate (95 mg, 0.21 mmol) was dissolved in MeOH (5 ml) and transferred to a Parr apparatus. The mixture was sparged with nitrogen. Pearlman's catalyst (25 mg, 0.036 mmol) was added and the apparatus pressurized with hydrogen gas (50 psi) and shaken for 22 hours. The reaction mixture was filtered through a pad of celite and the filtrate was concentrated. The resulting residue was dissolved in a small amount of DCM and loaded onto a silica gel column, which was eluted over 10 min with a gradient of 1%-5% MeOH/DCM to give a mixture of t-butyl-4-(2-(3,4-dimethoxyphenyl)- 3-methyl-III-pyrrolo[3,2b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5C) and the regioisomer tert-butyl-4-(3-(3, 4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (82 mg, 80%), m/z ( 452, M+H).

Intermediate 5D: 2-(3,4-dimethoxyphenyl)-3-methyl-5-(piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridine

Mixture of isomers of (tert-butyl-4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5yl)piperidine-1-carboxylate (Intermediate 5C) and tert -butyl-4-(3-(3,4-dimethoxyphenyl)2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-1-carboxylate (80 mg, 0.18 mmol) was suspended in 4 N HCl in dioxane (4 ml, 16.00 mmol), stirred for 30 min and concentrated to dryness The resulting residue was suspended in diethyl ether (1 ml) and the solids were filtered off and dried to give a mixture of 2-(3.4 -dimethoxyphenyl)-3-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2b]pyridine (Intermediate 5D) and 3-(3,4-dimethoxyphenyl)-2-methyl-5-( piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridine as bis-HCl salts (50 mg, 65%), m/z (352, M+H).

Example 5

To a solution containing a mixture of 3-(3,4-dimethoxyphenyl)-2-methyl-5-(piperidin-4-yl)-1Hpyrrolo[2,3-c]pyridine 2 HCl (Intermediate 5D) and 2-(3 ,4-dimethoxyphenyl)-3-methyl-5(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine, 2 HCl (30 mg, 0.07 mmol) in DMF (1 ml) was added 1isobutylpiperidine -4-one (55 mg, 0.35 mmol) followed by the addition of sodium triacetoxyborohydride (75 mg, 0.35 mmol) and a drop of acetic acid. The reaction mixture was stirred and treated with aqueous 1N NaOH (1 ml). The mixture was extracted with ethyl acetate (3X2 ml). The extracts were combined and washed with aqueous 10% LiCl solution (2x2 ml) and concentrated. The residue was suspended in DMF (2 ml), filtered through a 0.45 µm nylon syringe filter. The crude material was purified by preparative LC/MS under the following conditions: Column: Waters XBridge C18, 19x250 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0-40% B over 25 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 2(3,4-dimethoxyphenyl)-5-(1'-isobutyl-[1,4'-bipiperidin]-4-yl)-3-methyl-1H-pyrrolo[ 3,2-b]pyridineα, 3 TFA (25 mg, 0.03 mmol, 42%), m/z (491, M+H). Retention time, 1.3 min using LCMS Column: Waters Acquity UPLC WEEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.11 ml/min; Detection: UV at 220 nm.

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.31-8.17 (m, 1H), 7.35 (br m, 2H), 7.33-7.28 (m, 1H), 7 .18 (br d, J=8.1 Hz, 1H), 3.88 (s, 3H), 3.86 (m, 3H), 2.55 (m, 3H), 0.98 (d, J =6Hz, 6H).

Example 6 N-(2-(Dimethylαmino)ethyl)-N-ethyl-3-isopropyl-2-(8-methoxy-[1.2.4]triαzolo[1.5a]pyridin-6-yl)-6 -methyl-1 H-pyrrolo[3,2-b]pyridine-5-carboxamide

Intermediate 6A: 6-bromo-2-iodo-5-methylpyridine-3-amine

To a solution of 6-bromo-5-methylpyridin-3-amine (10 g, 53.5 mmol) in DMF (150 ml) was added NIS (12.03 g, 53.5 mmol). The resulting reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with DCM (100 ml), washed with sodium thiosulfate solution

- 26 041852 (100 ml), the organic layer was dried over sodium sulfate, filtered and concentrated to obtain the crude compound. The crude material was purified by Combiflash chromatography using a 120 g silica gel column, the compound was eluted with 22% EtOAc in petroleum ether, the fractions were collected and concentrated to give 6-bromo-2-iodo-5-methylpyridine-3-amine (16 g, 51.1 mmol, 96% yield) as a pale yellow solid. LCMS retention time 2.14 min [I]. MS m/z: 314.1 (M+2H).

Intermediate 6B: (E)-6-bromo-2-(2-ethoxyvinyl)-5-methylpyridine-3-amine Br^N^^O^CH ₃

Ύ Y h ₃ c^^nh _{2 (6B)}

To a solution of 6-bromo-2-iodo-5-methylpyridin-3-amine (16 g, 51.1 mmol) and (E)-2-(2-ethoxyvinyl)4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (15.19 g, 77 mmol) in THF (350 ml) sodium hydroxide (6.14 g, 153 mmol) was added. The mixture was degassed for 10 minutes with nitrogen, tetrakis(triphenylphosphine)palladium (1.182 g, 1.023 mmol) was added and the mixture was further degassed for 5 minutes. The resulting mixture was stirred at 80°C for 16 hours. The reaction mass was filtered through celite, extracted with EtOAc (100 ml) and washed with water (2x100 ml), dried over sodium sulfate, filtered and concentrated to give the crude compound. The crude compound was purified by Combiflash chromatography using a 120 g silica gel column, the compound was eluted with 22% EtOAc in petroleum ether, the fractions were collected, concentrated to give (E)-6-bromo 2-(2-ethoxyvinyl)-5-methylpyridine-3 -amine (7 g, 27.2 mmol, 53.2% yield) as a brown solid. LCMS retention time 2.41 min [D]. MS m/z: 259.1 (M+2H).

Intermediate 6C: 5-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine

Br\Y.

H ₃ C'

N ^H (6C)

Hydrochloric acid (8.27 ml , 272 mmol). The reaction mixture was heated at 85°C for 16 h. The reaction mass was concentrated to give 5-bromo-6-methyl-1H-pyrrolo[3,2b]pyridine (5.1 g, 24.16 mmol, 89% yield) in as a brown solid. LCMS retention time 1.19 min [R]. MS m/z: 213.1 (M+2H).

Intermediate 6D: Methyl 6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate o _(G)

To a solution of 5-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine (2.0 g, 9.48 mmol) in methanol (70 ml) and DMF (70 ml) was added DPPF (1.576 g, 2.84 mmol) and Pd(OAc) ₂ (0.425 g, 1.895 mmol). The reaction mixture was degassed for 10 min with nitrogen and TEA (2.64 ml, 18.95 mmol) was added. The mixture was stirred at 90°C in the presence of CO at 8 kg pressure for 12 h. The reaction mass was concentrated, the residue was dissolved in DCM (100 ml), washed with water (2x100 ml), dried over sodium sulfate, filtered and concentrated to obtain the crude compound . The crude compound was purified by silica gel column chromatography, the compound was eluted with 70% ethyl acetate in petroleum ether, the fractions were collected and concentrated to give methyl 6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate (1.1 g, 5 .71 mmol, 60.3% yield) as a pale yellow solid. LCMS retention time 0.80 min [R].

Intermediate 6E: methyl 3-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate O Br ^H ' ^c H (6E)

To a solution of methyl 6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate (1.0 g, 5.26 mmol) in DMF (30 ml) was added dropwise NBS (0.936 g, 5. 26 mmol) in DMF (15.00 ml). The resulting mixture was stirred at room temperature for 15 minutes. The reaction mass was poured into a mixture of ice and water (100 ml) and was extracted by adding ethyl acetate (3x100 ml). The combined organic layer was dried over sodium sulfate, filtered and concentrated to give methyl 3-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate (1.2 g, 4.24 mmol, 81 % yield) as a brown solid. LCMS retention time 1.17 min [R]. MS m/z:. 269.1 (M+2H).

Intermediate 6F: 1-tert-butyl-5-methyl-3-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine 1,5-dicarboxylate

- 27041852°Br

Vos (6F)

To a solution of methyl 3-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate (1.2 g, 4.46 mmol) in THF (10 ml) 4.91 mmol), TEA (1.243 ml, 8.92 mmol) and DMAP (0.109 g, 0.892 mmol) at room temperature. The reaction mixture was stirred at the same temperature for 0.5 h. The reaction mass was quenched with water (50 ml), extracted with the addition of ethyl acetate (3x50 ml), the combined organic layers were dried over sodium sulfate, filtered and concentrated to obtain the crude compound. The crude compound was purified by silica gel column chromatography eluting with 9% EtOAc in petroleum ether, the fractions were collected and concentrated to give 1-tert-butyl-5-methyl-3-bromo-6-methyl-1H-pyrrolo[3,2-b ]pyridine-1,5-dicarboxylate (1.3 g, 3.49 mmol, 78% yield) as a white solid. LCMS retention time 3.15 min [R]. MS m/z: 371.1 (M+H).

Intermediate 6G: 1-tert-Butyl-5-methyl-6-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[3,2b]pyridine-1,5-dicarboxyαt

H ₃ C. A /

H ₃ C^^N

Vos (6G)

To a solution of 1-tert-butyl-5-methyl-3-bromo-6-methyl-1H-pyrrolo[3,2-b]pyridine-1,5-dicarboxylate (1.3 g, 3.52 mmol) in THF (25 ml) and water (4 ml) were added tribasic potassium phosphate (1.840 g, 10.56 mmol). The mixture was degassed for 10 min with nitrogen, XPhos Pd G2 (0.083 g, 0.106 mmol) was added and the mixture was further degassed for 5 min. Then 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2dioxaborolane (0.769 g, 4.58 mmol) was added and the mixture was stirred at 70°C for 12 hours The reaction mass was filtered through celite, was extracted with the addition of EtOAc (100 ml), washed with water (2x100 ml), dried over sodium sulfate and concentrated to obtain the crude compound. The crude compound was purified by silica gel column chromatography. The compound was eluted with 6% EtOAc in petroleum ether and the fractions were collected and concentrated to give 1tert-butyl-5-methyl-6-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[3,2- b]pyridine-1,5-dicα-carboxylate (1.1 g, 3.26 mmol, 93% yield) as a pale yellow solid. LCMS retention time 3.08 min [R]. MS m/z: 331.1 (M+H).

Intermediate 6H: 1-tert-Butyl-5-methyl-3-isopropyl-6-methyl-1H-pyrrolo[3,2b]pyridine-1,5-dicarboxyαt o ⁿ ' ^s usn ₅ ^Η3%Λ ίΎ?

Vos (6H)

To a solution of 1-tert-butyl-5-methyl-6-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[3,2-b]pyridine-1,5-dicarboxylate (1.1 g , 3.33 mmol) in methanol (20 mL) Pd/C (0.6 g, 0.564 mmol) was added. The mixture was stirred at room temperature with a balloon of hydrogen attached for 3 h. b]niridine-1,5-dicarboxylate (0.65 g, 1.869 mmol, 56% yield) as an off-white solid. LCMS retention time 3.7 min [R]. MS m/z: 333.1 (M+H).

Intermediate 6I: 1-tert-Butyl-5-methyl-2-bromo-3-isopropyl-6-methyl-1H-pyrrolo[3,2b]pyridine-1,5-dicarboxyαt n ₃ c

About ^J y-CHz

H ₃ % A A. 7

X> ^vg

Vos (61)

To a solution of 1-tert-butyl-5-methyl-3-isopropyl-6-methyl-1H-pyrrolo[3,2-b]pyridine-1,5-dicarboxylate (0.55 g, 1.655 mmol) in DCE (20 ml) NBS (0.442 g, 2.482 mmol) was added in portions. The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water (50 ml), extracted with DCM (2x50 ml), the combined organic layers were dried over sodium sulfate, filtered and concentrated to obtain the crude compound. The crude compound was purified by silica gel column chromatography, the compound was eluted with 5% EtOAc/petroleum ether, the fractions were collected and concentrated to give 1-tert-butyl-5-methyl-2-bromo-3-isopropyl-6-methyl-1H-pyrrolo[3, 2-b]niridine-1,5-dicarboxylate (0.4 g, 0.807

- 28 041852 mmol, 49% yield) as a yellow oil. LCMS retention time 4.12 min [D]. MS m/z: 411.1 (M+H).

Intermediate 6J: 1-tert-Butyl-5-methyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl -1H-pyrrolo[3,2-b]pyridine-1,5-dicarboxylate

Solution of 1-tert-butyl-5-methyl-2-bromo-3-isopropyl-6-methyl-1H-pyrrolo[3,2-b]pyridine-1,5-dicarboxylate (0.2 g, 0.486 mmol), 8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)[1,2,4]triazolo[1,5-a]pyridine (0.147 g, 0.535 mmol) and tribasic potassium phosphate (0.254 g, 1.459 mmol) in a mixture of dioxane (10 ml) and water (1 ml) solvents were degassed with N2 for 10 min. Then PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (0.040 g, 0.049 mmol) was added and the mixture was degassed again for 5 minutes. The resulting mixture was stirred at 80° C. for 3 hours. The reaction mixture was extracted with ethyl acetate (20 ml), washed with water (2x10 ml), brine (50 ml), dried over sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography, the compound was eluted with 22% ethyl acetate in petroleum ether, the fractions were collected and concentrated to give 1-tert-butyl-5-methyl-3isopropyl-2-(8-methoxy-[1,2,4] triazolo[1,5-α]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b]n-pyridine-1,5-dicarboxylate (0.2 g, 0.396 mmol, 81% yield) as brown solid. LCMS retention time 2.96 min [R]. MS m/z: 480.1 (M+H).

Intermediate 6K: methyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-6-methyl-1H-pyrrolo[3,2-b ]pyridine-5-carboxylate

To a solution of 1-tert-butyl-5-methyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo [1,5-a]pyridin-6-yl)-6methyl-1H-pyrrolo [3,2-b]pyridine-1,5-dicarboxylate (0.2 g, 0.417 mmol) in DCM (2 ml) was added dropwise with 4 M hydrochloric acid in dioxane (0.209 ml, 0.834 mmol). The reaction mixture was stirred at room temperature for 1 h. The solvent was removed in vacuo and the solids were washed with diethyl ether to give methyl 3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a ]pyridin-6-yl)6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxylate (0.15 g, 0.376 mmol, 95% yield) as a yellow solid. LCMS retention time 1.91 min [R]. MS m/z: 380.1 (M+H).

Intermediate 6L: 3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6methyl -1H-pyrrolo[3,2-b]pyridine -5-carboxylic acid

To a solution of methyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1Hpyrrolo[3,2-b]pyridine -5-carboxylate (0.15 g, 0.395 mmol) in a mixture of solvents of methanol (2 ml), THF (2 ml) and water (1 ml) was added lithium hydroxide (0.095 g, 3.95 mmol). The resulting mixture was stirred at room temperature for 5 hours. The volatiles were removed in vacuo, diluted with water (5 ml) and neutralized with 1.5 N HCl. The aqueous layer was extracted with DCM (3x50 ml). The combined organic layer was dried over sodium sulfate, filtered and concentrated to give 3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-α]pyridin-6-yl)-6-methyl-1H- pyrrolo[3,2-b]pyridine-5-carboxylic acid (0.1 g, 0.235 mmol, 59.5% yield) as a yellow solid. LCMS retention time 0.98 min [R]. MS m/z: 366.1 (M+H).

Example 6

To a solution of 3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2b]pyridine-5 -carboxylic acid (0.02 g, 0.055 mmol) in DMF (2 ml) was added N1-ethyl-N2,N2-dimethylethane-1,2-diamine (6.36 mg, 0.055 mmol), TEA (0.015 ml, 0.109 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (0.023 g, 0.060 mmol) at room temperature. The mixture was then stirred at the same temperature for 3 hours. The reaction mixture was diluted with EtOAc (20 ml) and washed with water (2x20 ml), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by preparative LC/MS using method D2, the fractions containing the product were combined and dried by centrifugal evaporation to give N-(2-(dimethylamino)ethyl)-N-ethyl-3-isopropyl-2-(8methoxy-[1 ,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-5-carboxamide (7.8

- 29041852 mg, 0.017 mmol, 31% yield) as a pale yellow solid. LCMS retention time 1.30 min [E]. MS m/z: 464.1 (M+H).

1H NMR (400 MHz, DMSO-d ₆ ) δ ppm 11.49-11.45 (m, 1H), 8.66 (s, 1H), 8.52 (d, J=1.2 Hz, 1H), 7.62 (s, 1H), 7.21 (s, 1H), 4.08 (d, J=1.0 Hz, 3H), 3.90 (s, 1H), 3.63 (t, J=7.1 Hz, 2H), 3.56 -3.50 (m, 1H), 3.19-3.07 (m, 3H), 2.72 (br. s., 2H), 2.40 (br. s., 4H), 2.32 (s, 3H), 1.97-1.89 (m, 3H), 1.55-1.47 (m, 6H).

Examples 7, 8, and 9 b] pyridin-5 -yl)cyclopentan-1 -one

Intermediate 7A: 3-bromocyclopent-2-en-1-one

To a stirred solution of triphenylphosphine (23.53 g, 90 mmol) in DCM (350 ml) was added bromine (4.62 ml, 90 mmol) at 0°C. The reaction mixture was stirred at the same temperature for 15 minutes. Then TEA (13.64 ml, 98 mmol) and cyclopentane-1,3-dione (8 g, 82 mmol) in DCM (350 ml) were added. The mixture was stirred at room temperature for 16 hours. The reaction mass was concentrated, purified by silica gel column chromatography, the fractions were collected and concentrated to give 3-bromocyclopent-2-en-1-one (8.9 g, 55.3 mmol, 68 % yield) as an oil.

1H NMR (400 MHz, DMSO-d ₆ ) δ ppm 6.57 (s, 1H), 2.99 (m, 2H), 2.52 (m, 2H).

Intermediate 7B: 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one

„ , ^sn z

O^-CHz ^SN z (7V)

To a stirred solution of 3-bromocyclopent-2-en-1-one (10 g, 62.1 mmol) in 1,4-dioxane (250 ml) was added bis(pinacolato)diboron (18.93 g, 74.5 mmol) and potassium acetate (12.19 g, 124 mmol). The reaction mixture was degassed with N ₂ for 10 min, PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (3.55 g, 4.35 mmol) was added and the reaction mixture was stirred at 100°C for 16 h. The reaction mass was diluted with EtOAc , filtered through celite, washed with EtOAc, the filtrate was collected and concentrated to obtain the crude product. The crude product was purified by ISCO silica gel column chromatography, fractions were collected and concentrated to give 3-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)cyclopent-2-en-1-one (10.9 g, 52.4 mmol, 84% yield) as a white solid.

1H NMR (400 MHz, DMSO-d6) δ ppm 6.43 (s, 1H), 2.66 (m, 2H), 2.26 (m, 2H), 1.18 (s, 9H).

Intermediate 7C: tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1carboxylate ^H = ^C usn,

Br\7

Ύ T5

N

Vos (7Q

DIPEA (41.8 mmol) and Boc anhydride ( 7.28 ml, 31.4 mmol) at room temperature. The reaction mixture was stirred at the same temperature for 3 hours. The reaction mass was extracted with ethyl acetate and washed with water, brine, dried over sodium sulfate and concentrated to give the crude compound. The crude compound was purified by silica gel column chromatography, fractions were collected and concentrated to give tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (6.5 g, 19. 16 mmol, 92% yield) as an off-white solid. LCMS retention time 2.03 min [L]. MS m/z: 341 (M+H).

Intermediate 7D: tert-Butyl-3-isopropyl-5-(3-oxocyclopent-1-en-1-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Αη ⁿ %sn ₃ ί Te

N

Vos (7D)

To a stirred solution of tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1

- 30 041852 carboxylate (16 g, 47.2 mmol) in dioxane (400 ml) was added 3-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)cyclopent-2-en-1 -one (14.72 g, 70.7 mmol) and tribasic potassium phosphate (20.02 g, 94 mmol). The reaction mixture was degassed with nitrogen for 10 min and then PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (3.85 g, 4.72 mmol) was added. The reaction mixture was stirred at 100° C. for 16 hours. The reaction mass was filtered through a pad of celite, washed with EtOAc and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography, the fractions were collected and concentrated to give tert-butyl-3-isopropyl-5-(3-oxocyclopent-1-en-1yl)-1H-pyrrolo[3,2-b]pyridine-1 -carboxylate (15 g, 44.1 mmol, 93% yield) as a brown solid. LCMS retention time 1.76 min [L]. MS m/z: 341.6 (M+H).

Intermediate 7E: tert-Butyl 5-(3-hydroxycyclopentyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate _ n ₃ s.

Λη \- ^SN z | ^N °5L

N

Vos (7E)

To a stirred solution of tert-butyl 3-isopropyl-5-(3-oxocyclopent-1-en-1-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate (10 g, 29.4 mmol) in MeOH (20 mL) nickel(II) chloride hexahydrate (0.698 g, 2.94 mmol) and NaBH4 (4.45 g, 118 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 10 minutes. The reaction was quenched with a solution of NH ₄ Cl. The reaction mixture was concentrated to remove methanol, the residue was extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated to give tert-butyl-5-(3hydroxycyclopentyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1 -carboxylate (10 g, 29.0 mmol, 99% yield) as a brown solid. LCMS retention time 1.71 min [L]. MS m/z: 345.6 (M+H).

Intermediate 7F: tert-Butyl-3-isopropyl-5-(3-oxocyclopentyl)-1H-pyrrolo[3,2b]pyridine-1-carboxylate

To a stirred solution of tert-butyl 5-(3-hydroxycyclopentyl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine-1-carboxylateα (1 g, 2.90 mmol) in DCM (25 ml) was added Dess periodinan -Martin (6.16 g, 14.52 mmol) at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mass was diluted with an aqueous NaHCO ₃ solution, the solids were filtered off, the aqueous layer was extracted with DCM, the organic layer was dried over sodium sulfate and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography, fractions were collected and concentrated to give tert-butyl-3isopropyl-5-(3-oxocyclopentyl)-1H-n-pyrrolo[3,2-b]pyridine-1-carboxylate (380 mg, 1.110 mmol , 38% yield) as an off-white solid. LCMS retention time 1.75 min [L]. MS m/z: 343.6 (M+H).

Intermediate 7G: 3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2b]pyridine

To a stirred solution of tert-butyl 3-isopropyl-5-(3-oxocyclopentyl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (2.8 g, 8.18 mmol) in toluene (40 mL ) was added ethylene glycol (0.692 ml, 12.26 mmol) and p-toluenesulfonic acid (0.282 g, 1.635 mmol) at room temperature. The mixture was then stirred at 130° C. for 16 hours. The reaction mass was concentrated, diluted with EtOAc, and washed with saturated NaHCO ₃ solution, dried over sodium sulfate and concentrated to obtain the crude substance. The crude material was purified by silica gel column chromatography, fractions were collected and concentrated to give 3-isopropyl-5-(1,4dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridine (2.8 g, 7.24 mmol, 89% yield) as an off-white solid. LCMS retention time 1.18 min [L]. MS m/z: 287.5 (M+H).

Intermediate 7H: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate

- 31 041852

To a stirred solution of 3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2b]pyridine (2.2 g, 7.68 mmol) in THF (30 ml ), Boc anhydride (2.68 ml, 11.52 mmol), DIPEA (2.68 ml, 15.36 mmol) and DMAP (0.939 g, 7.68 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 3 hours. The reaction was quenched with water. The reaction mixture was extracted with EtOAc, dried over sodium sulfate and concentrated to give the crude material. The crude material was purified by ISCO silica gel column chromatography, fractions were collected and concentrated to give t-butyl-3-isopropyl-5(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2 -b]pyridine-1-carboxylate (2.8 g, 7.24 mmol, 94% yield) as a white foam. LCMS retention time 1.96 min [L]. MS t/z: 387.6 (M+H).

Intermediate 7I: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1 H-pyrrolo[3,2-b]pyridine-1-carboxylate.

To a stirred solution of tert-butyl 3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate (2.8 g, 7. 24 mmol) in THF (20 ml) was added LDA (10.87 ml, 21.73 mmol) at -78°C. The reaction mixture was stirred at the same temperature for 2 hours and then 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.00 mL, 14.49 mmol) was added slowly. The reaction mixture was brought to room temperature and stirred at room temperature for 1 hour. The reaction was quenched with water. The reaction mixture was extracted with EtOAc, dried over sodium sulfate and concentrated to give the crude compound. The crude compound was purified by silica gel column chromatography, the fractions were collected and concentrated to give tert-butyl-3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-2-(4,4,5, 5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (2.9 g, 5.66 mmol, 78% yield) as an off-white solid . LCMS retention time 2.29 min [L]. MS m/z: 513.7 [M+H] ⁺ .

Intermediate 7J: tert-Butyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-5-(1,4-dioxaspiro[4.4] nonan-7-yl)-III-pyrrolo[3,2-b]pyridine-1-carboxylate

To a stirred solution of tert-butyl-3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 -yl)-1 H-pyrrolo[3,2-b]pyridine-1-carboxylate (3 g, 5.85 mmol) in dioxane (100 ml) and water (2 ml) [1,2,4]triazolo[1,5-a]pyridine (1.602 g, 7.03 mmol) and tribasic potassium phosphate (3.73 g, 17.56 mmol). The reaction mixture was degassed with N ₂ for 10 min and PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (0.478 g, 0.585 mmol) was added. The mixture was stirred at 100° C. for 16 hours. The reaction mass was diluted with EtOAc, filtered, and the filtrate was concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography, the fractions were collected and concentrated to give tert-butyl-3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)- 5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate (2.9 g, 5.43 mmol, 93% yield) as an off-white solid substances. LCMS retention time 1.62 min [L]. MS m/z: 534.7 [M+H] ⁺ .

Intermediate 7K: 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1 H-pyrrolo[3,2-b] pyridin-5-yl)cyclopentan-1-one

To a stirred solution of tert-butyl-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin6-yl)-5-(1,4-dioxaspiro[4.4]nonane -7-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (2.9 g, 5.43 mmol) in DCM (20 mL) TFA (2.093 mL, 27.2 mmol) was added at room temperature. The reaction mixture was stirred at the same temperature for 16 hours. The reaction mixture was concentrated, extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated to give 3-(3-isopropyl-2-(8-methoxy-[1,2, 4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5

- 32 041852 yl)cyclopentan-1-one (2.1 g, 5.43 mmol, 93% yield) as a resinous solid. LCMS retention time 1.14 min [L]. MS m/z: 390.6 [M+H]+.

Examples 7, 8 and 9.

To a stirred solution of 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridin- 5-yl)cyclopentan-1-oneα (2.5 g, 6.42 mmol) in THF (3 ml), DMF (3 ml) was added ammonium acetate (4.95 g, 64.2 mmol), ammonium chloride ( 3.43 g, 64.2 mmol) and acetic acid (0.367 ml, 6.42 mmol) at room temperature.

The reaction mixture was stirred at the same temperature for 16 h, then NaCNBH ₃ (1.210 g, 19.26 mmol) was added and stirred for another 2 h at room temperature. The reaction mass was concentrated to obtain the crude compound. The crude compound was purified by prep. HPLC for isomer separation. After purification by prep. HPLC, fractions were collected, concentrated and lyophilized to isolate three isomers/mixtures.

Example 7: Isomer 1: mixture of diastereomers, LCMS retention time 1.79 min [E].

MS m/z: 391.4 (M+H).

Example 8: Isomer 2: homochiral. LCMS retention time 1.78 min [E].

MS m/z: 391.2 (M+H).

Example 9: Isomer 3: mixture of diastereomers, LCMS retention time 1.56 min [E].

MS m/z: 391.3 (M+H).

Example 10 2-((3-(3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b ]pyridin-5-yl)cyclopentyl)amino)-N-methylacetamide

To a stirred solution of 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridin- 5-yl)cyclopentan-1-amine (20 mg, 0.051 mmol) (Example 9) TEA (0.021 ml, 0.154 mmol) and 2-chloro-N-methylacetamide (6.61 mg, 0.061 mmol) at room temperature. The reaction mixture was stirred at the same temperature for 16 hours. The crude material was purified by preparative LC/MS using method D2, product-containing fractions were combined and dried by centrifugal evaporation to give 2-((3-(3isopropyl-2-(8- methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1 H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentyl)amino)-N-methylacetamide ( 3 mg). LCMS retention time 1.29 min [E]. MS m/z: 462.3 (M+H).

¹ H NMR (400 MHz, DMSO-d6) δ ppm 11.30 (s, 1H), 8.63 (d, J=1.0 Hz, 1H), 8.53 (s, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.20 (d, J=1.0 Hz, 1H), 7.04 (d, J=8.6 Hz, 1H), 4.09 (s, 3H), 3.17-3.11 (m , 4H), 2.90 (s, 1H), 2.63 (d, J=4.9 Hz, 3H), 2.32-2.23 (m, 1H), 2.00(q, J= 7.4 Hz, 2H), 1.94-1.81 (m, 3H), 1.74-1.61 (m, 2H), 1.61-1.50 (m, 6H).

Example 11 6-(6-Fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl[1,2,4 ]triazolo[1,5-а]pyridine

Intermediate 11A: 6-bromo-5-fluoropyridine-3-amine

To a solution of 5-fluoropyridine-3-amine (4.5 g, 40.1 mmol) in DMF (80 ml) was added NBS (7.14 g, 40.1 mmol) in portions at 0°C. The reaction mixture was stirred at room temperature for 20 minutes. The mixture was then partitioned between EtOAc (300 ml) and water (300 ml), both layers were separated, the organic layer was washed with saturated NaHCO ₃ , brine, dried over sodium sulfate, filtered and concentrated to give the crude compound. The crude compound was purified by silica gel column chromatography, the compound was eluted with 52% ethyl acetate/hexane, the fractions were collected and concentrated to give 6-bromo-5-fluoropyridine-3-amine (4.7 g, 24.61 mmol, 61% yield) in as a brown solid. LCMS retention time 0.98 min [R]. MS m/z: 193.1 (M+2H).

Intermediate 11B: tert-Butyl 5-amino-3-fluoro-5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)carboxylate

- 33 041852

tert-butyl 5-amino-3-fluoro-5',6'-dihydro-[2,4'-bipyridine]-G(2'H)-carboxylate (6.5 g, 22.16 mmol, 94% yield) was obtained according to the general procedure described for Intermediate 5B using 6-bromo-5-fluoropyridine-3-amine (4.5 g, 23.56 mmol) as starting intermediate. LCMS retention time 1.94 min [R]. MS m/z: 293.1 (M+H).

Intermediate 11C: tert-Butyl-4-(5-amino-3-fluoropyridin-2-yl)piperidine-1-carboxylate

A solution of tert-butyl 5-amino-3-fluoro-5',6'-dihydro-[2,4'-bipyridine]-G(2'H)-carboxylate (6.5 g, 22.16 mmol) and ethyl acetate (150 ml) was sparged with nitrogen (N ₂ ). Then Pd/C (3.30 g, 3.10 mmol) was added and the reaction mixture was again sparged with N 2 three times. Gaseous hydrogen (H ₂ ) was introduced using a balloon into the mixture. The reaction mixture was stirred at room temperature for 12 hours. The suspension was filtered through a pad of celite, the filtrate was collected and concentrated to give tert-butyl 4(5-amino-3-fluoropyridin-2-yl)piperidine-1-carboxylate (5.8 g, 19.64 mmol, 89% yield) as a yellow oil. LCMS retention time 1.68 min [R]. MS m/z: 296.1 (M+H).

Intermediate 11D: tert-Butyl 4-(5-amino-3-fluoro-6-iodopyridin-2-yl)piperidine-1carboxylate ^B0C ^N^

F^^^ ^NH 2 ( _11D )

NIS (4.27 g , 18.96 mmol) in portions. The mixture was stirred for 2 hours at room temperature. The reaction mass was diluted with water (200 ml) and extracted with ethyl acetate (3x200 ml). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated to give the crude compound. The crude compound was purified by chromatography on a Combiflash system using a silica gel column chromatography, the compound was eluted with 25% ethyl acetate/petroleum ether, the fractions were collected and concentrated to give tert-butyl-4-(5-amino-3-fluoro-6-iodopyridine-2- yl) piperidine-1-carboxylate (5.8 g, 13.77 mmol, 73% yield) as a brown solid. LCMS retention time 2.46 min [R]. MS m/z: 322.1 (M+H).

Intermediate 11E: tert-Butyl 4-(3-fluoro-6-iodo-5-((3-methylbut-2-en-1-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

To a solution of tert-butyl 4-(5-amino-3-fluoro-6-iodopyridin-2-yl)piperidine-1-carboxylate (3.0 g, 7.12 mmol) and 3-methylbut-2-enal ( 2.72 ml, 28.5 mmol) in MeOH (50 ml) was added acetic acid (1 ml, 17.47 mmol). The resulting light yellow solution was stirred at room temperature for 6 hours. Then sodium cyanoborohydride (2.238 g, 35.6 mmol) was added at 0°C and the reaction mixture was stirred at room temperature for 2 hours. The reaction mass was concentrated to remove methanol, diluted with water (100 ml) and extracted with ethyl acetate (3x100 ml). The combined organic extracts were dried over sodium sulfate, filtered and concentrated to give the crude compound. The crude compound was purified by silica gel column chromatography. The compound was eluted with 28% ethyl acetate/petroleum ether, the fractions were collected and concentrated to give tert-butyl-4-(3-fluoro-6-iodo-5-((3-methylbut-2-en-1-yl)amino)pyridine2- yl)piperidine-1-carboxylate (1.7 g, 3.35 mmol, 47% yield) as a pale yellow oil. LCMS retention time 3.39 min [R]. MS m/z: 490.1 (M+H).

Intermediate 1 11F: 4-(6-fluoro-3-isopropyl-III-pyrrolo[3,2-b]pyridin-5yl)piperidine-1-carboxylate

- 34 041852

A solution of tert-butyl 4-(3-fluoro-6-iodo-5-((3-methylbut-2-en-1-yl)amino)pyridin-2-yl)piperidine-1 carboxylate (1.6 g, 3.27 mmol), potassium carbonate (0.497 g, 3.60 mmol) and tetrabutylammonium bromide (3.16 g, 9.81 mmol) in DMF (20 ml) were degassed for 10 min with nitrogen, and Pd(OAc)2 (0.073 g, 0.327 mmol) was added. The reaction mixture was further degassed for 5 minutes. The reaction mixture was stirred at 80° C. for 14 hours. The reaction mixture was diluted with ethyl acetate (200 ml). The reaction mixture was washed with water (2x100 ml), brine (100 ml), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography, the compound was eluted with 65% ethyl acetate/petroleum ether, the fractions were collected and concentrated to give t-butyl-4-(6-fluoro-3isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperidine-1-carboxylate (0.5 g, 1.383 mmol, 42% yield) as a pale yellow oil. LCMS retention time 3.80 min [R]. MS m/z: 362.1 (M+H).

Intermediate 11G: tert-Butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

To a solution of tert-butyl 4-(6-fluoro-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-1-carboxylate (0.3 g, 0.830 mmol) in THF ( 2 ml) TEA (0.231 ml, 1.660 mmol), BOC2O (0.212 ml, 0.913 mmol), and DMAP (0.020 g, 0.166 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water (100 ml) and extracted with ethyl acetate (3x100 ml). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give the crude compound. The crude compound was purified by silica gel column chromatography eluting with 9% EtOAc:petroleum ether, the fractions were collected and concentrated to give t-butyl-5-(1-(t-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3-isopropyl- 1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.33 g, 0.715 mmol, 86% yield) as a white solid. LCMS retention time 3.92 min [R]. MS m/z: 462.1 (M+H).

Intermediate 11H: tert-Butyl-2-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)6-fluoro-3-isopropyl-1 H-pyrrolo[3,2-b]pyridine-1 -carboxylate

tert-Butyl-2-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3-isopropyl-1H-pyrrolo [3,2-b]pyridine-1-carboxylate (0 .6 g, 0.766 mmol, 58.9% yield) was prepared according to the general procedure described for Intermediate 6I using tert-butyl-5-(1-(tert-butoxycarbonyl)pineridin-4-yl)-6-fluoro -3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.6 g, 1.300 mmol) as starting intermediate. LCMS retention time 4.32 min [D]. MS m/z: 541.1 (M+H).

Intermediate 11I: tert-Butyl-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3isopropyl-2-(8-methyl-[1.2.4]triazolo[1.5 -а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Boc Ν (u) tert-Butyl-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[ 1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.25 g, 0.359 mmol, 64% yield) was prepared according to the general procedure described for intermediate 7J, using tert-butyl-2-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-1 -carboxylate (0.3 g, 0.555 mmol) as starting material. LCMS retention time 4.16 min [R]. MS m/z: 593.1 (M+H).

Example 11.

To a solution of tert-butyl-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-fluoro-3-isopropyl-2-(8methyl-[1.2.4]triazolo[1.5-a ]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.25 g, 0.422 mmol) in DCM (2 ml) was added 4 M hydrochloric acid in dioxane (2 ml, 8 00 mmol) drop by drop. The reaction mixture was stirred at room temperature for 1 hour. The reaction mass was concentrated to obtain the crude product. The crude product was purified by preparative LC/MS using method D2, product-containing fractions were combined and dried by method

- 35 041852 centrifugal evaporation to obtain 6-(6-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methyl-[1, 2,4]triazolo[1,5-a]pyridine (11.3 mg, 0.029 mmol, 7% yield) as a pale yellow solid. LCMS retention time 1.26 min [E]. MS m/z: 393.1 (M+H).

1H NMR (400 MHz, DMSO-d6) δ ppm 11.45 (br. s., 1H), 8.85 (s, 1H), 8.54 (s, 1H), 7.62 (s, 1H), 7.53 (d, J=11.0 Hz, 1H), 3.89 (s, 1H), 3.18-3.13 (m, 2H), 2.82-2.72 (m, 2H), 2.63 (s, 3H), 2 .06 (s, 2H), 1.83-1.76 (m, 2H), 1.53 (d, J=6.8 Hz, 6H).

Example 39 4-(1-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3, 2b]pyridin-5-yl)azetidin-3-yl)morpholine

Intermediate 39A: tert-butyl-3-((tert-butyldiphenylsilyl)oxy)azetidine-1carboxylate

TBDPSO^^

V-NBoc (39A) tert-Butyl-3-hydroxyazetidine-1-carboxylate (2.05 g, 11.8 mmol) was dissolved in DCM (40 ml) and imidazole (1.61 g, 23.7 mmol) and t -butylchlorodiphenylsilane (3.58 g, 13.0 mmol) was added sequentially. The reaction mixture was stirred for 17 hours at room temperature. Upon completion, the reaction was quenched by adding water and DCM. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give a clear oil. This material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-15% to give t-butyl-3((t-butyldiphenylsilyl)oxy)azetidine-1-carboxylate (11.8 mmol). LCMS retention time 1.22 [TS]. MS (E+) m/z: 823.4 (2M+H).

¹ H NMR (499 MHz, chloroform-d) δ 7.63-7.57 (m, 4H), 7.46-7.41 (m, 2H), 7.41-7.35 (m, 4H) , 4.52 (tt, J=6.6, 4.7 Hz, 1H), 3.97-3.90 (m, 2H), 3.89-3.83 (m, 2H), 1.42 (s, 9H), 1.06 (s, 9H).

Intermediate 39B: 3-((tert-butyldiphenylsilyl)oxy)azetidine

TBDPSCk_

VnH (39V)

Intermediate 39A (11.8 mmol)) was dissolved in DCM (20 ml), cooled to 0° C. and pre-cooled 0° C. TFA (20 ml) was added. When the reaction was complete according to LCMS analysis, the reaction mixture was concentrated, re-dissolved in DCM, and made basic by adding 1 M aqueous NaOH. The aqueous layer was extracted with DCM and the combined organics were dried over sodium sulfate, filtered, and concentrated to give 3((t-butyldiphenylsilyl)oxy)azetidine (11.8 mmol). LCMS retention time 0.84 [TS]. MS (E+) m/z: 312.2 (M+1).

1H NMR (499 MHz, chloroform-d) δ 7.64-7.59 (m, 4H), 7.44-7.40 (m, 2H), 7.39-7.34 (m, 4H), 4.62 (quin, J=6.5 Hz, 1H), 3.70-3.61 (m, 2H), 3.55-3.47 (m, 2H), 1.05 (s, 9H) .

Intermediate 39C: tert-Butyl 5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

tert-Butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1 g, 2.95 mmol), 3((tert-butyldiphenylsilyl)oxy)azetidine (1, 19 g, 3.83 mmol), 2nd generation RuPhos precatalyst (0.114 g, 0.147 mmol), and Cs ₂ CO ₃ (2.88 g, 8.84 mmol) were suspended in 1,4-dioxane (20 mL) in a reaction vessel with a lid with a safety diaphragm and a magnetic stirrer. The suspension was degassed with nitrogen gas for 10 minutes and then sealed and placed in a heating block with stirring at 130° C. for 45 minutes. Upon completion, the reaction mixture was cooled to room temperature, filtered, concentrated, and purified by silica gel column chromatography using a Teledyne Isco instrument, eluting with Hex/EtOAc 0-30% to give tert-butyl-5-(3-((tert-butyldiphenylsilyl)oxy) azetidin-1-yl)-3-isopropyl-1 H-pyrrolo[3,2-b]pyridine-1 carboxylate (1.42 g, 2.49 mmol, 85% yield). LCMS retention time 1.09 [TS]. MS (E+) m/z: 570.4 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.06 (br s, 1H), 7.69-7.63 (m, 4H), 7.47-7.33 (m, 7H), 6.23 (d, J=8.8 Hz, 1H), 4.79-4.71 (m, 1H), 4.14 (dd, J=8.6, 6.5 Hz, 2H), 3.95 ( dd, J=8.7, 5.0 Hz, 2H), 3.25-3.15 (m, 1H), 1.64 (s, 9H), 1.36 (d, J=6.8 Hz , 6H), 1.07 (s, 9H).

- 36 041852

Intermediate 39D: tert-Butyl-5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

TBDPSCL^ ^HcC y-CH ₃

O_/ ^SN s T I HK G ^SN s

Sun ₃ C ^CH3 _(39D)

Solution containing tert-butyl 5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1.42 g, 2.49 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2dioxaborolane (0.661 ml, 3.24 mmol) in dry THF (12.5 ml), cooled dry under nitrogen bath ice/acetone to -78°C and treated with LDA (2M in THF, 1.87 ml, 3.74 mmol). The mixture was allowed to warm to -30°C over 30 minutes and stirred at -30°C for 30 minutes. Upon completion, the reaction was quenched by adding a saturated aqueous solution of NH ₄ Cl, water and DCM. The organic layer was separated, dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel column chromatography using a Teledyne Isco instrument loading in hexanes and eluting with Hex/EtOAc 0-40% to give t-butyl-5-(3-((t-butyldiphenylsilyl)oxy)azetidine-1yl)- 3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]n-pyridine-1-carboxylate (1.64 g , 2.36 mmol, 95% yield). LCMS retention time 1.14 [TS]. MS (E+) m/z: 696.5 (M+H).

Intermediate 39E: 5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolαn-2-yl )-1H-pyrrolo[3,2-b]pyridine

TBDPSC<__ ^NzS y-CH ₃

O^/ ^CH 3 T XVb b of ^H H 3C ³ (39E) tert-Butyl-5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl-2-(4.4, 5,5-tetramethyl 1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1.64 g, 2.36 mmol) was heated pure at 165°C in a vessel with a lid with a safety diaphragm and a magnetic stirrer in a nitrogen atmosphere with a supply of gaseous nitrogen. The reaction mixture was heated for two hours, saturated at room temperature overnight, and then heated for another hour for a total of three hours of pure heating at 165°C. Upon completion, the reaction mixture was dissolved in DCM and concentrated to give 5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl-2-(4,4,5,5tetramethyl-1,3 ,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine (1.40 g, 2.35 mmol, 100% yield) as light brown foam. Note: LCMS showed partial conversion to the corresponding boronic acid, although NMR indicated that the product was pure. The retention time of boronic acid in LCMS is 0.98 [TS]. Boronic acid MS (E+) m/z: 514.1 (M+H). Product Characteristics: LCMS retention time 1.07 [TS]. MS (E+) m/z: 596.1 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.04 (s, 1H), 7.69-7.63 (m, 4H), 7.46-7.37 (m, 7H), 6.27 ( d, J=8.8 Hz, 1H), 4.80-4.70 (m, 1H), 4.13 (dd, J=8.7, 6.4 Hz, 2H), 3.95 (dd , J=8.7, 5.2 Hz, 2H), 3.64 (spt, J=7.0 Hz, 1H), 1.50 (d, J=7.0 Hz, 6H), 1.35 (s, 12H), 1.07 (s, 9H).

Intermediate 39F: 6-(5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7.8 -dimethyl-[1,2,4]triazolo[1,5-a]pyridine

To a mixture of 5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl-2-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl)- 1H-pyrrolo[3,2-b]pyridineα (500 mg, 0.839 mmol), 6-bromo-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (209 mg, 0.923 mmol ), and 2nd generation precatalyst Xphos (33.0 mg, 0.042 mmol) in 1,4-dioxane (6 ml) was added aqueous K ₃ PO ₄ (2M, 1.26 ml, 2.52 mmol). The biphasic mixture was degassed with nitrogen gas for 10 minutes. The reaction vessel was sealed with a septum cap and stirred at 70°C for 1.5 hours. Upon completion, the reaction mixture was cooled to room temperature, concentrated, and suspended in DCM for purification by silica gel column chromatography using a Teledyne Isco instrument. , eluting with Hex/EtOAc 0-100% to give 6-(5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-2- yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (355 mg, 0.577 mmol, 68.8% yield). LCMS retention time 0.99 [TS]. MS (E+) m/z: 615.2 (M+H).

Intermediate 39G: 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-ol

- 37 041852

To a stirred solution of 6-(5-(3-((tert-butyldiphenylsilyl)oxy)azetidin-1-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyrigin-2-yl)-7,8-dimethyl -[1,2,4]triazolo[1,5-a]pyridine (355 mg, 0.577 mmol) in THF (3.8 ml) was added TBAF (0.69 ml, 0.69 mmol). The reaction mixture was stirred at room temperature for 1 hour. Upon completion, the reaction mixture was concentrated directly, taken up in DCM, and purified by silica gel column chromatography using a Teledyne Isco instrument, eluting with 0-100% Hex/EtOAc to give 1-(2 -(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyrigin-5-yl)azetigin- 3-ol (195 mg, 0.518 mmol, 90% yield). LCMS retention time 0.59 [TS]. MS (E ⁺ ) m/z: 377.1 (M+H).

Intermediate 39H: 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-ylmethanesulfonate

MsO.____ ^H A _C u y J\>__<7 \=Ν N ^H H ₃ C CH ₃ (39H)

To a stirred solution of 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine -5-yl)azetudin-3-ol (190 mg, 0.505 mmol) in THF (10 ml) at 25° C. Et ₃ N (176 μl, 1.26 mmol) and MsCl (43.3 μl, 0.555 mmol). The reaction mixture was stirred for 2 h at room temperature and then another aliquot of each of Et ₃ N (176 μl, 1.26 mmol) and MsCl (43.3 μl, 0.555 mmol) was added. After adding these aliquots, the reaction quickly came to an end. The reaction was quenched by adding water and DCM. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl- 1H-pyrrolo[3,2-b]pyridin-5-yl)azetidin-3-ylmethanesulfonate (219 mg, 0.482 mmol, 95% yield. LCMS retention time 0.64 [TS]. MS (E+) m/ z: 455.1 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.55 (br s, 1H), 8.35 (s, 1H), 8.28 (s, 1H), 7.56 (d, J=8.7 Hz, 1H), 6.32 (d, J=8.7 Hz, 1H), 5.42 (tt, J=6.4, 4.5 Hz, 1H), 4.47-4.40 (m , 2H), 4.19 (dd, J=10.3, 4.6 Hz, 2H), 3.08 (s, 3H), 2.87 (spt, J=6.9 Hz, 1H), 2 .56 (s, 3H), 2.12 (s, 3H), 1.39 (d, J=6.8 Hz, 6H).

Example 39.

Solution 1 - (2- (7,8-dimethyl- [ 1,2,4] triazolo [ 1,5-a] pyridin-6-yl) -3 -isopropyl-1 H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-ylmethanesulfonate (22 mg, 0.048 mmol), Et ₃ N (0.034 ml, 0.242 mmol) and morpholine (0.013 ml, 0.145 mmol) in DMF (1 ml) was heated to 80°C with stirring for 2.5 h and the reaction mixture was cooled to room temperature. Another aliquot of morpholine (0.050 ml, 0.574 mmol) was added and the reaction mixture was heated to 100°C for 20 h. Upon completion, the reaction mixture was diluted with DMF and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5-μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 1959% B for 20 minutes, then 4 minutes at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 4-(1-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl- 1H-pyrrolo[3,2-b]pyridin-5-yl)azetidin-3yl)morpholine (5.3 mg, 0.011 mmol, 23% yield). LCMS retention time 0.77 [QC-ACN-TFAXB]. MS (E+) m/z: 446.1 (M+H).

1H NMR (500 MHz, DMSO-d6) δ 10.85 (s, 1H), 8.76 (s, 1H), 8.47 (s, 1H), 7.52 (d, J=8.6 Hz , 1H), 6.28 (d, J=8.7 Hz, 1H), 3.99 (brt, J=7.2 Hz, 2H), 3.73 (brt, J=6.4 Hz, 2H), 3.64-3.54 (m, 4H), 3.27-3.18 (m, 1H), 2.80 (dt, J=13.7, 6.9 Hz, 1H), 2 .58 (s, 3H), 2.35 (br s, 4H), 2.15 (s, 3H), 1.35 (br d, J=6.4 Hz, 6H).

Example 96 6-(3-Isopropyl-5-(4-methylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1,2,4] triazolo[1,5-а]pyridine

6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo[1, 5-a]pyridine, TFA (18.93 mg, 0.0376 mmol) and Et3N (0.1 ml, 0.717 mmol) were mixed in DMF (1 ml) at room temperature. Formaldehyde (37 wt% in water, 25 μl, 0.336 mmol) was added to the reaction vessel followed by sodium triacetoxyborohydride (36 mg, 0.170 mmol). After 1 h, the reaction was quenched by adding water, an aqueous solution of 1.5 M K2HPO4, and DCM. The organic layer is separated

- 38 041852, concentrated, taken up in methanol and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 15% B, 15-55% B for 19 minutes, then 5 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction collection was triggered by UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 2-yl)7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (13.9 mg, 0.033 mmol, 88% yield). LCMS retention time 1.31 min [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 404.3 (M+H). Selected NMR peaks:

¹ H NMR (500 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.71 (s, 1H), 8.45 (s, 1H), 7.59 (d, J=8.9 Hz, 1H), 6.80 (d, J=8.9 Hz, 1H), 2.84-2.73 (m, 1H), 2.59 (br s, 3H), 2.57 (s, 3H), 2.14 (s, 3H), 1.35 (br d, J=6.7 Hz, 6H).

Example 105 1-(4-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo [3,2- b] pyridin-5-yl)piperazin-1-yl)-2-methylpropan-2-ol

6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1 ,5-a]pyridine, TFA (18.93 mg, 0.0376 mmol) and potassium carbonate (27 mg, 0.195 mmol) were mixed in ethanol (1 ml). 2,2-dimethyloxirane (24 mg, 0.333 mmol) was added to the reaction mixture. The reaction vessel was sealed and heated to 80° C. with stirring for 3 hours. Upon completion, the reaction mixture was cooled to room temperature, filtered, concentrated, taken up in DMSO and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 27% B, 27-67% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation to give 1-(4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl- 1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1yl)-2-methylpropan-2-ol (9.9 mg, 0.021 mmol, 57.0% yield). LCMS retention time 1.92 [QCACN-AA-XB]. MS (E ⁺ ) m/z: 461.9 (M+H).

1H NMR (500 MHz, DMSO-d6) δ 10.81 (s, 1H), 8.72 (s, 1H), 8.45 (s, 1H), 7.53 (d, J=8.9 Hz , 1H), 6.72 (d, J=8.9 Hz, 1H), 3.54-3.38 (m, 4H), 2.82-2.72 (m, 1H), 2.66 ( br s, 4H), 2.57 (s, 3H), 2.26 (s, 2H), 2.16 (s, 3H), 1.36 (br d, J=6.7 Hz, 6H), 1.12 (s, 6H).

Example 164 1-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1 H-pyrrolo[3,2b] pyridin-5-yl)-N-(oxetan-3-yl)pyrrolidin-3-αmin

Intermediate 164A: 5-bromo-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl)-1 H-pyrrolo[3,2-b]pyridine

A solution containing tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (3.00 g, 8.84 mmol) and 2-isopropoxy-4,4, 5,5-tetramethyl-1,3,2-dioxaborolane (2.71 ml, 13.27 mmol) in dry THF (30 ml), under nitrogen, cooled in a dry ice/acetone bath at -78° C. and treated with LDA (2M in THF) (5.53 ml, 11.05 mmol). The mixture was stirred at -78°C for 30 minutes and allowed to warm to -30°C for 1 hour and stirred at -30°C for 30 minutes. The reaction was treated with 1.5M aqueous KH2PO4, water and DCM. The layers were separated and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography to give tert-butyl-5-bromo-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3 ,2-b]pyridine-1-carboxylate. LCMS retention time 1.32 min [Method A]. MS m/z: 465.1 (M+H). This material was transferred to a 40 ml tall flask which was sealed and purged with nitrogen gas. The reaction mixture was stirred and heated at 160°C for 1.5 h and 5-bromo-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1Hpyrrolo[3,2-b]pyridine (2.1 g, 5.75 mmol, 65% yield) was obtained as a yellow solid. At

- 39 041852 note: the substance was converted to free boronic acid on LCMS and observed unchanged: LCMS retention time 0.85 min [Method A]. MS m/z: 282.9/284.9 (M+H/(M+2)+H).

Intermediate 164B: tert-Butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3 ,2-b]niridine-1-carboxylate

5-Bromo-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine was added to a 40 ml reaction vessel. (1.500 g, 4.11 mmol), 6-bromo-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (1.14 g, 4.90 mmol), and Xphos precatalyst 2nd generation (0.162 g, 0.205 mmol) and THF (20 ml). The reaction vessel was sealed and nitrogen gas was sparged three times with a pump. Tribasic potassium phosphate (6.16 ml, 12.33 mmol) was added and the reaction mixture was heated to 65° C. for 1 hour. The mixture was diluted with ethyl acetate and washed with water, then brine and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated. To this was added THF (20 ml), DMAP crystal and BOC anhydride (0.954 ml, 4.11 mmol). The reaction mixture was stirred for 18 hours and concentrated in a stream of nitrogen gas. The residue was purified by silica gel chromatography to give tert-butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl -1Hpyrrolo[3,2-b]pyridine-1-carboxylate (2.1 g, 5.75 mmol, 65% yield) as a tan solid. LCMS retention time 1.22 min [Method A]. MS m/z: 486.2 (M+H).

Intermediate 164C: 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)pyrrolidin-3-one

tert-Butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo was added to a vessel with a capacity of 1 dram. [3,2-b]pyridine-1-carboxylate (0.150 g, 0.310 mmol), RuPhos 2nd generation precatalyst (0.024 g, 0.031 mmol), 1,4-dioxa-7-azaspiro[4.4]nonane (0.060 g , 0.464 mmol) and cesium carbonate (0.303 g, 0.929 mmol). The reaction vessel was closed with a Teflon-coated lid and nitrogen gas was sparged twice with a pump. To this, under a nitrogen atmosphere, dioxane (2 ml) was added and the reaction vessel was sparged three times with a pump and left to heat at 100° C. for 18 hours. The reaction mixture was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated and purified by silica gel chromatography to give tert-butyl-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-5 -(1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate as tan oil. LCMS retention time 1.06 min [Method A]. MS m/z: 533.4 (M+H). To this was added TFA (2 ml) and 1 drop of water and the reaction mixture was stirred for 6 h, then concentrated in a stream of nitrogen gas. The residue was diluted with a 1.5M solution of K ₂ HPO ₄ and DCM. The mixture was transferred to a separating funnel and the layers were separated. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H -n-pyrrolo[3,2-b]pyridin-5-yl)pyrrolidin-3-one (50 mg, 0.206 mmol, 42% yield) as a brownish solid. LCMS retention time 0.79 min [Method A]. MS m/z: 389.3 (M+H).

Example 164.

1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)pyrrolidin-3-one (0.025 g, 0.064 mmol), DCM (1 ml) and oxetan-3-amine (0.014 g, 0.193 mmol). The reaction mixture was stirred for 4 h at 25° C., then sodium triacetoxyborohydride (0.041 g, 0.193 mmol) was added. The reaction mixture was stirred for 12 hours at the same temperature. The sample was concentrated, diluted with DMF, filtered and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 24 min, then 5 min hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)3-isopropyl-1H- pyrrolo[3,2-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolidin-3-amine as a racemic mixture (6.7 mg, 0.0150 mmol, 23% yield), m /z (446.4, M+H). Retention time, 1.450 min using LCMS Column: Waters Acquity UPLC BEN C18, 2.1 x 50 mm, 1.7 µm particles; Movable

- 40 041852 phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM.

Example 368 2-((4-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-Spyrrolo[3,2 -b]pyridin-5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide

Intermediate 368A: 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-methylcyclohexanamine

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)cyclohexan-1-one (0.015 g, 0.037 mmol) and methylamine in THF (0.093 ml, 0.187 mmol) were mixed in DMF (1 ml) and AcOH (6.42 μl, 0.112 mmol). To this was added sodium triacetoxyborohydride (0.040 g, 0.187 mmol). The reaction mixture was stirred for 12 hours. The reaction was quenched by adding

1.5 M K ₂ HPO ₄ . Ethyl acetate was added and the mixture was extracted three times (3x50 ml). The organic layer was combined, washed with saturated NaCl solution, dried over anhydrous sodium sulfate, filtered and concentrated to give intermediate 368A. Intermediate 368A was separated into cis/trans isomers according to the conditions below. Alternatively, crude intermediate 368A could be carried forward as a cis/trans mixture for further derivatization and subsequent resolution to give individual derivatized isomers.

Example 367 (Isomer 1) and Example 369 (Isomer 2).

Intermediate 368A was purified and separated into cis and trans isomers by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate;

Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. Fractions containing individual isomers were dried by centrifugal evaporation to obtain the following:

Example 367: Isomer 1: 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b]pyridin-5-yl)-N-methylcyclohexanamine (4.3 mg, 0.00970 mmol, 26% yield), m/z (417.2, M+H). Retention time, 1.204 min [Method C].

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.16-10.99 (m, 1H), 8.79 (s, 1H), 8.48 (s, 1H), 7.62 (d, J =8.2 Hz, 1H), 7.07 (d, J=8.2 Hz, 1H), 3.18 (s, 1H), 2.90 (br s, 2H), 2.71 (br s , 1H), 2.60 (s, 2H), 2.55 (s, 1H), 2.32 (s, 2H), 2.18 (s, 2H), 2.06 (br d, J=14 .3 Hz, 1H), 1.86 (br s, 2H), 1.81-1.72 (m, 1H), 1.65 (br s, 2H), 1.56-1.47 (m, 1H), 1.40 (br d, J=6.7 Hz, 4H), 1.24 (s, 3H), 1.00 (d, J=6.4 Hz, 1H), 0.86 (brt , J=6.7Hz, 1H).

Example 369.

Isomer 2: 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine -5-yl)-N-methylcyclohexanamine (2.4 mg, 0.00576 mmol, 11% yield), m/z (417.2, M+H). Retention time, 1.323 min [Method C].

1H NMR (500 MHz, DMSO-d6) δ 11.19-11.01 (m, 1H), 8.78 (s, 1H), 8.48 (s, 1H), 7.60 (d, J= 8.2 Hz, 1H), 7.01 (br d, J=8.5 Hz, 1H), 2.96-2.83 (m, 1H), 2.72 (br t, J=11.9 Hz, 1H), 2.60 (s, 3H), 2.39 (s, 3H), 2.18 (s, 2H), 2.11-1.92 (m, 4H), 1.83 (br s, 3H), 1.75-1.58 (m, 2H), 1.40 (br d, J=6.7 Hz, 6H), 1.34-1.20 (m, 2H).

Example 368.

Intermediate 368a, 4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo [3,2-b]pyridin-5-yl)-N-methylcyclohexanamine (0.020 g, 0.048 mmol), DCM (1 ml) and DBU (0.025 ml, 0.164 mmol). The material went into solution and 2-chloro-N,N-dimethylacetamide (0.018 g, 0.144 mmol) was added. The reaction mixture was stirred at 25°C for 18 hours. The mixture was then concentrated in a stream of nitrogen gas, diluted 90:10:0.1 acetonitrile:water:TFA, filtered and purified by preparative LC/MS under the following conditions

- 41 041852 lines: Column: XBridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 24 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 2-((4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3- isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide as a single cyclohexyl isomer (0.9 mg, 0.00160 mmol, 3.3 % yield), m/z (502.3, M+H). Retention time, 1.249 min using LCMS Column: Waters Acquity UPLC BEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM.

1H NMR (500 MHz, DMSO-d6) δ 11.23-11.03 (m, 1H), 8.81 (s, 1H), 8.49 (s, 1H), 7.67-7.50 ( m, 1H), 7.00 (d, J=8.3 Hz, 1H), 3.06 (s, 2H), 2.93-2.79 (m, 4H), 2.77-2.66 (m, 2H), 2.60 (s, 4H), 2.23 (s, 3H), 2.18 (s, 3H), 1.99 (br d, J=12.6 Hz, 2H), 1.89 (br s, 2H), 1.66 (br d, J=11.9 Hz, 3H), 1.50-1.35 (m, 9H).

Example 424 and Example 430.

N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin5 -yl) cyclohexyl) -N-methyloxetan-3 -amine

Intermediate 368A, 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-methylcyclohexanamine (0.025 g, 0.060 mmol) and oxetan3-one (8.65 mg, 0.120 mmol) were mixed in DCM (1 ml). To this was added AcOH (0.344 µl, 6.00 µmol) and sodium triacetoxyborohydride (0.038 g, 0.180 mmol). The mixture was stirred for 2 h at 25° C. then quenched by adding 1.5 M K2HPO4 solution. Additional DCM was added and the contents were transferred to a separating funnel and the layers were separated. The combined organic fractions were washed with saturated NaCl solution, dried over anhydrous sodium sulfate, filtered, concentrated and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 24 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation to obtain the following separated products:

Example 424.

Isomer 1: N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1h-pyrrolo[3, 2b]pyridin-5-yl)cyclohexyl)-N-methyloxetαn-3-amine (2.5 mg, 0.00519 mmol, 7% yield), m/z (473.2, M+H). Retention time, 1.384 min [Method C].

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.08 (s, 1H), 8.78 (s, 1H), 8.48 (s, 1H), 7.60 (br d, J=8, 2 Hz, 1H), 7.00 (br d, J=8.2 Hz, 1H), 4.52 (br d, J=6.7 Hz, 4H), 4.04-3.90 (m, 1H), 3.18 (br s, 2H), 2.95-2.84 (m, 1H), 2.68 (br s, 1H), 2.60 (s, 3H), 2.45-2 .32 (m, 1H), 2.18 (s, 6H), 1.97 (brd, J= 11.3 Hz, 2H), 1.75 (br d, J=11.6 Hz, 2H), 1.64 (br d, J=12.8 Hz, 2H), 1.40 (br d, J=6.7 Hz, 8H).

Example 430.

Isomer 2: N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1 H-pyrrolo[3 ,2b]pyridin-5-yl)cyclohexyl)-N-methyloxetαn-3-amine (6.8 mg, 0.0140 mmol, 18% yield), m/z (473.3, M+H). Retention time, 1.537 min [Method C].

1H NMR (500 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.82 (s, 1H), 7.96 (s, 1H), 7.63 (d, J=8.2 Hz , 1H), 7.08 (d, J=8.2 Hz, 1H), 4.48 (quin, J=6.3 Hz, 4H), 3.95-3.81 (m, 1H), 3 .10 (br s, 1H), 2.90 (s, 2H), 2.61 (s, 2H), 2.412.16 (m, 6H), 2.07 (s, 3H), 1.90 (br s, 2H), 1.74 (br s, 3H), 1.45 (br d, J=7.0 Hz, 7H).

Example 438.

6-(( 1 r,4r)-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1 H-pyrrolo[3,2b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptan-2,2-dioxide

O=!

ⁿ zS CH ₃

Intermediate 438A: 2-thia-6-azaspiro[3.3]heptane-2,2-dioxide hydrochloride

IHCi hn ^/ \Os$°

K / o (43 8A)

- 42 041852

Intermediate 438B: 6-tosyl-2-oxa-6-azaspiro[3.3]heptane

Ts-Np^jo \Z\Z (438V)

To a solution of EtOH (500 mL) and 3-bromo-2,2-bis(bromomethyl)propan-1-ol (14.00 g, 43.1 mmol) was added 4-methylbenzenesulfonamide (16.23 g, 95 mmol) at 25° C. and the reaction mixture was heated at reflux for 20 hours. The solvent was removed by evaporation and 100 ml of 8% NaOH solution was added thereto. The suspension was stirred for another 2 h, filtered and the yellow filter cake was washed with water and air dried overnight to give 6-tosyl-2-oxa-6-azaspiro[3.3]heptane (9.05 g, 35.7 mmol, 83% yield) as a light yellow solid. LCMS retention time 0.72 min [Method A]. MS m/z: 254.3 (M+H).

Intermediate 438C: (3-(bromomethyl)-1-tosylazetidin3-yl)methanol

ΌΗ

Br (43 8C)

Ts-N'

A solution of hydrobromic acid in acetic acid (7.16 ml, 43.5 mmol) in 20 ml of ether, drop by drop. The resulting solution was stirred at 0° C. for 2 h, then 1N NaOH was added until pH = 8. The phases were separated and the aqueous phase was extracted with ethyl acetate (3x150 ml). The combined organic fractions were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give (3-(bromomethyl)-1-tosylazetidin-3-yl)methanol (13.5 g, 36.4 mmol, 88% yield) as solid. LCMS retention time 0.80 min [Method A]. MS m/z: 336.2 (M+H)

Intermediate 438D: 3,3-bis(bromomethyl)-1-tosylazetidine

Br

Br (43 8D)

Ts-N.

In a 500 ml round bottom flask, (3-(bromomethyl)-1-tosylazetidin-3-yl) methanol (14.44 g, 38.9 mmol) was dissolved in DCM (250 ml) and carbon tetrabromide (21.93 g, 66 .1 mmol) was added. The solution was cooled in an ice bath and triphenylphosphine (17.34 g, 66.1 mmol) was added in one portion. The resulting mixture was stirred at 0° C. for 2 h, then warmed to 25° C. and stirred for 4 h. Diethyl ether (200 ml) was added and the resulting yellow precipitate was filtered off and discarded. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography to give 3,3-bis(bromomethyl)-1-tosylazetidine (11 g, 27.7 mmol, 71.2% yield) as a white solid. LCMS retention time 0.99 min [Method A]. MS m/z: 398.1 (M+H)

Intermediate 438E: 6-tosyl-2-thia-6-azaspiro[3.3]heptane

Ts-N^X^S ++ (43 8E)

To a solution of 3,3-bis(bromomethyl)-1-tosylazetidine (36.0 g, 91 mmol) in a mixture of acetonitrile (30 ml) and water (5 ml) was added sodium sulfide nonahydrate (43.5 g, 181 mmol) and the reaction mixture was stirred at 50°C for 4 hours. This was concentrated under reduced pressure and diluted with EtOAc (100 ml) and 1N NaOH solution (30 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2x100 ml). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 6-tosyl2-thia-6-azaspiro[3.3]heptane (21.2 g, 79 mmol, 87% yield) as a yellow solid substances. LCMS retention time 0.9 min [Method A]. MS m/z: 270.2 (M+H).

Intermediate 438F: 6-tosyl-2-thia-6-azaspiro[3.3]heptane-2,2-dioxide

-O

Ts-N X

VV+ (438F)

To a 100 ml round bottom flask was added 6-tosyl-2-thia-6-azaspiro[3.3]heptane (3.50 g, 12.99 mmol) and DCM (50 ml). The mixture was cooled to 0°C and mCPBA (8.74 g, 39.0 mmol) was added. The reaction mixture was heated to 25° C. and stirred for 4 hours. The mixture was concentrated, diluted with MeOH (50 ml) and stirred for 30 minutes. The suspension was filtered and the solid washed with more MeOH and air dried to give 6-tosyl-2-thia-6azaspiro[3.3]heptane-2,2-dioxide (3.5 g, 11.61 mmol, 90% yield) as white solid. LCMS retention time 0.72 min [Method A]. MS m/z: 302.2 (M+H)

Intermediate 438A: 2-thia-6-azaspiro[3.3]heptane-2,2-dioxide hydrochloride

HCI hn/'X^s^ ⁰ ++++0 (43 8A)

In a 250 ml round bottom flask, 6-tosyl-2-thia-6-azaspiro[3.3]heptane-2,2 dioxide (0.750 g, 2.489 mmol) was dissolved in MeOH (30 ml). Fresh magnesium (0.907 g, 37.3 mmol) was added and the reaction mixture was heated at 50° C. for 16 hours with vigorous stirring. The reaction mixture was then concentrated almost to dryness and the resulting greyish substance was suspended in diethyl ether (100 ml). Sodium sulfate decahydrate (8.02 g, 24.89 mmol) was added and the mixture was stirred for 1 h, then filtered, dried over anhydrous sodium sulfate and filtered. The white solid was dissolved in DCM (2 ml) and 4M HCl/dioxane (5 ml) was added. White solid lunge

- 43 041852 precipitated and the suspension was left for 30 minutes, then concentrated. Diethyl ether was added and the suspension was stirred for 30 minutes. The solid was filtered off with a frit and washed with diethyl ether to give 2-thia-6-azaspiro[3.3]heptane-2,2-dioxide HCl (0.250 g, 1.361 mmol, 54.7% yield) as a white solid.

Example 438.

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)cyclohexan-1-one (Intermediate 4D, 0.755 g, 1.880 mmol), 2-thia-6-azaspiro[3.3]heptan2,2-dioxide hydrochloride (0.518 g, 2.82 mmol) and DBU (0.567 ml, 3 .76 mmol) was mixed in DCM (6 ml) with acetic acid (1.076 μl, 0.019 mmol). The reaction vessel was closed. The reaction mixture was stirred overnight at 25°C. The volatiles were removed under a stream of nitrogen gas and the residue was diluted with MeOH (1 ml). The reaction mixture was cooled to -78°C and lithium borohydride (2M in THF) (2.82 ml, 5.64 mmol) was added dropwise over 10 minutes. The mixture was stirred at the same temperature for 1 hour and then the reaction was quenched by adding 1.5M aqueous K2HPO4 solution. DCM was added and the mixture was transferred to a separating funnel and the layers were separated. The aqueous layer was extracted with DCM (3x50 ml) and the combined organic fractions were washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated to give 1.4 g of the crude material. The crude material was purified by preparative SFC using the following conditions: Sample preparation: 1.4 g/36 ml MeOH:DCM(4:1), 38.88 mg/ml; Column: Cellulose4 (3x25 cm, 5 µm, #121391); temperature = 35°C; elution rate: 200 ml/min; pressure BPR: 100 bar; mobile phase: _CO2 /MeOH:MeCN (1:1) with 0.1% NH4OH (45/55); separation program: General injection; Injection: 3.5 ml Cycle time: 4.2 min; productivity: 1.9 g/h; Detector wavelength: 220 nm. Product-containing fractions were concentrated and further purified according to the following procedure: Approximately 900 mg of the white solid after SFC purification was dissolved in refluxing ethyl acetate:methanol (4:1). The flask was closed and kept at room temperature for 48 hours. The white solid was filtered off and washed with ethyl acetate followed by MeOH. The solid was dried and collected to give 6-((1g,4g)-(4-(2-(7,8-dimethyl-[1,2,4]triαzolo[1,5a]pyridin-6-yl)-3 -isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane-2,2-dioxide (0.57 g, 1.070 mmol, 56, 9% yield) as a white solid LCMS retention time 0.56 min [Method A] MS m/z: 533.5 (M+H).

Study of reductive amination conditions in obtaining the compound according to example 438:

Reducing agent Solvent Pace. Ratio *cis : trans : **alcohol _NaBH4 DMF 25°C 8:1:0 _NaBH4 DCM 25°C 8:1:0 _NaBH4 MeOH -78°C no reaction LiBH ₄ MeOH -78°C 1:3:1 LiBH ₄ ***DCM/MeOH 25°C /-78°C 1:6:1

approximate ratios were obtained from HPLC data.

**Alcohol ratio refers to the reduction of ketone to alcohol.

***Iminium was preliminarily formed in DCM at 25°C. Reduction was carried out at -78°C in MeOH.

Alternative synthesis of the compound according to Example 438 Intermediate 1A: 2-bromo5-hydrazinylpyridine:

Sodium nitrite solution (19.94 g, 289 mmol) in water (312.5 ml). After 1 h at 0°C, a solution of tin(II) chloride dihydrate (157 g, 694 mmol) in HBr, 47% in water (345 ml) was slowly added at 0°C. Upon completion of this addition, the reaction mixture was left to stir for 1 hour at 0°C. The solid was collected by filtration and dried over 30 minutes with air and then washed with diethyl ether (500 ml). After drying to remove diethyl ether, 2-bromo-5-hydrazinylpyridinedihydrobromide (65 g, 186 mmol, 64.3% yield) was collected as a solid. LCMS retention time 0.68 min [DDS]. MS m/z: 188.1 (M+H).

Intermediate 1B: 5-bromo-3-isopropyl-III-pyrrolo[3,2-b]pyridine

Isovaleraldehyde (23.70 ml, 220 mmol) was added to a solution of 2-bromo-5-hydrazinyl-44 041852 pyridinedihydrobromide (70 g, 200 mmol) in sulfuric acid (70 ml, 1313 mmol) in water (630 ml) and the reaction mixture stirred for 30 min at room temperature. The reaction mixture was heated to 110° C. and stirred for 18 hours. The reaction mixture was diluted with ethyl acetate (2000 ml) and washed with water (200 ml). The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 5-bromo-3-isopropyl1H-pyrrolo[3,2-b]pyridine (200 mmol) as a brown liquid. The material was carried on without further purification. LCMS retention time 1.64 min [DDS]. MS m/z: 241.1 (M+H).

Intermediate 1C: tert-Butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1carboxylate

To a solution of 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine (55 g, 193 mmol) in THF (550 ml) at 0°C was added TEA (42.4 ml, 304 mmol) in for 10 min followed by the addition of DMAP (2.360 g, 19.32 mmol) at 0°C, BOC anhydride 30% in toluene (16.73 g, 23.0 mmol) was added in one portion and the reaction mixture was stirred for 1 h Another aliquot of Boc anhydride (67.3 ml, 290 mmol) was added and the reaction mixture was stirred for 18 hours at 25°C. Upon completion, the reaction mixture was concentrated in vacuo and the crude material was purified by silica gel chromatography to give tert-butyl 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (37 g, 104 mmol , 53.6% yield). LCMS retention time 1.59 min [DDS]. MS m/z: 339.0 (M+H).

1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J=8.5 Hz, 1H), 7.71 (s, 1H), 7.52 (d, J=8.5 Hz, 1H ), 3.27-3.08 (m, 1H), 1.63 (s, 9H), 1.32 (d, J=7.0 Hz, 6H).

Intermediate 4A: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate

Vos (4A)

tert-Butyl-5-bromo-3-isopropyl1H-pyrrolo[3,2-b]pyridine-1-carboxylate (42 g, 124 mmol) and 4,4,5,5-tetramethyl -2-(1,4dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (34.6 g, 130 mmol) in a mixture of tetrahydrofuran (360 ml) and water (42 ml) . To this was added tribasic potassium phosphate (52.6 g, 248 mmol) and 2nd generation X-Phos precatalyst (3.90 g, 4.95 mmol). The biphasic mixture was degassed with nitrogen gas for 10 min and the vessel sealed and stirred at 70° C. for 12 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The mixture was transferred to a separating funnel and the layers were separated. The combined organic fractions were washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. Further purification was carried out by silica gel chromatography to obtain tert-butyl-3isopropyl-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1H-pyrrolo[3,2-b]pyridin-1 -carboxylatea (39.00 g, 98.0 mmol, 79% yield) LCMS retention time 2.53 min [DDS2]. MS m/z: 399.5 (M+H).

1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, J=9.0 Hz, 1H), 8.48 (s, 1H), 8.41 (d, J=9.0 Hz, 1H ), 7.50-7.40 (m, 1H), 7.24-7.14 (m, 1H), 4.82 (s, 2H), 4.75 (s, 2H), 4.20 ( s, 3H), 3.69-3.59 (m, 1H), 3.36-3.29 (m, 1H), 3.173.01 (m, 2H), 2.74 (s, 1H), 2 .48 (s, 1H), 2.25 (d, J=7.0 Hz, 3H), 2.08 (s, 9H).

Intermediate 4B: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1Hpyrrolo[3,2-b]pyridine-1-carboxylate

Vos (4V)

To tert-butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1 H-pyrrolo[3,2-b]pyridine-1 carboxylate (80 g, 201 mmol) in ethyl acetate (800 ml) was added 10 wt.% Pd-C (29.9 g, 28.1 mmol). The flask was placed under vacuum and nitrogen gas was sparged with a pump. After evacuation, the vessel was backfilled with hydrogen gas using a hydrogen balloon and the reaction mixture was allowed to stir for 2-3 hours. The vessel was diluted with ethyl acetate and the contents were filtered through a tightly packed celite. After concentration, the crude material was purified by silica gel chromatography to give tert-butyl-3-isopropyl-5-(1,4dioxaspiro[4.5]decan-8-yl)-1H-pyrrolo[3,2-b]pyridin-1- carboxylate (67.00 g, 167.0 mmol, 83% yield) as a yellow oil. LCMS retention time 1.86 min [DDS2]. MS m/z: 401.4 (M+H).

- 45 041852 ¹ H NMR (400 MHz, DMSO-d6) δ 8.22-8.08 (m, 1H), 7.58-7.52 (m, 1H), 7.21-7.13 (m , 1H), 4.01 (d, J=7.0 Hz, 1H), 3.89-3.86 (m, 2H), 3.84 (s, 2H), 2.25-2.18 ( m, 2H), 2.18-2.10 (m, 2H), 1.89-1.72 (m, 6H), 1.60 (s, 3H), 1.59-1.53 (m, 1H), 1.32 (d, J=7.0 Hz, 4H), 1.23-1.18 (m, 1H), 1.16-1.13 (m, 1H), 1.18-1 .13 (m, 2H), 1.16-1.12 (m, 2H)

Intermediate 4E: tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1 H-pyrrolo[3,2-b]pyridine-1-carboxylate

To a 1 L round bottom flask was added tert-butyl-3-isopropyl-5-(1,4dioxaspiro[4.5]decan-8-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (45 g, 112 mmol) in tetrahydrofuran (675 ml) under nitrogen atmosphere. The reaction mixture was cooled in a dry ice/acetone bath to -78°C. To this was slowly added LDA (112 ml, 225 mmol) and the mixture was stirred at -78° C. for 45-50 minutes. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (34.5 ml, 169 mmol) was added and the reaction mixture was stirred at the same temperature for 1-2 hours. The reaction was quenched with saturated aqueous KH2PO4 solution at the same temperature, then water and ethyl acetate were added and the mixture was transferred to a separating funnel. The layers were separated and the combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was further purified by silica gel chromatography to give tert-butyl-3isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (35.0 g, 66.5 mmol, 60% yield). LCMS retention time 2.05 min [DDS2]. MS m/z: 527.5 (M+H).

Intermediate 4C: 3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-pyrrolo[3,2-b]pyridine

tert-Butyl-3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl )-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (35 g, 66.5 mmol) was added to a 500 ml round bottom flask. The reaction mixture was pumped three times with nitrogen gas and left to heat at 150° C. under nitrogen for 7-8 hours. The reaction mixture was cooled to room temperature, then 200 ml of petroleum ether was added and distilled completely. The solid was washed with ether and dried for 1-2 hours to give 3-isopropyl-5-(1,4dioxaspiro[4.5]decan-8-yl)-2-(4,4,5,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine (23.0 g, 54.0 mmol, 81% yield) as a yellow solid. LCMS retention time 1.47 min [DDS2]. MS m/z: 427.5 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.25 (br s, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.05 (d, J=8.6 Hz, 1H), 4.03 (t, J=2.6 Hz, 4H), 3.83-3.71 (m, 1H), 2.98-2.86 (m, 1H), 2.13-1 .90 (m, 6H), 1.79 (br s, 2H), 1.56 (d, J=6.9 Hz, 6H), 1.39 (s, 12H).

Intermediate 4F: 6-(3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl- [1,2,4]triazolo[1,5-а]pyridine

In a hermetically sealed 1 L flask, 3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-2(4,4,5,5-tetramethyl-1,3,2-dioxaborol 2-yl)-1H-pyrrolo[3,2-b]pyridine (22.5 g, 52.8 mmol), and 6-bromo7,8-dimethyl-[1,2,4]triazolo[1,5- a]pyridine (11.93 g, 52.8 mmol) was dissolved in tetrahydrofuran (225 ml) and water (22.5 ml). Tribasic potassium phosphate (33.6 g, 158 mmol) was added, then the mixture was sparged with nitrogen gas for 5 minutes. 1,1'-Bis(di-tert-butylphosphino)ferrocenepalladium dichloride (1.720 g, 2.64 mmol) was added and the reaction mixture was heated to 70°C for 2-3 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed water, then saturated brine and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated. The residue was further purified by silica gel chromatography to give 6-(3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl) -7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (19.0 g, 42.6 mmol, 81% yield) as an off-white solid.

- 46 041852

LCMS retention time 1.70 min [DDS2]. MS m/z: 446.6 (M+H).

¹ H NMR (300 MHz, DMSO-d6) δ 11.04 (s, 1H), 8.80 (s, 1H), 8.48 (s, 1H), 7.60 (d, J=8.6 Hz, 1H), 7.01 (d, J=8.6 Hz, 1H), 3.91 (t, J=2.8 Hz, 4H), 3.09-3.08 (m, 1H), 2.97-2.74 (m, 2H), 2.60 (s, 3H), 2.18 (s, 3H), 1.97-1.77 (m, 5H), 1.75-1, 58 (m, 2H), 1.41 (d, J=6.9 Hz, 6H)

Intermediate 4D: 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexan-1-one

In a hermetically sealed 1 L flask, 6-(3-isopropyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)1H-pyrrolo[3,2-b]pyridin-2-yl)-7 ,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (36 g, 81 mmol) was mixed in tetrahydrofuran (660 ml). Then HCl (101 ml, 1212 mmol) was added and the mixture was stirred at room temperature for 18 hours. A saturated potassium phosphate solution was added to the reaction mixture to pH = 8 and ethyl acetate (500 mlx2). The mixture was poured into a separating funnel and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was treated with petroleum ether (200 ml) and stirred for 15 minutes. The filter cake was washed with additional petroleum ether and dried to give 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H- pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-one (30.0 g, 74.8 mmol, 92% yield) as an off-white solid. LCMS retention time 1.53 min [DDS2]. MS m/z: 402.4 (M+H).

1H NMR (400 MHz, DMSO-d6) δ 11.12-10.98 (m, 1H), 8.78 (s, 1H), 8.47 (s, 1H), 7.58 (d, J= 8.5 Hz, 1H), 6.98 (d, J=8.5 Hz, 1H), 4.31 (s, 4H), 2.97-2.81 (m, 1H), 2.59 ( s, 2H), 2.17 (s, 3H), 2.13-2.00 (m, 1H), 1.97-1.76 (m, 4H), 1.72-1.53 (m, 2H), 1.39 (d, J=6.5 Hz, 3H), 1.18-0.98 (m, 2H)

Example 438.

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6yl)-3-isopropyl-1H-pyrrolo[3,2 -b]pyridin-5-yl)cyclohexan-1-one (29g, 72.2mmol), 2-thia-6azaspiro[3.3]heptan-2,2-dioxide hydrochloride (19.90g, 108mmol), DCM (435 ml) and acetic acid (0.413 ml, 7.22 mmol). To this was added DBU (32.7 ml, 217 mmol) and the reaction mixture was stirred for 18 hours at room temperature. The volatiles were removed under reduced pressure and the resulting residue was dissolved in methanol (435 ml). The mixture was cooled to -78 T. To this lithium borohydride (54.2 mL, 217 mmol) was added via syringe over 30-40 min. The reaction was stirred at -78°C for 2 hours. The reaction mixture was allowed to warm to room temperature and quenched with saturated potassium phosphate solution. This was diluted with water (150 ml), extracted with ethyl acetate (300 mlx3), dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was taken up in 100 ml IPA and stirred for 30-40 minutes at 50°C. The mixture was cooled to room temperature, filtered, and washed with 20 ml IPA to give an off-white solid containing 90% trans product. Further purification was carried out by the method of preparative SFC using the following conditions: Obtaining a sample: 18 g of the crude material; Column: Lux Cellulose-4 (250x4.6) mM 5 µm; temperature = 30°C; BPR pressure: 100 bar; mobile phase: 0.2%NH ₄ OH in ACN:MeOH (1:1); Injection: 10 ml; Detector wavelength: 220 nm. The product-containing fractions were concentrated and further purified according to the following procedure: This material was then collected (methanol, THF, acetonitrile) and the solid was taken up in 30% aqueous IPA 60 ml (18 ml water: 48 ml IPA), then heated to 70° C for 1 hour. The mixture was brought to room temperature, filtered, washed with IPA (20 ml) and dried over 10-12 hours to give 6-((1r,4r)-(4-(2-(7,8dimethyl-[ 1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-thia-6- azaspiro[3.3]heptane-2,2-dioxide (16.0 g, mmol, 41.4% yield)) as a white solid. LCMS retention time 1.31 min [DDS2]. MS m/z: 533.4 (M+H).

1H NMR (499 MHz, DMSO-d6) δ 11.16-11.02 (m, 1H), 8.80 (s, 1H), 8.48 (s, 1H), 7.59 (d, J= 8.2 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 4.32 (s, 4H), 4.10 (q, J=5.2 Hz, 1H), 3 .17 (d, J=5.2 Hz, 3H), 2.88 (quin, J=6.9 Hz, 1H), 2.74-2.56 (m, 4H), 2.17 (s, 3H), 2.13-1.99 (m, 1H), 1.98-1.88 (m, 2H), 1.84 (br d, J=10.7 Hz, 2H), 1.71- 1.55 (m, 2H), 1.40 (d, J=6.9 Hz, 6H), 1.19-0.97 (m, 2H).

Alternative synthesis of intermediate 438A: 2-thia-6-azaspiro[3.3]heptane-2,2 dioxide hydrochloride

HCI +/+/ o (43 8A)

Intermediate 438B: 6-tosyl-2-oxa-6-azaspiro[3.3]heptane

ITs-N^y o +/%/ (438V)

KOH (276 g, 4926 mmol) was dissolved in ethanol (2.5 L) and to this solution were added 3-bromo-2,2bis(bromomethyl)propan-1-ol (500 g, 1539 mmol) and 4-methylbenzenesulfonamide (316 d, 1847 mmol). Reak

- 47 041852 the mixture was heated to 85°C for 2 days, then cooled to room temperature and to this was added 8% sodium hydroxide solution (2.5 l). The mixture was stirred for 2 h and the white solid was filtered off. The collected solid was stirred in water (1 L) and filtered. This method was repeated 3 times. The solid was then stirred with methanol (1 L), filtered and air dried to give 6-tosyl-2-oxa-6-azaspiro[3.3]heptane (250 g, 984 mmol, 64% yield) as an off-white solid. LCMS retention time 1.16 min [DDS2]. MS m/z: 254.2 (M+H)

Intermediate 438C: (3-(bromomethyl)-1-tosylazetidin-3-yl)methanol

HE

Br (43 8C)

Ts-N

A solution of hydrobromic acid in acetic acid (171 ml, 1042 mmol ) in diethyl ether (1.5 L) dropwise. The resulting solution was stirred at 0° C. for 30 min, warmed to room temperature and stirred for another 2 h. To this was added 10% sodium bicarbonate solution until a pH of 8 was reached. MTBE was added and the phases were separated. The aqueous phase was extracted with ethyl acetate and the combined organic layers were washed with water and then brine, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give (3-(bromomethyl)-1-tosylazetidin-3-yl)methanol (302 g, 904 mmol, 95% yield) as a white solid. LCMS retention time 1.34 min [DDS2]. MS m/z: 334.1/336.1 (M+H).

1H NMR (300 MHz, chloroform-d) δ 7.83-7.64 (m, 2H), 7.47-7.32 (m, 2H), 3.69 (d, J=5.0 Hz, 2H), 3.653.59 (m, 2H), 3.58-3.52 (m, 2H), 3.46 (s, 2H), 2.48 (s, 3H), 1.71 (t, J =5.0 Hz, 1H).

Intermediate 438D: 3,3-bis(bromomethyl)-1-tosylazetidine

Br

Br (43 8D)

Ts-N'

In a 1 L round bottom flask, (3-(bromomethyl)-1-tosylazetidin-3-yl)methanol (54 g, 162 mmol) was dissolved in DCM (540 ml) and carbon tetrabromide (86 g, 259 mmol) was added. The solution was cooled in an ice bath and triphenylphosphine (67.8 g, 259 mmol) was added portionwise. The resulting mixture was heated to 25° C. and stirred for 18 hours. The reaction mixture was concentrated and ethyl acetate was added and the mixture was stirred for 10 minutes, then the white solid was filtered off. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography to give 3,3-bis(bromomethyl)-1-tosylazetidine (50 g, 126 mmol, 78% yield) as a white solid. LCMS retention time 1.87 min [DDS2]. MS m/z: 398.1 (M+H).

1H NMR (400 MHz, chloroform-d) δ 7.81-7.70 (m, 2H), 7.42 (d, J=8.0 Hz, 2H), 3.61 (s, 4H), 3 .55 (s, 4H), 2.50 (s, 3H).

Intermediate 438E: 6-tosyl-2-thia-6-azaspiro[3.3]heptane

Ts-N^^/^S

V X/ (43 8E)

To a solution of 3,3-bis(bromomethyl)-1-tosylazetidine (35 g, 88 mmol) in a mixture of acetonitrile (350 ml) and water (35 ml) was added sodium sulfide nonahydrate (106 g, 441 mmol) and the reaction mixture was stirred at 50°C for 3 hours, the Reaction mixture was concentrated under reduced pressure and diluted with EtOAc and water. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 6-tosyl-2-thia-6-azaspiro[3.3]heptane (21 g, 78 mmol, 88% yield) as a white solid substances. LCMS retention time 1.56 min [DDS2]. MS m/z: 270.1 (M+H).

1H NMR (300 MHz, chloroform-d) δ 7.76-7.68 (m, 2H), 7.37 (d, J=7.9 Hz, 2H), 3.78 (s, 4H), 3 .14 (s, 4H), 2.46 (s, 3H).

Intermediate 438F: 6-tosyl-2-thia-6-azaspiro[3.3]heptane-2,2-dioxide .o Ts-N X x/ \/ O (438F)

To a 4 L flask was added 6-tosyl-2-thia-6-azaspiro[3.3]heptane (175 g, 650 mmol) and DCM (2.75 L). The mixture was cooled to 0°C and mCPBA (320 g, 1299 mmol) was added over 30 min, then the reaction mixture was heated to 25°C and stirred for 3 h. The mixture was diluted with DCM and washed with 5% NaOH solution (3x1 L). The combined organic fractions were washed with water and brine, then dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography to give 6-tosyl-2-thia-6azaspiro[3.3]heptane-2,2-dioxide (135 g, 449 mmol, 69% yield) as a white solid. LCMS retention time 1.16 min [DDS2]. MS m/z: 302.1 (M+H).

1H NMR (300 MHz, chloroform-d) δ 7.79-7.66 (m, 2H), 7.40 (d, J=7.9 Hz, 2H), 4.12 (s, 4H), 3 .97 (s, 4H), 2.47 (s, 3H).

Intermediate 438A: 2-thia-6-azaspiro[3.3]heptane-2,2-dioxide hydrochloride

- 48 041852

HCI HN ^/ y^S$° O (43 8A)

6-tosyl-2-thia-6-azaspiro[3.3]heptane-2,2-dioxide (40 g, 133 mmol) and magnesium (32.3 g, 1327 mmol) were taken up in dry methanol (1600 ml) and heated to 50°C for 18 h. The mixture was cooled to room temperature and stirred for another 18 h. To this were added sodium sulfate decahydrate (428 g, 1327 mmol) and DCM (2 L) and the mixture was stirred for 1 h and filtered. The solid was suspended in DCM (2 L), stirred and the suspension filtered. The combined filtrate was concentrated almost to dryness. Residual water was evaporated and the resulting solid was taken up in DCM (200 ml). The suspension was filtered through sodium sulfate and the filtrate was collected. To this was added 4M HCl in dioxane (25 ml) and the resulting solid was filtered and washed with DCM to give 2-thia-6-azaspiro[3.3]heptane-2,2-dioxide HCl (15.2 g, 65% yield) in form of a white solid.

¹ H NMR (499 MHz, DMSO-d ₆ ) δ 9.47-9.16 (m, 2H), 4.50 (s, 4H), 4.30-4.09 (m, 4H).

Example 491 6-(3-Isopropyl-5-(2-azaspiro[3.5]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1, 2,4]triazolo[1,5-а]pyridine

H ₃ C CH ₃ (491)

Intermediate 491A: 5-chloro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl)-1 H-pyrrolo[3,2-b]pyridine ci

sn ₃

CH ₃ ^c (491 A) tert-Butyl-5-chloro-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate was prepared according to the general procedure described above for intermediate 1C. A solution containing tert-butyl-5-chloro-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (3.00 g, 10.18 mmol) and 2isopropoxy-4,4,5, 5-tetramethyl-1,3,2-dioxaborolane (3.11 ml, 15.27 mmol) in dry THF (25 ml), under nitrogen atmosphere, cooled in a dry ice/acetone bath at -78°C and treated with LDA ( 2M in THF) (6.36 ml, 12.72 mmol). The mixture was stirred at -78°C for 30 minutes and allowed to warm to -30°C for 1 hour and stirred at -30°C for 30 minutes. The reaction mixture was treated with 1.5 M aqueous KH ₂ PO ₄ , water and DCM. The organic layer was collected, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography to give tert-butyl-5-chloro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrrolo[ 3,2-b]pyridine-1-carboxylate. LCMS retention time 1.31 min [Method A]. MS m/z: 420.8/422.3 (M+H). This material was transferred to a 40 ml vessel and purged with nitrogen gas. The mixture was sealed and heated at 160°C for 1.5 h to give 5-chloro-3isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H -pyrrolo[3,2-b]pyridine (2.4 g, 7.49 mmol, 74% yield) as a tan solid. LCMS retention time 1.16 min [Method A]. MS m/z: 321.1/323.1 (M+H).

Intermediate 491B: tert-Butyl-5-chloro-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin6-yl)-3-isopropyl-1H-pyrrolo[ 3,2-b]pyridine-1-carboxylate

Nose

Cl

Vos H ₃ C CH ₃ (491V)

5-Chloro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine was added to a 40 ml reaction vessel. (1.000 g, 3.12 mmol), 1,1'-bis(di-tert-butylphosphino)ferrocenepalladium dichloride (0.041 g, 0.062 mmol) 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1 ,5a]pyridine (0.705 g, 3.12 mmol) and THF (40 ml). The reaction was sealed and nitrogen gas was sparged three times with a pump. To this was added aqueous tribasic potassium phosphate (2M, 4.68 ml, 9.36 mmol) and the reaction mixture was heated to 65°C for 1 h. The mixture was diluted with ethyl acetate and washed with water, then brine and dried over anhydrous sodium sulfate . The solids were filtered off and the filtrate was concentrated. The crude material was purified by silica gel chromatography to give 6-(5-chloro-3-isopropyl-III-pyrrolo[3,2b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[ 1,5-a]pyridine as a tan/brown solid. To this was added THF (100 ml) and BOC anhydride (0.724 ml, 3.12 mmol). A DMAP crystal was added and the reaction mixture was stoppered and stirred for 18 h at 25° C., then

- 49 041852 concentrated under reduced pressure. DCM and water were added to this residue and the mixture was transferred to a separating funnel. The layers were separated and the combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 5a: tert-butyl-5-chloro-2-(7,8-dimethyl-[1,2,4]triazolo[ 1,5-a]pyridin-6-yl)-3isopropyl-1H-n-pyrrolo[3,2-b]pyridine-1-carboxylate (0.9 g, 2.046 mmol, 65% yield). LCMS retention time 1.17 min [Method A]. MS m/z: 440.1 (M+H)

Example 491.

To a solution of tert-butyl-5-chloro-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2 -b]pyridine-1-carboxylate (0.20 g, 0.455 mmol), tert-butyl-7-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-2-azaspiro[ 3.5] non-6-en-2-carboxylate (0.119 g, 0.341 mmol), and tribasic potassium phosphate (0.682 ml, 1.364 mmol) in THF (300 ml) were added PdCl ₂ (dppf)-CH ₂ Cl ₂ adduct (9 .28 mg, 0.011 mmol) and the biphasic mixture was degassed with nitrogen for 10 min. The reaction vessel was hermetically sealed. The reaction mixture was stirred at 90°C for 2 h, then diluted with ethyl acetate and washed with saturated sodium chloride solution. The organic layer was dried with magnesium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography to give tert-butyl-5-(2-(tert-butoxycarbonyl)-2-azaspiro[3.5]nonan-7-yl)-2-(7,8-dimethyl[1,2, 4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate.

LCMS retention time 1.114 min [Method A]. MS m/z: 629.5 (M+H). To 0.2 g of this intermediate, ethyl acetate (15 mL) and 10% Pd/C (0.015 g, 0.014 mmol) were added in a Parr apparatus under nitrogen. The vessel was placed on a Parr apparatus and nitrogen gas was sparged three times with a pump. The vial was then pressurized to 50 psi with hydrogen gas and shaken for 1 hour. The vial was diluted with 100 ml of methanol and the contents filtered through tightly packed celite. After concentration of 0.020 g of the crude material, the residue was purified by preparative LC-MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 24 min, then 5 min hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(2-azaspiro[3.5]nonan-7-yl)-1H-pyrrolo[3,2b]pyridin-2-yl)-7 ,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (6.0 mg, 0.0140 mmol); m/z (429.4, M+H). Retention time, 1.262 min using LCMS Column: Waters Acquity UPLC BEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM.

¹ H NMR (500 MHz, DMSO-d6) δ 11.12-11.08 (m, 1H), 8.77 (s, 1H), 8.48 (s, 1H), 7.61 (d, J =8.2 Hz, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.61-3.39 (m, 1H), 2.89 (br t, J=6.9 Hz, 1H), 2.70 (br s, 1H), 2.59 (s, 3H), 2.55 (s, 5H), 2.17 (s, 3H), 2.14-2.03 ( m, 2H), 1.91-1.75 (m, 6H), 1.68-1.50 (m, 4H), 1.39 (br d, J=6.7 Hz, 6H).

Example 590 6-(3-Isopropyl-5-((1-methylpiperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2yl)-8-methoxy-[1,2,4 ]triazolo[1,5-а]pyridine

6-(3-isopropyl-5(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2 ,4]triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol), DMF (1 ml), and DIEA (4.04 μl, 0.023 mmol). Formaldehyde (37% in water) (8.61 µl, 0.116 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes. Acetic acid (1.324 µl, 0.023 mmol) and sodium triacetoxyborohydride (4.90 mg, 0.023 mmol) were added to the reaction mixture. The reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0100% B for 19 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 14-39% B over 25 min, then 2 min hold at 39% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters XBridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%V - 100%V for 3 min, then 0.75 min hold at

- 50 041852

100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection Results 1: Observed Weight:

435.39 (M+H); Retention time: 1.17 min. Injection conditions 2: Column: Waters XBridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B;

Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 435.43 (M+H); Retention time: 0.94 min. 6-(3-Isopropyl-5-((1-methylpiperidin-4-yl)methoxy)1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4] was isolated triαzolo[1,5-a]pyridine (5.9 mg, 0.013 mmol, 56.9% yield).

¹ H NMR (500 MHz, DMSO-d6) δ 11.30-11.25 (m, 1H), 8.51 (s, 1H), 8.46 (s, 1H), 7.69 (d, J =8.9 Hz, 1H), 7.12 (s, 1H), 6.58 (d, J=8.9 Hz, 1H), 4.20-4.14 (m, 2H), 4.04 (s, 1H), 3.63-3.51 (m, 1H), 3.30-3.20 (m, 2H), 3.03 (brd, J=11.6 Hz, 2H), 2, 37-2.28 (m, 4H), 1.81 (brd, J=11.0 Hz, 4H), 1.52-1.46 (m, 6H), 1.45-1.35 (m, 2H).

Example 591 6-(3-Isopropyl-5-((1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)methoxy)-Spyrrolo[3,2-b]pyridin-2-yl) -8-methoxy-[1,2,4]triazolo[1,5-а]pyridine

In a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol) DMF (0.5 ml), DIEA (0.012 ml, 0.069 mmol) and dihydro-2H-pyran-4(3H)-one ( 2.316 mg, 0.023 mmol). The reaction mixture was stirred for 5 minutes. Sodium triacetoxyborohydride (14.71 mg, 0.069 mmol) and acetic acid (1.324 μl, 0.023 mmol) were added and the reaction mixture was stirred for 6 h. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM , 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B for 19 minutes, then 5 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 505.53 (M+H);

Retention time: 1.23 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 505.52 (M+H); Retention time: 1 min.

6-(3-Isopropyl-5-((1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl) was isolated -8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (10.8 mg, 0.021 mmol, 89% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.59 (s, 1H), 8.50 (s, 1H), 7.67 (d, J=8.9 Hz , 1H), 7.17 (s, 1H), 6.57 (d, J=8.5 Hz, 1H), 4.17 (br d, J=6.4 Hz, 2H), 4.07 ( s, 3H), 3.89-3.82 (m, 2H), 3.29-3.22 (m, 2H), 2.91 (br d, J=10.4 Hz, 2H), 2, 09 (br t, J=11.1 Hz, 2H), 1.90 (s, 2H), 1.82-1.71 (m, 3H), 1.66 (br d, J=12.5 Hz , 2H), 1.54-1.50 (m, 6H), 1.41 (qd, J=12.0, 4.7 Hz, 2H), 1.33-1.21 (m, 2H).

Example 592 6-(3-Isopropyl-5-((1-isopropylazetidin-3-yl)methoxy)-1 H-pyrrolo[3,2-b]pyridin-2yl)-8-methoxy-[1.2, 4]triazolo[1,5-а]pyridine

In a 20 ml scintillation vial containing 6-(5-(azetidin-3-ylmethoxy)-3isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4 ]triazolo[1,5-a]pyridine (15 mg, 0.038 mmol) was added with DMF (1 ml) and propan-2-one (2.220 mg, 0.038 mmol). The reaction mixture was stirred at room temperature for 10 minutes. Acetic acid (2.188 μl, 0.038 mmol) and sodium triacetoxyborohydride (24.30 mg, 0.115 mmol) were added and the reaction mixture was stirred at room temperature overnight. A drop of water was added and the crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19 x 200 mM, 5 μm particles;

- 51 041852

Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B for 22 minutes, then 4 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B-100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 435.24 (M+H); Retention time: 1.27 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 435.21 (M+H); Retention time: 1.08 min. 6(3-isopropyl-5-((1-isopropylazetidin-3-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy[1,2,4]triazolo was isolated [1,5-a]pyridine (5.4 mg, 0.012 mmol, 31.5% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.57 (s, 1H), 8.50 (s, 1H), 7.68 (d, J=8.9 Hz , 1H), 7.17 (s, 1H), 6.57 (d, J=8.5 Hz, 1H), 4.41 (br d, J=6.7 Hz, 2H), 4.06 ( s, 3H), 3.33-3.19 (m, 3H), 2.98 (br t, J=6.7 Hz, 2H), 2.81-2.70 (m, 1H), 2, 36-2.25 (m, 1H), 1.56-1.48 (m, 6H), 0.86-0.81 (m, 6H).

Example 593 6-(3-Isopropyl-5-((1-propylpiperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)8-methoxy-[1,2, 4]triazolo[1,5-а]pyridine

Into a 1 dram vessel containing 6-(3-isopropyl-5-(piperidin-4-yloxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.024 mmol) DMF (500 μl), DIEA (12.39 μl, 0.071 mmol) and propionaldehyde (4.12 mg, 0.071 mmol) were added. The reaction mixture was stirred at room temperature for 5 minutes. Acetic acid (1.353 µl, 0.024 mmol) and sodium triacetoxyborohydride (15.03 mg, 0.071 mmol) were added to the reaction mixture. The reaction mixture was stirred for 1 hour. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 15-55% B over 19 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 448.94 (M+H); Retention time: 1.3 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 449.05 (M+H); Retention time: 1.05 min. 6-(3isopropyl-5-((1-propylpiperidin-4-yl)oxy)-1 H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (8.6 mg, 0.019 mmol, 79% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.58 (s, 1H), 8.51 (s, 1H), 7.67 (d, J=8.5 Hz , 1H), 7.18 (s, 1H), 6.55 (d, J=8.9 Hz, 1H), 5.05-4.93 (m, 1H), 4.08 (s, 3H) , 3.31-3.19 (m, 1H), 2.77 (br s, 2H), 2.27 (br t, J=7.3 Hz, 2H), 2.19 (br t, J= 9.8 Hz, 2H), 2.12-2.03 (m, 2H), 1.75-1.64 (m, 2H), 1.51 (s, 6H), 1.48-1.41 (m, 2H), 0.86 (t, J=7.2 Hz, 3H).

Example 594 6-(3-Isopropyl-5-((1-methylpiperidin-4-yl)oxy)-1H-n-pyrrolo[3,2-b]pyridin-2-yl)-8methyl-[ 1,2,4 ]triazolo[1,5-а]pyridine

Into a 1 dram vessel containing 6-(3-isopropyl-5-(piperidin-4-yloxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2, 4]triazolo[1,5-a]pyridine, 2 TFA (27 mg, 0.044 mmol) DMF (0.5 ml), DIEA (0.023 ml, 0.131 mmol), and formaldehyde (0.016 ml, 0.218 mmol) were added. The reaction mixture was stirred for 5 minutes. Acetic acid (2.499 µl, 0.044 mmol) and sodium triacetoxyborohydride

- 52 041852 (27.8 mg, 0.131 mmol) was added. The reaction mixture was stirred for 10 minutes. The material was dissolved in DMF (2 ml) and purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 4 minutes hold at 100% B;

Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 405.36 (M+H); Retention time: 1.01 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 405.37 (M+H); Retention time: 1.25 min. 6-(3isopropyl-5-((1-methylpiperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo was isolated [1,5-a]pyridine (0.8 mg, 1.879 µmol, 4.3% yield).

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.33 (br s, 1H), 8.85 (s, 1H), 8.54 (s, 1H), 7.67-7.61 (m, 2H), 6.53 (d, J=8.7 Hz, 1H), 4.99 (br s, 1H), 3.33-3.12 (m, 2H), 2.26-2.11 ( m, 5H), 2.06 (br d, J=10.9 Hz, 2H), 1.76 (s, 4H), 1.74-1.65 (m, 2H), 1.54-1, 44(m, 6H).

Example 595 6-(3-Isopropyl-5-((1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl)oxy)-1H-pyrrolo[3,2b]pyridin-2-yl) -8-methoxy-[1,2,4]triazolo[1,5-а]pyridine

Into a 1 dram vessel containing 6-(5-(azetidin-3-yloxy)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (10 mg, 0.026 mmol) DMF (1 ml), DIEA (0.014 ml, 0.079 mmol) and tetrahydro-4H-pyran-4-one (2.65 mg, 0.026 mmol) were added . The reaction mixture was stirred for 5 minutes. Acetic acid (1.513 µl, 0.026 mmol) and sodium triacetoxyborohydride (28.0 mg, 0.132 mmol) were added and the reaction mixture was stirred for 1 h. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM , 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 22 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 5-45% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 463.0 (M+H); Retention time: 1.45 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 463.4 (M+H); Retention time: 1.09 min. 6(3-isopropyl-5-((1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)- 8-methoxy-[1,2,4]triazolo[1,5-a]pyridine, 2 TFA (2.8 mg, 3.95 µmol, 15% yield).

1H NMR (500 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.57 (s, 1H), 8.47 (d, J=8.9 Hz, 1H), 7.21 (d , J=8.9 Hz, 1H), 7.16(s, 1H), 5.71 (br s, 1H), 5.41 (br t, J=10.3 Hz, 1H), 5.10 -5.02(m, 1H), 4.13-4.04(m, 3H), 3.96-3.88(m, 2H), 3.63-3.52(m, 1H), 3 .65-3.52 (m, 2H), 2.00-1.88 (m, 2H), 1.60-1.47 (m, 2H), 1.32 (dd, J=17,l, 7.1Hz, 6H).

Example 596 6-(3-Isopropyl-5-((1-methylazetidin-3-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy-[1,2,4 ]triazolo[1,5-а]pyridine

- 53 041852

In a vessel with a capacity of 1 dram containing 6-(5-(azetidin-3-yloxy)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (10 mg, 0.026 mmol) DMF (1 ml), formaldehyde (9.84 μl, 0.132 mmol) and DIEA (0.014 ml, 0.079 mmol) were added. The reaction mixture was stirred at room temperature for 30 minutes and acetic acid (1.513 μl, 0.026 mmol) and sodium triacetoxyborohydride (28.0 mg, 0.132 mmol) were added to the reaction mixture. After 10 min a drop of water was added and the crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 1050% B for 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B-100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 393.08 (M+H); Retention time: 1.01 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 393.22 (M+H); Retention time: 1 min. 6-(3-isopropyl-5-((1-methylazetidin-3-yl)oxy)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine (1.6 mg, 3.95 µmol, 15% yield).

¹ H NMR (500 MHz, DMSO-d6) δ 11.38 (br s, 1H), 8.60 (s, 1H), 8.55-8.49 (m, 1H), 7.74-7, 67 (m, 1H), 7.19 (s, 1H), 6.60 (br d, J=8.5 Hz, 1H), 5.16-5.07 (m, 1H), 4.09 ( s, 3H), 3.82 (brt, J=6.1 Hz, 1H), 3.32-3.19 (m, 1H), 3.19-3.11 (m, 1H), 3.05 -2.93 (m, 2H), 2.32 (s, 3H), 1.55-1.48 (m, 6H).

Example 597 2b] pyridin-5-yl)oxy)methyl)piperidin-1-yl)-2-methylpropan-2-ol

but (597)

In a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (25 mg, 0.039 mmol), MeOH (500 µl), potassium carbonate (10.65 mg, 0.077 mmol), and 2,2-dimethyloxirane (8.34 mg , 0.116 mmol). The vessel was sealed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered and concentrated in vacuo. The solid material was dissolved in DMF and the crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mm, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 15-55% B over 19 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Conditions: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 493.58 (M+H); Retention time: 1.28 min. 1-(4-(((3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)oxy)methyl)piperidin-1-yl)-2-methylpropan-2-ol (11 mg, 0.022 mmol, 57.9% yield).

¹ H NMR (500 MHz, DMSO-d6) δ 11.33-11.26 (m, 1H), 8.55 (s, 1H), 8.48 (s, 1H), 7.68 (d, J =8.5 Hz, 1H), 7.15 (s, 1H), 6.57 (d, J=8.5 Hz, 1H), 4.17 (br d, J=6.l Hz, 2H) , 4.08-4.03 (m, 3H), 3.29-3.18 (m, 1H), 2.99 (br d, J=11.0 Hz, 2H), 2.72 (s, 2H), 2.26 (s, 2H), 2.17 (brt, J=11.3 Hz, 2H), 1.69 (br d, J=12.2 Hz, 2H), 1.54-1 .47 (m, 6H), 1.43-1.29 (m, 2H), 1.10-1.04 (m, 6H).

Example 598 6-(3-Isopropyl-5-((1-isopropylpiperidin-4-yl)methoxy)-1 H-pyrrolo[3,2-Cpyridin2-yl)-8-methoxy-[1,2,4] triazolo[1,5-а]pyridine

- 54 041852

6-(3-isopropyl-5(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2 ,4]triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol), DMF (1 ml), and DIEA (4.04 μl, 0.023 mmol). Acetone (8.49 μl, 0.116 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes. Acetic acid (1.324 μl, 0.023 mmol) and sodium triacetoxyborohydride (4.90 mg, 0.023 mmol) were added. The reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 5-50% B for 20 minutes, then 5 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B-100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 463.26 (M+H); Retention time: 1.46 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 462.98 (M+H); Retention time: 1.22 min. 6-(3-isopropyl-5-((1-isopropylpiperidin-4-yl)methoxy)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine, 2 TFA (11.1 mg, 0.016 mmol, 67.4% yield).

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.35 (s, 1H), 8.56 (s, 1H), 8.53-8.47 (m, 1H), 7.70 (d, J=8.5 Hz, 1H), 7.30 (s, 1H), 6.59 (d, J=8.5 Hz, 1H), 4.22 (d, J=5.8 Hz, 2H) , 4.06 (s, 3H), 3.45-3.36 (m, 2H), 3.28-3.19 (m, 1H), 3.02-2.84 (m, 3H), 2 .14-2.05 (m, 1H), 2.02 (br d, J=15.3 Hz, 2H), 1.66-1.54 (m, 2H), 1.51 (d, J= 7.0 Hz, 6H), 1.24 (d, J=6.4 Hz, 6H).

Example 600 6-(3-Isopropyl-5-((1-methylpiperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy-[1,2,4 ]triazolo[1,5-а]pyridine

To a 20 ml vial containing tert-butyl-5-((1-(tert-butoxycarbonyl)piperidin-4yl)oxy)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1 ,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (60 mg, 0.099 mmol), DCM (500 μl) and TFA (500 μl) were added. The reaction mixture was stirred at rt. within 3 hours the Reaction mixture was concentrated in a stream of nitrogen and dried in vacuum. DMF (1 ml), DIEA (17.27 µl, 0.099 mmol), formaldehyde (37% in water) (36.8 µl, 0.494 mmol), and acetic acid (5.66 µl, 0.099 mmol) were added to the reaction mixture. . The reaction mixture was stirred for 5 minutes. Sodium triacetoxyborohydride (62.9 mg, 0.297 mmol) was added and the reaction mixture was stirred at RT. within 1 h. A drop of water was added and the crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mm, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Acquity UPLC VEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min; Detection: UV at 220 nm. Injection conditions 2: Column: Waters Acquity UPLC VEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min; Detection: UV at 220 nm. 6-(3-isopropyl-5-((1-methylpiperidin-4yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine (25.9 mg, 0.060

- 55041852 mmol, 61.0% yield). LC/MS time retention= 0.971 (m+1=421) [QC-ACN-TFA-XB].

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.30 (s, 1H), 8.58 (s, 1H), 8.51 (s, 1H), 7.67 (d, J=8.9 Hz, 1H), 7.18 (s, 1H), 6.55 (d, J=8.5 Hz, 1H), 5.00 (br s, 1H), 4.08 (s, 3H), 3 .32-3.11 (m, 1H), 2.70 (br s, 1H), 2.57-2.54 (m, 1H), 2.20 (s, 3H), 2.07 (br s , 2H), 1.91 (br s, 2H), 1.72 (br d, J=9.8 Hz, 2H), 1.52 (br d, J=6.7 Hz, 6H).

Example 601 6-(3-Isopropyl-5-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a] pyridine

Intermediate 601A: tert-butyl-5-chloro-3-isopropyl-1 H-pyrrolo[3,2-b]pyridine-1 carboxylate -

To a 100 ml round bottom flask cooled to 0°C was added 5-chloro-3-isopropyl-Spyrrolo[3,2-b]pyridine (1.33 g) [substance synthesized analogously to that above to obtain intermediate 1B] THF (10 ml), TEA (1.428 ml, 10.25 mmol), and DMAP (0.083 g, 0.683 mmol). BOC anhydride (1.745 ml, 7.52 mmol) was added slowly over 10 minutes and the reaction mixture was stirred for 30 minutes. The reaction was concentrated in vacuo to give an oil. The oil was purified by column chromatography using a Teledyne Isco instrument (24 g silica gel, 100% Hexanes-80% EtOAc/Hexanes). Similar fractions were combined and concentrated in vacuo to give a light yellow oil, t-butyl 5-chloro-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (2.06 g). LC/MS time hold=1.20 min. (m+1 =295) [B1].

¹ H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J=8.7 Hz, 1H), 7.71 (s, 1H), 7.38 (d, J=8.7 Hz, 1H), 3.22-3.08 (m, 1H), 1.62 (s, 9H), 1.31 (d, J=6.8 Hz, 6H).

Intermediate 601B: tert-Butyl 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

A 1 dram vial containing tert-butyl-4-hydroxypiperidine-1-carboxylate (137 mg, 0.678 mmol), cesium carbonate (166 mg, 0.509 mmol), toluene (1 ml), and methanesulfonato(2-(di-tert-butylphosphino )-3-methoxy-6-methyl-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) ( 8.53 mg, 10.18 µmol) under nitrogen was heated to 90° C. for 3 minutes. tert-Butyl-5chloro-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (100 mg, 0.339 mmol) was added to the reaction mixture and heated overnight at 90°C. The temperature was raised to 110° C. over 4 hours. The reaction was filtered through a pad of celite and concentrated in vacuo. The resulting oil was purified by column chromatography using a Teledyne Isco instrument (24 g silica gel, 100% Hexane-100% EtOAc). Similar fractions were combined and concentrated in vacuo to give tert-butyl-5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1- carboxylate (37 mg, 0.081 mmol, 24% yield). LC/MS time hold=1.33 min. (m+1 =460) [B1].

Intermediate 601C: tert-Butyl-5-((1-(tert-butoxycarbonyl)azetidin-3-yl)methoxy)3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

1 dram jar containing tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (60.7 mg, 0.324 mmol), cesium carbonate (158 mg, 0.486 mmol), toluene (2 ml), and methanesulfonate (2 -(di-tert-butylphosphino)-3-methoxy-6-methyl-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II) (8.16 mg, 9.73 µmol) under nitrogen, heated to 105°C for 5 min. tert-Butyl-5bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (110 mg, 0.324 mmol) in toluene (1 ml) was added to the reaction mixture and heated overnight at 105° WITH. The reaction was diluted with water (10 ml) and extracted with EtOAc (3x10 ml). The organic layers were combined and passed through a pad of celite and concentrated in vacuo to give a clear oil. Purified by column chromatography using a Teledyne Isco instrument (24 g silica gel, 100% Hexanes-50% EtOAc/hexanes). Similar fractions were combined and concentrated in vacuo to give tert-butyl-5

- 56 041852 ((1 - (tert-butoxycarbonyl) azetidin-3 -yl) methoxy) -3 -isopropyl-1 H-pyrrolo [3,2-b] pyridine-1 -carboxylate (107 mg, 0.228 mmol, 70, 4% yield). LC/MS time hold=1.26 min. (m+1 =446) [B1].

1H NMR (400 MHz, CHLOROFORM-d) δ 8.27-8.09 (m, 1H), 7.44 (br. s., 1H), 6.64 (d, J=8.9 Hz, 1H ), 4.51 (d, J=6.7 Hz, 2H), 4.08 (t, J=8.6 Hz, 2H), 3.85 (dd, J=8.7, 5.4 Hz , 2H), 3.21 (dt, J=13.2, 6.7 Hz, 1H), 3.02 (dquin, J=13.6, 6.8 Hz, 1H), 1.67 (s, 9H), 1.46 (s, 9H), 1.38 (d, J=7.0 Hz, 6H).

Intermediate 601D: tert-Butyl 5-((1-(tert-butoxycarbonyl)piperidin-4yl)methoxy)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Vos (601D)

1 dram jar containing tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (337 mg, 1.565 mmol), cesium carbonate (765 mg, 2.348 mmol), toluene (5 ml), and methanesulfonate (2-( di-tert-butylphosphino)-3-methoxy-6-methyl-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium( P) (39.4 mg, 0.047 mmol) under nitrogen, heated to 105°C for 5 min. tert-Butyl-5bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (531 mg, 1.565 mmol) in toluene (1 ml) was added to the reaction mixture and heated for 3 h at 105 °C. The reaction was diluted with water (10 ml) and extracted with EtOAc (3x10 ml). The organic layers were combined and passed through a pad of celite and concentrated in vacuo to give a clear oil. Purified by column chromatography using a Teledyne Isco instrument (24 g silica gel, 100% Hexanes-50% EtOAc/hexanes). Similar fractions were combined and concentrated in vacuo to give tert-butyl 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)methoxy)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (408 mg, 0.861 mmol, 55.0% yield). LC/MS time hold=1.33 min (m+1= 474) [B1].

¹ H NMR (400 MHz, CHLOROFORM-d) δ 8.26-8.00 (m, 1H), 7.50-7.33 (m, 1H), 6.67-6.57 (m, 1H) , 4.24 (d, J=6.5 Hz, 2H), 4.21-4.02 (m, 2H), 3.26-3.14 (m, 1H), 2.64 (br d, J=7.5 Hz, 2H), 2.10-1.92 (m, 1H), 1.87-1.79 (m, 2H), 1.74-1.61 (m, 9H), 1 .49-1.44 (m, 9H), 1.38 (d, J=6.8 Hz, 6H), 1.33-1.22 (m, 2H).

Intermediate 601E: tert-Butyl-3-isopropyl-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1carboxylate

H ₃ C ³ y-CHz „ .0. /N. 7 ⁿ c ^s

Vos (601E)

A 1 dram vessel containing methanol (0.918 ml, 22.70 mmol), cesium carbonate (1109 mg, 3.40 mmol), toluene (5 ml), and methanesulfonato (2-(di-tert-butylphosphino)-3- methoxy-6-methyl-2',4',6'triisopropyl-1,1'-biphenyl)(2'-αmino-1,1'-biphenyl-2-yl)palladium(II) (38.1 mg, 0.045 mmol) under nitrogen atmosphere, heated to 105° C. for 5 minutes. tert-Butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2b]pyridine-1-carboxylate (770 mg, 2.270 mmol) in toluene was added to the reaction mixture and heated at 105°C. After 30 min the reaction mixture was diluted with water (10 ml) and was extracted with the addition of EtOAc (3x10 ml). The organic layers were combined and passed through a pad of celite and concentrated in vacuo to give a clear oil. Purified by column chromatography using a Teledyne Isco instrument (24 g silica gel, 100% Hexanes-50% EtOAc/hexanes). Similar fractions were combined and concentrated in vacuo to give tert-butyl-3-isopropyl-5-methoxy-1H-pyrrolo[3,2b]pyridine-1-carboxylate (48 mg, 0.165 mmol, 7.3% yield. LC/MS hold time=1.22 min (m+1=291) [B1].

Intermediate 601F: tert-Butyl-3-isopropyl-5-methoxy-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b] pyridine-1-carboxylate

To a nitrogen-purged 20 ml septum vial was added tert-butyl 3-isopropyl-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (70 mg, 0.241 mmol), THF (2 ml) and 2isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.054 ml, 0.265 mmol). The vial was cooled to -40° C. in a dry ice/NMP bath. LDA (0.301 ml, 0.603 mmol) was added dropwise over 15 minutes. The reaction was heated to 0°C. The reaction was cooled to -40°C and quenched with saturated KHSO4. The reaction was warmed to room temperature, diluted with water (10 ml) and extracted with EtOAc (3x10 ml). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to give a clear oil. The clear oil was purified by column chromatography using a Teledyne Isco instrument (12 g silica gel, 100% Hexanes-50% EtOAc/Hexanes). Similar fractions were combined and concentrated in vacuo to give tert-butyl-3-isopropyl-5-methoxy-2-(4,4,5,5

- 57 041852 tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (50 mg, 0.120 mmol, 49.8% yield). LC/MS time hold=1.34 min. (m+1 =417) [B1].

Example 601.

tert-Butyl-3-isopropyl-5methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3 ,2-b]pyridine-1-carboxylate (50 mg, 0.120 mmol), 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (27.4 mg, 0.120 mmol ), Xphos 2nd generation precatalyst (4.72 mg, 6.00 µmol) and THF (1 ml). The reaction was evacuated and purged with nitrogen several times. Aqueous tripotassium phosphate (3 M, 0.040 ml, 0.120 mmol) was added and the vessel was evacuated and purged with nitrogen several times. The reaction was heated at 65° C. for 1 hour. The reaction mixture was diluted with brine (1 ml) and extracted with EtOAc (3x2 ml). The organic layers were combined, dried over sodium sulfate, filtered, and dried in vacuo. The resulting oil was purified by column chromatography using a Teledyne Isco instrument (12 g silica gel, 100% hexanes-100% EtOAc). Similar fractions were pooled and concentrated in vacuo. The resulting oil was treated with 1:1 TFA:DCM for 30 min, then concentrated in a stream of nitrogen. The resulting oil was neutralized with sodium bicarbonate and extracted with EtOAc. The organic layer was dried over sodium sulfate, filtered and concentrated to give a solid, 6-(3-isopropyl-5-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1, 2,4]triazolo[1,5a]pyridine (11.4 mg, 0.032 mmol, 26.7% yield). LC/MS time hold=0.77 min. (m+1= 338) [B1].

1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.60 (d, J=1.2 Hz, 1H), 8.52 (s, 1H), 7.68 (d , J=8.7 Hz, 1H), 7.19 (d, J=1.1 Hz, 1H), 6.59 (d, J=8.7 Hz, 1H), 4.08 (s, 3H ), 4.06-3.98 (m, 1H), 3.89 (s, 3H), 1.57-1.52 (m, 6H).

Example 602 2-(4-(((3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3, 2b]pyridin-5-yl)oxy)methyl)piperidin-1-yl)-N,N-dimethylacetamide

In a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol) DMF (1 ml), DIEA (0.012 ml, 0.069 mmol) and 2-chloro-X,X-dimethylacetamide (4.22 mg, 0.035 mmol). The reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 µm particles;

Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 15-55% B over 20 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 506.1 (M+H); Retention time: 1.28 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 506.25 (M+H); Retention time: 1.01 min. 2(4-(((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b ]pyridin-5-yl)oxy)methyl)piperidin-1-yl)-X,X-dimethylacetamide (4.2 mg, 8.06 µmol, 34.8% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.30 (s, 1H), 8.59 (s, 1H), 8.50 (s, 1H), 7.67 (d, J=8.9 Hz , 1H), 7.18 (s, 1H), 6.57 (d, J=8.5 Hz, 1H), 4.18 (d, J=6.1 Hz, 2H), 4.07 (s , 3H), 3.29-3.20 (m, 1H), 3.09 (s, 2H), 3.02 (s, 3H), 2.88-2.82 (m, 2H), 2, 80 (s, 3H), 2.00 (br t, J=10.7 Hz, 2H), 1.86-1.76 (m, 1H), 1.73 (br d, J=12.2 Hz , 2H), 1.53 (br d, J=1.0 Hz, 6H), 1.37-1.25 (m, 2H).

Example 603 6-(3-ISOPROPYL-5-((1-isopropylpiperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridin2-yl)-8-methoxy-[ 1,2,4 ]triazolo[1,5-а]pyridine

- 58 041852

In a vessel with a capacity of 2 dram containing tert-butyl-5-((1-(tert-butoxycarbonyl)piperidin-4yl)oxy)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1 ,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (31 mg, 0.051 mmol), DCM (1 ml) and TFA (1 ml) were added. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under nitrogen flow and dried in vacuo. DMF (1 ml), DIEA (0.027 ml, 0.153 mmol) and acetone (0.019 ml, 0.255 mmol) were added to the resulting oil. The reaction mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (54.1 mg, 0.255 mmol) and acetic acid (2.93 μl, 0.051 mmol) were added and the reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 5-45% B for 27 minutes, then 3 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. Product yield 4.5 mg. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 449 (M+H); Retention time: 1.22 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 449.29 (M+H); Retention time: 1.07 min.

Example 604 6-(3-Isopropyl-5-((1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl) -8-methoxy-[1,2,4]triazolo[1,5-а]pyridine

Into a 1 dram vessel containing 6-(3-isopropyl-5-(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol) DMF (0.75 ml), DIEA (4.04 μl, 0.023 mmol) and 1-bromo-2-(methylsulfonyl)ethane ( 4.33 mg, 0.023 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was heated to 70° C. for 3 hours. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 20-60% B for 19 minutes, then 5 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B-100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 527.45 (M+H); Retention time: 1.5 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 527.47 (M+H); Retention time: 0.98 min. 6-(3-isopropyl-5-((1-(2(methylsulfonyl)ethyl)piperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8- methoxy-[1,2,4]triazolo[1,5-a]pyridine (3.8 mg, 7.00 µmol, 30.3% yield).

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.29 (s, 1H), 8.58 (s, 1H), 8.50 (s, 1H), 7.67 (d, J=8.9 Hz, 1H), 7.17 (s, 1H), 6.57 (d, J=8.9 Hz, 1H), 4.18 (br d, J=6.4 Hz, 2H), 4.07 (s, 3H), 3.89 (s, 1H), 3.29-3.20 (m, 2H), 3.02 (s, 3H), 2.92 (br d, J=11.0 Hz , 2H), 2.68 (t, J=6.7 Hz, 2H), 1.95 (br t, J=10.8 Hz, 2H), 1.87-1.79 (m, 1H), 1.78-1.72(m, 2H), 1.55-1.49(m, 6H), 1.37-1.24(m, 2H).

Examples 605 and 611 4-((3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b] pyridin-5 -yl)oxy)-X,X-dipropylcyclohexane-1 -amine

- 59 041852

In a vessel with a capacity of 1 dram containing 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)oxy)cyclohexane-1-amine, 2 TFA (15 mg, 0.023 mmol) DCM (1 ml), DMF (0.5 ml), DIEA (8.08 μl, 0.046 mmol), and propionaldehyde (3.32 µl, 0.046 mmol). The reaction mixture was stirred at room temperature for 30 minutes. Acetic acid (1.324 μl, 0.023 mmol) and sodium triacetoxyborohydride (14.71 mg, 0.069 mmol) were added to the reaction mixture. The reaction mixture was stirred for 3 hours. A drop of water and DMF (1 ml) was added and then the crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 2262% B for 20 minutes, then 4 minutes at 100% B; Elution: 20 ml/min. The product containing fractions were combined and dried by centrifugal evaporation to give two compounds: Isolate 1 and Isolate 2. These compounds were cis and trans isomers, but isomer identities were not determined in isolates.

Example 605.

Isolate 1: 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine- 5-yl)oxy)-N,N-dipropylcyclohexane-1-amine (9.9 mg, 0.020 mmol, 85% yield). LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 505.48 (M+H); Retention time: 1.51 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 505.46 (M+H); Retention time: 1.24 min.

1H NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.58 (s, 1H), 8.50 (s, 1H), 7.68-7.60 (m, 1H) , 7.18 (s, 1H), 6.50 (d, J=8.9 Hz, 1H), 4.86 (br s, 1H), 4.27 (q, J=7.0 Hz, 1H ), 4.07 (s, 2H), 3.25 (br dd, J=10.2, 6.0 Hz, 1H), 3.19-3.10 (m, 1H), 2.89 (s , 1H), 2.70-2.67 (m, 1H), 2.73 (s, 1H), 2.47-2.33 (m, 3H), 2.26 (br s, 1H), 1 .79 (br s, 1H), 1.53 (br d, J=6.7 Hz, 6H), 1.44-1.33 (m, 6H), 1.32-1.20 (m, 1H ), 0.99 (d, J=6.4 Hz, 3H), 0.84 (t, J=7.3 Hz, 4H).

Example 611.

Isolate 2: 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine- 5-yl)oxy)-N,N-dipropylcyclohexane-1-amine (4.2 mg, 7.91 µmol, 34.2% yield). LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 505.46 (M+H); Retention time: 1.57 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 505.46 (M+H); Retention time: 1.3 min.

1H NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.58 (s, 1H), 8.50 (s, 1H), 7.94 (s, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.17 (s, 1H), 6.58 (d, J=8.5 Hz, 1H), 5.20 (br s, 1H), 4, 07 (s, 3H), 3.29-3.22 (m, 1H), 3.19-3.11 (m, 1H), 2.89 (s, 1H), 2.73 (s, 1H) , 2.46-2.34 (m, 2H), 2.13 (br s, 1H), 1.76 (br s, 1H), 1.60 (br d, J=8.9 Hz, 3H) , 1.51 (br d, J=6.7 Hz, 5H), 1.42-1.35 (m, 4H), 0.99 (d, J=6.1 Hz, 3H), 0.84 (t, J=7.2 Hz, 6H).

Example 606 6-(3-Isopropyl-5-((1-propylpiperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2yl)-8-methoxy-[1,2,4 ]triazolo[1,5-а]pyridine

In a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-ylmethoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.023 mmol), DMF (0.5 ml), DIEA (0.012 ml, 0.069 mmol), propionaldehyde (6.72 mg, 0.116 mmol) were added. The reaction mixture was stirred for 5 minutes. Sodium triacetoxyborohydride (14.71 mg, 0.069 mmol) and acetic acid (1.324 μl, 0.023 mmol) were added and the reaction mixture was stirred at room temperature for 6 h. One drop of water was added and the crude material was purified by the preparation method.

- 60 041852 active LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 25 minutes, then 5 minutes hold at 100% B; Elution: 20 ml/min.

The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 462.94 (M+H); Retention time: 1.51 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 463.3 (M+H); Retention time: 1.25 min. 6-(3-Isopropyl-5-((1propylpiperidin-4-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine (8.6 mg, 0.019 mmol, 80% yield).

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.33-11.26 (m, 1H), 8.62-8.55 (m, 1H), 8.53-8.47 (m, 1H ), 7.71-7.63 (m, 1H), 7.18 (s, 1H), 6.58 (d, J=8.5 Hz, 1H), 4.21-4.16 (m, 2H), 4.08 (s, 3H), 3.30-3.19 (m, 1H), 2.89 (br d, J=10.7 Hz, 2H), 2.23 (brt, J= 7.3 Hz, 2H), 1.93-1.80 (m, 3H), 1.75 (brd, J=12.2 Hz, 2H), 1.52 (brd, J=7.0 Hz, 6H), 1.44 (dq, J=14.5, 7.4 Hz, 2H), 1.38-1.26 (m, 2H), 0.84 (t, J=7.5 Hz, 3H ).

Example 607 6-(3-Isopropyl-5-((1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridine-2- yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine

Into a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-yloxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.024 mmol), DMF (500 µl), DIEA (12.39 µl, 0.071 mmol), and dihydro-2H-pyran-4(3H)- he (2.367 mg, 0.024 mmol). The reaction mixture was stirred at room temperature for 5 minutes. Acetic acid (1.353 µl, 0.024 mmol) and sodium triacetoxyborohydride (15.03 mg, 0.071 mmol) were added to the reaction mixture. The reaction mixture was stirred overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 5-45% B over 20 minutes, then 3 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 491.21 (M+H); Retention time: 1.33 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 491.16 (M+H); Retention time: 1.07 min. 6-(3-Isopropyl-5-((1-(tetrahydro-2H-pyran-4yl)piperidin-4-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8 -methoxy-[1,2,4]triazolo[1,5-a]pyridine (6.7 mg, 0.013 mmol, 56% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.57 (s, 1H), 8.50 (s, 1H), 7.66 (d, J=8.5 Hz , 1H), 7.16 (s, 1H), 6.54 (d, J=8.5 Hz, 1H), 5.03-4.93 (m, 1H), 4.11-4.03 ( m, 3H), 3.88 (br d, J=7.6 Hz, 2H), 3.32-3.21 (m, 3H), 2.86 (br d, J=10.4 Hz, 2H ), 2.41-2.32 (m, 2H), 2.13-2.03 (m, 2H), 1.94-1.86 (m, 1H), 1.73-1.61 (m , 4H), 1.51 (br d, J=7.0 Hz, 6H), 1.48-1.36 (m, 2H).

Example 608 6-(3-Isopropyl-5-((1-methylazetidin-3-yl)methoxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)8-methoxy-[1,2, 4]triazolo[1,5-а]pyridine

- 61 041852

In a 20 ml scintillation vial containing tert-butyl-5-((1-(tert-butoxycarbonyl) azetidin-3-yl)methoxy)-3-isopropyl-2-(8-methoxy-[1,2,4] triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine-1-carboxylate (40 mg, 0.067 mmol), DCM (500 ml) and TFA (500 ml) were added. The reaction mixture was stirred at room temperature for 3 hours, concentrated under a stream of nitrogen and dried in vacuo. The resulting oil was dissolved in DMF (1 ml) and DIEA (0.035 ml, 0.202 mmol) and formaldehyde (37% in water) (0.025 ml, 0.337 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes. Acetic acid (3.86 μl, 0.067 mmol) and sodium triacetoxyborohydride (42.9 mg, 0.202 mmol) were added and the reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B for 19 minutes, then 5 minutes at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 8-33% B over 25 minutes, then 2 minute hold at 33% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 407.34 (M+H); Retention time: 0.96 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 406.93 (M+H); Retention time: 1.11 min. 6-(3-isopropyl-5-((1-methylazetidin-3-yl)methoxy)-1H-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine, 2 TFA (1.7 mg, 2.63 µmol, 3.9% yield).

1H NMR (500 MHz, DMSO-d6) δ 11.47-11.38 (m, 1H), 8.61 (s, 1H), 8.53 (s, 1H), 7.74 (d, J= 8.7 Hz, 1H), 7.19 (s, 1H), 6.68 (dd, J=8.5, 5.9 Hz, 1H), 4.54-4.40 (m, 2H), 4.08 (s, 3H), 3.99-3.90 (m, 1H), 3.60-3.50 (m, 1H), 3.49-3.42 (m, 1H), 3. 29-3.23 (m, 2H), 2.90-2.81 (m, 3H), 2.73 (s, 1H), 1.54 (brd, J=5.6 Hz, 6H).

Example 609 2-(4-((3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b ]pyridin-5-yl)oxy)pineridin-1-yl)-N,N-dimethylacetamide

Into a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-yloxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine, 2 TFA (20 mg, 0.032 mmol), DMF (1 ml), DIEA (0.017 ml, 0.095 mmol) and 2-chloro-X,X-dimethylacetamide (11, 50 mg, 0.095 mmol). The reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 492.13 (M+H); Retention time: 1.25 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220

- 62 041852 nm). Injection results 2: Observed weight: 492.01 (M+H); Retention time: 1.28 min. 2(4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)oxy)piperidin-1-yl)-N,N-dimethylacetamide (11.2 mg, 0.023 mmol, 71.6% yield).

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.30 (s, 1H), 8.60 (s, 1H), 8.52 (s, 1H), 7.67 (d, J=8.9 Hz, 1H), 7.19 (s, 1H), 6.55 (d, J=8.5 Hz, 1H), 5.04-4.96 (m, 1H), 4.08 (s, 3H ), 3.32-3.22 (m, 1H), 3.18 (s, 2H), 3.04 (s, 2H), 2.892.73 (m, 4H), 2.36 (br t, J =9.3 Hz, 2H), 2.12-2.05 (m, 2H), 1.90 (br s, 1H), 1.74-1.64 (m, 2H), 1.56-1 .48 (m, 6H), 1.24 (s, 1H).

Examples 610 and 614 4-((3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b] pyridin-5-yl)oxy)-N,N-dimethylcyclohexane-1-amine

In a vessel with a capacity of 1 dram containing 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-III-pyrrolo[3,2- b]pyridin-5-yl)oxy)cyclohexane-1-amine, 2 TFA (15 mg, 0.023 mmol), DMF (0.5 ml), DCM (1 ml), DIEA (8.08 μl, 0.046 mmol) were added ), and formaldehyde (1.911 μl, 0.069 mmol). The reaction mixture was stirred at room temperature for 30 minutes. Acetic acid (1.324 µl, 0.023 mmol) and sodium triacetoxyborohydride (14.71 mg, 0.069 mmol) were added and the reaction mixture was stirred at room temperature for 1 hour. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18 , 19x200 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 5-50% B over 20 minutes, then 6 minutes at 100% B; Elution: 20 ml/min. The product containing fractions were combined and dried by centrifugal evaporation to give two compounds: Isolate 1 and Isolate 2. These compounds were cis and trans isomers, but isomer identities were not determined in isolates.

Example 610.

Isolate 1: 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine- 5-yl)oxy)-N,N-dimethylcyclohexane-1-amine, 2 TFA (8.5 mg, 0.012 mmol, 53.2% yield). LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 449.37 (M+H);

Retention time: 1.11 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B to 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 449.36 (M+H); Retention time: 0.91 min.

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 11.36 (s, 1H), 8.59 (s, 1H), 8.52 (s, 1H), 7.69 (d, J=8, 9 Hz, 1H), 7.17 (s, 1H), 6.54 (d, J=8.5 Hz, 1H), 4.96-4.86 (m, 1H), 4.12-4, 04 (m, 3H), 3.31-3.20 (m, 2H), 2.38 (brd, J=11.6 Hz, 2H), 2.18-2.07 (m, 2H), 1 .73-1.58 (m, 3H), 1.55-1.38 (m, 11H).

Example 614.

Isolate 2: 4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine- 5-yl)oxy)-N,N-dimethylcyclohexane-1-amine, 2 TFA (3.1 mg, 4.44 µmol, 19% yield). LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 449.38 (M+H); Retention time: 1.26 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 449.38 (M+H); Retention time: 0.99 min.

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.39-11.32 (m, 1H), 8.61-8.56 (m, 1H), 8.52 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 7.17 (s, 1H), 6.60 (d, J=8.9 Hz, 1H), 5.25 (br s, 1H), 4, 08 (s, 3H), 3.31-3.23 (m, 2H), 2.25 (br d, J=10.7 Hz, 2H), 1.95-1.84 (m, 2H), 1.81-1.66 (m, 4H), 1.55-1.47 (m, 6H).

Example 612 6-(3-Isopropyl-5-((1-isopropylazetidin-3-yl)oxy)-1 H-pyrrolo[3,2-b]pyridin-2-yl)8-methoxy-[1,2 ,4]triazolo[1,5-а]pyridine

- 63 041852

Into a vessel with a capacity of 1 dram containing 6-(5-(azetidin-3-yloxy)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine (10 mg, 0.026 mmol), DMF (1 ml), DIEA (0.014 ml, 0.079 mmol) and propan-2-one (1.535 mg, 0.026 mmol) were added. The reaction mixture was stirred at room temperature for 30 minutes. Acetic acid (1.513 μl, 0.026 mmol) and sodium triacetoxyborohydride (28.0 mg, 0.132 mmol) were added and the reaction mixture was stirred at room temperature overnight. The crude material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 15-55% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0%B-100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 1: Observed weight: 421.04 (M+H); Retention time: 1.4 min. Injection conditions 2: Column: Waters Xbridge C18, 2.1 mM x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0%B - 100%B for 3 min, then 0.75 min hold at 100%B; Elution: 1 ml/min; Detection: MS and UV (220 nm). Injection results 2: Observed weight: 420.96 (M+H); Retention time: 1.17 min. 6-(3-isopropyl-5-((1isopropylazetidin-3-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo was isolated [1,5-a]pyridine (5.2 mg, 0.012 mmol, 44.9% yield).

Example 613 2b] pyridin-5-yl)oxy)piperidin-1-yl)-2-methylpropan-2-ol

Into a vessel with a capacity of 1 dram containing 6-(3-isopropyl-5-(piperidin-4-yloxy)-1P-pyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine, 2 TFA (15 mg, 0.024 mmol), MeOH (500 µl), potassium carbonate (9.80 mg, 0.071 mmol), and 2,2-dimethyloxirane (1.705 mg, 0.024 mmol). The reaction mixture was stirred at rt. overnight, then filtered and concentrated in vacuo. The crude material was dissolved in DMF and purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 15-55% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. The fractions containing the product were combined and dried by centrifugal evaporation. LC/MS was used to analyze the final compound. Injection conditions 1: Column: Waters Acquity UPLC VEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min; Detection: UV at 220 nm. Injection conditions 2: Column: Waters Acquity UPLC VEN C18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50°C; Gradient: 0-100% B over 3 minutes, then 0.75 minute hold at 100% B; Elution: 1.0 ml/min; Detection: UV at 220 nm. 1-(4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1P-pyrrolo[3,2b]pyridine) was isolated -5-yl)oxy)piperidin-1-yl)-2-methylpropan-2-ol (9.8 mg, 0.019 mmol, 81% yield). LCMS retention time 1.20 min, m/z = 479.2 (M+H) [QC-ACN-AA-XB].

1H NMR (500 MHz, DMSO-d6) δ 11.30 (s, 1H), 8.59 (s, 1H), 8.51 (s, 1H), 7.67 (d, J=8.5 Hz , 1H), 7.18 (s, 1H), 6.55 (d, J=8.9 Hz, 1H), 4.98 (br s, 1H), 4.08 (s, 3H), 3, 25 (dt, J=13.6, 6.6 Hz, 1H), 2.91 (br d, J=11.0 Hz, 2H), 2.38 (br t, J=9.2 Hz, 2H ), 2.06 (br d, J=10.7 Hz, 2H), 1.79-1.62 (m, 2H), 1.57-1.46 (m, 6H), 1.23 (s , 3H), 1.10 (s, 6H).

Example 649 6-(5-(Azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo [1,5-a]pyridine

- 64 041852

Intermediate 649A: tert-Butyl 5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Suspension of tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (150 mg, 0.442 mmol), tert-butyl-3-bromazetidine-1-carboxylate (209 mg , 0.884 mmol), tris(trimethylsilyl)silane (165 mg, 0.663 mmol), [Ir(dF(CF ₃ )ppy) ₂ (dtbbpy)]PF ₆ (1.24 mg, 1.11 µmol) and Na ₂ CO ₃ (187 mg, 1.77 mmol) in 1,4-dioxane (3.5 mL) in a septum capped vial with magnetic stirrer was degassed with nitrogen gas for 5 minutes. In a separate vessel was added a complex of nickel(II) chloride, ethylene glycol and dimethyl ether (7.29 mg, 0.033 mmol) and 4,4'di-tert-butyl-2,2'-bipyridine (10.7 mg, 0.040 mmol) , then evacuated and backfilled with nitrogen gas followed by the addition of 1,4-dioxane (0.88 ml). This mixture was degassed with nitrogen gas for 10 minutes and stirred. The resulting solution containing the nickel complex was added to the slurry containing all other reactants, and then the resulting mixture was further degassed with nitrogen gas for another 10 minutes. The vessel was then sealed and placed in a rack with stirring and irradiation with 34 W Kessil KSH 150V blue phytolamps and a cooling fan for 17 hours. Upon completion, the reaction mixture was diluted with DCM, filtered, and concentrated. The crude material was taken up in hexanes with a trace of DCM for solubility and purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/DCM 0-100% followed by Hex/EtOAc 0-50% to give tert-butyl-5-(1 -(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-1 H-pyrrolo[3,2-b]pyridine-1-carboxylate (100 mg, 0.241 mmol, 54.4% yield). LCMS retention time 1.04 [TS]. MS (E ⁺ ) m/z: 416.3 (M+H). This reaction was repeated several times to obtain higher amounts of material.

Intermediate 649B: tert-Butyl-5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Solution containing tert-butyl 5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-1-carboxylate (456 mg, 1.10 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2dioxaborolane (448 μl, 2.195 mmol) in dry THF (5.5 ml) under nitrogen, cooled in a dry ice/acetone bath to -78 °C and treated with LDA (2M in THF, 2.75 ml, 5.50 mmol). The mixture was allowed to warm to -30°C over 30 minutes and stirred at -30°C for 30 minutes. The reaction was then quenched with saturated aqueous NH ₄ Cl, water and DCM. The organic layer was separated, dried over sodium sulfate, filtered and concentrated. The crude material was combined with the crude material from a similar experiment after the same procedure using 100 mg (0.241 mmol) starting material tert-butyl-5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-1H -pyrrolo[3,2-b]pyridine-1-carboxylate. The combined crudes were purified by silica gel column chromatography using a Teledyne Isco instrument loading in hexanes and eluting with Hex/EtOAc 050% to give t-butyl-5-(1-(t-butoxycarbonyl)azetidin-3-yl)-3 -isopropyl-2-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (340 mg) combined from two experiments. LCMS retention time 1.18 [TS]. MS (E ⁺ ) m/z: 542.3 (M+H).

1H NMR (499 MHz, chloroform-d) δ 7.96 (d, J=8.4 Hz, 1H), 7.03 (d, J=8.5 Hz, 1H), 4.34-4.27 (m, 2H), 4.27-4.22 (m, 2H), 3.99-3.89 (m, 1H), 3.37-3.26 (m, 1H), 1.66 (s , 9H), 1.47 (s, 9H), 1.48 (br d, J=7.0 Hz, 6H), 1.44 (s, 12H).

Intermediate 649C: tert-Butyl-3-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)azetidine-1-carboxylate

In a reaction vessel with a lid with a safety diaphragm and a magnetic stirrer, pure

- 65 041852 tert-butyl-5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 -yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (340 mg, 0.628 mmol) under nitrogen was heated to 160° C. with slow stirring for 45 minutes. Upon completion, the material was dissolved in DCM and concentrated to give tert-butyl-3-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)azetidine-1-carboxylate as a whitish foam, which was evaluated as a quantitative yield. Carried on as is. Note: The material converted to free boronic acid on LCMS and was observed unchanged, although NMR indicated that the product was a pure compound. LCMS retention time (boronic acid) 0.67 [TS]. MS (E ⁺ ) m/z: 360.2 (M+H, boronic acid).

Ή NMR (499 MHz, chloroform-d) δ 8.23 (br s, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.01 (d, J=8.5 Hz, 1H), 4.364.24 (m, 4H), 4.01-3.92 (m, 1H), 3.73 (spt, J=7.0 Hz, 1H), 1.53 (d, J=7 .0 Hz, 6H), 1.48 (s, 9H), 1.36 (s, 12H).

Intermediate 649D: tert-Butyl-3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-3-isopropyl-1H-pyrrolo[3, 2-b]pyridin-5-yl)azetidine-1-carboxylate

To a mixture of tert-butyl-3-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1Hpyrrolo[3,2-b]pyridin-5 -yl)azetidine-1-carboxylate (138 mg, 0.313 mmol), 6-bromo-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (78 mg, 0.344 mmol), and Xphos of the 2nd generation precatalyst (12.3 mg, 0.016 mmol) in 1,4-dioxane (2.1 mL) was added aqueous K3PO4 (3M, 0.31 mL, 0.93 mmol) and the biphasic mixture was degassed with nitrogen gas in within 10 min. The reaction vessel was sealed and stirred at 65°C for 1.5 hours Upon completion, the reaction mixture was cooled to room temperature and concentrated. The crude material was suspended in DCM and purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc ΟΙ 00% to give t-butyl-3-(2-(7,8-dimethyl-[1,2,4 ]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl)azetidine-1-carboxylate (111 mg, 0.241 mmol, 77% yield) . LCMS retention time 0.72 [TS]. MS (E ⁺ ) m/z: 461.3 (M+H).

Example 649.

To a solution of tert-butyl-3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b]pyridin-5-yl)azetidine-1-carboxylate (111 mg, 0.241 mmol) in DCM (4.8 ml) was added at room temperature with 4M HCl in 1,4-dioxane (1.2 ml, 4.80 mmol ). The reaction mixture was stirred at room temperature for 5 minutes. Upon completion, the reaction mixture was concentrated to give 6-(5-(azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[ 1, 2,4]triazolo[ 1,5-a]pyridine, HCl (0.241 mmol) in a quantitative yield.

Most of this substance was carried on as is. An aliquot of this material (approximately 0.012 mmol) was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 5-90% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(5-(azetidin-3-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[ 1,2,4]triazolo[1,5-a]pyridine (2.5 mg, 6.80 µmol). LCMS retention time 0.69 [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 361.3 (M+H).

Ή NMR (500 MHz, DMSO-d ₆ ) δ 8.80 (s, 1H), 8.47 (s, 1H), 7.65 (d, J=8.2 Hz, 1H), 7.08 ( d, J=8.5 Hz, 1H), 4.18-4.09 (m, 1H), 4.09-3.96 (m, 2H), 3.91-3.80 (m, 2H) , 2.96-2.87 (m, 1H), 2.59 (s, 3H), 2.16 (s, 3H), 1.42 (br d, J=6.7 Hz, 6H).

Example 653 6-(3-Isopropyl-5-(1-(2-(methylsulfonyl)ethyl)azetidin-3-yl)-1 H-pyrrolo[3,2-b]pyridin-2-yl)-7, 8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine

To a solution of 6-(5-(azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo[ 1,5-a]pyridine, HCl (18.26 mg, 0.046 mmol) in DMF (1 ml) was added Et ₃ N (0.032 ml, 0.230 mmol) and 1-bromo-2-(methylsulfonyl)ethane (12.9 mg, 0.069 mmol). The resulting solution was stirred for 90 minutes at room temperature and then another aliquot of 1-bromo-2 (methylsulfonyl)ethane (12.9 mg, 0.069 mmol) was added. The reaction mixture was stirred for an additional 60 minutes and then diluted with a few drops of water, DMF, and purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; mobile phase

- 66 041852

A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-100% B for 20 minutes, then 4 minutes at 100% B; Elution: 20 ml/min. Product containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)azetidin-3-yl)-1H-pyrrolo[3,2b]pyridin-2- yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (15.7 mg, 0.033 mmol, 71.7% yield).

LCMS retention time 0.8 min [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 467.4 (M+H).

1H NMR (500 MHz, DMSO-d6) δ 11.17 (s, 1H), 8.76 (s, 1H), 8.46 (s, 1H), 7.63 (d, J=8.2 Hz , 1H), 7.08 (d, J=8.2 Hz, 1H), 3.83 (quin, J=7.6 Hz, 1H), 3.75-3.69 (m, 2H), 3 .38 (t, J=7.2 Hz, 2H), 3.20-3.12 (m, 2H), 3.05 (s, 3H), 2.93-2.83 (m, 3H), 2.58 (s, 3H), 2.15 (s, 3H), 1.40 (br d, J=7.0 Hz, 6H).

Example 660 4-Isopropyl-2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b ]pyridin-5-yl)morpholine

2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5yl) morpholine, TFA (22.99 mg, 0.0454 mmol) and Et ₃ N (0.05 ml, 0.359 mmol) were mixed in DMF (0.454 ml). Acetone (0.018 ml, 0.245 mmol) was added to the reaction vessel followed by sodium triacetoxyborohydride (28.9 mg, 0.136 mmol) and the reaction mixture was stirred for 17 hours at room temperature. At this time, another aliquot of acetone (0.018 ml, 0.245 mmol) and sodium triacetoxyborohydride (28.9 mg, 0.136 mmol) was added. The reaction mixture was stirred for another 7 hours at room temperature. The reaction was quenched by adding water, 1.5 M aqueous K2HPO4 solution, and DCM. The organic layer was separated, concentrated, and diluted with DMSO. The material was purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 11% B, 11-51% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0 minute hold at 12% B, 12-35% B for 25 minutes, then 2 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by UV signals. The fractions containing the product were combined and dried by centrifugal evaporation.

The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 200 mM x 30 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 10% B, 10-50% B for 20 minutes, then 2 minute hold at 100% B; Elution rate: 45 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0 minute hold at 11% B, 11-35% B for 25 minutes, then 2 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction collection was triggered by UV signals. pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin5-yl)morpholine, TFA (10.5 mg, 0.019 mmol, 41.2% yield). LCMS retention time 1.02 [QCACN-TFA-XB]. MS (E ⁺ ) m/z: 435.1 (M+H).

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.49 (br s, 1H), 8.61 (s, 1H), 8.48 (s, 1H), 7.82 (br d, J=8 .3 Hz, 1H), 7.32 (br d, J=8.4 Hz, 1H), 7.17 (s, 1H), 5.06-4.89 (m, 1H), 4.36- 4.17 (m, 1H), 4.08 (s, 3H), 4.01 (brt, J=12.l Hz, 1H), 3.77-3.15 (m, 6H), 1.58 -1.47 (m, 6H), 1.40-1.26 (m, 6H).

Example 671 2-(3-Isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine-5 -yl) morpholine

Intermediate 671A: tert-butyl-2-(1-(tert-butoxycarbonyl)-3-isopropyl-1H

- 67 041852 pyrrolo[3,2-b]pyridin-5-yl)morpholine-4-carboxylate

Solution of tert-butyl-5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.925 g, 2.73 mmol), 4-(tert-butoxycarbonyl)morpholine-2-carboxylic acids (0.946 g, 4.09 mmol), [Ir (dF (Me)ppy) ₂ (dtbbpy)] PF ₆ (0.028 g, 0.027 mmol), 2-tert-butyl-1,1,3,3-tetramethylguanidine (0.701 g, 4.09 mmol), nickel(II) chloride complex, ethylene glycol and dimethyl ether (0.030 g, 0.136 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (0.037 g, 0.136 mmol) in DMSO (27.3 ml) in a septum capped vial with magnetic stirrer was degassed with nitrogen for 15 minutes. The resulting solution was hermetically sealed and placed in a rack with stirring and irradiation with Kessil KSH 150V blue phytolamps with a power of 34 W and a cooling fan for 68 hours. This reaction was started in two parallel vessels. Upon completion, duplicate reaction vessels were pooled and diluted with water and DCM. The organic layer was washed with water three times, dried over sodium sulfate, filtered, and concentrated to give a crude brown oil. This material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-50% to give t-butyl-2-(1-(t-butoxycarbonyl)-3-isopropyl-1Hpyrrolo[3,2- b]pyridin-5-yl)morpholine-4-carboxylate (1.7 g). LCMS retention time 1.23 [TS]. MS (E ⁺ ) m/z: 446.3 (M+H).

1H NMR (400 MHz, chloroform-d) δ 8.29 (br s, 1H), 7.51 (br s, 1H), 7.39 (d, J=8.5 Hz, 1H), 4.64 (dd, J=10.5, 2.7 Hz, 1H), 4.55-4.25 (m, 1H), 4.16-3.88 (m, 2H), 3.76 (td, J =11.7, 2.4 Hz, 1H), 3.38-3.25 (m, 1H), 3.18-3.01 (m, 1H), 3.00-2.91 (m, 1H ), 1.67 (s, 9H), 1.49 (s, 9H), 1.38 (d, J=6.6 Hz, 6H).

Intermediate 671B: tert-Butyl-2-(1-(tert-butoxycarbonyl)-3-isopropyl-2-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)morpholine-4-carboxylate

Solution containing tert-butyl 2-(1-(tert-butoxycarbonyl)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-5-yl)morpholine-4-carboxylate (1.67 g, 3.75 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2dioxaborolane (0.918 ml, 4.50 mmol) in dry THF (19 ml) under nitrogen, cooled in a dry ice/acetone bath to -78°C and treated with LDA (2M in THF, 2.81 ml, 5.62 mmol). The mixture was allowed to warm to -20° C. slowly over 2 hours. The reaction mixture was then recooled to -60°C and additional 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.31 ml, 1.52 mmol) and LDA (2M in THF, 0.93 ml, 1.86 mmol) were added sequentially. The reaction mixture turned dark, the bath was quickly changed to a -40° C. bath, and the reaction was soon completed. Upon completion, the reaction mixture was treated with saturated aqueous NH ₄ Cl, water and DCM. The organic layer was separated, dried over sodium sulfate, filtered and concentrated. The crude isolate was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-50%. Concentration of the fractions containing the product made it possible to obtain tert-butyl-2(1-(tert-butoxycarbonyl)-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1 H-pyrrolo[3,2-b]pyridin-5-yl)morpholine-4-carboxylate (1.65 g, 2.89 mmol, 77% yield). LCMS retention time 1.32 [TS]. MS (E ⁺ ) m/z: 572.5 (M+H).

1H NMR (499 MHz, chloroform-d) δ 8.01 (d, J=8.7 Hz, 1H), 7.32 (d, J=8.6 Hz, 1H), 4.67-4.55 (m, 1H), 4.54-4.34 (m, 1H), 4.16-3.84 (m, 2H), 3.81-3.70 (m, 1H), 3.36-3 .26 (m, 1H), 3.16-2.90 (m, 2H), 1.66 (s, 9H), 1.50 (s, 9H), 1.46-1.42 (m, 18H ).

Intermediate 671C: tert-Butyl-2-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)morpholine-4-carboxylate

Vessel with lid with safety diaphragm containing tert-butyl-2-(1-(tert-butoxycarbonyl)-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)morpholine-4-carboxylate (1.65 g, 2.89 mmol), heated with slow stirring at 165° C. under nitrogen atmosphere with nitrogen gas supply from the line and then left at room temperature overnight. Heating was then continued for 90 minutes until the material formed a brown melt which solidified into a brown glass upon cooling to room temperature. The material was dissolved in DCM, transferred to a round bottom flask and concentrated from

- 68 041852 by irradiation of whitish foam, tert-butyl-2-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrrolo[3,2 -b]pyridin-5-yl)morpholine-4-carboxylate, which was evaluated as a quantitative yield (2.88 mmol), and was transferred further as is. Note: LCMS analysis showed conversion to boronic acid although NMR indicated that the product was pure. LCMS retention time 0.73 (boronic acid) [TS]. MS (E ⁺ ) m/z: 390.2 (boronic acid).

¹ H NMR (499 MHz, chloroform-d) δ 8.27 (br s, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.30 (d, J=8.5 Hz , 1H), 4.654.61 (m, 1H), 4.59-4.32 (m, 1H), 4.13-3.86 (m, 2H), 3.82-3.67 (m, 2H ), 3.04 (br dd, J=13.4, 10.7 Hz, 2H), 1.521.48 (m, 15H), 1.36 (s, 12H).

Intermediate 671D: tert-Butyl-2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2- b] pyridin-5-yl) morpholine-4-carboxylate n ₃ with |γ y-sn ₃ o-sn ₃

BocN. J\.N. 7 /=/ .G/ - ^H N (67 ID)

To a solution of tert-butyl-2-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)morpholine-4-carboxylate (197 mg, 0.418 mmol), 6-bromo-8-methoxy[1,2,4]triazolo[1,5-a]pyridine (105 mg, 0.460 mmol), and Xphos of the 2nd generation precatalyst (16.4 mg, 0.021 mmol) in 1,4-dioxane (2.8 ml) was added aqueous K ₃ PO ₄ (2M, 627 μl, 1.254 mmol) and the biphasic mixture was degassed with nitrogen for 5 min. The reaction vessel was sealed and stirred at 70° C. for 2 hours. Upon completion, the reaction mixture was cooled to room temperature and concentrated. The crude material was suspended in DCM and purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-100% to give t-butyl-2-(3-isopropyl-2-(8-methoxy-[1,2 ,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin5-yl)morpholine-4-carboxylate (177 mg, 0.359 mmol, 86% yield). LCMS retention time 0.82 [TS]. MS (ES ⁺ ) m/z: 493.6 (M+H).

Example 671.

To a solution of tert-butyl-2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)morpholine-4-carboxylate (8.9 mg, 0.018 mmol) in DCM (0.5 ml) TFA (0.5 ml) was added at room temperature. The reaction mixture was concentrated after 30 min to give the crude material, which was taken up in DMF with a few drops of Et ₃ N and purified by preparative LC/MS under the following conditions: Column: Xbridge C18, 19x200 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 3-40% B over 20 minutes, then 4 minutes hold at 100% B; Elution: 20 ml/min. Product-containing fractions were combined and dried by centrifugal evaporation to give 2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[ 3,2-b]pyridin-5-yl)morpholine (5.3 mg, 0.013 mmol, 72.4% yield). LCMS retention time 0.97 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 393.1.

Ή NMR (500 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.62 (s, 1H), 8.51 (s, 1H), 7.73 (br d, J=8.5 Hz, 1H), 7.22 (br d, J=8.2 Hz, 1H), 7.18 (s, 1H), 4.57 (br d, J=8.5 Hz, 1H), 4, 07 (s, 3H), 3.93 (br d, J=10.4 Hz, 1H), 3.74-3.62 (m, 1H), 3.56-3.44 (m, 1H), 3.36-3.23 (m, 1H), 3.23-3.16 (m, 1H), 2.81 (br s, 2H), 2.71 (brt, J=11.3 Hz, 1H ), 1.52 (br d, J=6.7 Hz, 6H).

During the derivatization of this substance, this procedure was repeated on a larger scale, as described here: a]pyridin-6-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)morpholine-4-carboxylate (112 mg, 0.227 mmol) in DCM (6 ml) TFA (3 ml) was added at room temperature . The reaction mixture was concentrated after 30 min to obtain a substance, which was estimated as a quantitative yield of 2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)morpholine, TFA (0.227 mmol). Carried on as is.

Example 680 6-(3-Isopropyl-5-(piperazin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo [1,5-a]pyridine

A mixture of tert-butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3, 2-b]pyridine-1-carboxylate (72.3 mg, 0.100 mmol), 1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (49.6 mg, 0.150 mmol), [Ir(dF(Me) ppy) ₂ (dtbbpy)]PF ₆ (1.0 mg, 1.000 µmol), 2-tert-butyl-1,1,3,3-tetramethylguanidine (25.7 mg, 0.150 mmol), nickel(II) chloride complex, ethylene glycol and dimethyl ether (1.1 mg, 5.00 µmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (1.3 mg, 5.00 µmol) in

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DMSO (3 ml) in a septum capped vial with magnetic stirrer was degassed with nitrogen for 15 minutes. The resulting mixture was hermetically sealed and placed in a rack with stirring and irradiation with 34 W Kessil KSH 150V blue phytolamps and a cooling fan for 48 h. Upon completion, the reaction mixture was diluted with water and DCM. The organic layer was washed with water three times, dried over sodium sulfate, filtered, and concentrated to give a crude brown oil. The crude material was partially purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-50% to give material which still contained a significant amount of impurities. This material was taken further and suspended in DCM (1 ml) and TFA (1 ml) and stirred for 30 minutes at room temperature. Upon completion, the material was concentrated and suspended in TFA (2 ml) with stirring for 3 hours at room temperature. Upon completion, the reaction mixture was concentrated, dissolved in methanol with a few drops of Et ₃ N, and purified under the following conditions: Column: Xbridge C18, 200 mM x 30 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0 minute hold at 0% B, 0-40% B for 20 minutes, then 2 minute hold at 100% B; Elution rate: 45 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(piperazin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)7,8-dimethyl- [1,2,4]triazolo[1,5-a]pyridine, TFA (9.5 mg, 0.019 mmol, 19% yield). LCMS retention time 0.91 [QC-ACN-TFA-XB]. MS (E+) m/z: 390.0 (M+H). Selected NMR peaks:

1H NMR (500 MHz, DMSO-d ₆ ) δ 11.60 (s, 1H), 8.82 (s, 1H), 8.48 (s, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.30 (br d, J=8.5 Hz, 1H), 4.83 (br d, J=10.4 Hz, 1H), 3.92 (br d, J=13, 4 Hz, 1H), 2.97 (dt, J=13.5, 6.5 Hz, 1H), 2.59 (s, 3H), 2.13 (s, 3H), 1.40 (br d , J=4.9Hz, 6H)

Compounds according to the following examples were obtained in accordance with the General methods described in the above examples.

Table 1

No. n.p. Structure Mol. weight LCMS m ⁺ bp. hold on (min) HPLC ika method 12 CH ₃ ό _ ⁿ z% _CH h ₃ c X y-CH _{3 N} T [ __(/ \=N ^H H ₃ c CH ₃ 403.53 404.3 1.2 QC- ACN- AA-XV

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13 CH ₃ ό ⁿ z ^C x n ₃ s ΎΑ y-snz o-sn ₃ Vn. .n__7 /=/ Ύ -<C/^n HN 405.51 406.3 0.71 QC- ACN- TFA- XV 314 h ₂ n_ ^H3C vch _{3 s} Yn n / ν' y Y \>_# \=N YY )=( ^H H ₃ C CH ₃ 375.48 376.3 0.96 QC- ACN- AA-XV 15 SVm ⁿ ' ^s usn _{3 N} snz ο ^νΝ γ ^Ν γ%τΟ ^H H ₃ C CH ₃ 460.59 461.5 0.76 QC- ACN- TFA- XV 16 And ₂ m h,c _{o cHa} VN. _N. 7.—/LIH^n 377.45 378.2 0.67 QC- ACN- TFA- XV 17 H ₃ C^ ^H s\ pu ³ νΛτ VT U ^SNs o-ch ₃ ch ₃ 0 /=( h JL /—A /*N ^N ₄ H _N ^ 462.56 463.4 1.06 QC- ACN- AA-XV 18 9 H H ₃ C. D. N ⁿ s ^C _{h rH} ³ X-CH ₃ o-CH ₃ Dts .N. 7 .—/ ³ Y YW\_ L JL /—/^ ^{N H} N 462.56 463.2 0.7 QC- ACN- TFA- XV 19 CH ₃ ^nc U ^cnc CH ₃ 0 ⁿ H ₃ s sn ₃ 474.61 475.1 1 QC- ACN- TFA- XV 20 N H ₃ S__ H ₃ C ^X Y ³ N. #-N T | T \> __ # \ \= N N ^Z ) \u003d/ ^H H ₃ C CH ₃ 389.51 390.2 1D4 QC- ACN- AA-XV

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21 O CH ₃ h ₃ c. _n ^n n ₃ s \ί^N /=% ⁿ n ₃ s sn ₃ 474.61 475.2 0.76 QC- ACN- TFA- XV 22 That Ο-Ζ ΖΙ d O * O 460.59 460.9 0.97 QC- ACN- TFA- XV 23 N H ₃ C__ H ₃ C %% Y^z N. || | \>__# \^Ν ⁿ n ₃ with CH ₃ 389.51 390.1 1.05 QC- ACN- TFA- XV 24 CH ₃ ^Η H ₃ C CH ₃ 473.63 474.2 1.52 QC- ACN- AA-XV 25 ch ₃ ^HsC 'NY^ ^H3 %ch _s ch, o N )=\ ⁿ H ₃ s ch ₃ 474.61 475.1 1.18 QC- ACN- TFA- XV 26 9 n ™ \u003d ^ν γγ%% ρ _Ν ^H H ₃ C CH ₃ 460.59 460.9 0.68 QC- ACN- TFA- XV 27 9 n ^H 'V ^CH \u003d O-CH ₃ CH ₃ ^Ln _Y M / C JL / - A λ \u003d N Η 462.56 463.4 0.81 QC- ACN- AA-XV 28 CH ₃ ⁿ ' ^with '^^ ^Η '% 0Η _{3 0} _ _CH SN ₃ o ^ ^N v ^N vA aK N J 7-A λ=Ν ⁿ Ν 476.59 477.4 1.04 QC- ACN- AA-XV

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29 ^aSv ^; ^H ΪΓ 461.57 462.1 0.73 QC- ACN- TFA- XB thirty OA ⁿ not VK ^m sA _G and vn Y ³ / ° ~ ^{s n} zC tN \u003d / L JL / - C / \u003d N ⁿ 461.57 462.3 1.41 QC- ACN- AA-XB 31 Ν H ₃ C_ _sn H ₃ C y-CH3 o-CH3 VN. J ,=/ Ύ Xj/—^C/^N 391.48 392.2 0.67 QC- ACN- TFA- XB 32 h ₂ n^ ^NzS y-ch ₃ VN. .N. J ,CH ₃ Ύ Yy^J th ^and 360.47 361.2 1.19 QC- ACN- AA-XB 33 Q ZI d About g ^sda I° ,___/Αχ ι Cm " ^2G o I 444.58 445.1 1.37 QC- ACN- AA-XB 34 I about c><? ^>=o ZI d WX ¹² i ° Γ0 “ o I 445.57 446.1 0.82 QC- ACN- TFA- XB 35 ΗςΝ^ ^H A-CH ₃ VN. .N 7 ,CH ₃ VN V=7 _m ⁿ o 360.47 361.1 0.82 QC- ACN- AA-XB 36 z=\ - CM t AA о I ο·%Δ ^{ηι f} О P ΞΕΖ й 444.58 445.2 1.12 QC- ACN- AA-XB

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37 Το ο-ζ <? ^=ο ΖΙ d Ο ΐ 1 ο See ^χ ο I 445.57 446.1 0.72 QC- ACN- TFA- ΧΒ 38 _Η0 H ₃ C \ ' / I'M \-Ν ν' y ΊΓ \>__<7 \=Ν ⁿ n ₃ s CH ₃ 376.46 377.2 0.88 QC- ACN- TFA- ΧΒ 39 k/C ^H3 Vch. Μ-D M ^sn z _Ν ν / ν' y j __<7 \=Ν ^Η H ₃ C CH ₃ 445.57 446.1 0.77 QC- ACN- TFA- ΧΒ 40 ^Η0 ^% ⁿ z% _ch VA y-CH _{3 Ν} y φ \>__<7 \=Ν ⁿ n ₃ s CH ₃ 459.60 460.1 1.25 QC- ACN- ΑΑ-ΧΒ 41 0¾% ^Ν ν ^Нз У ^сНз % > ^ν υΜ Μ 7 у j __# \=N ⁿ N ₃ С SN ₃ 493.63 494 1.46 QC- ACN- ΑΑ-ΧΒ 42 0 <А^ снз %Ν ^НзС usn _{3 Ν} Un -N- ==) у ΊΓ χ>__(7 \=Ν Μ^-Ν )=\ ⁿ n ₃ s CH ₃ 502.62 503.1 1.66 QC- ACN- ΑΑ-ΧΒ 43 ^Η |Ά^, ^Nz Msn y-sn _{3 Ν} ^ ^ν υΜ /Γ\ y φ ( )=Ν Μ^'Ν )=\ ⁿ n ₃ s 0Η ₃ 429.57 430.4 1.1 QC- ACN- ΑΑ-ΧΒ

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44 CH ₃ I ₃ CH ₃ CO γοΗ _{3 Ν} %Ν Ν ^ _Ν ' E ]| γΝ ^Η H ₃ C CH ₃ 514.68 515.4 1.29 QC- ACN- AA-XB 45 Η ₃ ογ o' ⁿ z ^s h _S n OGL γθΗ ₃ |\k +NN / E || YY_# γΝ ^H H ₃ C CH ₃ 535.71 536.4 0.84 QC- ACN- TFA- XB 46 CH ₃ H ₃ AL h ₃ C On Y^ ₃ N λ—N' y γ _(7 γΝ YYn/ Υγ ^H H ₃ C CH ₃ 471.65 472.1 1.42 QC- ACN- AA-XB 47 on H ₃ C O U ^CHz Ν. \- ^N ^ ^N O. Z^N' y Y +>_<7 γΝ ^Η H ₃ C CH ₃ 485.64 486.4 0.8 QC- ACN- TFA- XB 48 Ν ⁼ Ν L ^ΝΗ Ν _{= Ν} Υ^ ^{7 ΗΝ} χΥ^Ν^/\ H ₃ s 565.69 566.6 0.81 QC- ACN- TFA- XB 49 Η Yen. 0-Υ <^ν ν^7 ν y γ γΝ ΥΥΥ γγ ^Η H ₃ C CH ₃ 487.65 488.3 1.46 QC- ACN- AA-XB 50 η ₂ ν^\ n ₃ s T 1 γεΗ _{3 Ν} ν^7 y γ \>_# γΝ ν γγ ⁿ H ₃ C sn ₃ 403.53 404.3 0.74 QC- ACN- TFA- XB

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51 ^CN NC. H ₃ C 1 ]y-snz k/ ^N \ ,Ν. 7 _ „SNz o 466.59 467.2 1.27 QC- ACN- AA-XB 52 ^CN NC. H ₃ C γη ³ usn ₃ k/N___N. 7 .,(¾ V YyY N o 466.59 467.2 1.36 QC- ACN- AA-XB 53 O H n r% T 1 >^ SN ₃ ³ ° k / k / N ^ 7, CH ₃ γ Tuk ι O 494.66 495.2 1.56 QC- ACN- AA-XB 54 H ₃ C. _N ,CH ₃ 0 ^^0 ^'Ν^γΥ ^НзС usn ₃ CH ₃ k/N. ,Ν^ 7 _ ,CH ₃ γ υυυυ kk^N \k\ ⁿ o 558.73 559.2 1.64 QC- ACN- AA-XB 55 CH ₃ rfp V "\u003e -, ° ^{J u} i" Y ^H H ₃ C CH ₃ 501.68 502.2 0.8 QC- ACN- TFA- XB 56 р ZI ύ X bjl ? Ο ^ω 'il-f 501.66 502.2 1.62 QC- ACN- AA-XB 57 Η ⁿ zS _sn // Τ Ί γθΗ _{3 Ν} ν^7 ν y ηΥ_# γΝ kY-N γγ ⁿ H ₃ C sn ₃ 457.63 458.2 0.85 QC- ACN- TFA- XB

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58 L ? ^Nz * _g and. nW ^H H ₃ C CH3 471.65 472.3 0.89 QC- ACN- TFA- XV 59 CH ₃ ^CHz N) \u003d \ ^H H ₃ C CH ₃ 471.65 471.9 1.58 QC- ACN- AA-XV 60 rm SNz NzS MF ^N N ₃ C SNz 509.66 510.2 1.49 QC- ACN- AA-XV 61 CH ₃ ί V 9 ^N z ^Ν Λ ^Ν η ^NzS _G n ₃ ^b w ⁿ N ₃ C sn ₃ 569.71 570.2 1.64 QC- ACN- AA-XV 62 CH ₃ TO U ^CH s H ₃ C z ^ n' 1 y f \\> __V \ \u003d ^{N H} H ₃ C CH ₃ 511.68 512.2 0.85 QC- ACN- TFA- XV 63 ,Γ-Ν CH ₃ HzC H ₃ C,-n' 7 y __V \=N )=\ ⁿ H ₃ C sn ₃ 512.67 513 0.82 QC- ACN- TFA- XV 64 ^H ' ^C Y% CH3 ^H3C ^CH T 1 V ^CH 3%' ^ν Ύ' ^ν ^Α y j y__y=N ⁿ n ₃ s CH ₃ 523.69 524.2 1.72 QC- ACN- AA-XV

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65 CH ₃ - ^H H ₃ C CH ₃ 473.63 474.2 0.79 QC- ACN- TFA- XB 66 SN ₃ Hundred ^Nz U ^SN _% ^H H ₃ C CH ₃ 445.62 446.1 1.22 QC- ACN- AA-XB 67 Η ₃ 0'°γ% CH ₃ H ₃ C 1 1 l ^CH3 n. || C __ (7 \= ^N H H ₃ C CH ₃ 539.69 540.3 0.84 QC- ACN- TFA- XB 68 CH ₃ ^{CH3 H} H ₃ C CH ₃ 512.67 513.2 1.28 QC- ACN- AA-XB 69 CH ₃ n Ύ n ⁿ z \ ey T T 1 G ^SNz Ν. ⁿ z ° y η Y__# ν=Ν \T^N }=\ ^H H ₃ s CH3 555.69 556.1 1.14 QC- ACN- TFA- XB 70 H ₃ C ^ ⁿ H ₃ C SN ₃ 459.64 460.3 1.39 QC- ACN- AA-XB 71 CH3 ' ^h PO ⁿ ^ ^N γ° (Г N^J^/N^2/CH ₃ n ₃ С T 1 1 VCH _{3 N H} ^{3 C} ji __(7 \^Ν \ί^Ν )=\ ⁿ H ₃ s sn ₃ 707.84 708.5 1.13 QC- ACN- TFA- XB

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72 η H,c ₃ ^L w ^H H ₃ C CH ₃ 525.66 526.3 1.64 QC- ACN- AA-XV 73 nn h ₃ cY^ /ί ^Ό ΧΧτ ^H 3 ^CH H ₃ C 'DH ₃ 593.74 594.1 1.56 QC- ACN- AA-XV 74 XX XXX H ₃ c CH ₃ 615.79 616.2 1.18 QC- ACN- TFA- XV 75 _Z O ₄ X h ₃ c γ > ^N ^XX XxXr O ^H H ₃ C CH ₃ SN ₃ 647.79 648.5 1.07 QC- ACN- TFA- XV 76 /Г-N ^N ' A •Qp V· ., ^B,c 'i· Ain-· ^H H ₃ C CH ₃ 593.74 594.2 1.54 QC- ACN- AA-XV 77 CH ₃ X|P \ X, ^ \ H ₃ C YX y-CH _{3 N} N / X y Y _// \=N ^H H ₃ C CH ₃ 515.68 516.8 1.67 QC- ACN- AA-XV 78 f^N CH ₃ H ₃ C N || __(/ \=N Xy^n x=/ ⁿ n ₃ with CH ₃ 509.66 510.3 1.15 QC- ACN- AA-XV

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79 h ₂ n^^ h ₃ c T ] \--0H3 y-OH kN /N. 7 /=< IXM/An NJ H 405.51 406.1 0.65 QC- ACN- TFA- ΧΒ 80 Q ΖΞ ύ w _? TZ\0^0 1 °Gt AG 1 489.62 490.4 0.73 QC- ACN- TFA- ΧΒ 81 Η •'-AT Η 461.57 462.3 0.62 QC- ACN- TFA- ΧΒ 82 ? YES TO ° 1 ° Vj ^{1 f} =0 ΧΖ SI ο-^ ^τ 489.62 489.9 1.32 QC- ACN- ΑΑ-ΧΒ 83 Η Η ₃ Ο 1 ] y-CH ₃ ^ΟΗ 7 J-7—(7Γν ^ th ^V v 444.54 445.4 1.33 QC- ACN- ΑΑ-ΧΒ 84 X O Ο-Ζ c? ΖΙ ύ Ο ϊ ^Ι2 /Λγ” Ok ΑΓ AI 490.61 491 1.24 QC- ACN- TFA- ΧΒ 85 τ Ο 0' < 0 ΙΖ £ ζ-° ο Τ 490.61 490.9 0.9 QC- ACN- TFA- ΧΒ 86 0^1 ^H3 V ^CH 3 N. e ^Ν ϊ5>^ ^Ν V ⁿ H3C^2H ₃ 459.60 460 0.83 QC- ACN- TFA- ΧΒ

- 80 041852

87 ³ U- ^CH s L/xRr fc ^H 3 ^H H ₃ C CH ₃ 0* *0 535.71 536.2 0.89 QC- ACN- TFA- XB 88 t 0 W f 1 Ο ζ 1ζ ^ω 375.48 376.3 1.09 QC- ACN- AA-XB 89 Τ 0 Ο X / \ ω ΙΖ 1 Ο Λ“ νϊό ICO 391.48 392.3 0.98 QC- ACN- AA-XB 90 CH ₃ 0 ^{n s 3} V ^CH 3 O-CH3 L/NN^7 /=/ X JX?/—C H 476.59 477.22 1.44 QC- ACN- AA-XB 91 H ₃ Ck H ₃ C y-CH ₃ o-CH ₃ k/N. _N. 7 /=/ ΊΓ X//—^C/^N ^th ^Vfj % 405.51 406.2 1.48 QC- ACN- AA-XB 92 CH ₃ H ₃ C ³ y-CH ₃ o-CH ₃ /=/ Ύ Tj/—<C/^N H ' _N ^ 433.56 434.4 1.01 QC- ACN- TFA- XB 93 / 0 W z / \ co i ° O Vi A I ω 447.54 448.4 0.93 QC- ACN- TFA- XB 94 MG ³ U ^CH s O-CH ₃ ¹ ^N /=/ L J-/-C ^{N H} N 430.52 431.3 1.58 QC- ACN- AA-XB

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95 N ₃ S./ _{n g} o .s''''''·'*. χΧ* ⁴ *". P *3 O o' 7 1 VCH ₃ 0-CH3 k/N. 7 /=/ Ύ X/ - ^th ^V v 497.62 498.2 1.6 QC- ACN- ΑΑ-ΧΒ 96 H ₃ C. X \ H ₃ C O Y ^CH N. n / n y [ __# \= Ν Ν ) \u003d ζ ⁿ n ₃ with CH ₃ 403.53 404.3 1.31 QC- ACN- ΑΑ-ΧΒ 97 ^H zC ³ \-CH ₃ m ή / I 1 / y # \^Ν Ν / \u003d\ ^Η H ₃ C CH ₃ 473.63 474.4 1.84 QC- ACN- ΑΑ-ΧΒ 98 Hz-N^p zusnz y η Y_# \= ν /=\ ^Η H ₃ C CH ₃ 488.64 489.4 1.23 QC- ACN- ΑΑ-ΧΒ 99 H _S C _o _ _cHj CH ₃ /=( x XC/—C ^N ₄ ^H N 490.61 491.2 1.12 QC- ACN- ΑΑ-ΧΒ 100 CH ₃ H ₃ C^N^ ^H3C y-CH _{3 N} y ΊΓ^_# \^N ^Η H ₃ C CH ₃ 431.59 432.11 1.62 QC- ACN- ΑΑ-ΧΒ 101 ' ^{^ Ν} ' ^Ζ ^Ί ^NzS y-sn _{3 Ν} 1 1 Г y J # \=^Ν ^H H ₃ C CH ₃ 473.63 474.4 1.5 QC- ACN- ΑΑ-ΧΒ 102 HcC _n ] ³ V-CH3 o-CH ₃ ^U ~^ X/ ^N \/N. 7 ,=/ Ύ jXJ/— ^N 'M Η 475.60 476.4 0.84 QC- ACN- TFA- ΧΒ

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103 ^H ' ^C 4-CH I 1 y-CH3 o-CH3 to .N. /N. 7 /=/ ^th ^V v 461.57 462.2 1.47 QC- ACN- ΑΑ-ΧΒ 104 0 0 1 О ,Oi V A 475.60 476.4 0.84 QC- ACN- TFA- ΧΒ 105 H ₃ C. H ₃ C but ^ O ^U CH 3 CH ₃ k ^ NN ^/ ^-n ¥ [ \> __ (/ \ \= N ^H H ₃ C CH ₃ 461.61 461.9 1.92 QC- ACN- ΑΑ-ΧΒ 106 H ₃ S. n ₃ with but ^ O U ^CH3 o-CH3 CH ₃ N^7 /=/ Ύ Χ / ζ-C / \u003d ν Μ ^Η Hch 463.59 464 1.5 QC- ACN- ΑΑ-ΧΒ 107 ck'/l ^^1 ³ U ^CH3 O-CH ₃ V- ^J k/N. 7 ,=/ Ύ JX^—C ^H 475.60 476.2 1.72 QC- ACN- ΑΑ-ΧΒ 108 WH ₃ C y-CH ₃ 0-CH3 k/ ^N ^ ^N ^A /=/ XT JXJz— NNJ H ' _N ^ 445.57 446.2 1.13 QC- ACN- TFA- ΧΒ 109 ^НзС ^ы^ ^НзС \^en III y-CH ₃ o-CH ₃ CH ₃ %/NN^7 /=/ to J- / A ^H N 447.59 447.9 2.18 QC- ACN- ΑΑ-ΧΒ 110 I 0 k > 0 w ? 1 ° ,cv Vz ό I co 461.61 462.2 2.07 QC- ACN- ΑΑ-ΧΒ 111 ^NzS ^m^ ^NzS \ GN n ₃ cI ΐ 1 U- ^CH3 p-sn ₃ ³ CH ₃ k^N _x .N _x _7 /=/ XJL/-C Η 461.61 462.2 1.3 QC- ACN- TFA-

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XB 112 CH ₃ 1 ^X ^HzS Y- ^s o-sn ₃ ^O 'CH ^ M / H. 0 JL /—A /^N ⁿ 463.59 464.2 1.7 QC- ACN- AA-XB FROM H ₃ C 7 | y-CH ₃ o-CH ₃ k^hk^hL J =( Ύ X/—O=N ^th ^V v 489.62 490.2 1.04 QC- ACN- TFA- XB 114 X? X ^NZ X ^CH s O-CH ₃ AN-toYau ⁿ \u003e G 475.64 475.9 1.42 QC- ACN- TFA- XB 115 X^X ^H3C \-CH ₃ o-CH3 ^J ^txKb n 447.59 448.3 1.89 QC- ACN- AA-XB 116 Χ'^^^Ί ³ U ^s o-sn ₃ CF ₃ k^NN^7 ==/ X XX-Y X ^N k^-N % H 487.53 488.3 2.06 QC- ACN- AA-XB 117 CH ₃ ^H °Xu/\ H ₃ C 7 | y-CH3 o-CH3 k^N.^N. J ,=( X Xv—XX n ^th ^V v 449.56 450.3 1.47 QC- ACN- AA-XB 118 CH ₃ | XX ³ U ' ^CH s o-sn ₃ 1! JL /—y λ=Ν ^N - 4 H 463.59 463.9 1.42 QC- ACN- AA-XB 119 HsC^N'X ³ y-CH ₃ o-CH ₃ Xn^n^X /=< ^H 419.53 420.13 1.04 QC- ACN- TFA- XB

- 84 041852

120 ^H ₃ C \/l ] 445.57 446.2 0.97 QC- ACN- TFA- XV 121 CH ₃ ι JL / h. η with X 1 ³ X ^s o-CHz Ύ ΧΧ—ΧΧ^ ^ν 'Μ Η 516.65 517.1 1.54 QC- ACN- AA-XV 122 CO τ ⁴ Ζ=λ tLU £ ο ^ζ ^Ύ> ^{τ £} ο 0- 375.48 376.11 1.17 QC- ACN- AA-XV 123 _{CH 3} ⁰ 7. _Z CH ₃ Ύ TyX] Γ^ν ⁿ JJ 460.59 461.2 0.88 QC- ACN- TFA- XV 124 Hs%/\A^ H ₃ C CH ₃ LzN. ,N ₄ J _ ,CH ₃ V Vy^N Γ'Ν XJ/ 474.61 475.4 0.67 QC- ACN- TFA- XV 125 ^ ^z =\ £ o ] ^£ o rj o 389.51 390.3 1.25 QC- ACN- AA-XV 126 I ω O _ο O t 1 O .__ t ^{ω 2} w 417.56 418.3 0.75 QC- ACN- TFA- XV

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127 CO τ °' /Ch I o T o% A ^{zi f} o a 0 459.60 460.4 1.43 QC- ACN- AA-XB 128 Ln „Yj T o T Q £ V° o-z ъ ΞΕ 476.59 477.4 1.41 QC- ACN- AA-XB 129 ^H s \ CH N' // 7 ] U ^CH s o-CH ₃ </NN^7 /=/ H ₃ C fl J VL Ln ^H N 486.58 487.4 0.87 QC- ACN- TFA- XB 130 ^H2N >^n^ ^NzS \ GI π । I y-CH ₃ 0-CH3 X XX—CV ^H N 448.53 449.4 1.29 QC- ACN- AA-XB 131 ⁿ sC ³ yCH ₃ 0-CH3 ^ ^N ^N.7 =/ X XX—C Xn ^H N 449.56 450.37 0.93 QC- ACN- TFA- XB 132 ^НзС % ^сн з O-CH3 ^{3 0} L/N^/N^7 =/ x Χχ—CH ' _N ^ 511.65 512.2 1.51 QC- ACN- AA-XB 133 % O 0 X ^z ? X ⁰ .0^ Vi AI co 523.66 524.3 1.65 QC- ACN- AA-XB 134 £ M ⁰ o^x> ^{x £} a ^Xz x ^0 xW °' 4 T 512.63 513.3 1.47 QC- ACN- AA-XB

- 86 041852

135 ³ yCH ₃ o-CH ₃ kJJ J ,=/ Ύ Xj/—<C/^ ^NH 501.56 502.4 1.14 QC- ACN- TFA- XV 136 0 ^CH, o-CH, CH ₃ k^NN^7 /=/ X JO*—a ^{n H} N 490.61 491.2 1.08 QC- ACN- TFA- XV 137 0 H ₂ N'^ ^X/ ^N ^x ^ ^X | ³ \—CH ₃ o-CH ₃ %/N N.,7 /=/ ΊΓ JXf/—A \=N ^H N 462.56 463 1.28 QC- ACN- AA-XV 138 H H ^Nz %GN ^H 3 ^G Π 1 1 X ^GH 3 o-CH ₃ o k/N. ,N. 7 ,=/ k 7/7—( km V _v 462.56 463.4 1.4 QC- ACN- AA-XV 139 ⁿ O ^Nz U ^{snz ν} > ΥϊχΗ7 ^Η N ₃ C CH ₃ 403.49 404.2 0.87 QC- ACN- TFA- XV 140 °l YtxHF ^H H ₃ C CH ₃ 459.55 460.3 1.05 QC- ACN- TFA- XV 141 CH ₃ H ₃ C' ^N ^N^ ^HzC y-CH _{3 n} ° YOHF ⁿ H ₃ C CH ₃ 488.60 489.4 1.28 QC- ACN- AA-XV 142 n ₃ s. H ₃ C O\u003e - ^CH3 N. / current ^{1 H} H ₃ C CH ₃ 417.52 418.3 1.34 QC- ACN- AA-XV

- 87 041852

143 0 ^Nz y-z _n z^NYT # \=n N /=\ ^H H ₃ C CH ₃ 516.65 517.4 1.49 QC- ACN- AA-XB 144 CH ₃ h ₃ c' ⁿ Yn^ ^НзС usn _{3 N} ⁰ Z^N Y ΊΓ _v \=n N )=\ ^H H ₃ C CH ₃ 474.61 475.1 1,H QC- ACN- TFA- XB 145 ^H V ^H = N \^-N )=\ ^H H ₃ C CH ₃ 500.65 501.2 1.47 QC- ACN- TFA- XB 146 ^h v ^h 3 n Y [ # \=n N )=( ^H H ₃ C CH ₃ 486.62 487.4 0.8 QC- ACN- TFA- XB 147 h 1% SN _{3 N} ^{3 0} Ν ₄₄ Γ N Y __<7 \=ν )=ζ ^Η H ₃ c CH ₃ 509.67 510.4 1.41 QC- ACN- AA-XB 148 NC.^ _K1 ^ H ₃ C O Г^ ³ N. 7| ΊΓ^__(/ \=N N )=\ ⁿ H ₃ C CH ₃ 442.57 443.2 1.82 QC- ACN- AA-XB 149 0 11 ______ _______ un ³ y-CH _{3 N} /r^ TT __// \=N a^-n )=( ^H H ₃ C CH ₃ 460.59 460.9 1.41 QC- ACN- AA-XB 150 HN^ ^НзС уСН _{3 N O} ^NN / _N ' ° | Y / V=N ^H H ₃ C CH ₃ 403.49 404.4 1.36 QC- ACN- AA-XB

- 88 041852

151 ° \ / ° _ H, C CH ₃ E || __(/ \=N xAn )=( ^H H ₃ C CH ₃ 524.69 525.1 1.74 QC- ACN- AA-XV 152 ^H O N. tw ^H H ₃ C CH ₃ 403.53 404.1 1.95 QC- ACN- AA-XV 153 ^NzS \ CH πν η y-snz _Ν ζ—ν ^ζ \u003d Γ II% __s Υν CH ₃ ) \u003d ( ⁿ H ₃ C sn ₃ 403.53 404.1 1.31 QC- ACN- AA-XV 154 O'^ ^N 1 U-CH3 _m 1 1 / IA _O ^NN / E ° y γΝ \Αν ) \u003d ( ⁿ H ₃ C sn ₃ 516.65 517.2 1.14 QC- ACN- TFA- XV 155 L H ₃ C ? 1 U ^CH3 N ° y ίΓ^_# \^ν ^H H ₃ C CH ₃ 516.65 517.2 1.49 QC- ACN- AA-XV 156 % ΗΝ^ НзС _ν ^YyV-гР Ν )=( ⁿ Н ₃ с сн ₃ 500.65 501.2 1.4 QC- ACN- AA-XV 157 ⁿ U H ₃ C. A H ₃ C Ύ U ^CH3 CH3 </N Ί γ |y / γΝ ^H H ₃ C CH ₃ 488.64 488.9 1.38 QC- ACN- AA-XV

- 89 041852

158 Ar v. ΗΝ / ^- ν' 7 Ί Τ' φ _<7 vn όη /=\ ^Μ H ₃ C sn ₃ 490.61 491.1 1.05 QC- ACN- TFA- XV 159 0 Λρ ^Нз у _Нз HN k^NN^J | [ π %__(7 >N to ₀ ,sn ₃ ^H H ₃ c CH ₃ 504.64 1009.4 (2M+H) 1.4 QC- ACN- AA-XV 160 'yl-, -v„ 1 1 n ^-n' E ( J __Δ \=N TT-n )=\ ^H H ₃ c CH ₃ 530.68 531.2 1.35 QC- ACN- AA-XV 161 about Lr N. 1 L ΡΡ Ρ Δ ^p >=< ⁿ H ₃ C sn ₃ 500.65 501.20 1.43 QC- ACN- TFA- XV 162 ΗΝ-Χ H ₃ C / Ί y-CH _{3 Ν} OvVi Τ Ρ +>_Δ V=N \Ρ^Ν pp ^Η H ₃ C CH ₃ 403.53 404.3 0.8 QC- ACN- TFA- XV 163 /—\ H ₃ C ⁿ sC /— Ν 1 V-CH _{3 Ν} N'T V/NN / _Ν ' ^HcC ° Τ W\ )^ ^Ν \Ρν / ⁼ \ ⁿ n ₃ s sn ₃ 488.64 489.3 1.38 QC- ACN- AA-XV 164 ⁿ zS /T U ^CH 3 Ν Η >^ ^Ν b> ) \u003d { H ₃ with SN ₃ 445.57 446.4 1.43 QC- ACN- AA-XV 165 _and / - NH H3C-SZ V H ₃ C oT> L ³ usn _N y f # \\=N N ) \u003d ( ⁿ H ₃ C sn ₃ 521.68 522.4 0.83 QC- ACN- TFA- XV

- 90 041852

166 CH ₃ H ₃ C _y -CH ₃ o-CH3 NC and A /-a A ^N 'M ⁿ N 471.61 471.9 1.06 QC- ACN- TFA- XB 167 H H ₃ C^N^^ H ₃ C T|| y-CH3 o-CH3 CH ₃ MAMA /=( 1 JL /—a /^ ^{n n} N 446.60 447.2 1.06 QC- ACN- TFA- XB 168 CH ₃ H ₃ C^N^^ H ₃ C III y-CH3 O-CH3 CH ₃ MA^xMA /=( I JL /—A /^ ^N n Ν 460.63 461.2 1.35 QC- ACN- AA-XB 169 CH ₃ χ ^N ^% H ₃ C [Τ 1 y-CH3 O-CH3 HO^ ^N yX/Xv |i JL /—A /== ^{141 H} N 462.60 463 1.21 QC- ACN- AA-XB 170 CH ₃ H ₃ C^N^^ H ₃ C III y-cH ₃ o-CH ₃ ch ₃ JAzjJ /=( 1 JL /—a L ^{n H} 460.63 461 1.56 QC- ACN- AA-XB 171 ch ₃ НзС VI 1 y-CH ₃ 0-CH3 LA/N. 7 /=/ Xj/ - ^H 458.61 459.4 0.77 QC- ACN- TFA- XB 172 ch ₃ H ₃ C ₄ \A II \-ch ₃ 0-CH3 LA/N. 7 =/ xr/—X/^ ^{n vn} % 458.61 459.3 1.49 QC- ACN- AA-XB 173 abs/^-QH ^H Ach 1 ] y-CH ₃ o-CH ₃ xX—O^ ⁿ H 488.64 489 1.28 QC- ACN- AA-XB

- 91 041852

174 n ₃ s T 1 Y ^CH 3 o-sn ₃ kAnA /=^ ^^χ xX—XX^ ^ν On 458.61 459.2 1.02 QC- ACN- TFA- ΧΒ 175 CH ₃ H ₃ C III γοΗ ₃ o-сnz ng ^^V ^N Yy_/ ⁼ V 11 JL /—A /^N %N ^H 471.61 472.2 0.75 QC- ACN- TFA- ΧΒ 176 H ₃ C 1 1 Y ^CH 3 o-ch ₃ kA/N. J /=/ 1/IW-n H 403.49 404.2 1.68 QC- ACN- ΑΑ-ΧΒ 177 CH ₃ H ^H Och ^H 3 ^G | | γθH ₃ o-CH ₃ kA/N. J ,=/ ^^X XX—X/^ ^N HN 432.57 433.1 1.29 QC- ACN- ΑΑ-ΧΒ 178 H H ₃ C //11 y-cH ₃ 0-CH3 k^k J =/ XX—XX^ O N ^H N 460.58 461.4 0.73 QC- ACN- TFA- ΧΒ 179 ch ₃ h ^N Aen ⁿ zO T 1 γοΗ ₃ o-CH ₃ kA/N. J /=/ XT/—X/^ ⁿ AA~N ^N _s ^H 432.57 433.1 1 QC- ACN- TFA- ΧΒ 180 H ^H 3 ^C h // Y 1 γΟΗ ₃ p-CH3 /A X XX—C Χ ^{ν Η} 460.58 461.1 1.6 QC- ACN- ΑΑ-ΧΒ 181 ? ^{Η Η} 3°'ΝΑ ^Ν γ^ ⁿ zC. ρμ Υ ] γοΗ ₃ o-sn ₃ snz ΑΑ^Ν.7 /=/ X XX—C Χ ^ν Α^ν Α _ν ^Η Ν-^ 489.62 490.3 1.14 QC- ACN- ΑΑ-ΧΒ

- 92 041852

182 II n H ₃ C CH ₃ ΡΑχ/ ^Ν ^7 /^m' ^CH Ύ VyAY 472.64 473.4 0.92 QC- ACN- TFA- ΧΒ 183 Η ^H NzC ^ A / N ^ h ₃ c CH AUhk __ _r CH ₃ A str "_ o 472.64 473.3 1.42 QC- ACN- AA-XB 184 H LU Tl U-sn ₃ ° ⁷ ^A^N^7 /-M' ^CH 3 J Yy^i \iA~N ⁿ o 443.60 444.2 1.51 QCACNAA-XB 185 H H ₃ C ' / T 1 y-sn ₃ ^ΧΗ ₃ Ύ YykY 443.60 444.3 0.88 QC- ACN- TFA- XB 186 Η (CY Y-CH3 p-CH3 Η 460.58 461.5 0.75 QC- ACN- TFA- XB 187 sn ₃ ,Ν. H ₃ C ⁿ zS y U u-sn ₃ o-sn ₃ kL / N. 7 /=/ HG/—Can ⁿ 432.57 433.3 1.26 QCACNAA-XB 188 Η ⁿ zC ι \--sn ₃ o-sn ₃ kA/UU 418.55 419.2 0.67 QC- ACN- TFA- XB 189 H ^N. _{H 3} C ^N _{C ]} 418.55 419.1 1.28 QCACNAA-XB

- 93 041852

190 Η /Ν. H ₃ C G II \-CH ₃ o-CH3 n Ln ϋ JL /—A /=N 1 p CH ₃ ^N 510.65 511.2 1.23 QC- ACN- AA-XB 191 CH ₃ H ₃ C 111 y-CH ₃ o-CH ₃ ^h ° ⁿ yO ⁼ V [I JL /—L /^n HN 462.60 463 1.07 QC- ACN- AA-XB 192 Yn. H ₃ C || V-ch ₃ 0-CH3 J /=/ ^^X XX—X/^N ^V 'V 458.61 459.1 1.31 QC- ACN- AA-XB 193 H H ₃ C^N^^ H ₃ C TI 1 /CH3 0-CH3 CH3 L^^n.7 =/ X XX—4 Y ^{n H} 446.60 447.1 1.48 QC- ACN- AA-XB 194 O'X NZS T 1 U-CHz o-CHz Xj/-Γαν 'M Η Ν 474.61 475.2 0.98 QC- ACN- TFA- XB 195 Υν.H ₃ C γη y-sn ₃ o-sn ₃ /=/ X XX—4 /=ν Η Ν 458.61 459.3 0.76 QC- ACN- TFA- XB 196 Η ^uCH _{3 o} . _SNz L ⁿ -LLL _n ~j CH ₃ ^Ν 510.65 511.5 1.43 QC- ACN- AA-XB

- 94 041852

197 abs/^QH H ₃ C _pH T 1 / ^CH3 O-CH3 ^^XXX—χχ^ ^Ν Η Ν 488.64 489 1.16 QC- ACN- ΑΑ-ΧΒ 198 CH3 H ₃ C? II u-sn ₃ o-sn ₃ SNz 7 \u003d / ^x χχ - o ^ n ^ th ^V v 476.63 477.3 1.19 QC- ACN- ΑΑ-ΧΒ 199 O^\ n ₃ c T 1 y-CH3 o-CH3 Υ/ΎΥ /=/ X XX—C Χν _NNJ 458.61 459.2 0.79 QC- ACN- TFA- ΧΒ 200 I ω O Ο-Ζ ω ZO __/ IW ¹ jX-x cX ^z o c? 486.66 487.4 1.58 QC- ACN- ΑΑ-ΧΒ 201 I ω O ο-ζ' ω Ζ-Ο __/ I Ο * jΧχ χχ ^Ζ ο with? 486.66 487.1 1.53 QC- ACN- ΑΑ-ΧΒ 202 ^NzS /X CH ₃ H ₃ C _o _ _cnz ^Χί χΧ—ΧΧν V _v 524.67 525.2 0.81 QC- ACN- TFA- ΧΒ 203 ^NzS Ht ? ^Hs H,C _o _ _cHj ^Xί χχ—CX^n ^Η Ν 524.67 525.4 0.81 QC- ACN- TFA- ΧΒ 204 /^9 and ^Ν \Αχ/Ν _χ ^. ^НзС ^сн 1 ] y-CH3 o-CH3 <Α _ζ ν. J /=( ^^χχχ—χχ^Ν Η Ν 485.59 486.3 1.26 QC- ACN- ΑΑ-ΧΒ

- 95 041852

205 H ₃ CNH ₃ C IN ^{T 1} 493.66 494.2 1.17 QC- ACN- TFA- XB 206 NzS _ρH 1 1 A ^CH 3 o-sn ₃ X/z— AA N ^H N 485.59 486.2 1.7 QC- ACN- AA-XB 207 H ₃ C_N. H ₃ C in T 1 /—^^3 LA.N___7 γ YyYJ \A _N \=A ^H V 493.66 494.2 0.94 QC- ACN- TFA- XB 208 XY CH ₃ H ₃ C ^N T 1 Vch ₃ o-ch ₃ XX—^Γζ== ^{ν H} 510.65 511.4 0.87 QC- ACN- TFA- XB 209 XX CH ₃ H ₃ C _pH ^N II% CH ₃ o-ch ₃ 7AzN _v 7 \u003d/ ^^Xί X / S - Xz ^N AS v _n ^H 510.65 511.32 1.19 QC- ACN- AA-XB 210 0 CH ₃ H ₃ CH ₃ C ΰ T 1% ^GH 3 O-CH ₃ LA/ ⁿ a /=( -C~7n ^V v 489.62 490.4 1.06 QC- ACN- TFA- XB 211 0 CH ₃ HsC^A/N,/. h ₃ c Y 11 A ^CH 3 o-ch ₃ CH3 AA^n^J =/ Ίί X/z—a Yn ^H 503.65 504.4 1,H QC- ACN- AA-XB 212 0 CH ₃ hn^Y ^N Y% ^НзС \ ch ^h 2 ⁿ i | \^ch ₃ o-ch ₃ kA^N _v J =/ ^lTHTYn ^H N 475.60 476.1 1.17 QC- ACN- AA-XB

- 96 041852

213 II n nc% n ₃ s CH3 c/k ^^U /=/ bn ₃ 1 A /—A /==N ⁿ Ν 503.65 504.3 1.16 QC- ACN- AA-XV 214 Η ha ιι U ^SNz a / \ ' ^SNz [I D /—Τ Αν Η 474.61 475.3 0.85 QC- ACN- TFA- XV 215 Η H ₃ C γ^Ύ II V ^CH 3 he ^Ίί XG/—^Αν V _V 460.58 461.1 1.21 QC- ACN- AA-XV 216 ? ^{Η H} 3 ^C 'mA ⁿ v% ⁿ ₃ ^C gi U II A s _n ^s s / Aum / \u003d < A XA - C An Η 489.62 490.3 0.78 QC- ACN- TFA- XV 217 ^H3C V^N Τ ι Η ν^Αν^ h ₃ c Τ 1 V ^CH 3 ^ΟΗ ΧΑ—χ^Ν αα ν _ν 510.65 511.4 0.83 QC- ACN- TFA- XV 218 Ρ ΖΞ W ϊ ^IZ V% ο Ux ι A Mi I 485.60 486.1 1.06 QC- ACN- AA-XV 219 o \/ n λΧχΝ.^ n ₃ s _Hz X _b kZH N D ^SN D° " ^CH3 XS/— 536.70 537.3 1.62 QC- ACN- AA-XV 220 n pD τι U ^SNz ^ ^he XX/-pA 460.58 461.3 0.76 QC- ACN- TFA- XV

- 97 041852

221 P ZI w? 1 about SP I 485.60 486.1 0.63 QC- ACN- TFA- XB 222 Η Η Y I Ί γοΗ ₃ he CH ₃ Πν ^Ν Η ΎXX—CX ⁿ H _N ^ 489.62 490.3 1.07 QC- ACN- AA-XB 223 ^Nz P _sn Nz^% ΤΧ Ν XX^Нz χχ—χχ^Ν Η 536.70 537.3 0.85 QC- ACN- TFA- XB 224 ^H s ^C ^ _M 1 I Η H ₃ C Τ 1 l ^uMz ^° ^Η kAx 7 /=< χΧ—XΧν π y Η _Ν -^ 510.65 511.3 1.03 QC- ACN- AA-XB 225 o CH3 ^η 2 ^ν ~ΤΧ ³ H ^CH 3 O-CH3 L ΑΧ J ,=( ^lXMTXn 475.60 476.4 1.37 QC- ACN- AA-XB 226 0 CH ₃ ^H 3 ^C ' _N X^ h ₃ c y | | V ^CH 3 o-CH3 SN ₃ \/PP \u003d/ χ XX-C Χν ^Η 503.65 504.4 1.32 QC- ACN- AA-XB 227 o CH3 H ₃ C th II YCH ₃ o-CH3 ^m kL/N___/ /=/ ^lXXXXn ^H 489.62 490.1 0.73 QC- ACN- TFA- XB 228 0 CH ₃ H ₃ C N || \-CHz o-CHz CAxN. J ,=/ ^Xi Ty<X _N ^H 489.62 490.3 1.53 QCACNAA-XB

- 98 041852

229 Η n ₃ s ΊΟ U ^SNz /0 ^SNz U JL /—a Ον Η 0 474.61 475.1 0.76 QC- ACN- TFA- XV 230 ? ^Η Hs%L^^ HsS CHs ΤΧνΟ _/ qh ₃ I JL /—A On Η Ν 503.65 504.3 1.24 QC- ACN- AA-XV 231 Η Η ^Η ₃ ^ H3C 7 489.62 490.3 1D QC- ACN- AA-XV 232 9 ^H AC^/O^-N.^-^ H3C T| V-CH3 ο-CH3 CH3 /=( L DO—C ⁿ N 489.62 490.3 1.26 QC- ACN- AA-XV 233 H ^h ' ^c _V ch, ° ^J kX% A _N y y y_y \u003d N ^H H ₃ C CH ₃ 458.61 459.4 1.27 QC- ACN- AA-XV 234 H NzS y TU_/ y ^ N 00-N) \u003d\ ^N H ₃ C CH ₃ 458.61 459.3 1.09 QC- ACN- AA-XV 235 7 ΖΣ About I 1 O Ok ASU 460.58 461.3 0.62 QC- ACN- TFA- XV 236 o V n ncO ° ^ ^H V ^H \ ^{u003d H3C 0} OJk ^ N /, CH ₃ y TuO n O 519.71 520 1.8 QC- ACN- AA-XV

- 99 041852

237 Y ^oJ υΧμ y / yN Ν )={ ^Η H ₃ C CH ₃ 498.68 499.2 1.79 QC- ACN- ΑΑ-ΧΒ 238 o \/ n nD% ⁿ ^ ^H V ^H > ^{3 0} k Λ + J ,sn ₃ Ύ TUU! "O 519.71 520.3 0.93 QC- ACN- TFA- ΧΒ 239 Y n ₃ with y f Y)_Y yN ν Yy ^N N ₃ C CH ₃ 498.68 499.3 1.9 QC- ACN- ΑΑ-ΧΒ 240 CH ₃ ut Υι U ^CHz / ^o-CH z xx - 'Μ ^Η 474.61 475.2 1.53 QC- ACN- ΑΑ-ΧΒ 241 CH ₃ ^НзС ^сн нзА XX ν У ^н ъ°- ^СНз X/-ΧΧν ^Η Ν·^ 524.68 525.2 0.76 QC- ACN- TFA- ΧΒ 242 O ? ^{Nz Nz} % _ΓΗ ^{Nz s} Λ XX _Ν U ^CHz P-CHz ^(ΤΗΓΧν ^Ν ₄ ^Η Ν 524.68 525.3 1.58 QC- ACN- ΑΑ-ΧΒ 243 4 x ^z ,? 1 ° ___/Αχ Si I 427.60 428.1 1.52 QC- ACN- ΑΑ-ΧΒ

- 100 041852

244 H ₃ C Ύ] y-CH3 o-CH ₃ ^itXX—O- ^V v 486.62 487.3 1.1 QC- ACN- AA-XV 245 OA 'ύ-Ν. H ₃ C γη y-cnz WrUf Hu 469.63 470.3 1.35 QC- ACN- AA-XV 246 CH ₃ H ₃ C su Τι U ^CH3 ^on ° ⁷ TA / k / / \u003d < XX-XXn V _v 474.61 475.3 0.63 QC- ACN- TFA- XV 247 m £ tX> Xχ? ^{τ τ} ο ΙΖ ° 4 τ 493.67 494.3 0.92 QC- ACN- TFA- XV 248 0 w _ °ΧΧ Η ₃ 0 | | usn ₃ o-sn ₃ %/-k/N.7 /=/ X XX—CX ⁿ Η 534.68 535.2 1.52 QC- ACN- AA-XV 249 CH ₃ ⁿ zC _ph n / I 1 / ^{C 3} / ^CH z A'yM /g \ 1 I / - / ) \u003d ° N G \u003d \ ^H H H ₃ C CH ₃ 462.64 463.1 0.75 QC- ACN- TFA- XV 250 CH ₃ H ₃ C OST XX x ^cNz / ^sn * 1 / XXX ° ⁿ CH ₃ 448.61 449 1.55 QC- ACN- AA-XV

- 101 041852

251 I ω ,Ο „s/g Ί ΖΙ W*1° I fv o I 493.67 494.3 1.47 QC- ACN- AA-XB 252 CH ₃ H ₃ C / / T 1 y-sn _{3 0H} XX-X / ^N ^H 474.61 475.3 1.34 QC- ACN- AA-XB 253 0 \\ _ os% H ₃ C ] ] Vch ₃ 0-CH3 kAx J ,=( ^XX/—X/^N H 534.68 535.2 1.32 QC- ACN- AA-XB 254 ch ₃ ZT XX U ^CH3 p ^h 3 XX/—\ )=° N ^H H ₃ C CH ₃ 462.64 463.3 1.55 QC- ACN- AA-XB 255 About °' ^s CXa \^-N. H ₃ ^{C γη} 517.69 518.1 1.45 QC- ACN- AA-XB 256 0 0 _ °=ΥΥ\ H ₃ C γη y- ^CH3 4 ^M vYf H O 517.69 518.2 1 QC- ACN- TFA- XB 257 η %ΛΗ ₃ H,CS _b ⁿ ' ^c 'Ao ~'^ύ ^{ν CH} ' 564.75 565.3 1.3 QCACNAA-XB

- 102 041852

258 0 sn % X ^e Η 3 Wn. /x H ₃ C Y γη ³ usn ₃ G O ^^Ύ ^Ν γγ_γΝ ^u 561.75 562.4 1.23 QC- ACN- AA-XV 259 O \__ ΖΣΓ O ¹ Jγ/ 1 o C0 " ^{ζ 4} --\ U ω'O' o o ω 611.82 612.2 1.52 QC- ACN- AA-XV 260 I o Su Ζ 1 o __Uh. t Hn ⁴ --\ U _su o' O I 480.63 481.3 1.49 QC- ACN- AA-XV 261 n ( Υ1 H ^CH ₃ H ₃ s _χΟ ^Hc % A) sn ₃ ΥΑ / ΛΥ ⁿ o 564.75 565.5 0.9 QC- ACN- AA-XV 262 I 'C -o _SL' o-\__ X ZI W ^{1 τζ} χΛγ° 1 O Ux I fp .o .ω' ° ^x o s? 611.82 612.4 1.74 QC- ACN- AA-XV 263 n H ₃ C ^N ^^ ^HzC uCH ₃ NC /^kU y Ύγ^ί ^{1 n} o 426.57 427.3 1.28 QC- ACN- AA-XV 264 n ^N A n ₃ s /S n ₃ s γ η ³ ^sn ₃ g 'o /-kU y Yy ^i ^{N n} o 493.67 494.1 0.88 QC- ACN- TFA- XV

- 103 041852

265 Η H ₃ C ιι Τι U ^CH3 Ck JZ^^ ^CH ₃ Ύ ⁿ O 471.65 472.4 1.37 QC- ACN- AA-XB 266 n ^N s ^S h ζθ H ₃ C / ^S 7 IT II X ^SNz \ O O% LA / N.7 J Ύ Wxfj \ An V \u003d X ⁿ o 563.76 564.2 0.92 QC- ACN- TFA- XB 267 Q ZI W ^{1 τζ} νΎ° 1 o C0 * ^Z^ o I 471.65 472.4 1.48 QC- ACN- AA-XB 268 Η NzS MS °-k ⁿ t+x~j 496.66 497.4 1.47 QC- ACN- AA-XB 269 b ZI W x / \ w iz\A^/° ϊ ° ^{ωΙ 2} —\ 0 O'b 493.67 494.4 1.27 QC- ACN- AA-XB 270 O—\ 7 ζ© o T o%_7 ^{x £} o TZ ъ T 426.57 427.3 1.38 QC- ACN- AA-XB 271 H ⁿ zA _x o NzS / S' G TTI x ^GM 3 । o ⁿ TmΪ o 563.76 564.1 1.44 QC- ACN- AA-XB

- 104 041852

272 x 0-7 o ] ωΧΧ ^£ Ο ιζ °Χ £ ζ-ο ο 497.65 498.4 0.98 QC- ACN- TFA- XV 273 ο η ^H V ^H 3 ^s ° o 518.68 519.1 1.57 QC- ACN- AA-XB 274 Η Η,Ο °o UyUzJ ο 496.66 497.2 1.44 QC- ACN- AA-XB 275 Η ^H3 V ^ch 3 ^ν 9 V 00^7 ³ 9 '% ΙχΗα ^Η θ' 518.68 519.3 1.47 QC- ACN- AA-XB 276 0 Η 3°'^^ ^ΟΗ, NC CH ₃ J ΎΧΧΟ ο 497.65 498.4 1.41 QC- ACN- AA-XB 277 N ₃ C G II \--CH ₃ o-CH ₃ CN __J Ν Η 499.62 500 1.27 QC- ACN- TFA- XB 278 Η nsG ^M ^ ^NzS usn, 4M ^ν η>γ ⁰ 'sn ₃ VA.. ^no 521.72 522.3 0.99 QC- ACN- TFA- XB

- 105 041852

279 Η cP XXn/U p ^SNz XX—ΧΧ^ν 444.58 445.3 1.31 QC- ACN- AA-XB 280 9 η ^H 3 ^C 'nX ^N VY ⁿ z \ ch Ν II V ^CH 3 _C n ₃ CH ₃ \u003d/ 1 X / -A Xn ^H N 473.63 474.4 0.81 QC- ACN- TFA- XB 281 °·^\ ^Χ-Ν. H ₃ C II U-CH _{3 CH} < ,ν. 7 /=/ xx—χχ^Ν H 470.62 471.2 0.77 QC- ACN- TFA- XB 282 Η H ₃ C 1 / T Ί u-sn _{3 SNz} ° ⁷ kX\/N. 7 \u003d/ ^ hhme ^H CH ₃ 418.59 419 1.55 QC- ACN- AA-XB 283 °^\ \_-hL H ₃ C II y-CH _{3 CH3} kA/N. 7 \u003d / (XXI 'M: ⁿ 'sn ₃ 444.62 445 1.45 QC- ACN- AA-XB 284 n H ₃ s 7/11 u-sn _{3 SNz} 7 \u003d / 444.58 445.3 0.79 QC- ACN- TFA- XB 285 0 H ₃ cs=o _H Xn ^H V ^H = ³ ^mXn- ^ch3 ^0 521.72 522.4 1.96 QC- ACN- AA-XB

- 106 041852

286 ^O _\ ^H ₃ C T ₁ 444.62 445.19 1.57 QC- ACN- TFA- XV 287 n H ₃ C oA Sl ν gΥ TMA \Αν Μ ⁿ sn ₃ 418.59 419.3 0.62 QC- ACN- TFA- XV 288 ογ__ ^N A _S N T 1 A ^s s SNz to / A __ ( / = / - "C / ^ n ^H 470.62 471.2 0.79 QC- ACN- TFA- XV 289 HH ₃ C _u _ f γ || U ^s n ₃ n ₃ s O,J LA/ΝΑ ,./ ¹ Ύ \=A ^H M 485.68 486.3 1.07 QC- ACN- TFA- XV 290 AA ^HzC y-CH ₃ H ₃ c ''' ^ AT / A ^o 483.66 484.4 1.05 QC- ACN- TFA- XV 291 ΞΓ O o-z ΖΞΕ W X 1 O See X\-o 486.66 487.4 1.06 QC- ACN- TFA- XV 292 n ⁿ z \ pi ns | | | | )—CH ₃ ⁿ zS oM > o 485.68 486.4 1.58 QC- ACN- AA-XV

- 107 041852

293 BUT. n ₃ s _w _ γη usn ₃ n ₃ s but 402.54 403.2 1.62 QCACNAA-XB 294 o-d ^H 3 ^S H Hz NS | \-CH ₃ H ₃ O o 483.66 484.3 1.52 QCACNAA-XB 295 H ₃ C / OH n ₃ s ³ y-sn ₃ ( ⁿ O 431.58 432.2 1.12 QC- ACN- TFA- XB 296 n n ^NzS \^sn pzSg । Ί \—CH ₃ __J /^ _k1 ,CH3 μ YyZd cd/ 402.55 403.3 1.06 QC- ACN- AA-XB 297 N N ₃ S n ₃ s γη ³ usn ₃ /~- _to G ^CH 3 μ RkT U y \ 402.55 403.32 QCACNAA-XB 299 LJ H ₃ C' ^N 0<% ^НзС у сн ₃ < ^0Н ^J ^N Yy_ZN ^and V 431.58 432.4 0.78 QC- ACN- TFA- XB 300 n H ₃ C n ₃ s γη ³ usn ₃ /^ _K / ^CH 3 η here j 0% y^N 402.55 403.1 1.49 QC- ACN- TFA- XB

- 108 041852

301 Η H ₃ C н ₃ with γη ³ γ-снз \J\zN _s J —..CH3 y YyXi N ^Z VX. Η / Ν 4 7 402.55 403.3 1.14 QCACNAA-XB 302 Η H ₃ C n ₃ s γη \-ch ₃ WvMrr ³ o 401.56 402.1 0.8 QC- ACN- TFA- XB 303 and ⁿ H ₃ %A/N^ НзС ^έΗ3 ML η ν Μ 473.63 474.2 1.14 QC- ACN- AA-XB 304 ° H ₃ C Η C^' Ύι u ^{SN 3 0} L Λ ^|\L 7 ,CH ₃ Ύ ηχ^γχ Γν ^Η J 494.66 495.2 0.64 QC- ACN- TFA- XB 305 Η H ₃ C Τ Τ 1 /- ^υΗ 3 XX 7 /^,' ^CH ₃ Ύ ΥΥΧΐ Η Ν 4 7 472.64 473.3 1.22 QC- ACN- AA-XB 306 CH ₃ NzS 1 γ 1 y-CH ₃ he ό YxQX γ 526.66 527.1 1.68 QC- ACN- AA-XB 307 Η H ₃ C Γ γ 1 Y-snz /—one f ₃ X Y. /7 /--A /= ^N H 500.57 501.4 1.53 QC- ACN- AA-XB

- 109 041852

308 Η H ₃ C ΓΤ| y-CH ₃ ^OH f ₃ X H A / -A An ⁿ 500.57 501.1 ι, οι QC- ACN- TFA- XB 309 ⁿ H ₃ C ^{/ y} 1 474.61 475.3 1.6 E 310 H ₃ C n AyN^x H3C _sn 1 / T ] U CH3 p-CH3 ^xx xx—χχ^N 488.64 489 1.66 E 311 H ₃ C n Α ^Ν ^Α H3C 1 / T 488.64 489.4 1.81 E 312 Η,Ν. H ₃ C I ^x 7/ ι \-CH ₃ o-CH H ₃ cJ [1m / / ³ υ Λ JL / —Ά Αν 502.66 503.3 1.5 E 313 CH ₃ /N^χ ^H s ^C h. _gn ί Τ ] y-CH3 o-CH3 CH3 \Ax/ ^N xA. /=( A JL7—C An FromC^^m '-wy 460.63 461.3 1.44 E 314 Η <N^x H ₃ C III ^у -CH3 O-CH3 ^h ₃ cA _oh ^ ^A ^ ⁿ ^A 490.65 491.4 1.46 E 315 n N ₃ S ^N U UUnM % ^0-CH3 o JL TLA (TAn ⁰ n _zC A=% ^v Ny 502.66 503 1.67 E

- 110 041852

316 Η H ₃ C _ _and // I 1 Y ^CH 3 p-CH ₃ ° ⁷ kA/N. J =( A Jxk—C/=N Нз+Ά V 474.61 475.4 1.69 E 317 on. H ₃ C _ _h 1 1 A ^SN o-CH ₃ to J\.N. J =( to nk—ckw H ₃ C^^NA* ¹ 500.65 501.3 1.51 E 318 h ₂ n^^ h ₃ c _r T 1 A ^CH 3 0-CH3 kA/N. A /=/ XX—XV and ₃ (00 418.55 419.3 1.24 E 319 ots k?N^^ H ₃ C 1 1 A ^CHz o-ch ₃ kA+A /=/ A tsk - H ₃ C^^N 500.65 501.3 1.5 E 320 CH ₃ H ₃ C III ΥΆ o-CH ₃ ^CH 3 O^n.7 /=< X XX—a Xn h ₃ c^^n A _n ^ 460.63 461.4 1.44 E 321 ^{H H 3} % _rH III ACH ₃ ^{0 - CH3} 490.65 491.4 1.4 E 322 H ^НзС \^рн 111 / ^сн з о-сн _{3 F} ^ _F OU /=< L II 7—k An HaC^k/^N Yp 482.58 483.3 2.01 E 323 H ₂ NxZx H ₃ C 1 1 A ^sn z o-ch ₃ to / to /Ν.__/ /A οι Xx—ΧΧ^ ^ν H ₃ slo Ογ 418.55 419.3 1.26 E

- 111 041852

324 Η ^НзС У- ^н з О-СНз FF L II / <x /= n H ₃ O ^ N ^V N ^ 482.58 483 2.16 E 325 On. h ₃ c || \--CH ₃ o-CH ₃ k>\/N. 7 / \u003d < T / - Ohm H ₃ C ^ ^ N 458.61 459 1.39 E 326 On. h ₃ c Ύ| Y-CH3 0-CH3 to A,n ₄ 7 =/ 0/—0/= N ^H 3C^^N 458.61 459 1.15 E 327 H,N. H ₃ C 6 ]] γ-CPS 0-CH3 nSHIS ³ nrr 476.63 477.4 1.46 E 328 H -^N^y H ₃ C < TT 1 rsn ₃ o-ch ₃ Cr +O ^N O /=( L £ /—A An 488.64 489 1.45 E 329 _{H H 3} ^C _{_ _} 488.64 489 1.52 E 330 CH ₃ H ₃ c. // 1 1 pCH3 0-CH3 kA/N. 7 /=/ ^OX 0m—0+=n ssMr 488.64 489 1.8 E 331 CH ₃ PvP ^NzS \ RI / / I ] A ^CH s p-CH3 kP \ / N. 7 /=/ -Akm ⁿ = ^c ^^n V 488.64 489.3 1.83 E

- 112 041852

332 CH ₃ H ₃ C III y-CH ₃ o-CH3 Λ __7 =/ ν ν ^ν γ \ % _to | L JL / A A h ₃ cA^n Ά sn ₃ ° N n 527.68 528.4 1.51 Ε 333 CH ₃ III y-sn ₃ o-sn ₃ NNY Ua / \ Ύκί J A / -a An A HjcA n V _n J CH ₃ ° H n 527.68 528.4 1.49 Ε 334 CH3 ⁿ 3C _h GN III y-CH3 o-CH3 /k k 7 ,—/ H3C^CH3^^ CH ₃ || 1 / \\ AN From C^^M 502.71 503 1.8 Ε 335 n <N ^ \ H ₃ C III y-sn ₃ o-sn ₃ A TAJa \u003d / ^sn aa ^ d 476.63 477 1.43 Ε 336 CH ₃ ^H3C \ GN [|] y-CH3 O-CH3 ^H3C X ^H >^Vw^ H ₃ X^N 502.71 503 1.89 Ε 337 F ^F V?N^a ^НзС \ si 1 | y-CH ₃ o-CH ₃ kA/ΝκΑ /=/ X?—An ⁿ sC^~A A. _n ^j 494.59 495.3 2.1 Ε 338 F. ^F An^a ^НзС \ γη T 1 u-sn ₃ o-sn ₃ ΧΛ.v, 7 =/ Ύχ χ5—Υγν 494.59 495.3 2.35 Ε

- 113 041852

339 CH ₃ ^HcC usn ₃ o-CHc L II z—An HcC^^J 485.64 486.3 1.95 E 340 CH ₃ Γ ^Ν γΡ ^НзС У-СН _{3 0} -CH ₃ CN AL / a An H ₃ C^^N 485.64 486.4 2 E 341 n G T1 U-sn ₃ o-sn ₃ /-G to /G L. J .-/ o ^ nug hmu _F -A V 506.63 507 1.57 E 342 n H ₃ C G T ] y-CH3 o-CH3 oC/ n ₃ AA\/ ^N yA / ⁼ \ L A /—y An ^n _s d Η 506.63 507 1.76 E 343 oy, \? _Ν ^χ H ₃ C Τ ₁ 504.61 505.3 1.65 E 344 οη \ZN^xh ₃ c ^T 1 504.61 505.3 1.71 E 345 H N^^ H ₃ C / / I 1 usn ₃ p-CH ₃ ^υ ~^ kA/N. 7 =( _f ^a ^V v 478.57 479.3 1.65 E 346 H N^^ H ₃ C nl 1 1 y ^CH 3 0-CH3 ^υ ~^ kA/N _x J =( ^~X DE— 478.57 479.3 1.77 E

- 114 041852

347 Η H ₃ C' ^N ^^ ^H s+ _ph ³ T 1 γΟΗ ₃ o-CH3 /=( X XX—C Χ ^ν F^^-N y Η 436.54 437 1.33 E 348 Η H3C' ^s \/\ H ₃ C ³ 1] y-CH3 o-CH3 k^k/PN 436.54 437 1.41 E 349 ¢4^ НЗС _сн | ] y-CH _{3 N} k / kI ^ X y η_k γΝ \Υν χχ ⁿ H ₃ C CH ₃ 401.51 402.3 1.69 QC- ACN- AA-XV 350 Η,Ν. H ₃ C oSL ΤΊ + ^CHz y η \>_# γΝ kkN XX ^Η H ₃ C CH ₃ 458.61 459.5 1.32 QC- ACN- AA-XV 351 Η H ₃ C o'3 / Τ 1 / ^{C 3} , ^Ν ^ Μγ ^Ν <Χ u φ \>__</ γΝ μ χχ ⁿ H ₃ s sn ₃ 458.61 459 1.67 QC- ACN- AA-XV 352 and n H,C^N_ H,C snz η y fu—/ Y ^N kk^N XX ⁿ H ₃ C sn ₃ 487.65 488.5 0.8 QC- ACN- TFA- XV 353 sn ₃ H ₃ C' ^N ^ ^НзС usn _{3 N} ^ ^N Ykr ^N P kk^N Χ=ς ⁿ n ₃ s CH ₃ 430.60 431.5 1.19 QC- ACN- AA-XV 354 II n ^Η 3%Α/ ^Ν χ/\ ⁿ zS „ _n Ν γη usn _{3 Ν} ^Sn z kk\/ ^N ^k Ζ^Ν E y fu_U γΝ kk^N γγ ⁿ n ₃ s n ₃ 487.65 488.4 0.8 QC- ACN- TFA- XV

- 115 041852

355 CH ₃ , / x H ₃ C n ₃ s ³ usn _{3 Ν} Ζ^N 0 y γη_# yy ⁿ H ₃ s c ₃ 430.60 431.3 0.8 QC- ACN- TFA- XV 356 sn ₃ n ⁿ z% _sn PzO T 1 y-OH _{3 Ν} kUxy ^ U ζγ 0 y γ η_ (/ yy 04 yy ⁿ H ₃ C CH ₃ 430.60 431.1 1.31 QC- ACN- AA-XV 357 Ok o 00 % \ 1 t ^£ O ^T vyy 508.67 509 1.26 QC- ACN- AA-XV 358 _Η H ₃ ^C. ^ _x ^H ₃ C 444.63 445.4 0.81 QC- ACN- TFA- XV 359 H 00 ·; CH ₃ ^{N n} zS SNz 508.67 509 1.42 QC- ACN- AA-XV 360 O^U H ₃ C T | usn _{3 N} k y γη_(/ uy ⁿ n ₃ s n ₃ 456.64 457.1 0.85 QC- ACN- TFA- XV 361 SN ₃ U ^ yu ^N s ^C to _CH III y ^SN z ν. To . Ύ Xgu OU-Ν yu ⁿ N ₃ C SNz 469.64 470.2 0.74 QC- ACN- TFA- XV

- 116 041852

362 H ₃ C _gn Τ 1 A ^CH z Ν. kL/D ζΑ y φ / V=N \Αν ⁿ n ₃ s CH ₃ 472.64 473.2 1.28 QC- ACN- AA-XV 363 Η H ₃ C. .Ν. H ₃ C Ύ ΥΥ D ⁿ s SNz DaD D y # V=N \ An / ⁼ \ ⁿ H ₃ C sn ₃ 444.63 445.4 1.37 QC- ACN- AA-XV 364 CH ₃ H ₃ s. /N. H ₃ C τ YES d ^sNz a SNz Oh / HELL D y D\>_# \=N \A _n DD ⁿ N ₃ S sn ₃ 458.65 459.1 1.43 QC- ACN- AA-XV 365 CH ₃ H ₃ C G m U ^CHz a DHAd ^ D, D ^he and 1 / _ \ A \ Αν ^Ζ DD ⁿ H ₃ C sn ₃ 460.63 461.2 1.25 QC- ACN- AA-XV 366 CH ₃ H ₃ C G ΥΊ A ^CHz a ^CN U 1 u__k A ^{N n} H ₃ C sn ₃ 469.64 470 1.69 QC- ACN- AA-XV 367 n ^Nz Den ^m zS Τ Ί y-OH _{3 N} y y X) __<7 \== N ⁿ H ₃ C sn ₃ 416.57 418.3 1.2 QC- ACN- AA-XV 368 CH ₃ Sur ^H V ^Hs n> ^-Ao W D7 CHz ADDD ^H H ₃ C CH ₃ 501.68 502.3 1.23 QC- ACN- AA-XV

- 117 041852

369 Η ^NzS \_sn n ₃ and γ η \-sn _{3 Ν} ζ^Ν E y φ \># \\=Ν ta / y \u003d x ⁿ H ₃ C sn ₃ 416.57 417.1 1.32 QC- ACN- AA-XV 370 F ^F tN. H ₃ C II z^N E y _(/ γ \An χχ ^H H ₃ c CH ₃ 478.59 478.9 2.06 QC- ACN- AA-XV 371 „fT Ο О co \ 1 t oA/ ¹ о IZ \ ₌ 440.60 440.9 1.7 QC- ACN- AA-XV 372 /-ab^OH XX H ₃ C Ti U ^CH3 A y J __// \^N TAn χχ ^H H ₃ C CH ₃ 486.66 486.9 1.08 QC- ACN- TFA- XV 373 H ,NH ₃ C r γΧ yc _H3 \An XX ^H H ₃ C CH ₃ 498.60 498.9 1.87 QC- ACN- AA-XV 374 F ^F tN. H ₃ C γη ³ u-sn ₃ ... Γ ζγ E u £ \>—# \ί=Ν \Α _ν χυ ⁿ H ₃ C s ₃ 478.59 479.2 1.12 QC- ACN- TFA- XV 375 n ^H H ₃ C CH ₃ 440.60 441.2 1.06 QC- ACN- TFA- XV

- 118 041852

376 Η H ₃ C 111 U ^CHz n. ^CF 3 y # \= ν ^Η H ₃ C CH ₃ 498.60 499.2 1.68 QC- ACN- AA-XB 377 ~ab%'^OH n ₃ s | 1 U-cNz _{N n} ' |j 1 \> ___ (/ V ^ N ) \u003d ( ⁿ n ₃ with CH ₃ 486.66 486.9 1.32 QC- ACN- AA-XB 378 H ₃ C^ HRzX H ₃ C T | У-н _{3 N} Z^N y ) __7 )=^Ν Ν )=( ^H H ₃ C CH ₃ 458.65 458.97 1.1 QC- ACN- TFA- XB 379 N.N. H ₃ C g τΊ U ^{CHz he} Ϊ 1 /__ \ N ) \u003d ( ^H H ₃ C CH ₃ 446.60 446.9 0.95 QC- ACN- TFA- XB 380 sn ₃ H ₃ C _gn V T 1 U-CH3 _N [1 ΊΓ / )=Ν ⁿ n ₃ s CH ₃ 456.64 457.1 1.41 QC- ACN- AA-XB 381 F. НзС _н 1 1 у-сНз _N Z^N T) Г^>_7) = N ⁿ n ₃ with CH ₃ 506.65 506.9 1.14 QC- ACN- TFA- XB 382 O ^N 3% pn T 1 y-CH3 _N Z ^ N ' y [ __7) \u003d ^ ^N H H ₃ C CH ₃ 520.70 521.2 1.08 QC- ACN- TFA- XB

- 119 041852

383 0 ΧΧ U ^SNz Ν. y γ γ__(/ \=ν ⁿ H ₃ C sn ₃ 520.70 521.1 1.82 QC- ACN- AA-XV 384 Η /Ν^\ H ₃ C Γ Τ 1 U ^{CHz CN} y γ / χ \u003d ⁿ H ₃ C sn ₃ 455.61 456.2 1.45 QC- ACN- AA-XV 385 F ^F iX H ₃ C XX X ^SNz N. l-ή L y γ # v \u003d n ⁿ H ₃ C sn ₃ 506.65 506.9 1.13 QC- ACN- TFA- XV 386 XX n ₃ s Τ I U-sn ₃ ... l-ή l u f / y \u003d N N) \u003d\ ⁿ H ₃ C sn ₃ 442.61 443.19 ι, θι QC- ACN- AA-XV 387 sn ₃ .N. H ₃ C \ X XX X ^CH y γ # \ ^ ⁿ H ₃ C sn ₃ 456.64 457.2 0.78 QC- ACN- TFA- XV 388 sn ₃ G XX Y^From ^sn z \u003d N y η yy ΥΝ N ) \u003d \ ⁿ H ₃ with sn ₃ 444.63 445.3 0.78 QC- ACN- TFA- XV 389 sn ₃ H ₃ C g VX usn ₃ ° γ 1 VX y \u003d ^N CH ₃ X \u003d \ ⁿ n ₃ with sn ₃ 474.65 475.1 1.27 QC- ACN- AA-XV

- 120 041852

390 CH ₃ ⁿ zS 1 | ] y-snz _N ^sn </00 0 0 y GT 00 0N \An /=\ ^H H ₃ C CH ₃ 444.63 445.3 1.3 QC- ACN- AA-XV 391 CH ₃ .N. N ₃ S G O 0 Nz _N 0 YES / 0 0 0 9 y 00 mind CH ₃ / \u003d \ ^N N ₃ C CH ₃ 474.65 475.3 1.36 QC- ACN- AA-XV 392 00ΌΗ ^Nz 0sn T 1 \-sn _{3 N} z^N 0 y 0_V 0N 00- ^N yy H _{H 3} C CH ₃ 486.66 487.4 0.79 QC- ACN- TFA- XV 393 y^bs/^QH ^H3 0CH T] usn _{3 N} O0\^ ^N 0 y^N 0 y y_0N 00-N ^0 ^H H ₃ C CH ₃ 486.66 487 1.17 QC- ACN- AA-XV 394 CH ₃ A-A< p CH ₃ ^{H n} zC CH ₃ 522.70 523.1 1.56 QC- ACN- AA-XV 395 CH ₃ / O20 ³ i ⁿ H ₃ C CH ₃ CH ₃ 538.70 539.3 1.85 QC- ACN- AA-XV 396 CH ₃ 00 0 ^Nz HsC^J 00С CH ₃ OO-|\| / \u003d ξ ^H H ₃ C CH ₃ 501.68 502.3 1.27 QC- ACN- AA-XV

- 121 041852

397 CH ₃ ^H H ₃ C CH ₃ 497.65 498.2 1.3 QC- ACN- AA-XV 398 CH ₃ H ₃ C G T 1 / ³ Ά A E ΥΑ ) \u003d ( ⁿ H ₃ C CH ₃ 473.63 474.3 1.56 QC- ACN- AA-XV 399 SNz 3¾ ^N N ₃ S SNz 497.65 520.1 1.4 QC- ACN- AA-XV 400 SNz /N. H ₃ C < T । U-cNz _m G „N CH ₃ ^H N ₃ C CH ₃ 487.65 488.2 0.79 QC- ACN- TFA- XV 401 CH ₃ ⁿ zS A / II G ^CHz y £ __<7 V \u003d N \A _n y \u003d ( ⁿ H ₃ C CHz 472.64 473.2 1.54 QCACNAA-XB 402 CH ₃ CH ₃ ^{N N} zS SNz 522.70 523.2 1.8 QC- ACN- AA-XV 403 CH ₃ ^NzS x_en III U-snz _N nAo CHz AAn) \u003d ( ^H H ₃ C CH ₃ 487.65 488.1 1.66 QC- ACN- AA-XV

- 122 041852

404 CH ₃ VTA % n, _s y ^m^p CH ₃ ^H H ₃ C CH3 501.68 502.2 1.49 QC- ACN- AA-XV 405 CH ₃ S-Usbu o. ⁿ N ₃ S SN ₃ SN ₃ 538.70 539.2 0.86 QC- ACN- TFA- XV 406 sn ₃ ζ ^Ν γ% H ₃ C ill G ^CHz ή n ₂ Lo ⁿ H ₃ C sn ₃ 473.63 474.1 1.53 QC- ACN- AA-XV 407 H ₃ ST Ί rsn _{3 Ν} y [ η_# pN ν )=ς ⁿ H ₃ C SNz 456.64 457.2 1.43 QC- ACN- AA-XV 408 SNz Uuh ^Nz Usn ₃ -y 4vLrQ ^N N ₃ C CH ₃ 501.68 502.2 1.44 QC- ACN- AA-XV 409 H.N. / x H ₃ C G usnz ^OH y η _U ΥΝ ^H H ₃ C CH ₃ 446.60 447 0.99 QC- ACN- TFA- XV 410 CH ₃ Vyx Ych ₃ ^Ao Mur CH ₃ \ ₃ Y^'N ^/ / ⁼⁼ \ ^H H ₃ C CH ₃ 501.68 502.2 0.84 QC- ACN- TFA- XV

- 123 041852

411 H ₃ C^ H ₃ C. _N. H ₃ C ^{3 3} usn ₃ ΑΑ^νΑ ζ^ν γ fu_s Α ^{Ν H} H ₃ C CH ₃ 458.65 459.4 1.39 QC- ACN- AA-XB 412 H.N. H ₃ C ( U ^CH3 n. / A g V ,, ^N II 7 W\u003e n ΗΝ-N AAr ) - ( ^Η H ₃ C CH ₃ 483.62 484.1 1.19 QC- ACN- AA-XB 413 Η /Ν. H ₃ C ( ΊΟ U ^SNz / A A ^ VA ζ ^ Ν A ν 9 II GW pN ^{Ν ζ} AAru \u003d ( ⁿ H ₃ s sn ₃ 483.62 484.4 1.48 QC- ACN- AA-XB 414 CH ₃ r ^N r+ Ύη ^ΛΜΑ Ρ CH ₃ ^{Η n} sC CH ₃ 522.70 523.2 0.83 QC- ACN- TFA- XB 415 CH ₃ f G+ ^N % snz _N> CH ₃ ^{N N} zS CH ₃ 522.70 523.4 1.37 QC- ACN- AA-XB 416 n NzS. g γη ucs _Ν ν 9 γ 7 VP pN ^n=/ v^n3=( ^H H ₃ C CH ₃ 483.62 484.1 1.57 QC- ACN- AA-XB 417 CH ₃ uj ^Ύν-τΑ AA AAn )=( ^H H ₃ C CH ₃ 508.67 509.2 1.41 QC- ACN- AA-XB

- 124 041852

418 CH ₃ H ₃ C G T 1 / ^SNz y and U DUud ⁿ N ₃ s SNz 508.67 509.3 1.55 QC- ACN- AA-XV 419 Ω \/ N ΡΟγ-X % _C N ^{NzSG b} CLn/U ³ a y D # )=Ν kU-N U( ^N N ₃ C CH ₃ 534.72 535.3 1.66 QC- ACN- AA-XV 420 CH ₃ NzS [ T 1 usnz m CHz 0A /) \u003d/ ⁿ H ₃ C CHz 487.65 488.3 1.37 QC- ACN- AA-XV 421 n _Nz C V T 1 y-CHz _Ν kUu^U ζ^Ν u η yy UCH ) \u003d ( ^N N ₃ C CH ₃ 442.61 443.1 1.29 QC- ACN- AA-XV 422 CH ₃ U ^ \ H ₃ C III usn _{3 N} C H s UY *) - ( ^H H ₃ C CH ₃ 487.65 488.29 1.48 QC- ACN- AA-XV 423 n Y^\ H ₃ C O G T 1 / ³ N. ^F = ^c'b I TV/ 0 ^{N H} H ₃ C CH ₃ 562.66 563.4 1.39 QC- ACN- TFA- XV 424 ch ₃ H ₃ C ₄ + Y 1 1 \--ch _{3 M} P / / y η _# yy Y^n )=( ⁿ H ₃ with CH ₃ 472.64 473.3 1.38 QC- ACN- AA-XV

- 125 041852

425 SNz n ₃ co ( U U ^SNz ,Ν. ⁿ z ^s Ύ TUl Χ ^Ν MA )=( ⁿ n ₃ s n ₃ 522.71 523.2 1.44 QC- ACN- AA-XV 426 n H ₃ C VII / ³ Ά || C 7__K A ¹⁴ AAU) \u003d ( ⁿ n ₃ with CH ₃ 442.61 443.3 1.31 QC- ACN- AA-XV 427 0 '” ³ s^ ^N \M ^H3C ^s ny g A T 1 M ^im z _N ⁰ % Aa l u A C \=N W )=( ^H H ₃ C CH3 522.71 523.2 1.62 QC- ACN- AA-XV 428 Y C ⁿ Vl ⁿ A ^SNz x UAa) \u003d ( ⁿ H ₃ C SNz 495.68 496.2 2.22 QC- ACN- AA-XV 429 n H ₃ C G p U ^CH3 A θ y TyJ V ^N CH3 UA/)=( ^H H ₃ C CH ₃ 460.63 461 1.21 QC- ACN- AA-XV 430 CH ₃ H ₃ WITH SL TU U ^CH3 ή. y Y)_MN AA-n )=( ⁿ H ₃ C CHz 472.64 473.4 0.77 QC- ACN- TFA- XV 431 n ,N. H ₃ s G ΥΊ U ^SNz A aCh ° T Ί UU W SN ₃ yA _N ^)=( ⁿ n ₃ s SN ₃ 460.63 461 0.83 QC- ACN- TFA- XV

- 126 041852

432 Η,Ν. H ₃ C ( ΥΧ U ^{SNz CN} Τ 1 > _Κ Υ ^{Ν n} H ₃ C sn ₃ 455.61 456.2 1.23 QC- ACN- TFA- XB 433 Y r ^N r+ ΎΎΥ—s ⁿ H ₃ C CH ₃ 495.68 496.1 2.34 QC- ACN- AA-XB 434 NC._ H ₃ C 1 1 y-CH3 _N ΜγM y J / \=N XX ^H H ₃ C CH ₃ 467.62 467.9 0.79 QC- ACN- TFA- XB 435 O \ n ₃ s | 1 Y-CH3 _N Uv%4 y y x>__γ \=ν LY-n χχ ⁿ H ₃ C CH ₃ 484.65 485.2 0.81 QC- ACN- TFA- XB 436 NC._Ln. n ₃ s ΥΥ U ^SNz u Gu __Υ \=Ν χΑν χχ ⁿ n ₃ s sn ₃ 467.62 468.3 1.96 QC- ACN- AA-XB 437 O') H ₃ c 1 I P ^CH3 N. Z^N y ΊΓ __/ \=^N l^n χχ ^H H ₃ C CH ₃ 484.65 485.3 1.14 QC- ACN- AA-XB 438 0 w _ °^ ^S Or\ H ₃ c 1 1 y-CH _{3 N} Z^N' y [ __(/ \^N L7 _n ^z χχ ^H H ₃ c CH ₃ 532.71 533.4 1.41 QC- ACN- AA-XB

- 127 041852

439 CH ₃ n ₃ s 1 Τ 1 / ³ SNz k / XVi \u003d ν η y γχχ \= ή kY ^ N / \u003d\ ⁿ H ₃ with CH ₃ 458.61 459.4 ι, οι QC- ACN- TFA- XB 440 SN ₃ NzS ill usnz ^SN Z z^N 1 T J Χ^Ν kY^N XX ⁿ n ₃ s CH ₃ 458.61 459.3 0.97 QC- ACN- TFA- XB 441 ^CN ⁿ z% _gn oM Τ 1 / ^Hz k ^ ^ b ^ X Ζ ^ n u f }> __G χΝ kY-N XX ^H H ₃ C CH ₃ 497.65 497.9 1.77 QC- ACN- AA-XB 442 ^H \u003d ^C 'N ^ ₀ L ^ _G n ₃ with XX ⁿ H ₃ with sn ₃ 499.66 500.2 1.51 QC- ACN- AA-XB 443 ^Hz %^ ⁰ Υ X ^CHz y η Y__(7 \^Ν kk^-N χχ η n ₃ s sn ₃ 499.66 500.2 1.58 QC- ACN- AA-XB 444 H ₃ C (ΥΊ U ^CHz ν. ^ΟΗ Τ ι /_\ Χ ^Ν kk-'N χχ ^H N ₃ C CH ₃ 502.66 503.1 1.45 QC- ACN- AA-XB 445 H ₃ CyR ⁰ Χ-Χ H ₃ C ΥΧ U ^CH3 Ζ^Ν γ y γ \=Ν kT^N XX η H ₃ C CH ₃ 520.70 521.4 0.81 QC- ACN- TFA- XB

- 128 041852

446 on ^Η 3% CH ^{nx h} ° ΧΛααΓ ha y fu_ (7 γΝ \Αν γγ ^H H ₃ s CH ₃ 509.67 510.3 0.78 QC- ACN- TFA- XV 447 o n ^{nx h} ° XXyXZVa y fu_\ Υ ^Ν \Αν γγ ⁿ N N ₃ C sn ₃ 509.67 510.4 0.8 QC- ACN- TFA- XV 448 ^NzS A ⁰ N _ZS /g y f y_# γΝ \Αν Υγ ⁿ N ₃ C sn ₃ 520.70 521.4 0.83 QC- ACN- TFA- XV 449 ΥγM H ₃ C G T 1 y ^ch 3 m o% AuCrQ sn kA _N A \u003d ( ⁿ H ₃ s s ₃ 529.69 530.3 1.4 QC- ACN- AA-XV 450 H ₃ C n g A Τι γοΗ _{3 Ν} ⁰ Am A y y_(7 γΝ \Αν γγ ⁿ H ₃ C sn ₃ 508.69 509.4 1.25 QC- ACN- AA-XV 451 n NzS si 1 1 1 1 Y ^CH 3 _N L-N' y A y-# γΝ μΑ-ν Υγ ⁿ n ₃ with CH ₃ 486.66 487.3 0.9 QC- ACN- TFA- XV 452 n sA Υ^Ί γθΗ _{3 N} y fu_7 γΝ \Α _ν γγ ⁿ H ₃ s sn ₃ 508.69 509.4 0.84 QC- ACN- TFA- XV

- 129 041852

453 Η H ₃ C _sn । T T 1 u ^SN C _N η t t \>_V \^Ν )=( ⁿ H ₃ with CH ₃ 486.66 487.4 1.41 QC- ACN- AA-XB 454 CH ₃ ^{0 \} u003d U ° n H ₃ C ^ ^ N ^ x H ₃ C H ₃ ST] U ^uMz _N T fu_& MN) \u003d ( ^H H ₃ C CH ₃ 536.74 537.2 0.84 QC- ACN- TFA- XB 455 CH ₃ °T ° n H ₃ C ^ ^ N ^ x H ₃ C H ₃ C T] y-^ n _{3 N} JA ^ mA y fu_<7) \u003d N LAn) \u003d ( ^Η H ₃ C CH3 536.74 537.4 1.86 QC- ACN- AA-XB 456 ^CN r ^N M ⁿ U ^ss % ^η Ά MUy□ SNs ⁿ H ₃ s SNs 526.69 527.4 1.09 QC- ACN- TFA- XB 457 ^CN n ₃ with H3C ( TX N. ° ъ X JaW a ^{n n} H ₃ with CH ₃ 547.72 548.4 1.86 QC- ACN- AA-XB 458 ^CN ζ ^Ν χ/\ HsS Hos G T 1 l ^{3 3} % > U-yM. 7 ⁰ 'b I J7M A ^N )=( ^H H ₃ c CH ₃ 547.72 548.1 1.78 QC- ACN- AA-XB 459 ^CN_N. ^x H ₃ C G TX U-CH3 _n ^H3C 'N ^ O 1 ° II Ί VA MN ch ₃ AA _n ^) \u003d ( ^H H ₃ c CH ₃ 526.69 527.4 1.8 QC- ACN- AA-XB

- 130 041852

460 ^CH ₃ _N. H ₃ C G TO T ^SNz NzS. > n^o y HERE T ^N o cAmr( ^H H ₃ C CH ₃ 536.74 537.2 0.77 QC- ACN- TFA- XV 461 he gT ⁿ³ pHz s T UCnP l ⁰ 'o 1 TUd M URR pp ⁿ n ₃ s sn ₃ 552.74 553.4 0.86 QC- ACN- TFA- XV 462 ^CH3 .N. N ₃ S G TA rsnz _Ν Ρ ^Ν 1 ° T Ί e__e Ρ ^Ν CH ₃ AAn pp ⁿ N ₃ C sn ₃ 515.71 516.1 0.94 QC- ACN- TFA- XV 463 he H ₃ C III / ^{s 3} ν. ^N s% Υ / MN 1 ° Η T A 7 pN CH ₃ ΜίΤ'Ν / \ ^N H ₃ C CH ₃ 531.71 532.4 0.95 QC- ACN- TFA- XV 464 II n ⁿ zTsn L T 1 r ^sn z _N ^{0 0} y ΊΓ Δ pN \An pp ⁿ H ₃ s SN ₃ 548.75 549.1 0.85 QC- ACN- TFA- XV 465 n ^NzS x SN < T t | g ^CH3 ν. λ-ν O ^X q y [ A_C pN \An Y a ⁿ H ₃ s n ₃ 520.70 521.4 1.46 QC- ACN- AA-XV 466 H ₂ N. N ₃ C _H 11 U-sn _{3 m} G N^ Z^N y ΊΓ\>_# pN \ An pp ⁿ N ₃ C sn ₃ 402.55 403.3 0.85 QC- ACN- TFA- XV

- 131 041852

467 γΗ ₃ ΥνΛ ^N s ^C \ ee [ΤΙ γοΗ _{3 N} ⁿ A ^lo A*A>a CH ₃ AA/ )=\ ⁿ H ₃ c CH ₃ 515.71 516.4 0.78 QC- ACN- TFA- XB 468 OH gX ^H 'V ^CH \u003d η ^Η χχ γ ΑΑ ^Ν Ρ CH3 <AA \u003d ( ⁿ H ₃ with CH ₃ 531.71 532.4 1.52 QC- ACN- AA-XB 469 H ₂ 1\k^\ n ₃ with ΥΧ U ^CH3 Ν. || [y__// γΝ XX ^H H ₃ C CH ₃ 402.55 403.3 0.87 QC- ACN- TFA- XB 470 H H ₃ s < 1 T 1 U- ^sn z Ν ζ^Ν O y £ y_γ γΝ Α=^ ν XX ⁿ n ₃ s sn ₃ 520.70 521.4 1.84 QC- ACN- AA-XB 471 II n k n ₃ s ΥΧ U ^{CHz 0 0} AA ^ n ^ J \u003d n' Y y Y _Λ' ΑΑ _Ν ^Ζ ) \u003d ζ ⁿ n ₃ s sn ₃ 548.75 549.4 0.96 QC- ACN- TFA- XB 472 ϋ H ₃ c οΥ ΥΊ g-a y Υ Υ_(>=Ν \Αν XX ^Η H ₃ C CH ₃ 472.64 473.4 0.8 QC- ACN- TFA- XB 473 НзС n H ₃ c O / Τ 1 / ^СНЗ ζΝ^ y Υ γ_/ >=Ν \Αν )=\ ⁿ Н ₃ С СНз 472.64 473.4 0.82 QC- ACN- TFA- XB

- 132 041852

474 Η ⁿ H ₃ C SN ₃ 486.66 487.1 1.18 QC- ACN- AA-XB 475 ^CN ^H s ^C \_sn U c Г T 1 Г ³ N. sA7 ^V ^N AAY °% ^v Ύ TDG Χ ^{Ν n} H ₃ s CH ₃ 573.76 574.5 1.86 QC- ACN- AA-XB 476 CH ₃ ⁿ NzS ⁷ SN ₃ 548.75 549.4 2.17 QC- ACN- AA-XB 477 n / M ^N H ₃ C CH ₃ 486.66 487.5 1.34 QC- ACN- AA-XB 478 ^CN °V Adku ^{N n} H ₃ C sn ₃ 573.76 574.2 1.62 QC- ACN- TFA- XB 479 CH3 H ₃ C A Adku ^{N H} H ₃ C CH ₃ 548.75 549.5 1.95 QC- ACN- AA-XB 480 n ₃ u ^H H ₃ C CH ₃ 562.78 563.5 0.93 QC- ACN- TFA- XB

- 133 041852

481 OH ⁿ H ₃ C SN ₃ 578.78 579.3 1.85 QC- ACN- AA-XV 482 he X" ⁿ n3s ⁷ sn3 578.78 579.5 1.85 QC- ACN- AA-XV 483 n N ₃ S O / U 1 1 D ^SNz _Ζ Ν. 1 ΤΛ / Ν,_7 ζ-Ν ^he if A ¹⁴ \Αν DD ⁿ n ₃ s sn ₃ 488.64 489.4 0.76 QC- ACN- TFA- XV 484 n N ₃ C _h oOchtch d ^snz 1 Α \ ζ ^Ν Α z - N he ^ D TrA A ud dd ⁿ N ₃ C sn ₃ 488.64 489.2 1.04 QC- ACN- TFA- XV 485 n N ₃ S _sn 111 U- ^sn z ν ° N ₃ sfsN ₃ AD DD sn ₃ ⁿ N ₃ s sn ₃ 515.71 516.5 1.59 QC- ACN- AA-XV 486 H n NAb _P h _s c _n 7 D uSd ⁿ N ₃ s sn ₃ 531.71 267 1.13 QC- ACN- TFA- XV 487 H ₃ C n ^H3C 7 ^N Y% U- ^CH 3 HC αόΤυ ^N N ₃ C CH3 501.68 502.4 0.81 QC- ACN- TFA- XV

- 134 041852

488 ίϊ Η ^1C AP n ₃ s _Ν to Ogi ^Ν Ρ °'sn ₃ H ₃ s s ₃ 531.71 532.6 1.52 QC- ACN- AA-XV 489 ίϊ n H ₃ C ^HzSH CH ₃ ^Hz ^y y \u003d ( ⁿ H ₃ C sn ₃ 515.71 516.5 1.9 QC- ACN- AA-XV 490 n n ₃ s _h ( YX U ^{SNz n} > ^ν+ο UguItS! oU ⁿ N ₃ s n ₃ 529.69 552.2 1.38 QC- ACN- AA-XV 491 Ή ⁿ ' ^with ^sn Ό | usn _{3 N} kUx^yO Z^N 4 y η η </ y ν OO Ν yun ⁿ H ₃ C sn ₃ 428.58 429.4 1.26 QC- ACN- AA-XV 492 sn ₃ ^Hssl b>% n ₃ with kUx / uO 4 y ητ η_/ y \u003d N Ο^Ν yy ^H H ₃ C sn ₃ 470.67 236.1 1.51 QC- ACN- AA-XV 493 SN ₃ ^Nz ° ^L P^ ^Η Ο, _ΓΗ n | y ^SNz N. y y η_/ y \u003d NO ^ N yy ^H H ₃ C sn ₃ 470.67 471.4 2.55 QC- ACN- TFA- XV 494 /Ή ^H ( ^NzS \^gn T 1 y ^s _{n N} ^NsS uO ₀ kUx / UY z^N 4 sz ⁿ H ₃ s s ₃ 541.74 542.3 2.34 QC- ACN- AA-XV 495 NzS n ^Η ΌΌ Y- ^ν > Y ΠχηΥ ^N H ₃ C CHz 515.71 516.5 0.88 QC- ACN- TFA- XV

- 135 041852

496 AH ⁿ ' ^s usn, _N G Ao XHO °X ΧΧ^χχ ⁿ H ₃ C sn ₃ 557.74 558.3 1.03 QC- ACN- TFA- XB 497 AaHya ^N N ₃ C CH3 541.74 564.2 2.33 QC- ACN- AA-XB 498 ^Nz XX H ₃ C NzS "U TXX CH ₃ ν G A χγχρ °X ΧΧ^χχ ⁿ N ₃ s CH3 557.74 558.4 0.92 QC- ACN- TFA- XB 499 ^N s ^C ^ NzS „ _n oJS T 1 / ³ f 1 __J l~N | OH [f Yz ^- XY ^N \An χχ ^H H ₃ c CH ₃ 546.72 547.4 1.56 QC- ACN- AA-XB 500 ^Н з ^С ^ H ₃ C nX T 1 / ³ zN<, 1 X^s/XT^N OH y Yz_X A ^N xv χχ ^H H ₃ c CH ₃ 546.72 547 1.09 QC- ACN- TFA- XB 501 CH ₃ IzXsH [Tl / ^{c 3} x h ₂ nX ^Y ^N wryN x ^ n χχ ^H H3C CH ₃ 473.63 474.5 0.87 QC- ACN- TFA- XB 502 H ^N s ^C x, _gn O / T 1 / ³ [1 Y _# V \u003d N h ₃ cXXn) \u003d ( ⁿ H ₃ C CH ₃ 472.64 473.4 1.69 E

- 136 041852

503 Η H ₃ C O / Τ 1 / ³ Η y γ^_/ γΝ Ν >=< ⁿ 3^ |_| / \ ^I H ₃ C CH ₃ 472.64 473.3 1.74 Ε 504 N NzS „N G Τ T 1 y ^ch 3 _N C>Y kYY E y γ _ν γΝ _ρ Υ-ν χχ ⁿ n ₃ with CH ₃ 504.65 505.3 1.48 Ε 505 n N ₃ SG Τ T 1 y ^ch 3 _N °Υ <Υγ.γ ζγ ι y Υ # γΝ rkky XX ⁿ N ₃ s sn ₃ 504.65 505.4 1.54 Ε 506 η ₂ ν^^ h ₃ c γ η γοΗ _{3 Ν} Uv ^N Y ,γ to _F Yk _N χχ ⁿ H ₃ s sn ₃ 420.54 421.3 1.31 Ε 507 η ₂ ν^^ h ₃ c Τ 1 g ^SNz _Ν kY^HY ,γ k y ] Ν_γΝ _F kk _N γγ ⁿ H ₃ C sn ₃ 420.54 421.3 1.36 Ε 508 ^CH ₃ H ₃ C sn 111 y ^ch 3 _N ^N s% A) \u003d N η । ° II T k—ek ^N CH ₃ fYYYY ^H H ₃ c CH ₃ 533.70 534 1.59 Ε 509 ^CH ₃ Chi ^Nz Pen III γ^Η _{3 N} ^NzS ^X kkm to । ° Η Ί k__e k= ^N CH ₃ fAYn^Y ^H H ₃ C CH ₃ 533.70 534.3 1.66 Ε 510 ^CH ₃ kvk ^НзС \ сн 0 1 1 1 / ³ zN^ нз+% Ύ XXX Χ ^{Ν υ} f^+^n γγ ⁿ Н ₃ s сн ₃ 554.73 555.4 2.09 Ε

- 137 041852

511 γΗ ₃ НзС О / ^{3 n} \u003d ^s 'o I IH A ^{N n} H ₃ with CH ₃ 554.73 555.3 2.03 Ε 512 HN^ ^HsC \--CH _{3 CH3} kL L_7 /=/ X/L/ N ⁿ <zn ₃ 348.49 349.3 1.63 QC- ACN- ΑΑ-ΧΒ 513 O co II X A £ 0 and oXj ^{1 £} Q z—' 350.47 351.3 0.58 QC- ACN- TFA- ΧΒ 514 HN^ ^HzC y-CH _{3 CHz} k^k „N.__/ /=/ ^ιΓ Ν n ⁿ sn ₃ 365.48 366 0.67 QC- ACN- TFA- ΧΒ 515 HN^X ^NzS \ ri । η y-sn _{3 SNz} kL / N. 7 ,=/ ⁿ SNz 364.49 365.3 0.99 QC- ACN- ΑΑ-ΧΒ 516 nm^X ^H3C \ GC ην η y-ch _{3 CH3} kJ\nN ₄ 7 /=/ Xx— 'M Η 374.49 375.1 1.15 QC- ACN- ΑΑ-ΧΒ 517 Ο'> „Ίο τ ο Τ ° ν_7 ^{τ τ} Ο Z—f τ 375.48 376 0.99 QC- ACN- TFA- ΧΒ 518 ΗΝ^ ^НзС y-CH _{3 CH3} to „Ν. 7 /=/ ^ίΤΜ^Ν Lm 374.49 374.9 0.95 QC- ACN- ΑΑ-ΧΒ

- 138 041852

519 HN^ ^H3C y _{CH3 CH3} Y I/-\ X° A^n )=( ^H H ₃ C CH ₃ 378.52 379 1.47 QC- ACN- AA-XB 520 ³ ASNz o-sn ₃ k / OA / A U / -Ο \u003d ^ν A Η Ν 390.49 391.4 0.52 Bl 521 ΗΝ^ ^H3 AcH3 Ν ΥΑ-α<Α /A y £ χ,__/ \==ν ΑΑν )=( ⁿ H3C CH ₃ 388.52 389.3 0.58 Bl 522 ³ A ^SNz SN ₃ k / AA \u003d / ALIh) h ₃ c ^A Yn A ⁿ SNz 362.52 363.3 1.46 E 523 ^{N _} _{_} 404.52 405.1 1.25 E 524 Ύ^Χ ³ CH ₃ O-CH3 Xa—^(α^ν _f AAn v _v 408.48 409.1 1.23 E 525 HN^ ^H3C y CH3 _CH3 ^7777-7>7n H3C^^J 388.52 389.2 2.46 R 526 ^Η Ψ^Χ ³ ACH3 O-CH3 ΥΥ\/ ^Ν \Υ /=( TAn CH ₃ Π 379.50 380.7 2.524 D

- 139 041852

527 ³ usn _{3 C} n ₃ ΙΛ / NA /=/ ^N CH ₃ 448.61 449.3 0.52 Bl 528 OU 'Ά.,ΖΧ N ₃ S usnz SNz kLzhD /=/ GTN> 0 ^N SNz 420.56 421.3 0.51 Bl 529 O^/χ. H ₃ C 1 | | Hsn _{3 CH3} Η ₃ 0' ^Ν ^H ₃ 4^γ ^Ν γ4/=( U A /—a UA ⁿ CH3 449.60 450.3 0.52 Bl 530 ^H _{3 s} 111 Vch ₃ ^CH3 435.57 436.3 0.51 Bl 531 O La _CH3 H ₃ C'%H ₃ ^^% A/=^ ΑΑ-ν α _ν ⁿ CH3 449.60 450.3 0.51 Bl 532 ί g% -O T uU O T s / TG ^t co \_____ / ¹ o o o o 1? 445.57 446.3 0.54 Bl 533 co 2-L t II A U A U -O T Uu o T Au ^{t £ o} U o o t 459.60 460.3 0.55 Bl 534 °-r ³ Hsn _{3 SNz} H//-Ο^Ν Η 430.56 431.3 0.55 Bl

- 140 041852

535 £ /--Z. Ο ΐ 1 ° ΓΓ Ai A I 446.56 447 0.53 Bl 536 °GP ^Nz %sn ₃ O-CH, H ₃ cr ^NH H J 7-A >N 0 ^V v 461.57 462 1.4 QC- ACN- AA-XB 537 00 '% o-CH, H.C' ^N 'CH>Αγ ^Ν γ%/=( |l JZ—A 0N ^H N 475.60 476.1 0.72 QC- ACN- TFA- XB 538 oy 0 ^N %V% ^N U 00-N yy ^H H ₃ C CH ₃ 444.58 445.3 0.55 Bl 539 H ₃ C 0-1-% _HC -NH X / _V "% p ⁿ z ° y η well __ (/ y n h yy ^H H ₃ C CH ₃ 459.60 460.3 0.55 Bl 540 CH ₃ H ₃ c' ^N Y ^ N0 ^NzS y-sn _{3 N} O U% M 00 T 1 A_(/ vn 00- N yy ^H H ₃ C CH ₃ 473.63 474.4 0.56 Bl 541 ^H 3 ^C ^ _N 0 ^{Nz (} 0SN NoI 7 1 U ^CH 3, Ν. CHz 0ν ^N 0 0 y GT (/ y \u003d N 00-N yy ⁿ H ₃ C CH ₃ 460.63 461.4 0.58 Bl 542 oy %0 H ₃ C P 0CH _{3 C} H ₃ 00140 Z^N Y £ >—/ )=0 N yy ^H H ₃ C CH ₃ 434.58 435.4 0.53 Bl

- 141 041852

543 kX..^ H ₃ C _CH 1 U ^CH3 SN ₃ k^^ ^N ^kz^N U I /—\ k ⁰ )=( ^H H ₃ C CH ₃ 462.64 463.4 0.55 Bl 544 % ^ N ^ ^{H3 <} k ^ H III y-CH3 _CH3 HC / ^NH \u003d N ³ T Th > ° VS ) \u003d ( ⁿ H ₃ C CH ₃ 449.60 450.4 0.52 Bl 545 °<^ _N ^ ^H3C \^PH 1 7 | y-CH ₃ CH ₃ μ LutskA/UL H ₃ U UH ₃ E| A__H \θ kk'''k )=( ^H H ₃ c CH ₃ 463.63 464.4 0.54 Bl 546 H ₃ C _{H c} HsC ^ nO ³ y-CH3 _C h ₃ ° ^H / _ _N ' Y I / - \ k ° ) \u003d ( ^H H ₃ c CH ₃ 450.63 451.4 0.55 Bl 547 ^NzS \ her ^but x Ou rx ^H N 446.60 447.3 0.55 Bl 548 ^H ₃ C. ^H ₃ C 462.60 463.9 0.52 Bl 549 CH ₃ 0 η kkA _N /\ n ₃ s H ₃ C Ν Ί \-CH ₃ 0-CH ₃ kF J r=( —CXXn ^H N 475.60 476.4 1.15 QC- ACN- AA-XB 550 Ciz 0 H3C'' ³ V ^CH 3 CH ₃ kx ^x k^ ^N '^k /=( XX/—C km ^^N 4 ^H N^ 459.60 460 1.4 QC- ACN- AA-XB

- 142 041852

551 CH ₃ 0 H ₃ C' ^N /+n^| ^Η 'θ\_ΟΗ, _n || | ___(/ \=N AP^n )=( ^H H ₃ C CH ₃ 473.63 474 0.53 Bl 552 h ₃ c./ NS o' Y ] ^{3 Y} ch ₃ ΤΛ,νΥ /=( T JL /—A An H 480.63 481.3 0.53 Bl 553 NC^N^P ³ yCH _{3 C} H ₃ A^^ ⁿ ^A /=( T JL /—4 /^N H 413.53 414.3 0.63 Bl 554 H ₃ A'R HC θ' Y ] ³ V ^CH 3 O-CH ₃ X/S-C/^N V _v 496.63 497.3 0.56 Bl 555 NC^N^ ³ usn ₃ o-CH ₃ AAx/ ^N ^A /=( XX/—4 An NNJ H ' _N ^ 429.53 430.9 0.58 Bl 556 ^NzS A ° NS 0' U A ³ - ^CH z N. AA^n )=( ^H H ₃ c CH ₃ 494.66 495.3 0.6 Bl 557 /\ H ₃ C NC NI pCH _{3 N} z^N ]| 1 \>___// )=N A^n )=( ^H H ₃ C CH ₃ 427.56 428.3 0.66 Bl 558 ^H2N _^ ^{n ^} k /=/ ^Τί LJ/—^C/^N AAn v _v 447.54 448 1.12 QC- ACN- AA-XB

- 143 041852

559 О T co \______/ ¹ о 0 z T 431.54 432.4 0.67 QC- ACN- AA-XV 560 _{H 2} ^N. H ₃ C 3 ₊ ^1T 445.57 446 1.16 QC- ACN- AA-XV 561 I ω O 1 W τ 1 o A- 471.61 471.9 0.53 IN 1 562 ⁿ zS-\U /. n ₃ S U U ³ usn ₃ o-SNz ⁰ /Ad. / /=( X//— 487.61 487.9 0.51 IN 1 563 V' y η __<7 )=Ν \Αν g=\ ^Η H ₃ C CH ₃ 485.64 485.9 0.52 IN 1 564 ^U IU-'CHz _CHz kUU μ 1m - \ ) \u003d ° ) \u003d ( ^H H ₃ C Cl 483.05 471.9 0.53 IN 1 565 ^Hs UsN ₃ CHs ⁰ VuU U U £/—7 )=o \ί0^N )=( ^H H ₃ C CI 470.01 470.3 1.46 QC- ACN- AA-XV 566 °γ ^Y ^H3C ^sn _{3 CH3} Y y 1 /—\ Y ⁰ )=( ^H H ₃ C CI 455.00 455.4 0.71 QC- ACN- TFA- XV

- 144 041852

567 CH ₃ H ₃ C ^NzS ΐί 1 I U-CH ₃ CH ₃ ⁰ / U y 1U \ U ° mA) \u003d ( ^N N ₃ C CI 484.04 484.5 0.74 QC- ACN- TFA- XB 568 ^NzS ^y^ ^Nz Usn 1 1 U-CHz _C N ₃ / U y \ Uo mA) \u003d ( ⁿ N ₃ C CI 441.02 441.1 1.39 QC- ACN- AA-XB 569 ^HsC ^u^ ^H ₃ C T 1 | MSN _{3 SNz} SNz UOU l ^- N y HERE\u003e o mA) \u003d / ^N N ₃ C CI 455.04 455.15 0.84 QC- ACN- TFA- XB 570 ^NzS UsN ₃ rn ₃ H ₃ C'% hS ^ Y% Xa ^N x _o MA / \u003d \ ^H H ₃ C CI 484.04 483.9 0.53 Bl 571 ^НзС Т\^ ^Нз Usn Til U-снз _СНз СНз kA/A y T Yy>0 xAm )=( ^H H ₃ C CI 471.04 471.9 0.54 Bl 572 ^Η 3 ^ο ψ\^ ^H ₃ C Til \—CH _{3 CH3} CH3 k/k/NA /=/ ΎJ/z—4 /=n From C^A ^N _Ntfl 460.63 461.2 1.6 E 573 ^NzS U _ _ ns 0' ³ U ^CH s O-CH3 514.62 515.2 2.14 E 574 ^z o 1 O.U” s? 464.55 465.2 1.66 E

- 145 041852

575 07 £ Μ Ο οΑΑ ^£ Q /—\ 9, d 472.64 473.2 1.5 E 576 sn ₃ 0 ⁿ sC' l ³ \^CH ₃ O-CH3 c / c -N. 7 =/ YlXMAn Н3С^П ^V N/ 489.62 490.2 1.52 E 577 CH ₃ 0 H ₃ s ^{n s} n η psn ₃ o-sn ₃ 7Α^ν _χ 7 =/ ΧΧ—С Χν _f AAn v _v 493.59 494.1 1.85 E 578 i 17 £ M 0 oYd ^{1 £} Q /—\ ° r 444.58 445.2 1.94 E 579 I \ / ω \ / o 2— O ^z 1 o Ok z' k/y 7-Z o 460.58 461.2 1.88 E 580 SNz _n H ₃ С _rn ⁿ ₃ s γ ν η y-CH _{3 SNz} 0 kA^N. 7 =/ OXmAn ^Vv 477.59 478.3 1.4 E 581 _{CH 3 Hp} , _N ^ _{H 3} C H ₃ C γ Ν η 473.63 474.2 1.54 E 582 ^H ' ^C OH ₃ C o' 7 1 U ^sn ' CH ₃ kA/N ₄ __J ^ITMAn _f A^n V _n ^ 498.62 499.3 1.63 E

- 146 041852

583 CH ₃ H ₃ C n ₃ s μ ν η usn ₃ o-sn ₃ 493.59 494.3 1.36 E 584 sn ₃ ⁿ sC'Ύ'^Ν'Χ ³ usn ₃ o-CH ₃ o 7 \u003d/ ^XX XX / -Ο \u003d _N H ₃ C'^ ^< N 489.62 490.2 1.5 E 585 CH ₃ O H ₃ ^{C ' N} _^ X^ 477.59 478.2 1.89 E 586 Siz OH ₃ C ^{n s c} ν η \-CH _{3 CH} LA ^ n. 7 _/ jf 7L—C/Ln H ₃ C^^N N.^ 473.63 474.2 1.55 E 587 ⁿ zC\kxx /x H ₃ C Τ 7 ] y-sn ₃ o-sn ₃ CH ₃ \ΖΧζ ^Ν \Α /=/ X XX/—C Xn NzC^^J 476.63 477.2 1.56 E 588 °k ^HzC y-CH ₃ cn ₃ k __( =/ ^yx jxX—χχ^Ν 448.55 449.3 1.71 E 589 °^Ί kY n ₃ s 7] y-CH ₃ o-CH3 ΧχΧ—CX=N 488.64 489.2 1.46 E 590 ρτΑττ\7 "\l H ₃ C 434.54 435.4 0.94 QC- ACN- TFA- XV

- 147 041852

591 Mr V th chu ό ' 504.64 505.5 1.23 QC- ACN- AA-XB 592 CH ₃ NzSA-d ^N s ^C \_ _SN AAn L \ o- _CHz A? 434.54 435.2 1.08 QC- ACN- TFA- XV 593 H ₃ C _p SDSz / ° ~ sn ₃ HsC - ^ ^ nu (/ JTy / y -r 448.57 448.9 1.3 QC- ACN- AA-XB 594 ⁿ zC y-CHz SN ₃ i J 1 T / -4 Z®N ^N z ^C ' A A 404.52 405.4 1.01 QC- ACN- TFA- XV 595 n ₃ s /^An/U ^SNz /°~ ^SN z G\A U PAL °\U An Η Ν Ί 462.55 463.3 1.31 QC- ACN- AA-XV 596 NzS / O-CHz H ₃ C- ^N A U TU / y \Αν ^ζ An Η Ν Ί 392.46 393.2 1 QC- ACN- TFA- XV 597 NzS Are y chu SSN ₃ N LSN ₃ NO 492.62 493.6 1.28 QC- ACN- AA-XB

- 148 041852

598 CO t o // ”- XY o co 1 -C--L. T 1__ / s; '--r \ o \ ² A o sot 462.60 463 1.22 QC- ACN- TFA- XV 599 ΗθΥγ-l n ₃ s ^{N s C} Αο Ν X ^SNz o-sn3 1 Rear η N j A 464.57 465.2 1,I QC- ACN- TFA- XV 600 n ₃ with ArMA Ύ, th cLu hr 420.52 421.2 1.17 QC- ACN- AA-XV 601 n ₃ s ~ Asn ₃ VW / A ^CHz AA / V _m A _n N J 337.38 338 0.77 IN 1 602 όΑγ CH ₃ \> th H ₃ C' ^N yk Ύ 0 505.62 506.2 1.01 QC- ACN- TFA- XV 603 t s? О °Y Q о сх /—( - ¹ V/ ? ^ζ о t ω 448.57 449 1.22 QCACNAA-XB 604 I ω ° _s O ^h s / \ o XX / 1 g ^ 1 ^ω Ά \ χ ° gAk o -A ¹ m ⁷ ? o I co 526.66 527.5 0.98 QC- ACN- TFA- XV 605 “-.o + A n ₃ s 504.68 505.5 1.51 QC- ACN- AA-XV

- 149 041852

606 H ₃ C ^_ N ^ X to J ^H sC ^ ° _V N Dz _n to Ada ^SNz Al 462.60 462.9 1.51 QC- ACN- AA-XV 607 490.61 491.2 1.33 QC- ACN- AA-XV 608 CO Τ O 7-s „TU o s / γ F co \ / ^to o A o sot 406.49 407.3 0.96 QC- ACN- TFA- XV 609 n ₃ s DBP n,s MChL X 491.60 492 1.28 QC- ACN- AA-XV 610 H ₃ C ^SNz P'CHz la Dl _Nz g Ur 448.57 449.4 1.11 QC- ACN- AA-XV 611 NzS CPCH ₃ S H ₃ C 504.68 505.5 1.3 QC- ACN- TFA- XV 612 NzS n.s ^SN !/°' ^SN yj τ Υ5-/Κ n ₃ s VmA ³ Η Ν 1 420.52 421 1.4 QC- ACN- AA-XV 613 n ₃ \ _ NzSuSN'UUDDA ³ HO^A ^N AV _n Y ^N 478.60 479.2 1.2 QC- ACN- AA-XV

- 150 041852

614 ⁿ zC g XXl 448.57 449.4 0.99 QC- ACN- TFA- XV 615 CH ₃ ⁿ % CH ₃ bi ₃ o xAn / ^\u003d \ ⁿ H ₃ with CH ₃ 473.63 474.25 1.31 QC- ACN- AA-XV 616 9A ⁿ ns Μ ^m zS \ gn XX XX NX X ^SNz ^X XX—Χ~Χ ^{ν n} 460.58 461.3 1.38 QC- ACN- AA-XV 617 ^НзС usn _{3 N} ζ^ν' [1 ΊΓ у__<7 \=Ν ΑΑ-ν )=( ^Η Н ₃ with CH ₃ 374.49 375 0.7 QC- ACN- TFA- XV 618 CH ₃ ^{Nz L} _ N ₃ S ML U ³ N. AA.%7 λ T f _(7 Μ ^Ν λα-'ν y \u003d\ ⁿ H ₃ C CH3 402.55 403.2 0.99 QC- ACN- TFA- XV 619 ^η3 %Μύλ ^Hs U ^{s s} °- ^s > CHs 0 \Χφ ^Ν νΧ/Χ |l J 7—\ We Αν 'M y Η Ν 461.57 462.2 1.24 QC- ACN- AA-XV 620 H ₂ _ ⁿ ' ^s usn, ₀ _ _SNz \-Ά / Ν. 7 \u003d / A tL - L ' ^{\u003d n} 376.46 377.4 0.96 QC- ACN- AA-XV 621 CH ₃ ^H M ^Hz Asn ΎΛ U- ^{CHz 0 0} Α-Αν^Λ Λ μ m yA MN AAJ )=( ⁿ H ₃ c CH ₃ 494.66 495.2 0.77 QC- ACN- TFA- XV

- 151 041852

622 0 sn ₃ H ₃ S. D___N.__ ^NzS \ _CH ³ N rD r ^sn z _N A _and \ ___J n' J ³ [G ΤταΥ \ An ρρ ^H N ₃ C CH ₃ 473.63 474.1 0.98 QC- ACN- TFA- XV 623 sn ₃ N H ₃ C ^{n s} ΎΛ G ^SNz N. MM E u [ +>__# pN AA N pp ⁿ H ₃ C sn ₃ 402.55 402.9 0.72 QC- ACN- TFA- XV 624 H ₃ S. ^Nz A _sn TU m / '% o AlA ζ^ν η y T \>_<7 pN \Αν ρρ ⁿ H ₃ s sn ₃ 480.63 481.4 1.19 QC- ACN- AA-XV 625 SN ₃ DdKh ⁿ 'U ^SNz °- ^SN \u003d CH ₃ 0 / \u003d < 11 A / - to An V _n Η Ν '-' 475.60 476.3 1.22 QC- ACN- AA-XV 626 CH ₃ \ AN n ₃ s ³ usn _{3 N} ^H s ^C VA ^ y XT A_ (7 pN \ An pp ⁿ H ₃ s sn ₃ 472.64 473.2 0.78 QC- ACN- TFA- XV 627 0 CH ₃ % - +% pH, ₀ _ _CHj 7' Μί ^Ν γγ_/Α C J /—\ /=Ν ⁿ 475.60 476.2 0.73 QC- ACN- TFA- XV 628 _{on Η 3} ^Μ _ν Α^ ^Ν 447.54 448.2 0.67 QC- ACN- TFA- XV 629 CH ₃ A ^NzS \-en H ₃ C pp rsn ₃ o-CH ₃ / \u003d/ T TO - C On AAn ⁿ N 404.52 405 1.1 QC- ACN- AA-XV

- 152 041852

630 CH ₃ A ¹ * o-sn ₃ CHz 0 / \u003d K N A / -A An XA _n y η Ν 475.60 476.4 0.74 QC- ACN- TFA- XV 631 9 Η n ₃ t,Χα._ ^NzS ^sn ^Η y fr_αν \Αν χχ ⁿ N ₃ C sn ₃ 445.57 446.2 1.19 QCACNAA-XB 632 ^γΝ ^H3C yCH ₃ o-CH3 ^|f ^N Yv-/=4H A /—A An X y H [A 460.58 461.2 1.19 QCACNAA-XB 633 ^HcC X/° n _cC γ—D )--^3 _N ^HcC y γ _// AN \An χχ ^H H ₃ C CH ₃ 542.73 543.3 1.04 QC- ACN- TFA- XV 634 ^H A N. ^H 3A PH VA A ^sn z 0-CH3 ⁰ 'ο νγ,Ν^Τ Y YX%—a Y ^nv V 482.60 483 1.22 QCACNAA-XB 635 X ^НзС г ^з у Y^_(/ V=N X=A _n χχ ^H H ₃ C CH ₃ 458.61 459.22 1.23 QCACNAA-XB 636 CH ₃ ^H A ^NzS KhsN γ-d y-snz _Ν XnJ χχ y γ XX An ΑΑ-ν XX ^Η N ₃ C CHz 494.66 495.2 1.54 QCACNAA-XB 637 9Ά Η μ o V-An HcC HcC VAnA NY y Υ^>_(/ AN \A _n XX ⁿ H ₃ C n ₃ 458.61 459.1 1.43 QCACNAA-XB

- 153 041852

638 I ω O ο-ζ A ΖΙ Ο /\W at 1 Ο I O/ ζ' Α> νί ό ζ 461.57 462.4 0.74 QC- ACN- TFA- XV 639 CH3 N H ₃ C H3C^AL U-CH3 o-CH3 Ax 7 =/ XG/-AA A y Η N 404.52 405 1D2 QC- ACN- AA-XV 640 CH ₃ H ₃ C. H ₃ C ³ V3 uCH ₃ O-CH3 o O \u003d / X Xu C Chi Η N 496.63 497.1 1.42 QC- ACN- AA-XV 641 BUT 9 ^Nz 9 ^Nz >X N.__, ^N zS. „ _n H ₃ C^^ AL / ^CHz N. A / A A y y_# γΝ Aya χχ ⁿ N ₃ C CHz 460.63 461.1 0.78 QC- ACN- AA-XV 642 CH3 ^Η %^ ^Ν ΎΛ ^H 'U ^SN ' o-CH, o'o 496.63 497.1 1.47 QC- ACN- AA-XV 643 o-l 9 ^{Hs Hs} Asn XX n > ^CH Y-3 XX—'C^Xu AY v _v 474.61 475.3 0.71 QC- ACN- TFA- XV 644 z'usNz bn ₃ o αΥυΥ y^ _N XX ⁿ H ₃ C sn ₃ 459.60 460.5 1.2 QC- ACN- AA-XV 645 ^H2N >Y ^N y ^sC y-CH ₃ o-CH3 ° I'iXyC /X AND A /-A An AA γ y Η ν 419.49 420.3 0.93 QC- ACN- AA-XV

- 154 041852

646 H ₃ N^^^x___g HsS.__ E1 ^Ν Ά y-CHs _Ν o _Ν ' η y J η_# An 04 yy ^H H ₃ c CH ₃ 417.52 418.4 0.96 QC- ACN- AA-XB 647 0.0 S ^3% h ₃ c ^x usn ₃ o-CH ₃ A-A. n.7 =/ X XX—C Xn ^H 468.58 469.4 0.78 QC- ACN- TFA- XB 648 H ₃ C HNy yCH ₃ 0-CH3 A\.N, / /—/ iXM+n 362.44 363.3 0.65 QC- ACN- TFA- XB 649 H ₃ C H _N y usn _{3 N} A / A ^ _N ; 4 y γη_/ AN O^N yy ^H H ₃ C CH ₃ 360.47 361.3 0.69 QC- ACN- TFA- XB 650 CH ₃ 0 N A H ₃ C ΑΆη USNz _N y γ η_// an yy ^H H ₃ c CH ₃ 445.57 446 0.98 QC- ACN- TFA- XB 651 MH ₃ C V ^CH 3 o-CH ₃ ™ (XA " ^H N ^ 443.52 444.4 0.74 QC- ACN- TFA- XB 652 siz 0 AL ^Nz Asn H ₃ C - Ny y-CH ₃ o-CH ₃ A^ ⁿ A /=( X XX—aXXn H 447.54 448.4 0.68 QC- ACN- TFA- XB 653 c> 0 'q' ^H sA H ₃ C ^S ^^Ny U ^s s _N o^yj ^ _N ; 4 y γ η_(/ hn 4A-n yy ^H H ₃ C CH ₃ 466.60 467.4 0.8 QC- ACN- TFA- XB

- 155 041852

654 V ¹ .% sn, Lmu ^H H ₃ C CH ₃ 432.57 433.4 0.84 QC- ACN- TFA- XB 655 CH ₃ Ϊ H ₃ C H ₃ C NA y-CH ₃ o-CH ₃ X/N. 7 ,=/ XX—XX^n H 404.52 405.2 1.2 QC- ACN- AA-XB 656 _{CH 3 1} ^H ₃ C ^H _{3 C} ^ ^NA 402.55 403.3 0.89 QC- ACN- TFA- XB 657 II H3C ³ >yNA CHSNz o-CH ₃ U / NX X ³ η Υν / χ to JL / -A AN ^H 434.54 435.41 0.83 QC- ACN- TFA- XB 658 n ₃ with f 0 ³ \—-CH _{3 N} HsC^N^^N. / \u003d n L 1 H TVa > Ν CHz ^H H ₃ c CH ₃ 432.57 433.2 1.48 QC- ACN- AA-XB 659 H ₃ C ₄ [ 9 u-sn ₃ o-sn ₃ / k „N. J _/= / oXT Xx—XXn °a -AV _v 476.58 477.4 1.42 QCACNAA-XB 660 1^9 y-ch ₃ o-ch ₃ ηχν^Λ/NX /=/ CH 4. ' \\ °n ₃ N j H 434.54 435.1 1.02 QC- ACN- TFA- XB 661 ⁿ zS _h |γ y-sn ₃ o-sn ₃ H ₃ C y / A\\ / to JL / - A / ^ Ν ^N Ν 406.49 407.3 1.26 QC- ACN- AA-XB

- 156 041852

662 ^N 3 ^SCH G 9 U ^CH s Ν. ^ΗΝ Α/ ^ν Α X y £ >_V W aAn )=\ ^H H ₃ C CH ₃ 390.49 391.2 0.99 QC- ACN- AA-XB 663 About ^H A % yAU. a CH3 o AnA \u003d ( ^H H ₃ C CH ₃ 475.60 476.2 0.79 QC- ACN- TFA- XB 664 H ₃ c O' ³ usn, l-NX G T 11 G Y / On oj <AA=f ^H H ₃ C CH ₃ 474.61 475.3 1.41 QC- ACN- AA-XB 665 H ₃ C ΓΥ y--CH _{3 CH3} ..αΑΆχΑ /А ³ YHr° Ά'Ν ^H CH ₃ 380.49 381.1 1.34 QCACNAA-XB 666 H ₃ c | 9 U-CH ₃ 0-CH3 hn. Λ. _n. 7 /—( AX4Y A ^V v 392.46 393.2 0.75 QC- ACN- TFA- XB 667 H ₃ c | 9 Y-CH3 _CH3 oA XC/^C/^ AA ^H CH3 422.53 423.2 0.75 QC- ACN- TFA- XB 668 H ₃ c A? At ^CH3 o-CH ₃ H ₃ C, /\.NA .N. J ,—( ^N p A\ / \ cun L 7L ' vi /¾ N CH ₃ o ^_ _n i ^H Yr 477.57 478.3 1.06 QC- ACN- AA-XB 669 H ₃ C γ ³ V-ch _{3 CH3} ^hn \ ^ AaA / A ΥΥθ \u003d ° ^H CH ₃ 366.47 367.1 0.86 QC- ACN- AA-XB

- 157 041852

670 n ₃ s I 9 Psn _{3 SNz} NC..N. A.N. 7 =/ ΪΗ A A ⁿ SN ₃ 405.50 406.3 1.38 QC- ACN- AA-XV 671 n ₃ s _h [γ Hsn ₃ o-sn ₃ ΗΝ. a. .N. 7 =/ Η 392.46 393.1 0.97 QC- ACN- AA-XV 672 9+ ^NzS ACH ₃ o-CHz n ϋ ^Μ 3 ^υ ΤΓ ]ί 'К___/ \ η LA /—Α Αν Η ν 491.60 492.3 1.06 QC- ACN- AA-XV 673 H ₃ c at ^SN z ν. _{Η s} - ^b ^ Y ^N U l-N e ^H 3 ^C y 1 t__k AN kk ^ N XX ⁿ H ₃ s CH ₃ 404.52 405.2 1.2 QC- ACN- AA-XV 674 γ-. Hc+ Huh? U ^CH 3 N. H ₃ C ^^N sAzNH \u003d n to L II | W/ An ° ° ⁿ H ₃ C sn ₃ 496.63 497.3 1.35 QC- ACN- AA-XV 675 H ₃ s | 9 Psn _{3 SNz} ΗΝ. 7 =/ υν γ ⁿ CH ₃ 366.47 367 0.77 QC- ACN- TFA- XV 676 x? ^NzS P ^SNz o-sn ₃ ^ΗΝ χ/ΥχΝ^Υ. /=( X XX—C Χν ⁿ 392.46 393.3 0.76 QC- ACN- TFA- XV 677 n ₃ + 1 9 Isn _SNz HaY ^ N ^ NY / Y SN ₃ o LA aLA ^H CH ₃ 451.57 452.2 0.95 QC- ACN- AA-XV 678 H ₃ C 1 9 Psn _{3 SNz} sn ίHiL x ° CH ₃ Η _n ⁿ sn ₃ 408.55 409.3 0.82 QC- ACN- TFA- XV

- 158 041852

679 n ₃ with I ? y-sn _{3 SNz} HN. kNJ ,=/ ΑΑ-ν Α _ν ⁿ sn ₃ 366.47 367.2 0.97 QC- ACN- AA-XB 680 ^νη ^НзС usn _{3 Ν} HN^^N^ yN' у Ф η_# Yу УУ-N γγ ⁿ Н ₃ С CH ₃ 389.51 390.1 1DZ QC- ACN- AA-XB 681 H ₃ c fl U ^CH3 CH3 k_A/U.A./ /=k JX/—O^n \An J η 402.55 403.1 1.24 QC- ACN- AA-XB 682 H ₃ c O ³ V-CH3 p-SN ₃ /=/ ί Xa\ ΛΝ UU-NNJ n 418.55 419.4 0.77 QC- ACN- TFA- XB 683 CH ₃ H _s cVn A A O 458.61 458.9 1.31 QC- ACN- AA-XB 684 co I °> /X - ζΆ t Y/ o ] ^£ o J ά 479.64 480.1 1.47 QC- ACN- AA-XB 685 SNz 0 ύ I ^NzS \ en n ₃ with usn _{3 Ν} η y η η_7 γΝ ^Η N ₃ C CH ₃ 473.63 474.3 1.49 QC- ACN- AA-XB 686 ° CX H ₃ C ^ _N y Y-CH3 _N \u003d N y η X\u003e __ # HN yy-N A \u003d\u003d \ ^H H ₃ C CH ₃ 444.58 445.2 0.92 QC- ACN- AA-XB

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687 °ΓΪ H ₃ C ³ Y-CH3 _N y [ 5)__7 \=N kA _N )=( ⁿ H ₃ C sn ₃ 444.58 445.1 0.73 QC- ACN- TFA- XV 688 L -O t ° 1 Xm - X k Ζ t 471.57 472.2 1 QC- ACN- AA-XB 689 sn ₃ Ν N ₃ S U-sn ₃ o-sn ₃ N JL /—A AN n _N 475.60 475.9 1.28 QC- ACN- AA-XB 690 n ₃ with hna \-ch ₃ 373.50 374.1 0.84 QC- ACN- TFA- XB 691 ^z About j TZ\kk/° 1 O (L "o" I 457.62 457.9 1.64 QC- ACN- AA-XB 692 _ ^N s% _gn HNA y-CH _{3 N} \u003d _N ; to y ΊΓ __7 \=: Ν WN )=( ^H H ₃ C CH ₃ 388.52 389.1 0.72 QC- ACN- TFA- XB 693 HP H3C ^H k>v ^N o VCH3 _O _ _C H ₃ ⁿ⁰ cn L/X/NO /=/ CH3 YY\^/V |l J /—\ AN Η 462.60 463 1.29 QC- ACN- AA-XB 694 ^f A - C0 t A / o T k0 ^{x t} O k 429.57 430.2 0.71 QC- ACN- TFA- XB

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695 xA ⁿ Msn _n / usn _{3 Ν} u f > C Y ^{N n} n ₃ s sn ₃ 494.66 495.4 1.14 QC- ACN- AA-XV 696 CH ₃ ώ ^H s \ gn H ₃ C Y NX Ύ ³ A o e y UU / >n A^n ) \u003d ( ^H H ₃ C CH 473.63 474.37 1.07 QC- ACN- AA-XV 697 n ₃ s NMA V-CH3 o-CH3 Amx/U /=( T XT—C Tn U ⁿ 390.49 391.3 0.95 QC- ACN- AA-XV 698 Οχ Ρ up Ao' Π3Ο _u / Г ^CH 3 O-CH3 ^зС A/XN J _/ —C/^NA H 496.63 497.3 1.09 QC- ACN- AA-XV 699 CH ₃ 0,<A ^НзС \ GN H ₃ C Г ^CH 3 0-CH3 ylHV Y + n HN ^ 475.60 476.4 0.76 QC- ACN- TFA- XV 700 AL H ₃ C NA U-CHz ₀ _ _CHz U u ⁿ 446.56 447.3 1.08 QC- ACN- AA-XV 701 η/A ^Ν ,Ά V ^CH3 .Ν^ ^NO D _n Vx^xN. 7 _N E SNz HERE T \ An )=( ^H H ₃ C CH ₃ 460.63 461.4 1.1 QC- ACN- AA-XV 702 ^NzS x_sn Ar NA y-SNz _N ohm _ _n e y T / _\ U ⁴ mA ^mA H N ₃ C CH ₃ 472.64 473.4 1.12 QC- ACN- AA-XV 703 SNz o ν L n ₃ s HgC^x^NM usn ₃ ph.g ^s n y YyMy ΑμΎ V=a ⁿ o 458.61 459.4 1.2 QC- ACN- AA-XV

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704 Ι,Ζ Η ^ζ Ά χ 1 ο C0 “ο I 454.58 454.9 1.35 QC- ACN- AA-XB 705 _Ν ^Η 3% η _Η to cancer U ³ ν. h' _n J/ n to ^HN y ηρ y—to P ^{N n} H ₃ with CH ₃ 469.60 470.47 0.74 QC- ACN- TFA- XB 706 H ₃ C H ₃ s AURU rsn ₃ o-CH ₃ kJ A/x/NA ,=/ θ ]f U A / |1 A /—A Η 474.61 475.4 1.1 QC- ACN- AA-XB 707 7 ΙΖ ^< C( ^Z I / \ ω 1 ° ΓΓ I ω 474.61 475.4 1.27 E 708 ο ₄ Χ ^ΝΗ2 Η 0 \ /A ³ usus O-CHz / vA / NX / \u003d ( pH ₂ CXuX An 0 n 'r 504.60 505 1.26 E 709 co x M AA ^{1 1} O ΖΙ Ο=ω=ο o <o T 496.63 497 1.05 E 710 ⁿ ' ^s \ mon IXmAn ^V v 474.61 475.3 1.27 E 711 P ^H 3 n g r—L—κ /--, ⁿ zC. οΑΑν-<χ _ν u ^SN r°- ^cNz Χχ—ν Α=^ν 'M n 474.61 475.3 1.33 E 712 _ НзС ην-<7 А ^С р ^с ^ °°S lXH + H ₃ CN H ' _N ^ CH ₃ 475.60 476.3 1.55 E

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713 NC-\ /u ^NzS \-CH _{3 0} - _CH ^NC 1 ΧΜΓον n Ν 468.57 469 1.8 E 714 ⁿ earth 0T^A ⁿ AA° ^CH3 НзС-N UL Ύ YuS ° 0Ν 0. % Η 515.66 516.4 1.35 E 715 ^NzS \ CH AAXo o ° ' ^CHz o 1L JX - ^H 446.56 447.3 1.43 E 716 _ H ₃ C hn-Ό 0 ^SNz / ^o-CHz on L JO—A 0 ⁿ CN 00 NA _n \ ^H 'n 429.53 430.3 1.94 E 717 0 *0 °' ⁴ \lO ^H3C 0 ^CH 3 O-CH3 o-/ TA /-4 /=n Oo 00 0 <1 H ₃ C ^H N 602.77 603.3 1.34 E 718 AJ /—, ^Nz 0sn 00-0 _N U ^CH 'O-CHz ιΧΜ0 00 0 ^H N 474.61 475.4 1.34 E 719 ^H 3% ΗΝ-/Ί J ^CH3 / ^{o-CH3 H} / ^N /=(>o ΎJ00 Xn H ₃ C-NH H ^N '0 461.57 462.3 1.29 E 720 h ₂ n X°/0 ^NzS ASN \|__/| uSN _{3 0} _ _CH3 / v\z ^N /=( 0 _O L JO—AX ^N 0 \0N A _n I H ₂ N η Ά 504.60 505.3 1.26 E 721 „ Yj o T - M ZI 0 474.61 475 1.27 E

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722 CH ₃ H ₃ CN ³ \= o G g-. ^N s% gn y-sn ₃ o-CH3 4 \u003d 0 to X / z - A Xn / VS J H ₃ C - NH ' _N 0 CH ₃ 560.70 561 1.5 Ε 723 /-, ^H = ^c \ ™ “Αν/Τ Ta ⁿ c ^s + _ch UIH+n CH ₃ N j ^H A 432.57 433.3 1.32 Ε 724 Y ΓΗ ^hn TS 0 D 1 3 -/- CH ₃ NJ HA 458.61 459.3 1.46 Ε 725 /_ H ₃ C HN^l _N il Xa— ^< C>y HN H Ά CH ₃ 461.57 462.3 1.3 Ε 726 ! r% -To o ^£ O V ^X L °' o k £ I 602.77 603 1.34 Ε 727 _ /-, ⁿ \u003d ^c x GN Ι,ΧΜΓΤν 474.61 475.4 1.38 Ε 728 ™-<1 n A t ° ^CH3 0\Ίί DE—(/n H ₃ sL> 474.61 475.3 1.35 Ε 729 _ /-^ n ₃ c {b<Vy y°- ^CH3 0< ⁿ Ok / \ HzSDD II L UL Αν CH3 Ν \ Η 502.66 503.3 1.41 Ε 730 _ H ₃ s NC - \ / 1 y-CH ₃ o-CH ₃ ^NC TDCH A Η 468.57 469 1.8 Ε

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731 sn ₃ A n ₃ s NzS + γ-M o ³ usn _{3 0} -sn ₃ YrA-X / Y ⁿ II J 7-A / == N 489.62 490.1 1.34 E 732 CH ₃ CH ₃ H ₃ C ⁿ zC N \--CH ₃ o-CH ₃ 449.56 450.1 1.19 E 733 n ^НзС \ CH О y-CH3 0-CH3 0 ^N 475.55 476.1 1.29 E 734 ^F 3 ^ _N + H ₃ H ₃ C N y-CH ₃ o-CH ₃ 474.49 475.1 1.86 E 735 -kJ t O T ¹ O O z ό T 440.56 441.2 1.32 QC- ACN- AA-XB 736 /--\ MH ₃ C 0 U ^CH3 CH ₃ -- 7 /=/ nr ++— 470.58 470.9 1.57 QC- ACN- AA-XB

Example 737 6-(5-((2S,5R)-2,5-Dimethylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2yl)-7,8-dimethyl - [1,2,4]triazolo[1,5-a]pyridine

Intermediate 737A: tert-butyl-5-((2S,5R)-4-(tert-butoxycarbonyl)-2,5-dimethylpiperazin-1-yl)-2-(7,8-dimethyl-[1,2, 4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

A suspension of tert-butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b] pyridine-1-carboxylate (600 mg, 1.24 mmol), tert-butyl (2R,5S)-2,5-dimethylpiperazine 1-carboxylate, HCl (466 mg, 1.86 mmol), Pd ₂ (dba) ₃ (113 mg, 0.124 mmol), dicyclohexyl (2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (69.4 mg, 0.149 mmol) and Cs ₂ CO ₃ (1, 82 g, 5.57 mmol) in 1,4-dioxane (12.5 ml) in a reaction vessel with a septum lid and magnetic stirrer was degassed with nitrogen gas for 5 minutes. The reaction vessel was sealed and placed in a heating block with stirring at 105°C for 6.5 h, then cooled to room temperature and left at room temperature overnight. The reaction was then restarted by adding tert-butyl (2R,5S)-2,5-dimethylpiperazine-1-carboxylate, HCl (233 mg, 0.93 mmol), Pd ₂ (dba) ₃ (57 mg, 0.062 mmol), dicyclohexyl ( 2',6'-di-isopropoxy-[1,1'-biphenyl]-2-yl)phosphine (35 mg, 0.075 mmol), and Cs ₂ CO ₃ (908 mg, 2.79 mmol), degassed with nitrogen gas , and heated to 105° C. with stirring for another 4 h. Upon completion, the reaction mixture was cooled to room temperature and left at room temperature overnight. The reaction mixture was then filtered, concentrated, and taken up in DCM. The crude material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-100% to give t-butyl-5-((2S,5R)-4-(t-butoxycarbonyl)-2,5-dimethylpiperazine -1-yl)-2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridine-1-carboxylate (698 mg, 1.130 mmol, 91% yield). LCMS retention time 1.26 [TS]. MS (E ⁺ ) m/z: 618.7 (M+H).

Example 737.

tert-Butyl-5-((2 S, 5 R)-4-(tert-butoxycarbonyl) -2,5-dimethylpiperazin-1 -yl)-2-(7,8-dimethyl- 165 041852

[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (698 mg, 1.13 mmol) suspended in TFA (6 ml) at room temperature and stirred for 3 hours, the Reaction mixture was then concentrated, re-dissolved in CHCl ₃ /iPrOH 3/1 and neutralized with 1.5M aqueous K ₂ HPO ₄ in a separating funnel. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated to obtain the substance, which was estimated as a quantitative yield of 6-(5-((2S,5R)-2,5-dimethylpiperazin-1-yl)-3-isopropyl-1H -pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (1.13 mmol). For characterization purposes, a portion of the crude product from a separate formulation of 6-(5-((2S,5R)-2,5-dimethylpiperazin-1-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-2- yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine prepared on a smaller scale was purified by preparative LC/MS using the following conditions: Column: XBridge C18, 200 mM x 19 mM , 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0 minute hold at 0% B, 0-40% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(5-((2S,5R)-2,5-dimethylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine2- yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine, TFA (15.5 mg). LCMS retention time 0.93 [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 418.5 (M+H). Selected NMR peaks:

1H NMR (500 MHz, DMSO-d6) δ 11.09 (s, 1H), 9.03 (br s, 1H), 8.78 (s, 2H), 8.47 (s, 1H), 7, 64 (br d, J=8.9 Hz, 1H), 6.82 (br d, J=8.5 Hz, 1H), 4.18-4.04 (m, 1H), 3.67-3 .53 (m, 1H), 3.45-3.33 (m, 1H), 3.11-2.97 (m, 1H), 2.86-2.75 (m, 1H), 2.59 (s, 3H), 2.17 (s, 3H), 1.42-1.35 (m, 6H), 1.29 (br d, J=6.4 Hz, 3H), 1.16 (br d, J=6.4 Hz, 3H).

Example 738.

-((2R,5S)-4-(2-(7,8-dimethyl-[ 1,2,4]triazolo [1,5-a]pyridin-6-yl)-3-isopropyl-1 H-pyrrolo [3,2b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)-2-(pyrrolidin-1-yl)ethan-1-one

Intermediate 738A: 2-chloro-1-((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3 -isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)ethan-1-one

6-(5-((2S,5R)-2,5-dimethylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1 ,2,4]triazolo[1,5-a]pyridine (0.496 mmol) was suspended in DCM (4 ml). Et ₃ N (0.346 ml, 2.48 mmol) and 2-chloroacetyl chloride (0.079 ml, 0.992 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 30 minutes. Another aliquot of 2-chloroacetyl chloride (0.025 ml, 0.314 mmol) was added. The reaction mixture was stirred for an additional 2 minutes. The reaction was quenched by the addition of water, DCM and 1.5M aqueous K2HPO4. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude material, which was estimated as a quantitative yield of 2-chloro-1-((2R,5S)-4-(2-(7,8-dimethyl-[1, 2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)ethan- 1-she (0.496 mmol). LCMS retention time 0.70 [TS]. MS (E+) m/z: 494.4 (M+H).

Example 738.

2-Chloro-1 -((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl -1 H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)ethan-1-one (0.0496 mmol) was suspended in DMF (1 ml). Pyrrolidine (0.050 ml, 0.609 mmol) was added and the reaction mixture was stirred for 19 hours at room temperature. Upon completion, the reaction mixture was diluted with a few drops of water, DMF, filtered, and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 16% B, 16-56% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 1((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6- yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 166 041852

5-yl)-2,5-dimethylpiperazin-1-yl)-2-(pyrrolidin-1-yl)ethan-1-one (14.2 mg, 0.027 mmol, 54.1% yield). LCMS retention time 1.46 [QC-ACN-AA-XB]. MS (E+) m/z: 529.5 (M+H). Selected NMR peaks (rotamers were present):

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.82 (s, 1H), 8.70 (br s, 1H), 8.45 (s, 1H), 7.54 (d, J=8 .9 Hz, 1H), 6.71 (br dd, J=8.8, 6.0 Hz, 1H), 2.80-2.72 (m, 1H), 2.56 (s, 3H), 2.15 (s, 3H), 1.76-1.61 (m, 4H), 1.36 (br d, J=5.8 Hz, 6H), 1.29-0.93 (m, 6H ).

Example 739 1Hpyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one

Intermediates 739A and 739B: 3-chloro-1-((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl) -3-isopropyl-III-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)propan-1-one and 1-((2R,5S)-4-( 2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl )-2,5-dimethylpiperazin-1-yl)prop-2-en-1-one

6-(5-((2S,5R)-2,5-dimethylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl- [1,2,4]triazolo[1,5-a]pyridine (0.496 mmol) was suspended in DCM (4 ml). Et ₃ N (0.35 ml, 2.48 mmol) and 3-chloropropanoyl chloride (0.095 ml, 0.992 mmol) were added sequentially and the reaction mixture was stirred for 15 min at room temperature. Upon completion, the reaction was quenched. The reaction mixture was worked up by dilution with water, DCM and 1.5M aqueous K ₂ HPO ₄ solution. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude material, which was carried to the next steps as is and evaluated as a quantitative yield of both substances (0.496 mmol total) as a mixture of an undetermined ratio of 3-chloro-1-((2R ,5S)-4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo [3,2- b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)propan-1-one (LCMS retention time 0.72 [TS]. MS (E+) m/z: 508.5 (M+ H)) and 1-((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl -1H-pyrrolo[3,2b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)prop-2-en-1-one (LCMS retention time 0.68 [TS]. MS (E ⁺ ) m/z: 472.5 (M+H).

Example 739.

A mixture of 3-chloro-1-((2R,5S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3- isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)propan-1-one and 1-((2R,5S)-4-(2-(7, 8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5- dimethylpiperazin-1-yl)prop-2-en-1-one (0.0413 mmol) was suspended in DMF (1 ml). Pyrrolidine (0.05 ml, 0.609 mmol) was added and the reaction mixture was stirred at room temperature for 20 hours. Upon completion, the reaction mixture was diluted with a few drops of water, DMF, filtered and purified by preparative LC/MS under the following conditions: Column: XBridge C18 , 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 15% B, 1555% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 1-((2R,5S)-4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine-6- yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one ( 18.0 mg, 0.032 mmol, 78% yield). LCMS retention time 1.07 [QC-ACN-TFA-XB]. MS (E ⁺ ) m/z: 543.4 (M+H). Selected NMR peaks (rotamers were present):

¹ H NMR (500 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.73 (br s, 1H), 8.47-8.44 (m, 1H), 7.54 (d, J=9.0 Hz, 1H), 6.76-6.67(m, 1H), 2.81-2.62(m, 3H), 2.57(s, 3H), 2.16(s , 3H), 1.68 (br d, J=2.8 Hz, 4H), 1.37 (br d, J=6.6 Hz, 6H), 1.30-0.94 (m, 6H) .

Example 740 [1,2,4]triazolo[1,5-а]pyridine

- 167 041852

Intermediate 740A: tert-Butyl-5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(7,8-dimethyl-[1,2,4] triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine-1-carboxylate

A suspension of tert-butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b] pyridine-1-carboxylate (150 mg, 0.310 mmol), tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate, 0.5 oxalate (113 mg, 0.464 mmol), RuPhos 2nd generation precatalyst (11 mg, 0.014 mmol) and Cs ₂ CO ₃ (353 mg, 1.084 mmol) in 1,4-dioxane (3.1 ml) were degassed with nitrogen for 5 min in a reaction vessel with a septum lid. The reaction vessel was sealed and placed in a heating block at 100° C. with stirring. After 2 hours, more 2nd generation RuPhos precatalyst (27 mg, 0.035 mmol) was added, the suspension was further degassed, and the reaction mixture was returned back to 100° C. with stirring for 2 hours. Upon completion, the reaction mixture was filtered, concentrated and purified by column chromatography on silica gel eluting with Hex/EtOAc 0-100% to give t-butyl-5-(6-(t-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(7, 8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2b]pyridine-1-carboxylate (124 mg, 66.5 % yield) containing a certain amount of co-eluting impurities. LCMS retention time 0.99 [TS]. MS (E ⁺ ) m/z: 602.3 (M+H).

Example 740.

A solution of tert-butyl-5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(7,8-dimethyl[1.2.4]triazolo[1, 5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (124 mg, 0.206 mmol) in TFA (3 ml) was stirred at room temperature for 2 hours Upon completion, the reaction mixture was concentrated and evaluated as a quantitative yield of 6-(3-isopropyl-5-(2,6diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-ul )-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine, TFA (0.206 mmol). 90% of this substance was used further as is. 10% of this material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 0 minute hold at 0% B, 0-40% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 0% B, 0-40% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25 C. Fraction sampling was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(2,6-diazaspiro[3.3]heptan2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl) -7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (3.1 mg, 0.0075 mmol). LCMS retention time 1.21 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 402.0 (M+H). Selected NMR peaks:

Ή NMR (500 MHz, DMSO-d6) δ 10.85 (s, 1H), 8.75 (s, 1H), 8.46 (s, 1H), 7.52 (br d, J=8.5 Hz, 1H), 6.28 (br d, J=8.9 Hz, 1H), 4.00 (s, 4H), 2.84-2.77 (m, 1H), 2.16 (s, 3H), 1.36 (br d, J=6.7 Hz, 6H).

Example 741 6-(3-Isopropyl-5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7 ,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine

6-(3-Isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyrudin-2-yl)-7,8-dimethyl[1, 2,4]triazolo[1,5-a]pyridine, TFA (15.93 mg, 0.0309 mmol) and Et ₃ N (0.05 ml, 0.359 mmol) were mixed in DMF (1 ml). Formaldehyde (37 wt% in water, 25 μl, 0.336 mmol) was added to the reaction vessel followed by sodium triacetoxyborohydride (54 mg, 0.255 mmol). The reaction mixture was stirred at room temperature for 90 minutes. Upon completion, the reaction was quenched by the addition of water, 1.5M aqueous K2HPO4, and DCM. The organic layer was separated and concentrated. The crude material was dissolved in DMF for purification by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetate

- 168 041852 citric acid; Gradient: 0 minute hold at 0% B, 0-40% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 1%B, 1-41%B for 20 min, then 4 minute hold at 100%B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b] pyridin-2yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (3.2 mg, 7.70 µmol, 25% yield). LCMS retention time 1.29 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 415.9 (M+H). Selected NMR peaks:

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.82 (s, 1H), 8.73 (s, 1H), 8.45 (s, 1H), 7.51 (d, J=8, 5 Hz, 1H), 6.26 (d, J=8.5 Hz, 1H), 3.96 (s, 4H), 2.84-2.75 (m, 1H), 2.57 (s, 3H), 2.22 (s, 3H), 2.14 (s, 3H), 1.34 (br d, J=6.7 Hz, 6H).

Example 742 2-b] pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N,N-dimethylacetamide

CH ₃

γγ ^Η H ₃ C CH ₃ ¢742) 6-(3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl )-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine, TFA (15.93 mg, 0.0309 mmol) and DBU (0.05 ml, 0.332 mmol) were mixed in DMF (1 ml). An excess of 2-chloro-N,N-dimethylacetamide (approximately 18 µl) was added to the reaction vessel and the mixture was stirred for 1.5 h. Upon completion, the reaction mixture was diluted with a few drops of water, DMF, and the crude material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 10% B, 10-50% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 2-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3- isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N,N-dimethylacetamide (6.6 mg, 0.013 mmol, 43.6% exit). LCMS retention time 1.33 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 486.9 (M+H). Selected NMR peaks:

1H NMR (500 MHz, DMSO-d6) δ 10.81 (s, 1H), 8.74 (s, 1H), 8.46 (s, 1H), 7.51 (d, J=8.5 Hz , 1H), 6.27 (d, J=8.5 Hz, 1H), 2.58 (s, 3H), 2.15 (s, 3H), 1.35 (br d, J=6.4 Hz, 6H).

Example 743 b] pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(dimethylamino)ethan-1-one

A solution of 6-(3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1, 2,4]triazolo[1,5-a]pyridine, TFA (15.93 mg, 0.0309 mmol) in methanol was converted to the HCl salt form by adding 1 ml of 4N HCl in dioxane and concentrating to dryness. The material was taken up again in methanol, 1 ml of 4N HCl in dioxane was added again and the material was concentrated to dryness. The substance was then suspended in DMF (1 ml) and N,N-dimethylglycine (20 mg, 0.194 mmol), Et ₃ N (0.1 ml, 0.717 mmol), and T3P (50% in DMF, 0.090 ml, 0.155 mmol) were added sequentially at room temperature with stirring. After 1.5 h, another aliquot of N,N-dimethylglycine (9 mg, 0.087 mmol), Et ₃ N (0.1 ml, 0.717 mmol) and T3P (50% in DMF, 0.090 ml, 0.155 mmol) was added and the reaction the mixture was stirred for 26 hours at room temperature. Upon completion, the reaction was quenched by adding water, 1.5M aqueous K ₂ HPO ₄ and DCM. The organic layer was separated, concentrated, and the crude isolate was diluted with DMF. The crude material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 16% B, 16-56% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction Selection

- 169 041852 were launched by MS signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge Phenyl, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 12% B, 12-52% B for 25 min, then 6 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. The fractions containing the product were combined and dried by centrifugal evaporation to give 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3- isopropyl-1 H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(dimethylamino)ethan-1-one (2.5 mg , 5.03 µmol, 16% yield). LCMS retention time 1.17 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 487.1 (M+H).

1H NMR (500 MHz, DMSO-d6) δ 10.85 (s, 1H), 8.72 (s, 1H), 8.45 (s, 1H), 7.53 (br d, J=8.9 Hz, 1H), 6.29 (br d, J=8.5 Hz, 1H), 4.35 (s, 2H), 4.07 (br s, 2H), 4.04 (s, 4H), 2.90 (s, 2H), 2.84-2.74 (m, 1H), 2.57 (s, 3H), 2.17 (s, 6H), 2.14 (s, 3H), 1 .34 (br d, J=6.4 Hz, 6H).

Example 744 6-(5-(6-Ethyl-2,6-diazaspiro[3.3]heptan-2-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin2-yl)-7.8 -dimethyl-[1,2,4]triazolo[1,5-а]pyridine n ₃ s

Alternative synthesis of an intermediate

H ₃ C CH ₃ ( ₇₄₄ ) of compound 740A: tert-butyl-5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(7,8-dimethyl-[1 ,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1 H-pyrrolo[3,2-b]pyridine-1-carboxylate

CH ₃ CH ₃ (hoopoe)

A suspension of tert-butyl-5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2- b]pyridine-1-carboxylate (332 mg, 0.685 mmol), Pd ₂ (dba) ₃ (62.8 mg, 0.069 mmol), dicyclohexyl (2',6'-di-isopropoxy-[1,1'-biphenyl ]-2-yl)phosphine (38.4 mg, 0.082 mmol) and Cs ₂ CO ₃ (902 mg, 2.77 mmol) in 1,4-dioxane (6.9 ml) in a vial with a septum lid and degassed with nitrogen for 5 minutes with a magnetic stirrer. The mixture was sealed and placed in a heating block at 105°C with stirring for 7 hours and then left at room temperature overnight. The reaction mixture was filtered, concentrated, and purified by silica gel column chromatography eluting with Hex/EtOAc 0-100% to give tert-butyl-5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptane-2- yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-1- carboxylate (0.685 mmol), which was evaluated as a quantitative yield.

Alternative synthesis of the compound according to example 740: 6-(3-isopropyl-5-(2,6diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7.8 -dimethyl-[1,2,4]triazolo[1,5-a]pyridine

A solution of tert-butyl-5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(7,8-dimethyl

[1,2,4]triαzolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (0.685 mmol) in TFA (3, 5 ml) was stirred at room temperature for 2 hours. Upon completion, the material was concentrated, taken up in 3/1 CHCl ₃ /z'PrOH and neutralized by mixing with 1.5 M aqueous K ₂ HPO ₄ and water in a separating funnel. The aqueous layer was extracted with 3/1 CHCl ₃ /PrOH. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude material, which was estimated as a quantitative yield of 6-(3-isopropyl-5-(2,6diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (0.685 mmol). LCMS retention time 0.53 [TS]. MS (E+) m/z: 402.3 (M+H).

Intermediate 744A: 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2 -b]pyridin-5-yl)-2,6-diazαspiro[3.3]heptan-2-yl)ethan-1-one

- 170 041852

To a stirred suspension of 6-(3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-III-pyrrolo[3,2b]pyridin-2-yl)-7,8-dimethyl-[ 1,2,4]triazolo[1,5-a]pyridine (0.173 mmol) in DCM (3 ml) were added successively Et ₃ N (0.121 ml, 0.865 mmol) and acetic anhydride (0.025 ml, 0.260 mmol). After 10 minutes, the reaction mixture was concentrated to give the crude material. This material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-100% followed by DCM/MeOH 0-10% to give 1-(6-(2-(7,8-dimethyl-[ 1,2,4]triazolo[1,5-a]pyridin-6yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan- 2-yl)ethan-1-one (66 mg, 0.149 mmol, 86% yield). LCMS retention time 0.60 [TS]. MS (E ⁺ ) m/z: 444.5 (M+H).

Example 744.

To a stirred solution of 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1 H-pyrrolo [3,2 -b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)ethan-1-one (66 mg, 0.149 mmol) in THF (3 ml) was added LiAlH4 (17 mg, 0.446 mmol ), and the vessel was sealed at room temperature. After 90 minutes, the reaction was quenched by adding DCM and 1.5M aqueous K ₂ HPO ₄ . The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was obtained, taken up in DMF and purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 30 mM, 5 μm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 9% B, 9-49% B for 20 min, then 2 minute hold at 100% B; Elution rate: 45 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 8% B, 8-48% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(5(6-ethyl-2,6-diazaspiro[3.3]heptan-2-yl)-3-isopropyl-1H-pyrollo[3,2-b]pyridine -2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (43.4 mg, 0.100 mmol, 67.5% yield). LCMS retention time 1.31 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 430.1 (M+H).

L NMR (500 MHz, DMSO-d ₆ ) δ 10.83 (s, 1H), 8.67 (s, 1H), 8.44 (s, 1H), 7.53 (d, J=8.9 Hz, 1H), 6.28 (d, J=8.5 Hz, 1H), 3.99 (s, 4H), 2.83-2.75 (m, 1H), 2.68-2.59 (m, 2H), 2.55 (s, 3H), 2.12 (s, 3H), 1.32 (br d, J=6.4 Hz, 6H), 0.93 (brt, J=7 .0 Hz, 3H).

Example 745 6-(3-Isopropyl-5-(2-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1, 2,4]triazolo[1,5-a]pyridine

Intermediate 745A: tert-Butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2carboxylate

IBocN OMs „ _h

A V (745A)

Et ₃ N (3.27 ml , 23.4 mmol) and MsCl (1.1 ml, 14.1 mmol) in series. After 3.25 hours the reaction was quenched by adding water and DCM. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude material, which was estimated as a quantitative yield of tert-butyl-6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (9.38 mmol, 100% yield).

Intermediate 745B: tert-butyl-6-iodo-2-azaspiro[3.3]heptane-2-carboxylate

IBocnX/X-I _{z h} \Z\Z (745V) tert-Butyl-6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (4.69 mmol) was suspended in ethyl methyl ketone (19 ml ) and sodium iodide (3.52 g, 23.5 mmol) were added. The mixture was degassed with nitrogen gas for 10 minutes, then the reaction vessel was sealed with a septum cap and heated to 100° C. with stirring for 19.75 hours. In parallel, an identical reaction was run. Upon completion, the reaction mixtures were cooled to room temperature and quenched by adding water and DCM. Parallel reaction mixtures were combined during processing. The layers were separated and the aqueous layer was extracted with DCM.

The combined organic layer was dried over sodium sulfate, filtered, and concentrated to give a crude oil. This material was dissolved in DCM and purified by column

- 171 041852 silica gel chromatography using a Teledyne Isco instrument, eluting with Hex/EtOAc 0-60%. Substance-containing fractions were concentrated and repurified as above eluting with Hex/EtOAc 040% to give tert-butyl 6-iodo-2-azaspiro[3.3]heptane-2-carboxylate (2.1 g) total including pooling both parallel reactions as a white solid.

¹ H NMR (499 MHz, chloroform-d) δ 4.29 (quin, J=7.8 Hz, 1H), 3.95 (s, 2H), 3.92 (s, 2H), 2.97- 2.87 (m, 2H), 2.75-2.66 (m, 2H), 1.42 (s, 9H).

Intermediate 745C: tert-Butyl-5-(2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptan-6yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1, 5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

In a 100 ml round bottom flask with a magnetic stirrer, a suspension of tert-butyl-5-bromo-2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3 -isopropyl-III-pyrrolo[3,2-b]pyridine-1-carboxylate (1.57 g, 3.25 mmol), tert-butyl-6-iodo-2-azaspiro[3.3]heptane-2-carboxylate ( 2.1 g, 6.50 mmol), tris(trimethylsilyl)silane (1.21 g, 4.87 mmol), [Ir(dF(CF ₃ )ppy) ₂ (dtbbpy)]PF ₆ (0.036 g, 0.032 mmol) and Na ₂ CO ₃ (1.38 g, 13.0 mmol) in 1,4-dioxane (30 ml) were degassed with a rubber septum under nitrogen gas for 15 min. Nickel(II) chloride, ethylene glycol, dimethyl ether complex (0.018 g, 0.081 mmol) and 4,4'-di-tert-butyl-2,2'bipyridine (0.026 g, 0.097 mmol) were added to a vessel with a magnetic stirrer, which sparged with nitrogen gas. 1,4-Dioxane (6 ml) was added and the resulting mixture was degassed with nitrogen gas for 10 min and stirred. The resulting solution was then added to the reaction flask. The resulting mixture was further degassed with nitrogen gas for an additional 15 minutes and then the nitrogen gas supply was removed and a nitrogen balloon was attached to the flask with a needle through the diaphragm. The reaction vessel was placed on a stirring plate for stirring, ventilation, and irradiation with 34 W Kessil KSH 150V blue phytolamps (12 cm apart, flask in the middle) for 66 h. When complete, the reaction mixture was filtered, concentrated, and redissolved in DCM. The material was purified by silica gel column chromatography using a Teledyne Isco instrument eluting with Hex/EtOAc 0-60% to give t-butyl-5-(2-(t-butoxycarbonyl)-2-azaspiro[3.3]heptan-6-yl )-2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (1.27 g, 2.11 mmol, 65.1% yield) containing a small amount of co-eluting impurities. LCMS retention time 1.13 [TS]. MS (E+) m/z: 601.7 (M+H).

¹ H NMR (499 MHz, chloroform-d) δ 8.35 (s, 1H), 8.34 (d, J=8.6 Hz, 1H), 8.33 (s, 1H), 7.05 ( d, J=8.6 Hz, 1H), 4.05 (s, 2H), 3.96 (s, 2H), 3.60 (quin, J=8.1 Hz, 1H), 2.86- 2.77 (m, 1H), 2.66 (s, 3H), 2.65-2.56 (m, 4H), 2.13 (s, 3H), 1.46-1.41 (m, 15H), 1.22(s, 9H).

Example 745.

A solution of tert-butyl-5-(2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptan-6-yl)-2-(7,8-dimethyl[1.2.4]triazolo[1.5- a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate α (584 mg, 0.972 mmol) in TFA (6 ml) was stirred for 2 hours at room temperature. Upon completion, the reaction mixture was concentrated and dissolved in 3/1 CHCl ₃ /PrOH. This organic layer was neutralized by mixing in a separating funnel with a 1.5 M aqueous K ₂ HPO ₄ solution. The aqueous layer was extracted with 3/1 CHCl ₃ /iPrOH and the combined organic layer was dried over sodium sulfate, filtered, and concentrated to give the material, which was estimated as a quantitative yield of 6-(3-isopropyl-5-(2-azaspiro[3.3] heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (0.972 mmol). Most of this substance was carried on as is. A portion (5%) of this material was purified by preparative LCMS using the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 μm particle; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 5% B, 5-45% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS and UV signals. The fractions containing the product were combined and dried by centrifugal evaporation. The material was further purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 5% B, 5-55% B for 20 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 6-(3-isopropyl-5-(2-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl) -7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (4.5 mg, 0.0106 mmol). LCMS retention time 1.05 [QC-ACNTFA-XB]. MS (E ⁺ ) m/z: 401.3 (M+H). Selected NMR peaks:

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1H NMR (500 MHz, DMSO-d6) δ 8.76 (s, 1H), 8.46 (s, 1H), 7.59 (d, J=8.5 Hz, 1H), 6.96 (d , J=8.2 Hz, 1H), 2.93-2.83 (m, 1H), 2.58 (s, 3H), 2.15 (s, 3H), 1.39 (br d, J =6.7Hz, 6H).

Example 746 1-(6-(2-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1 H-pyrrolo[3 ,2-b] pyridin-5-yl)-2-azaspiro[3.3]heptan-2-yl)-3-(dimethylamino)propan-1-one

To a solution of 6-(3-isopropyl-5-(2-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1,2 ,4]triazolo[1,5-a]pyridine (19.5 mg, 0.0486 mmol), 3-(dimethylamino)propanoic acid (18 mg, 0.154 mmol), and Et ₃ N (0.05 ml, 0.359 mmol) in DMF (1 ml) was added T3P (0.057 ml, 0.097 mmol). The mixture was stirred at room temperature for 1.5 hours. Upon completion, the reaction was quenched. The reaction mixture was worked up by adding water, 1.5M aqueous K2HPO4 and DCM. The organic layer was separated, concentrated and diluted with DMF. The material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 10% B, 10-50% B for 25 minutes, then 4 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Fraction selection was triggered by MS signals. Product-containing fractions were combined and dried by centrifugal evaporation to give 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl- 1H-pyrrolo[3,2-b]pyridin-5-yl)-2-azaspiro[3.3]heptan-2-yl)-3-(dimethylamino)propan-1-one (6.2 mg, 0.012 mmol, 24 % exit). LCMS retention time 1.31 [QC-ACN-AA-XB]. MS (E ⁺ ) m/z: 500.3 (M+H). Selected NMR peaks, rotamers were present:

1H NMR (500 MHz, DMSO-d6) δ 11.13 (br s, 1H), 8.80 (s, 1H), 8.47 (s, 1H), 7.60 (d, J=8.5 Hz, 1H), 6.97 (br d, J=8.5 Hz, 1H), 4.25 (s, 1H), 4.17 (s, 1H), 3.96 (s, 1H), 3 .84 (s, 1H), 3.62-3.52 (m, 1H), 2.94-2.86 (m, 1H), 2.59 (s, 3H), 2.16 (s, 6H ), 2.14 (s, 3H), 1.47-1.37 (m, 6H).

Compounds according to the following examples were obtained in accordance with the General methods described in the above examples.

table 2

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742 CH ₃ HsC^EU'N'D Η ₃ %_ 0 UA U ^CH3 Ν. An n.7 \u003d N A II y \\u003e _ # AN μΆ χχ ^H H ₃ C CH ₃ 487.20 0.96 QC- ACN- TFA- XB 743 CHz 0 h ₃ c' ⁿ X^na_ n ₃ s Ϊ-ΑΛ y-CHz _N An Ny χ Ί y \>_# αν χχ ^{H H} ₃ C CH ₃ 486.90 0.99 QC- ACN- TFA- XB 744 H ₃ C^NA H ₃ C AAL V-CH3 _N Αν^νΧ χ E y U>_# AN \An XX ^H H ₃ C CH ₃ 430.10 1.21 QC- ACN- AA-XB 745 HNA H ₃ C UH V-CHz _N A / A / ^- H y _ (/ AN \αν χχ ⁿ H ₃ C CHz 401.30 1.04 QC- ACN- TFA- XB 746 0 Xa snz Ύ HAG A) \u003d \ ⁿ H ₃ with CH ₃ 500.30 1.31 QC- ACN- AA-XB 747 НзС 9 ,νΧν^ n ₃ s Н ₃ С X АСНз _N pN аа =ν η 1 11 z__\ Y ^N χχ ^H H ₃ C CH ₃ 501.50 1.45 QC- ACN- AA-XB 748 I about oXy O/z Xz <Hz \=/ j: xJL s XT 522.30 1.17 QC- ACN- TFA- XB

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749 ⁿ H ₃ C sn ₃ 487.20 1.55 QC- ACN- AA-XV 750 n ₃ s 9 ζ ^Ν Μ Ν-A H ₃ C ~ n ₃ s A usn _{3 Ν} ArA /A AJ # pN aa _n ur ⁿ H ₃ C sn ₃ 515.40 1.02 QC- ACN- TFA- XV 751 TaD n ₃ s \ _p pSN _{3 N} N ₃ S'T Ο _Ν /mN 0 o T ιΓ / _\ Τ ^Ν h + h ur ⁿ N ₃ S sn ₃ 536.20 2.02 QC- ACN- AA-XV 752 CH ₃ 0 ύ Α lSN ₃ H,s H A rsn _{3 Ν} wy ⁿ H ₃ C sn ₃ 503.40 1.42 QC- ACN- AA-XV 753 0 A lSNz H,s H ₂ NN p ³ rsn _{3 N} Υ ^ν ΆμΑ. /g^ 1 T |G E__S y \u003d N ^{CHz n} H ₃ C CHz 489.40 0.87 QC- ACN- TFA- XV 754 НзС 9, Ν-Α^Ν - Н ₃ С Н ₃ С А CH _{3 Ν} Ааа /А р Tw pN yAn ur ^Н Н ₃ С CH ₃ 487.10 1.53 QC- ACN- AA-XV 755 N ₃ C n N ₃ C ^{NzS W} U ^CH 3 N. ^N AA mN 1 I T y_Δ pN ur ⁿ N ₃ C sn ₃ 444.20 1.33 QC- ACN- AA-XV

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756 H ₃ C ⁰ ΝΗ Y ³ Ν. p Y \>_# \=N L+n )=/ ^H H ₃ c CH ₃ 473.40 1.16 QCACNAA-XB 757 CH _{3 HN} YH ₃ C_ HN Ί \-CH _{3 N} H ₃ C γ γΰ CHA / οο ⁿ H ₃ C sn ₃ 418.20 1.22 QCACNAA-XB 758 0 SNz n ₃ s _{n n} XvU ⁿ z ° T F \> _ya Ο ^Ν ΑΑ-ν οο ⁿ N ₃ C SN ₃ 489.00 1.38 QC- ACN- AA-XB 759 η ₂ ν^ο 1 1 ^{3 L} A N. AY'n oo ^H H ₃ C CH ₃ 475.20 1.73 QC- ACN- AA-XB 760 CHz 0 CH ₃ HzC^X^u^ ^HzC usn _{3 N} J =N ^Z X H ₃ C γ ΥΟη+Γ γΝ οο ^Η H ₃ C CH ₃ 503.30 0.84 QC- ACN- TFA- XB 761 0 SN ₃ ^NC % -CH _{3 Ν} CH _{3 Η Γ} ν'</Ν =Ν H ₃ C Τ' 0 # ν ^ Ν AY-Ν οο ⁿ H ₃ C SNz 517.30 0.87 QC- ACN- TFA- XB 762 1 ^NzS \^-sn Λ G ^CHz Α^ ^Ν Ύ ί ΥΥ Υ ^Ν η ₂ ν 00 ⁿ n ₃ s sn ₃ 459.40 0.76 QC- ACN- TFA- XB

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763 - n ₃ s. il ³ \--CH3 ... JI / ^ύ ζ ^Ν U to γ_( > ^Ν ί ₀ X \ ⁿ H ₃ C CH3 νη ₂ 472.90 1.33 QC- ACN- AA-XV 764 H ₃ C A U ^SNz χ ζ^ν η < ^Ν y TU / U ^y Οχ J / \ X ⁿ H ₃ C SNz °' CH ₃ 508.10 0.98 QC- ACN- TFA- XV 765 - H ₃ s A U ^SNz N. CH ₃ .,ΥχΝ^/ΝΧ /L / 1 T /_\ Y ^N n ) \u003d/ O sh / \ ^m H ₃ C CH ₃ 522.50 0.81 QC- ACN- TFA- XV 766 n ₃ s A Y ^SNz x Ζ^Ν η ζ ^Ν Y φ 5_\ Y ^y CN Η / ' ^m n ₃ s CH ₃ 440.90 1.76 QC- ACN- AA-XV 767 n ₃ s A U ^SNz Ζ^Ν η < ^Ν U 1 7__ \ U ^Ν \ y \u003d ( °U ⁿ H ₃ s CH ₃ z ^N CH H ₃ C ^CH s 501.20 1.49 QC- ACN- AA-XV 768 °p 1 ⁿ > n ₃ ^N N ₃ C CH ₃ 458.10 0.96 QC- ACN- TFA- XV 769 O ^ \ - H ₃ with _h ? ) I U ^CHz X L-ή Ί N y Y)_7 W Y \u003d \ ⁿ H ₃ C CHz 243.60 1.44 QC- ACN- AA-XV 770 o _{h 0} 7s^ ^HzS x sn k / T / ^{C 3 Ν} U 1 ζ__ \ U ^Ν ) \u003d ( ^H H ₃ C CH ₃ 534.10 1.64 QCACNAA-XB

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771 O A ⁿ A ^CH3 γγ ⁿ H ₃ C CH ₃ 470.10 1.66 QCACNAA-XB 772 4 From ^ CH I Υ° ^Η 3 Ν. .ΥνΥΥ L ^- H / O^N y fu_7 γΝ b ^H z )=( H ⁿ n ₃ s SN ₃ s ₃ 244.00 1.50 QCACNAA-XB 773 4 ^НзС ^CH I Y ^GH 3 _N l-ν' ] ζχ ^{Ν Y} T)_\ Υ ^Ν ' o )=( H ₃ c' ^N 'CH3 ^H НзС СНз 501.20 1.48 QCACNAA-XB 774 _f ⁿ z% _sn h Y ^CH 3 _N l-ν' i / ^N ^ Ύ γΝ ί \Αν γγ Η ₂ Ν ^{0 n} H ₃ C CHz 459.10 1.58 QCACNAA-XB 775 F ^НзС <CH h Y ^CH 3 _N Л-ν' Ί γ У 1т CY ^N „ ; AM )=( °YH ₃ c CH ₃ nh ₂ 473.40 1.20 QCACNAA-XB 776 f ^НзС \^en h Y ^CH 3 N. to g Y I 7__\ Y ^N ( ₀ χΛν )=( y ^M H ₃ C CH ₃ H ₃ C' ^{N CH} 3 501.00 1.42 QCACNAA-XB 777 F ^НзС \^CH y ^c h _{3 N} z^n η < ^N y TU / A ^N Y CH3 ^-N >=< ₀ A ^H H ₃ C CH ₃ ^U 0 508.40 0.99 QC- ACN- TFA- XB

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778 '' w ¹ A f „fT O co \ 1 x PA ^£ o X D-O nA 522.20 1.40 QC- ACN- AA-XV 779 9η h ^NzS psn _{3 N} \An ^z yy ⁿ N ₃ s sn ₃ 458.10 0.98 QC- ACN- TFA- XV 780 oA - NzS GN G /,-D y-CH _{3 N} A zN 1 ^Ν ϋ T 7_\ A \Αν uu ⁿ H3C sn ₃ 486.20 1.43 QC- ACN- AA-XV 781 A. H ₃ C G 1 __D L ^{s 3} A A Αν ^Ν Υ Y ' ^Ν 11 7_\ Α ^Ν \ An uu ⁿ N ₃ s CH ₃ 534.40 0.98 QC- ACN- TFA- XV 782 oZh to ^U^z W yy ⁿ H ₃ s ch ₃ 236.30 0.99 QC- ACN- TFA- XV 783 SNz 1 ^N usn ₃ „ nzsl ^ y ^ uur 1A _n yun ⁿ H ₃ s SNz 444.40 1.40 QC- ACN- AA-XV 784 t ^Nz Asn K U-CH3 _N z^n / ^N y y_# γΝ A' ^CH3 ''^n W H ⁿ H ₃ s CH ₃ SN ₃ 487.50 1.33 QC- ACN- AA-XV

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785 t ⁿ z% _sn h Y-siz _{N k} X\N _y ⁿ A Λ-Ν 1 o^/ ^N + у γη_/ an kO^N yy \ ^H H ₃ C CH ₃ H ₃ C ^{,N CH} 3 501.50 0.82 QC- ACN- TFA- XV 786 fM ^NzS u-sn _{3 N} kAn yy ⁿ H ₃ c CH ₃ 444.20 0.81 QC- ACN- TFA- XV 787 N Y ³ ,N. H ₃ c' ^{N 3 n} H ₃ C sn ₃ 497.30 0.80 QC- ACN- TFA- XV 788 0 sn ₃ kA ⁿ % - ₃ n ₃ s sn ₃ γ y γ y_# um CH ₃ C ^ s) \u003d \ ⁿ H ₃ C sn ₃ 503.00 1.13 QC- ACN- TFA- XV 789 0 sn ₃ kA ⁿ \u003d y- ₃ n _zS y HuAUur sn ₃ sn ₃ <Ai) u ⁿ N ₃ C sn ₃ 517.40 0.92 QC- ACN- TFA- XV 790 0 sn ₃ kA ^NzS y _{3 Ν} ^NzS A O _Y M A to U A TVa a=n sn ₃ ΑΑ _Ν ^γ=η ⁿ H ₃ C sn ₃ 503.40 0.84 QC- ACN- TFA- XV 791 ^H 3 ^C. and c and ³ U-CH _{3 s} V their II η \_// ΗΝ η ₂ ν \+^ν γς ⁿ n ₃ s sn ₃ 475.30 0.80 QC- ACN- TFA- XV

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792 H ₃ C H H ₃ C g ³ H ₃ C \ N _v ⁿ A / A/ η γ # pN \Αν ρ=( ⁿ H ₃ C sn ₃ 446.20 1.15 QC- ACN- TFA- XB 793 NzS ^N Ch N ₃ C Ar/Λ / ³ Zh ^ncs ηΎ vrAp CH ₃ )=( ^m H ₃ C sn ₃ 460.30 ι, ιο QC- ACN- TFA- XB 794 H ₃ C ^H ₃ C A'Akg Η ₂ Ν sn ₃ ) \u003d ( H H ₃ C CH ₃ 489.30 0.98 QC- ACN- TFA- XB 795 H ₃ C n g 1 pzi ° CHz Η ηΥ ^x _CHz 538.30 1.00 QC- ACN- TFA- XB 796 O CH ₃ LA y-z _n.LnAMGO CHz H ^N ₃ C CH ₃ 503.30 1.49 QC- ACN- AA-XB 797 O CH ₃ Ai ^ΟΗ, n ₃ s > X ^m mu ^Ν' Ί Y - ιι η \> // >ν CH ₃ CH ₃ ΑΑ-ν U = ( ^H H ₃ C CH ₃ 517.40 0.95 QC- ACN- TFA- XB 798 NzS _n _ ί ^NzS \ GN V A / Ρι Ύ p # ν^Ν Α^ο ί to / \ / Η ₂ Ν sn ₃ \^Ν ) \u003d ζ ^Η H ₃ with CH3 489.00 0.86 QC- ACN- TFA- XB

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799 H ₃ C n e Λ-. ³ y-snz _m /A νη ₂ i UG T / - \ Χ ^Ν sn ₃ ΑΑ ) \u003d ( H ₃ C CHz 475.20 0.88 QC- ACN- TFA- XV 800 n ₃ s Η s /О ³ \—-CH ₃ °^X ^N \ ,Νγ ^Ν νΓ AX nh2 a Ύ TyX y ^N ch3 )=( H ₃ c CH ₃ 475.20 0.86 QC- ACN- TFA- XV 801 0 A H ^ ⁿ ThV ⁿ y ⁿ AA ^N Y ^H ₃ C CH ₃ γ Y γ _// γ CH ₃ ⁿ H ₃ C sn ₃ 489.50 1.36 QC- ACN- AA-XV 802 ^Nz AyL ^Nz Asn noI 9 1 U ^SNz Ν. 7ΎΗγ ^H H ₃ C CH ₃ 476.20 1.70 QC- ACN- AA-XV 803 Ar ^Nz U ^Nz ν. “'OtSfr ^H H ₃ C CH3 489.60 1.69 QC- ACN- AA-XV 804 -AAr ^H H ₃ C CH ₃ 475.10 0.76 QC- ACN- TFA- XV 805 H ₃ C ^H H ₃ C CH ₃ 524.50 0.71 QC- ACN- TFA- XV 806 L YC ^H H ₃ C CH ₃ 524.10 1.05 QC- ACN- TFA- XV

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807 χί; > ^Η H ₃ C CH ₃ 474.90 1.49 QCACNAA-XB 808 CH ₃ 0 HcC^^A ^HcC y-ch _{3 Ν} Mn =N Λ = II η Λ__/ CH ₃ )=( ^Η H ₃ C CH ₃ 489.50 1.44 QC- ACN- AA-XB 809 ^h 2 ⁿ nAnA ^NzS \ en T 7 । Y ³ v. ° ttiHr ⁿ N ₃ C sn ₃ 461.10 1.58 QC- ACN- AA-XB 810 _____ _____ |_| p 'uSNz ⁿ H ₃ C SN ₃ 443.10 2.02 QC- ACN- AA-XB 811 sn ₃ sn ₃ AM / y / ^N H ₃ C CH ₃ 502.90 1.45 QC- ACN- AA-XB 812 Oh / x N ₃ C U ^SNz _N shd ⁿ N ₃ C sn ₃ 475.10 1.60 QCACNAA-XB 813 A Ύ> Ύ“ , ⁿ H ₃ C sn ₃ 460.10 1.85 QC- ACN- AA-XB 814 °~Ί ⁿ H ₃ C SN ₃ 474.20 1.95 QC- ACN- AA-XB

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815 o _h ok'L ^Nz to ^CHz s Shy ^{1 n} N ₃ C sn ₃ 536.20 1.80 QC- ACN- AA-XB 816 sn ₃ NzS'Kh ^NzS u-sn _{3 N} ⁿ H ₃ C sn ₃ 446.20 1.62 QCACNAA-XB 817 sr ^NzS g ^Nz a ⁿ N ₃ C sn ₃ 510.10 1.66 QC- ACN- AA-XB 818 ΧίιΟΧ ^N N ₃ C CH ₃ 489.50 1.54 QC- ACN- AA-XB 819 ⁿ H ₃ C sn ₃ 525.10 1.70 QC- ACN- AA-XB 820 kk'Ai'O, H ₃ C ^H H ₃ C CH ₃ 487.90 1.94 QCACNAA-XB 821 _sn ΗΝ η usn _{3 Ν} 7tiHr ^H H ₃ C CH ₃ 418.40 1.27 QC- ACN- AA-XB 822 HN^ ^HcC yCH _{3 N} Lllk =n to H ₃ c y ΊΓ __7 V=N \An / ⁼⁼ \ ^H H ₃ C CH ₃ 404.40 1.16 QC- ACN- AA-XB

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823 / p I " _N SN ₃ ^SN ₃ ΥΥ H H ₃ C CH ₃ 503.50 1.24 QC- ACN- AA-XB 824 0 Αρ o ΧοΧχ ^H H ₃ C CH ₃ 501.13 1.08 QC- ACN- TFA- XB 825 Ar ^H pCH ₃ to XXxnX ^H H ₃ C CH ₃ 515.60 1.00 QC- ACN- TFA- XB 826 0 Ar ^HzC pz ^ ^NH XyhX ⁿ H ₃ C sn ₃ 500.90 1.13 QC- ACN- TFA- XB 827 0 Lr ^NzS r „ CHz sn ₃ ΥΑ/γγ ⁿ H ₃ C sn ₃ 502.90 1.15 QC- ACN- TFA- XB 828 0 Υρ p _С n ₃ ⁿ ' ^s Υγγγ τυ χχ ^Н Н ₃ С CH ₃ 487.30 1.35 QCACNAA-XB 829 0 gTr ^NzS uSN _{3 N} H ₃ C' ^N ' ⁷ P l-v' 7 Υ n Tu_/ AN CH ₃ kk _N ^/ Xp ^H H ₃ C CH ₃ 501.30 1.41 QCACNAA-XB

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830 0 ^Nz A ^cNz ά _NzS , mn \Ον )=ς ⁿ n ₃ s sn ₃ 460.90 0.98 QC- ACN- TFA- XB 831 0 Lo ^NzS + ^CHz % to .N. _N. 7 = ν' Ί D ₃ C CD ₃ + AAn )=o ^H H ₃ C CH ₃ 481.60 1.30 QC- ACN- AA-XB 832 0 Ao 0-3 _N nh ₂ n^7 λ—n' 7 || η \>___(/ \On )=0 ^H H ₃ C CH ₃ 447.10 1.26 QC- ACN- AA-XB 833 CH ₃ Υγ ^НзС usn _{3 N} N^7 =n' η A ]| 7 \__(/ >=N CH ₃ ΥΑ/γγ ^H H ₃ C CH ₃ 446.50 1.02 QC- ACN- TFA- XB 834 0 Ao ^H3 V ^{CH3 n} > ν n^7 =n' η a Η Ί e/ O ^N ch3 %ΑΝγ=< ⁿ H3C ch ₃ 501.20 1.42 QC- ACN- AA-XB 835 0 Αο About ^{CH n} > Ν Ν^7 =ν η \ / a η 1 χ>__/ Ο ^Ν CH ₃ ΥΑν ⁷ θ \ ⁿ H ₃ C sn ₃ 515.40 1.57 QC- ACN- AA-XB 836 0 Αο ^Hs A ^CHs _ _X NH A/N^,N^7 ^n' 1 V/ a Τ η \ (/ \= ^{N v} CH ₃ ^H H ₃ C CH ₃ 501.10 1.00 QC- ACN- TFA- XB

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837 H II H ₃ C _ν CH3 Α ^Ν ν ^Ν Χ Λ \u003d II η \__ / Μ ^Ν CH3 y ^H H ₃ C CH ₃ 503.20 1.57 QCACNAA-XB 838 CD ₃ 0 □ ₃ Γ ^Ν Χμ ^NzS u-sn _{3 Ν} CHz JAAy ^H H ₃ C CH ₃ 495.20 1.53 QC- ACN- AA-XB 839 0 SNz LA ^Nz U ^sz % n s'Chn^^AA M ^N NzS sn ₃ ; || | \__/ M ^N CH ₃ CHA/ ^N H ₃ s CH3 503.00 1.64 QC- ACN- AA-XB 840 O CH ₃ LA ^Nz U ^snz ν. n ₃ s J LMx/MA ζ^ν η U DNT E Λ Μ ^Ν CH3 CH3 ^H H ₃ C CH3 517.70 0.98 QC- ACN- TFA- XB 841 CH3 CH3 A A H3C H3Mu^y ³ y-CH3 _Ν 4 ^Ν χ/ ^Ν <Χ Ζ^Ν Λ = π Μ_Λ Μ ^Ν snz ΑΑΑ)={ ⁿ H ₃ C sn ₃ 460.40 1.01 QC- ACN- TFA- XB 842 CH ₃ O sn ₃ tss-MA ^NzS usn _{3 Ν} ^H N ₃ C CH ₃ 503.40 1.52 QCACNAA-XB 843 O CH ₃ ^H s ^C -m ^ x ^ mA H ₃ C Ν Ν y uCH _{3 Ν} ^H H ₃ C CH ₃ 517.00 1.51 QC- ACN- AA-XB

- 187 041852

844 CH ₃ sn ₃ H ₃ JnA ^Η3 °ν-ΟΗ _{3 N} SHA ⁿ H ₃ C sn ₃ 460.40 1.59 QC- ACN- AA-XV 845 sn ₃ O P ⁿ A O <00 Ζ^Ν 0 H3C'% 4n 1X0 Y ^u CH ₃ 0— _N y \u003d/ ⁿ H ₃ C sn ₃ 538.30 1.66 QC- ACN- AA-XV 846 sn ₃ ⁿ H ₃ C sn ₃ 538.30 0.95 QC- ACN- TFA- XV 847 0 sn ₃ Η ₂ νΟ^ν^ H ₃ С _ν <00 0 0 = n η Λ__// у ν sn ₃ <Α/>=( ⁿ H ₃ С sn ₃ 488.90 1.56 QC- ACN- AA-XV 848 O sn ₃ ^H1 usz, 7:0% ⁿ H ₃ C sn ₃ 489.20 1.56 QC- ACN- AA-XV 849 CH ₃ o _ηγ , ν _χ/ Α n ₃ s n ₃ s ν η u-in _{3 Ν} N Λ ⁿ zs η y% _# mind <A _n ^z yy ⁿ n ₃ s sn ₃ 489.20 1.52 QCACNAA-XB 850 o ^H V ^H ' A ^SN \u003d 00-N yu ⁿ n ₃ s CH ₃ 503.20 1.41 QC- ACN- AA-XV

- 188 041852

851 CH ₃ n ₃ suy ^NzS usn _{3 N} n% U ⁿ z ° y η A_# γΝ mu-N H ^N ₃ C CH ₃ 446.00 0.92 QC- ACN- TFA- XV 852 0 n ₂ uXm^ ^Hz Usn _{3 ν} Η _C ^N ^N / _ _N ; А ^н зС Ύ ητ # γΝ УУ/ )=( ⁿ Н ₃ С н ₃ 474.90 1.45 QC- ACN- AA-XV 853 CH ₃ 0 n ₃ s'UU ^NzS usn _{3 Ν} CHz k/N NA y G \=N \An )=( ⁿ H ₃ C CHz 489.30 0.92 QC- ACN- TFA- XV 854 CH ₃ 0 n/U Y _% y ] A__# \=N \An ^z )=( ⁿ H ₃ C sn ₃ 501.10 1.69 QC- ACN- AA-XV 855 ^CH _{3 0} НзС'Ум ^НзС usn _{3 N} CHз У^У y 245.30 1.02 QC- ACN- TFA- XV 856 ^{3 0} n yT ^N Um-U /U ⁿ zS τ ητ A_# mu-N )=( ^N N ₃ C CH ₃ 524.30 0.88 QC- ACN- TFA- XV 857 DD HnT^ _d NzS _n Y Y D L T || \__(/ >N D ° UL/y=( ⁿ H ₃ C sn ₃ 398.20 1.12 QC- ACN- AA-XV

- 189 041852

858 CH ₃ 0 DD h ₃ c ^zN XnX^D ^НзС usn3 N D Λ T |T \/ pN ^{DD H} H ₃ C CH ₃ 483.10 0.78 QC- ACN- TFA- XV 859 CD ₃ 0 DD НзС _n PWA Z^' A DAIF v_/ Y ^{N DD} ^N^>=( ^H H ₃ C CH ₃ 489.20 0.78 QC- ACN- TFA- XV 860 0 CH ₃ ⁿ \u003d usn ₃ ^CH3 nLukgy PA) \u003d ( ^H H ₃ C CH ₃ 517.00 1.60 QC- ACN- AA-XV 861 _n N / _N - = Г II \__(/ pN CH ₃ ΑΑΆ)=( ^H H ₃ C CH ₃ 418.20 0.82 QC- ACN- TFA- XV 862 SizO CH3 H3C'^A ⁿ \u003d Mn, _N Ρ^N ) \u003d ( ^Η H ₃ C CH ₃ 503.30 1.52 QCACNAA-XB 863 0 A^CH3H3C _N Η C' ^N CH ^{^ N ^ N} <^X n ₃ s υι-ι _{3 Ξ} 'η γ a__// γΝ CH ₃ ⁿ H ₃ C sn ₃ 503.20 1.38 QC- ACN- AA-XV 864 ΑνΥ ^η = ^η =Ύ3 ν from ^s U %γΡγρΝ sn ₃ s ₃ Wn^)=( ⁿ H ₃ C s ₃ 517.40 1.33 QC- ACN- AA-XV

- 190 041852

865 CH _{3 c} A _N ^xCH ₃ ^H ₃ C n zb Ν y \--CH ₃ m ΑνΆ a A \u003d η | D/ y sn ₃ kA/ DD ⁿ N ₃ S sn ₃ 460.40 1.66 QCACNAA-XB 866 A en T 7 t U ^CHz ν. NH ₂ kz^Ny 7 ξ y η k_/ yy sn ₃ kA/ DD ⁿ H ₃ C sn ₃ 475.10 0.84 QC- ACN- TFA- XV 867 ^N X ° sn ₃ L L n ₃ s ν η usn _{3 Ν n} (Λ-Μνί X 7 ⁿ z ° y η Y_# χν kA _N DD ⁿ N ₃ s sn ₃ 475.10 1.56 QC- ACN- AA-XV 868 sn ₃ Dk D / A-n DD ^H N ₃ S CH ₃ 538.20 0.93 QC- ACN- TFA- XV 869 / A ^N N ₃ C CH ₃ 538.10 1.64 QCACNAA-XB 870 0 Ar ^NC U ^SN \u003d N. _{n with} x + vU 7 ⁿ z ° । GN e_S An sn ₃ kAyDD ⁿ n ₃ s sn ₃ 489.00 1.38 QC- ACN- AA-XV 871 0 /у ДсНз H ₃ C^N /ν ν.7 Ί ι Τ 1GUD A CH ₃ Αν DD ⁿ n ₃ s sn ₃ 503.40 1.42 QCACNAA-XB

- 191 041852

872 0 Ar A n. h ₃ AN An nA A 4 | CH ₃ γ y /χ__// SNz MCh'Uu ⁿ H ₃ C SNz 503.40 1.42 QC- ACN- AA-XV 873 0 Lr V i. A uUr ^to SN ₃ LL ⁿ N ₃ with CH ₃ 503.40 0.87 QC- ACN- TFA- XV 874 0 Lo ^4 ^ ³ N. y LL / yy CH ₃ ^{N H} zC CHz 517.10 1, Yu QC- ACN- TFA- XV 875 CH ₃ O .N. A H ₃ C 0 N T ³ \--CH3 _{K |} n ₃ sun ₃ ^ ^N y ^N y4AOy^ Y^Y /=\ ^H H ₃ C CH ₃ 517.00 2.03 QCACNAA-XB 876 0 Lo N. ^H 3C^^N U AN A A H η u n UU U CH ₃ UA|/yy ^H H ₃ C CH3 531.40 1.74 QC- ACN- AA-XV 877 _{n s} ⁿ II HC ³ 0 ^N xA _N 0 ^Nz USN ^{n s} 7 ν η y-cNz _Ν n ₃ s ^ν' Λ u u UCH uun ^N ₃ S n ₃ 503.00 1, Yu QC- ACN- TFA- XV 878 CH ₃ 0 H ₃ S. at. A N ₃ C nX AT + ^{CH3 3} sn ₃ Ui a A A h T O u 4k _N uu ⁿ H ₃ C CH3 517.50 1.48 QC- ACN- AA-XV

- 192 041852

879 N ₃ sU ^N s ³ γ o NzS SNz U N N. / \u003d _N 7 y Guu / γΝ CHU / \ ^u003d \ ⁿ N ₃ with sn ₃ 517.40 1.40 QC- ACN- AA-XB 880 NzSu ^S T X "_; 1 . Г Н С^сн У ^Ν ν ^Ν Χ ' ^m z^ ^ ^m z T || L__l γΝ UU-N ) \u003d ( ^N H ₃ C CH ₃ 545.40 2.02 QC- ACN- AA-XB 881 SNz Η ₃ ο^η o NX H ₃ C / k k „N. J \u003d ν' Ί H ₃ C ^ CH ₃ γ HN Y W ) \u003d ( ^H H ₃ C CH ₃ 559.50 2.53 QCACNAA-XB 882 ^NzS y ^CHz o NX n ₃ s to CH ₃ UUU> = ( ⁿ H ₃ C CHz 545.20 1.85 QC- ACN- AA-XB 883 CH ₃ Nzsu _o h ₃ c _v nX n ₃ s T 7 । At ^CHz ν. CH ₃ \u003d Ν η Ύ J # Αν ΥΧ'Ν ) \u003d ( ^Η H ₃ C CH ₃ 531.20 1.51 QC- ACN- AA-XB 884 CH ₃ ηνΎ ^НзС usn3 Ν Η c^/ ⁿ -A ^N aX xk Н3С Τ γ L_# γΝ УУ-N )=( ^Η H ₃ С CH ₃ 418.30 1.23 QC- ACN- AA-XB

- 193 041852

885 sn ₃ o CH ₃ HA ^N Oy>p ⁿ z% CH _{3 Ν} n Λ/ ^Ν Υ ^Ν Α aCh ⁿ z ° y A_/ pN CHA/ ur ⁿ H ₃ C CHz 503.10 1.43 QC- ACN- AA-XB 886 0 CH ₃ ^Hs %A p H ₃ C ^CH3 ncsArA^p tr ur ^H H ₃ C CH ₃ 517.00 1.02 QC- ACN- TFA- XB 887 sn ₃ osn ₃ NzS'AA ⁿ ₃ s _N T^AAA T u fU_<7 pN \An ur ⁿ n ₃ s s ₃ 489.40 0.85 QC- ACN- TFA- XB 888 CD ₃ O oAd AH' N ^D D An^NA r u TU_A pN \An ur ⁿ n ₃ s sn ₃ 483.00 1.26 QC- ACN- AA-XB 889 sn ₃ about us Μ SNz. DDN^AJ y Tz_\ Τ ^Ν kA/ ur ⁿ n ₃ s sn ₃ 477.00 1.02 QC- ACN- TFA- XB 890 A From ⁰ 'Τ' ⁰ D _D oT _N Ty _D ⁿ z c ^to CH _{3 N} ^D kv ^N AA A d Δ TT \_/7 y= ^{N d D} MN^yy ^H H ₃ C CH ₃ 485.40 1.25 QC- ACN- AA-XB 891 0 ³ ° D ₃ C ^X Y DD qOn^P ^{0 НзС} рСН _{3 N} d AT if A__A \= ^{N DD} MN^yp ^H H ₃ C CH ₃ 491.30 0.76 QC- ACN- TFA- XB

- 194 041852

892 0 CH ₃ La ^Hz usn ₃ snz ΧΑΥχχ ^H H ₃ C CH ₃ 529.50 1.39 QC- ACN- AA-XB 893 0 SN ₃ LA Asnz n cX V ^N V ^N Y А^ н3с η Ϊ | G \/ AN ch3 ch3 X/ u/ ⁿ n3s ch ₃ 517.50 1.48 QC- ACN- AA-XB 894 o sn ₃ LA ^NzS _G nz „Nzs'% AL / O n ₃ A ^SNz n ₃ s n ₃ 531.50 1.00 QC- ACN- TFA- XB 895 0 CH ₃ La ^Hz y _n A ΛγΧΛ SN ₃ SN ₃ SN ₃ X / y / ^N H ₃ C CH ₃ 531.00 1.72 QC- ACN- AA-XB 896 About CH ₃ La ^Hz x ^SN z ν. g XXXVQ- V ⁿ n ₃ s d ₃ 557.00 1.62 QCACNAA-XB 897 CH ₃ 0 η ₃ ΑνΤΛ _ν α n ₃ s 7 1 U ³ a n cY ^N vM ACh ⁿ h ^s r || # an τΑν уу ^н Н ₃ С н ₃ 503.30 0.86 QC- ACN- TFA- XB 898 ⁿ z<A „ ³ η o H ₃ C 7 1 U ^SNz ν. μ _p vXn Ν^ =Ν ^Ζ Λ Ά γ F # Αν ΛΑν ^Η H ₃ C CH ₃ 517.30 1.46 QCACNAA-XB

- 195 041852

899 ^NzS usn _{3 Ν} ΜγΑρ CHU / )=( ^N H ₃ C CH ₃ 515.30 0.85 QC- ACN- TFA- XV 900 ^{0 N} z \ gi 7 । Y ³ v. n suum y NzS A |G A_# dy ) \u003d\ ⁿ H ₃ s sn ₃ 543.40 0.87 QC- ACN- TFA- XV 901 A~~Z co u \\ ¹ „ST δ ^|σ> \ 1 m A ( Y ⁰ 543.40 1.35 QC- ACN- AA-XB 902 0 Ud ^NzS >- ^sn ' ν a to / Chg A sn3 sn3 sn3 /A / u / ⁿ H3S sn ₃ 517.30 1.37 QC- ACN- AA-XV 903 Nzu ^SNz o NzDyD / x N ₃ S t 7 । At ^CHz ν. “garden ⁿ H ₃ S n ₃ 545.40 1.15 QC- ACN- TFA- XV 904 CH ₃ 0 Η ₃ ΑΝχΜ /X AND ₃ S n ₃ sI U 1 U-sn ₃ ^CH s and U Ν NA to ^N sS γ |G 'Ν__# y \u003d: N ΑΜ _ν ⁿ N ₃ S SN ₃ 531.50 1.53 QC- ACN- AA-XV 905 ^NzS U ^CHz ν. ϊχ^ΥτΤγΡ ³ CH3 CH3 ^H H ₃ C CH ₃ 531.40 1.59 QC- ACN- AA-XB

- 196 041852

906 0 CH ₃ n ₃ to sn ₃ H ₃ s CH3 531.00 1.59 QCACNAA-XB 907 0 SNz oJ+J? ⁿ H ₃ C sn ₃ 559.00 1.75 QC- ACN- AA-XB 908 °~Ί pho ,—ζ 0—< Y'0 ω z' co V \--/I kA x Oh" yil 571.40 0.91 QC- ACN- TFA- XB 909 about sn ₃ 5...........ΪΥ ^H H ₃ C CHz 561.00 1.79 QCACNAA-XB 910 H ₃ C. / ^CH 3 ³ Υ O CH ₃ H ₃ C Ν^Λ A H ₃ C ° "· / oh? ^H H ₃ C CH ₃ 559.50 1.64 QCACNAA-XB 911 Lu 'γ"., ⁿ H ₃ C SN ₃ 545.50 1.60 QC- ACN- AA-XB 912 O cn ₃ Δη ^Nz U ^cn c ^NzS _t + ΑγγΑηΑ cn ₃ cn ₃ cn ₃ AA/ γγ ^H H ₃ C CHc 545.50 1.04 QC- ACN- TFA- XB

- 197 041852

913 0 H ₃ C 1 U ^CHz Ν ν Ί CH < Τ ΥΥΥ Υ ^{Ν CHz} ΥΥχοο ⁿ H ₃ C CH ₃ 515.40 0.90 QC- ACN- TFA- XB 914 0 SN ₃ Nzs + sNz ^SNz k + d> \u003d < ^sn z ^m N ₃ C CH ₃ 559.50 1.52 QC- ACN- AA-XB 915 0 Lo ⁿ A ^SNz Ν Λο ν./ =ν χ x UkMO ^{N HzS SNz N} NzS ^M CHz 515.30 1.38 QC- ACN- AA-XB 916 0 Lo ^NzS o ^{Nz n} >% N ₃ ^{N n} zS CH ₃ 517.30 0.81 QC- ACN- TFA- XB 917 O Lo s H ChH>0G ^{F n} H ₃ C sn ₃ 519.20 1.51 QC- ACN- AA-XB 918 O Lo ^Nz L ^CHz s l ko + O >=< \/ ^and n ₃ s sn ₃ 529.20 1.60 QC- ACN- AA-XB 919 O Lo ^Hs L ^CHs % _Ζ Ν = _Ν ; A ^^H / \ ^FM H ₃ C CH ₃ 537.40 0.90 QC- ACN- TFA- XB

- 198 041852

920 O ^NC U SN _{3 n} 0 ^{n n} ₃ s sn ₃ 555.40 1.36 QCACNAA-XB 921 0 <\ _k1 n ₃ s G A A ^CH3 <% Am A A 7 VJ g T γ yy γΝ W yun ⁿ n ₃ s sn ₃ 527.20 1.49 QC- ACN- AA-XV 922 0 Yes ^Nz U ^sz ,ν rY LYrCyP ^SNz AA/ ⁿ N ₃ s SNz 515.20 0.93 QC- ACN- TFA- XV 923 0 H ₃ C 1 u-sn ₃ ⁿ APn, AAA A A ' T Hm A ^CHz Ά-νΎα ^H N ₃ C CHz 529.40 0.96 QC- ACN- TFA- XV 924 0 N ₃ S _sn 1 u-sn _{3 n} ^{n s} u% n ₃ XX γ .G a ^NzS sn T iTVy y ^{n 3} 4an u ⁿ N ₃ s CH 543.40 1.00 QC- ACN- TFA- XV 925 0 N ₃ C 1 y-sn _{3 N} ⁿ s ^s _x % fnX NzSD _n 1 G T Tuu YN sn ₃ \ AA- / \_/ he G~\ ^m N ₃ C CH ₃ 573.50 1.49 QC- ACN- AA-XV 926 CH ₃ 0 CH ₃ H ₃ cYA _Ν Ϋ n ₃ s H ₃ si Υ 1 n. ³ CH _{3 n Γ} λ/Ν ΝΥ ν ⁿ zS y y_# y UU-ν yun ⁿ 545.50 1.59 QC- ACN- AA-XV

- 199 041852

927 ^Nz< J ^{0 CH} ₃ ^h ₃ ^{c'n ^} n ^{^} A__# \=sN CHA/ )=( ^Η H ₃ C CH ₃ 517.20 0.84 QC- ACN- TFA- XV 928 _А. ^_ _{_ _} ^{_ _ _ _} _{_ _} 529.30 1.51 QCACNAA-XB 929 O^\ E CH3 O ^L 0 O™' N _n Αν·4 O 7 ⁿ zC p || A__# pN W )=( ^H H ₃ C CH ₃ 557.40 1.40 QC- ACN- AA-XB 930 OH X o CH3 H ₃ C. .N. A A H ₃ C ³ Y y-CH3 _N ^{3 CH3} n cXU ^N XT ^H cC γ |G # V^N W _N ^Z )=( ^H H ₃ C CH ₃ 575.00 1.75 QC- ACN- AA-XB 931 0 L ⁿ L ⁿ s N l An^n A _N E k ^ ⁿ 'khk) k o ^m H3s sn ₃ 543.00 1.03 QC- ACN- TFA- XB 932 0 Lo ^NzS u ^{s n s} n P WAp I CH ₃ CH ₃ ChoA /) ^ ⁿ H ₃ C sn ₃ 503.50 1.41 QCACNAA-XB

- 200 041852

933 0 Lr A™' m γΟγγρΟ CH3 CH ₃ ⁿ H ₃ C sn ₃ 517.20 1.48 QCACNAA-XB 934 Lr ^H A \u003d _N> H ₃ sI ^CHz A] KW pN CH ₃ CH ₃ ) \u003d ( ^H H ₃ C CH ₃ 531.50 0.96 QC- ACN- TFA- XV 935 O CH ₃ LA ^Hz A ν. l LrArr ^Lenz AA V ^H H ₃ C CH ₃ 557.40 1.47 QC- ACN- AA-XV 936 O CH ₃ LA A _Ν Ν Α ^Ν ρΑ Λ \ / ί g Η Λ__Λ Ό ^Ν CH ₃ ΑνΧ=( ^Η H ₃ C CH ₃ 529.50 1.44 QC- ACN- AA-XV 937 O ch ₃ LA ^HzS p, „ n cA Υ ^Ν ν ^Ν Α A n ₃ s η = Τ μ y_L pN CH ₃ CH ₃ 4AnX = ( ^H H ₃ C CH ₃ 517.30 1, Yu QC- ACN- TFA- XV 938 ^D ₃ ^{_ _} _{_} 531.50 1.53 QC- ACN- AA-XV 939 CH ₃ O CH ₃ AAL A ^{Nz 3} CH ₃ ζ^Ν Λ ξ f II \__// >=Ν CH ₃ UL|CHN )=( H ₃ C CH ₃ 545.10 1.73 QCACNAA-XB

- 201 041852

940 O A. 1 gLyP ⁿ z + ΓΗ ° 1 1 y-CH _{3 Ν} Η Χ ^Ν ν ^Ν Υ iCh ⁿ z ° y || k__# pN χχ ⁿ N ₃ C sn ₃ 543.20 1.52 QC- ACN- AA-XV 941 k + C n ₃ s _n n X ^N v ^N Y /gL Ή y |G U_# pN OA χχ ^{H N} ₃ C CH ₃ 515.30 1.50 QC- ACN- AA-XV 942 W „OS O T h ¹ t / \u003d p CO CO .---- VQ about X 503.20 1.44 QCACNAA-XB 943 CH ₃ 0 payp H ₃ S t 7 । Y ³ v. CH _{3 μ} N / _Ν ' ^{n s} γ γ 'X__# y \u003d: N member / χχ ⁿ H ₃ C sn ₃ 517.00 1.07 QC- ACN- TFA- XV 944 CH ₃ 0 H ₃ cYyY H ₃ C H ₃ s + ϊ 1 U ^CHz N. ^sn _{n c} A / N ν Υ \u003d ν k ⁿ z ° y Ν # y \u003d N ΟΥ-Ν χχ ⁿ H ₃ C s ₃ 531.30 1.59 QC- ACN- AA-XV 945 0 NzUO ^Hz + ^ ^Ν χΧγΧ Υ ⁿ H ₃ C sn ₃ o 571.30 0.85 QC- ACN- TFA- XV

- 202 041852

946 0 Ar ^NzS u- ^sn z ν. l ^{but sn} z N n / a 517.30 1.00 QC- ACN- TFA- XV 947 Ar ^NzS p ₃ , ν AVA H \ 7 Srrr I / ^{0 n} H ₃ s sn ₃ 557.00 1.03 QC- ACN- TFA- XV 948 Αρ ^Η ρ^ ₃ AyUpQ ' Asn ₃ /=( OH ⁿ H ₃ C sn ₃ 531.00 1.01 QC- ACN- TFA- XV 949 0 Ar ^NzS r ₃ U/ ΑγArr n ₃ s Arn ₃ /—( ^{he n} n ₃ s s ₃ 533.30 1.04 QC- ACN- TFA- XV 950 οΎ 0 UUh ⁿ rn ₃ H ₃ C CH ₃ λ Τ' |G^_(/ pN %α _ν UCH ⁿ H ₃ C n ₃ 545.00 1.81 QC- ACN- AA-XV 951 O Ar ^HzS rn ₃ l ^uLrr <> d D N ₃ C sn ₃ o''o 577.20 1.01 QC- ACN- TFA- XV 952 H || D ₃ C ^N ^^N _^ ^HzS _{uSN 3} ^N 464.00 0.98 QC- ACN- TFA- XV

- 203 041852

953 OH SJ H3C^M^A n ₃ c H ₃ cI 1 1 / ^CH3 N. ³ CH ₃ N = Ν η Ξ \ |[ # \= ^Ν CH ₃ 4An)={ ^Η H ₃ C CH ₃ 561.20 1.65 QC- ACN- AA-XV 954 he S O CH ₃ O ^l L O ^CHz .% ³ CH ₃ \u003d n L a \ y __ (/ Ό ^Ν CH ₃ ^Η Η3Ο ^Ζ CH3 575.50 0.98 QC- ACN- TFA- XV 955 OH S ° ΑϊΊ Ό ^η = ν ³ -z _{Η C} A^M ^N >A 7 ⁿ s ^r O \>__# ) ^ N kA / ) \u003d ⁿ H ₃ with CH ₃ 561.50 1.55 QC- ACN- AA-XV 956 0 Ao ^NzS + ^CHz % l A ^N p-A A Y A ⁿ zS CH ₃ 543.40 1.35 QC- ACN- AA-XV 957 O Ar ^H V-3 Υο / \ '-o ^m H ₃ C sn ₃ 543.50 1.37 QC- ACN- AA-XV 958 about sn ₃ ⁿ H ₃ C sn ₃ 571.20 1.55 QC- ACN- AA-XV

- 204 041852

959 O CH ₃ o n ₃ s ch ₃ 619.30 1.08 QC- ACN- TFA- XB 960 0 sn ₃ qjr snz 4Λ _Ν )=( ⁿ H ₃ C sn ₃ 585.50 1.42 QC- ACN- AA-XB 961 and Ι—-Ζ. ok UO ¹ A / ¹ ω Z -' ω lCh \ - / t to X 2 Xr 585.30 1.09 QC- ACN- TFA- XB 962 O sn ₃ kA O ^CH3 s 9 X W0r F ^M H ₃ C CH ₃ 579.30 1.92 QCACNAA-XB 963 0 CH ₃ H ₃ CCH ₃ AX ^НзС usn _{3 N} key vaa zA to η Ν YT ШШ AN oO ^сн з W γ ^H H ₃ C CH ₃ 587.20 1.85 QC- ACN- AA-XB 964 0 CH ₃ -i Sha CD ₃ CH ₃ A / ^N kA ^H H ₃ C CH ₃ 506.30 1.54 QC- ACN- AA-XB 965 0 CH ₃ AX A .% ° H Hsha- 0% CH ₃ A / ^ N kA ^H H ₃ C CH ₃ 523.40 1.46 QC- ACN- AA-XB

- 205 041852

966 0 n ₃ s% ^γΑγρ △ >=< H ₃ s CH ₃ 515.60 1.01 QC- ACN- TFA- XV 967 0 Λ γ ^Nz % ^sz _% ^CHz T O_\ X ^N xAn )=( ⁿ H ₃ C CH ₃ 517.60 0.91 QC- ACN- TFA- XV 968 0 Λγ ^Nz % ^CHz _Ν _ ΝΗ 7/Ν,.νΜ ,—ν' 7 ξ/ Τ' |J \>__# γΝ ⁿ H ₃ C sn ₃ 487.20 1.46 QC- ACN- AA-XB 969 0 Λγ ^Нз unz γ γΑγΡ Τη ΛΑν Γ\ ^m n ₃ s sn ₃ 505.20 1.24 QC- ACN- AA-XB 970 o Αγ ⁿ % ^snz _h ΗΝ Ζ^Ν Λ Ί Τ KW Μν CH ₃ ΑΑν) \u003d ( ⁿ H ₃ C sn ₃ 475.50 0.92 QC- ACN- TFA- XB 971 he h ^NzS usn3 Ν ζ^N' A t f L_S W ⁿ H3C CH ₃ 545.40 1.25 QCACNAA-XB 972 ATU ^N H3C ^Z SN3 432.10 1.25 QCACNAA-XB

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973 ΗίΖΑ ^НзС рСН3 m ΑγΥρΥ AP^N )=( ⁿ Н3с CH ₃ 416.10 1.29 QC- ACN- AA-XV 974 hnAA ^НзС usn _{3 N} Ζ^' γ p О_A pN AA _n )=( ^H H ₃ C CH ₃ 430.00 1.44 QC- ACN- AA-XV 975 HN^ ^НзС рСн _{3 N} Z^N γ 1 ύ γ \>_# pN H ₃ C^CH ₃ ΑΛ N )=( ^M H ₃ C CH ₃ 223.90 1.28 QC- ACN- TFA- XV 976 CH ₃ HN'X ^НзС рСН _{3 N} h ^{нз с} p |[ A_# pN AP-n )=( ^H H ₃ C CH ₃ 418.10 1.07 QC- ACN- TFA- XV 977 HN^ ^HcC pCH _{3 N} HcC I G Η e / P ^N cn3 ΑΡ-ν) \u003d ( ⁿ H3C cn ₃ 418.10 1.08 QC- ACN- TFA- XV 978 ΗΝ^ ^НзС рСН _{3 Ν} AJn^NxV ζ^Ν γ ρ |px>_A pN AP^n )=( ^H H ₃ C CH ₃ 402.10 1.01 QC- ACN- TFA- XV 979 ^H YH ₃ C 3 P-nn^7 E ^A ' 7__\ P ^N 4A _n )=( ^H H ₃ c CH ₃ 416.10 1.31 QC- ACN- AA-XV 980 Y ⁿ \u003d ^with usnz ^υυΡυΡ Α / Ά ) \u003d ( ⁿ H ₃ with CH ₃ 416.10 1.02 QC- ACN- TFA- XV

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981 GIZA? XX 402.10 0.99 QC- ACN- TFA- XV 982 HN^J Izu CH _{3 N} On N0 0 Λ p |T __(/ y N <O _N yy ^H H ₃ c CH ₃ 416.20 1.31 QC- ACN- AA-XV 983 HN^ ^HzC yCH _{3 N} ^H 3Cx'-<00 Z^N Λ Ί y ryJ yy CH ₃ C0- _N yy ^H H ₃ C CH ₃ 432.10 1.19 QC- ACN- TFA- XV 984 HN^ ^H sC _N Onn.7 0 Λ y y_(/ y ν 00 N yy ⁿ H ₃ C sn ₃ 402.10 1.01 QC- ACN- TFA- XV 985 igu ⁿ usn ₃ ^s UgiR 00 N uu ⁿ N ₃ s sn ₃ 402.10 1.32 QC- ACN- AA-XV 986 /CH ₃ HNy' ^HzS y-CH ₃ N <00 0 L y T p_/ u ⁿ H ₃ s SN ₃ 432.40 1.45 QC- ACN- AA-XV 987 HN^ _{0CH 3 N} ^{H 0} \/00 / ₀ 420.00 1.27 QC- ACN- AA-XV 988 NYU0N ₃ ^sC y-CH _{3 N} O000 0 t] y y 00 N Ut and H ₃ C sn ₃ 418.40 1.36 QC- ACN- AA-XV

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989 ΗΝ^ Un _{3 N} H sTAU / U ^N zS y A A_# V ^ N AaU / \u003d \ ^H H ₃ C CH ₃ 404.40 1.25 QCACNAA-XB 990 ΗΝ^ΜΑ^ N UCH ⁷ T \ ⁿ n ₃ with sn ₃ 418.40 1.26 QCACNAA-XB 991 CH3 HN^ ^H3 UsN _{3 N} ama U T II T \ _/ VN CH3) =/ ^H H ₃ C CH3 418.20 1.50 QC- ACN- AA-XV 992 CH3 NY^UsnTu-CH3 _N UN nV y T A/ \=ν \Αν / ⁼ \ ^Η H ₃ C CH ₃ 432.30 0.94 QC- ACN- TFA- XV 993 SNz ηνΤ ^NzS usn _{3 Ν} U ^N v ^N y U \u003d II η \# an SNz ⁿ H ₃ C sn ₃ 418.50 1.37 QCACNAA-XB 994 nGU ^Nz Usn _{3 N} noU / N nA \u003d n y A _# MN ΑίΑ-N ) \u003d ( ⁿ N ₃ with CH 420.00 1.20 QC- ACN- AA-XV 995 n .Νχ НзС н ₃ с у·! ³ usn _{3 Ν} Tn ν^7 y __<7 ΑΝ ΑίΑ-Ν )=( ⁿ H ₃ C SNz 418.10 1.15 QC- ACN- AA-XV 996 SNz r ^N A ^Nz A ^SN ' ν. ^Nz A ATP ⁿ n ₃ s sn ₃ 502.30 0.81 QC- ACN- TFA- XV

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997 CH ₃ H ₃ C III U ³ N. ^H 3% A An nA A e 1 ° II I \ CH ₃ kA / DD ^H H ₃ C CH ₃ 503.30 0.81 QC- ACN- TFA- XV 998 CH ₃ H ₃ s O 1 / N^ V Μ Ν 7 _ _n g n ₃ s'% Ύ Τ> - / τ ^ν \ D dd ⁿ n ₃ s sn ₃ 524.20 0.82 QC- ACN- TFA- XV 999 n ₃ s^sn ₃ ΗΝ DsNz _Ν Ζν νΥ zN y Du_/ ^N \An dd ⁿ H ₃ S sn ₃ 418.10 1.00 QC- ACN- TFA- XV 1000 χΝ^-d ^N s ^S h _sn g A \ G ³ _N to AN A A 0 IV to DI snz An DD N ₃ s s ₃ 434.30 1.00 QC- ACN- TFA- XV 1001 nh ₂ H A GN । Y ³ N. hn n A^ /g^ ( d Dk—/ d^m χΑ-ν dd ⁿ H ₃ C sn ₃ 364.00 1.09 QCACNAA-XB 1002 n _{3 s h} n d ^s h n. _hn /^nn A to ^H j y D to_\ Υ ^Ν od g\ Ν H ₃ C CH ₃ n ₃ c ^x + n ₃ 449.10 0.79 QC- ACN- TFA- XV 1003 CH ₃ hYh ^NzS \.gn Du y-snz _N zN j y Dk_ / A YA / dd ⁿ H ₃ C sn ₃ 444.30 0.81 QC- ACN- TFA- XV

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1004 ΪοΑΑ h ₃ c A A. _s U '.% ³ WN Ν _< 7' Λ ^- Ν / y Τ D_Η yN ΛΑν uu ⁿ N ₃ with CH ₃ 473.90 0.99 QC- ACN- TFA- XV 1005 n _zS η ₂ ν^ο \u003d ν 4 y /G \\>__<7 yN yy ⁿ H ₃ C sn ₃ 473.50 1.07 QC- ACN- AA-XV 1006 O Aa CH ₃ XX / - \ X ^N An y \u003d ( ⁿ H ₃ C sn ₃ 500.90 1.32 QC- ACN- AA-XV 1007 ο, Α Az. NzS < AMgr uu ⁿ N ₃ C sn ₃ 522.10 1.44 QC- ACN- AA-XV 1008 NC^NH H ₃ C. APL U ^CHz N. AA A Ch y ΊΓ __<7 u Ν mCh yun ^N N ₃ C CHz 440.90 1.57 QC- ACN- AA-XV 1009 ^H V ^N X Asnz Ν ^sn z AU DA T to D / yN 4a ^ n yy ^H H3C CH ₃ 458.20 1.36 QCACNAA-XB 1010 _u \ _ ^Nz °\ SI ^NzS CH ₃ IL _m U ³ N ³ on nA ,-n] y η \>__<7 y Ν ΑΑν ^Ζ UU ⁿ N ₃ C CH ₃ 472.20 1.53 QC- ACN- AA-XV 1011 SI n ₃ s Aul U ^SNz Ν- kN _v ^N A A 1 y ίΓ\>_/ yN 4A^n yun ⁿ N ₃ C sn ₃ 458.20 0.76 QC- ACN- TFA- XV

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1012 ^NA H ₃ C aul U ^sn h n. AN N./ ^N ^z L YY \>_# AN YU|CHN )=( H ₃ c CH ₃ 486.20 0.79 QC- ACN- TFA- ΧΒ 1013 ^HI 3°. _rH Q. / ^{3 X CH} _{3 An n.7} 460.20 1.02 QC- ACN- TFA- ΧΒ 1014 U il n ₃ with 1 \ \--Apz _K| CN IC. _m / ,% AN.,N^7 Z^N / y γ γ_# \=ν UCH y=( ^H H ₃ C CH ₃ 455.10 1.44 QC- ACN- ΑΑ-ΧΒ 1015 H ₃ C sn ₃ Αγγ _m / ³ / A, A-Ν l-N / Υ γγ_G Α \u003d Ν UU U ( ^Η N ₃ C CH ₃ 444.20 0.83 QC- ACN- TFA- ΧΒ 1016 ΗΝχ H ₃ C AAL CHSN ₃ o-CH ₃ An /=/ τ χχ—C Χν Η Ν 404.20 1.06 QC- ACN- ΑΑ-ΧΒ 1017 HsCx..^ Η r N^ ^HsS \ rui ΑΧΛ y-cH3 o-CH3 Αν. ,ν. 7 /=/ Tsa—CAn ^V v 418.20 1.13 QC- ACN- ΑΑ-ΧΒ 1018 HjC^NA H ₃ C A-Al y-cH3 o-CH3 An Νχ^7 /=/ X XX—C Xn Η 432.10 1.00 QC- ACN- TFA- ΧΒ 1019 UUD ⁿ zS snz At, _n Y ^with 7a ° - ^SN - χχχ - Γχ _Ν Α^ν ^-ν ₄ Η Ν 446.20 1.32 QC- ACN- ΑΑ-ΧΒ

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1020 CH3 H3C^YP H ₃ C CA-p y-CH ₃ o-CH ₃ VN. /N. 7 ,=/ —O^ Η 446.20 1.27 QC- ACN- AA-XB 1021 ^NzS Chi H ₃ s ⁿ⁰ sn Asn ₃ o-sn ₃ CH3 AL nA /=/ ί XX—C Χν Η hr 476.20 1.23 QC- ACN- AA-XB 1022 ^H 3 ^C NM Η C Ν \ H ₃ C μυ Y ³ A A / A to T f \> _γΝ \Αν γγ ⁿ H ₃ with CH ₃ 415.10 1.35 QC- ACN- AA-XB 1023 SNz Η ₃ ΧνΥ n ₃ s ΜΥ γΟΗ _{3 Ν} z^N to T f \>_# γΝ \An W ⁿ H ₃ C sn ₃ 443.20 1.46 QC- ACN- AA-XB 1024 ο^γ H ₃ C ν—y \ / s A/M ζ^Ν k φ| f \\>__γΝ γγ ^H H ₃ C CH ₃ 485.20 1.44 QC- ACN- AA-XB 1025 n ₃ s YAny H ₃ C \ \ Ι-An y-ch ₃ ⁰ ,χΧ y f # γΝ \Αν γγ ⁿ H ₃ C ch ₃ 485.20 1.37 QC- ACN- AA-XB 1026 Mmu H ₃ C o4 \u003d o _{ml s} U ³ .% ¹ A l - ν / CH ₃ f γγ_A γ _Ν ΑΔν γγ ⁿ H ₃ s sn ₃ 507.30 1.46 QC- ACN- AA-XB

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1027 OH ₃ C N Y™ ³ _N n ₃ s' xn ₃ ΛΑνΑ η y Υ# An γχ ⁿ H ₃ s sn ₃ 971.40 1.51 QC- ACN- AA-XV 1028 _and A \ ^N Z ^and \ GN CH ₃ HELL .. Y ⁵ Υ ³ X / X \u003d N 7 y Υ # AN xXn uy ⁿ H ₃ C sn ₃ 473.10 1.34 QCACNAA-XB 1029 Dm-; n ₃ s ί Hell U- ^sn \u003d ν. H ₂ nX CLH ] y U # AN aAn UX ⁿ N ₃ C sn ₃ 472.30 0.93 QC- ACN- TFA- XV 1030 y ^ NA H ₃ with A AD D' ^ν υ ⁿ zC 'φ y_χ AN \ Yn uh ⁿ H ₃ C sn ₃ 521.30 1.31 QC- ACN- AA-XV 1031 CHI ^H 3 ^C A _CH o Ad \ ³ , Ν^ cn ₃ ΙΧνΧ \u003d _ν Λ y Y S # An xXn VX ⁿ H ₃ C c ₃ 459.30 0.82 QC- ACN- TFA- XV 1032 0 /L ^H y C _Hz ,Ν^ Λ ^N^N^ J ^n Y H ₃ C FhX y XyXyN χΥ _Ν VX ^H H ₃ C CH ₃ 475.30 1.45 QC- ACN- AA-XV 1033 SAHA ^v )=° O XX s 71/ 529.40 1.27 QC- ACN- AA-XV 1034 0 CH ₃ ΛΑ NzAsnz l Huua sn ₃ CH ₃ XA _N /yx ⁿ H ₃ C sn ₃ 503.00 1.43 QCACNAA-XB

Example 1035 1-(Aminomethyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1 H-pyrrolo[ 3,2-b]pyridin-5-yl)cyclohexan-1-ol

Intermediate 1035A:

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1 H-pyrrolo[3,2-b]pyridine-5 -yl) -1 - (nitromethyl) cyclohexanol he o ₂ n

H ₃ C CH ₃ ( _1035A )

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)cyclohexan-1-one (0.200 g, 0.498 mmol), MeOH (5 ml), diethylamine (0.052 ml, 0.498 mmol) and nitromethane (0.269 ml, 4.98 mmol). Then 20 μl of water was added and the reaction mixture was stirred for 5 days at 25°C. The reaction mixture was concentrated under a stream of nitrogen gas, diluted with water and stirred for 30 minutes. The white precipitate was filtered off and washed with water and air dried to give 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo [3,2-b]pyridin-5-yl)-1-(nitromethyl)cyclohexanol (0.200 g, 0.552 mmol, 100% yield) as a white solid. LCMS retention time 0.64 min [Method A]. MS m/z: 363.2 (M+H).

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Example 1035.

4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)-1-(nitromethyl)cyclohexanol, and 1:1 ethyl acetate: MeOH (7 ml). The vessel was sparged with nitrogen gas and 10% Pd-C (0.053 g, 0.050 mmol) was added. The bomb was placed on a Parr apparatus and nitrogen gas was sparged with a pump three times and refilled with hydrogen gas. The reaction vessel was left to shake for 6 hours at 40 psi. inch. The reaction mixture was diluted with MeOH and then filtered through a pad of celite and concentrated. The residue was suspended in DMF (2 ml), filtered through a 0.45 µm nylon syringe filter. The crude material was purified by preparative LC/MS under the following conditions: Column: XBridge C18, 200 mM x 19 mM, 5 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 0 minute hold at 6% B, 6-42% B for 28 minutes, then 6 minute hold at 100% B; Elution rate: 20 ml/min; Column temperature: 25°C. Product-containing fractions were combined and dried by centrifugal evaporation to give 1-(aminomethyl)-4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]πiridin-6-yl)- 3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-ol (0.8 mg, 0.00185 mmol, 0.4% yield), m/z (432.9 , M+H). Retention time, 1.253 min using LCMS Column: Waters Acquity UPLC BEHC18, 2.1 x 50 mm, 1.7 µm particles; Mobile phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile phase B: 95:5 acetonitrile: water with 10 mM.

¹ H NMR (500 MHz, DMSO-d6) δ 11.15-10.98 (m, 1H), 8.79 (s, 1H), 8.47 (s, 1H), 7.60 (br d, J=8.5 Hz, 1H), 7.08-6.93 (m, 1H), 4.80-4.80 (m, 1H), 3.33-3.19 (m, 1H), 2 .91 (br d, J=7.0 Hz, 2H), 2.68 (br d, J=7.0 Hz, 3H), 2.17 (s, 3H), 2.06-1.93 ( m, 2H), 1.89 (s, 3H), 1.70 (br t, J=15.9 Hz, 4H), 1.40 (br d, J=6.4 Hz, 8H).

Compounds according to the following examples were prepared according to the general procedures described in the examples above.

Table 3

No. n.p. Structure Obs. MS ion temp. hold on QC Methodology 1035 HO _ NS ⁿ 3% _G1 , / ] | usnz _N Η ₃ Ν /A y [ Y__(/ pN k+P yp ⁿ H ₃ C SNz 433.10 1.24 QC- ACN- AA-XV

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1036 ^uCH3 YyAJ \Υ _Ν \^κ, ^Η ο 470.30 1.27 QC- ACN- AA-XV 1037 Ο'') H3C _SN T 1 y-CH3 o-CH3 kL/N. 7=/ ^H 487.30 0.75 QC- ACN- TFA- XV 1038 A НзС ill u ^н з _N ^CH 3 = _N η y yyy yN \ An oo ^H H ₃ C CH ₃ 487.40 0.82 QC- ACN- TFA- XV 1039 A,N. H ₃ C G ΥΊ Υ™ ₃ CH ₃ \u003d n A y YY y ^N \ Y o \u003d\ ^H H ₃ c CH ₃ 487.40 0.82 QC- ACN- TFA- XV 1040 H ₃ C H ₃ cY kN./\ H ₃ C YY Y ^CH3 y Z^N' Λ y \>_# mind \Y _N oo ^H H ₃ C CH ₃ 471.40 1.00 QC- ACN- TFA- XV 1041 ^H3 Y _ ^H3 Y.CH HO-A N^/Y y-CH3 _N XZ y # O^N \Y _N n\ ^H H ₃ C CH ₃ 473.20 1.38 QC- ACN- AA-XV 1042 ζ°Όλ ^NzS \-sn NzS Ln γ Χ-Ζ ]| y X)__# O^N γγγ οο ⁿ H ₃ s n ₃ 473.40 1.39 QC- ACN- AA-XV

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1043 n ^Η Α _CH ΝΑ \ V-CHz _N A V AA Ah \ \ A A A 'N_// y=N \An /={ ^{0 n} H ₃ C sn ₃ 535.10 0.99 QC- ACN- TFA- XV 1044 A ^Nz Msn NOLYD \ / ³ A ν aM a; </ ]| y \>_# )^n \An )=( ⁿ n ₃ s n ₃ 473.30 0.84 QC- ACN- TFA- XV 1045 ζ°Ά+ ^NzS \_ _sn n ₃ s vnA) γΆ _n V AM Ah A A A L_# γ=Ν HH )=( ⁿ H ₃ C CHz 473.30 1.01 QC- ACN- TFA- XV 1046 ^Η0 Ά ^NzS \-sn VnA / ³ A V AM A ΑΎ Αγ_# ν^ν \Αν )=\ ^H H ₃ C CH ₃ 459.30 0.81 QC- ACN- TFA- XV 1047 0 Kd _ ^H ₃ S ei H ₃ S-D \.nA+ y-CH _{3 Ν} GN \ A ⁿ A z^n I CH ₃ AZA AL # γ=N ΚΜν ^ζ )=( ⁿ H ₃ c CH ₃ 514.40 1.22 QC- ACN- AA-XB 1048 CH ₃ Η ₃ ΑΝ^χ H ₃ C T T 1 A ³ A CH3 Vv ^N AAY T A y_7 vn \Kn )=( ⁿ H ₃ C sn ₃ 459.00 1.08 QC- ACN- TFA- XV 1049 H°A ^HzS ACH MnA A ^Hz N. t AA Ah AAA γ_# γ^N \An )=( ⁿ H ₃ C CH ₃ 459.10 0.75 QC- ACN- TFA- XV 1050 0 L___ _{_} H ₃ C ^H 3 ^C - _N ^ \ N-AK uSNz _N sn ν AA z ^ n ' CH ₃ A / A AL <7 TN \ An ) \u003d ( ⁿ H ₃ C sn ₃ 514.40 0.87 QC- ACN- TFA- XV

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1051 On НзС Τ 1 У-СНз _Ν kk^ll αν to WN )=( ^Η Н ₃ С CH ₃ 443.10 1.45 QC- ACN- AA-XB 1052 H ₃ C H3sAo An-xOo h ₃ c Τ ι U ^CHz ν. Y __7 \^Ν Vk )=( ^H H ₃ C CH ₃ 471.10 1.04 QC- ACN- TFA- XB 1053 0 \' _ 0=S^\ V?N^^ ^H s% n 1 1 λ^ ³ _N k^^ ^N ok ON a y T _7 \O \An )=( ^H H ₃ C CH ₃ 533.50 0.56 Al 1054 H H ₃ CN^. H ₃ C nu n ₃ si II U ^SNz Ν. ³ SNz Uv ^N VA ⁿ A у j __7 V^N \An )=( ^H H ₃ C CH ₃ 459.50 1.54 QC- ACN- AA-XB 1055 r° ΧγΑ pr Τ 1 y-snz _Ν Τ Г \>__# \==N )=( ^H H ₃ C CH ₃ 485.50 1.45 QC- ACN- AA-XB 1056 H H ₃ CN ^ ^ H ₃ C ch H ₃ sI II r ^ ³ N. CH3 \u003d N to y ηΤ ^)_7 \ ^ NW ^ N ) \u003d ( ^H H ₃ C CH ₃ 459.10 1.48 QC- ACN- AA-XB 1057 r° \-N^^ H ₃ C Τ 1 y-sn _{3 N} /O' to U ΊΓ __7 \^N \An )=( ^H H ₃ c CH ₃ 485.20 0.81 QC- ACN- TFA- XB

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1058 About ^snz \Αν Υς ⁿ H ₃ with sn ₃ 475.00 1.59 QC- ACN- AA-XV 1059 \ Ζ^ ^Ν Λ =-/ || 1 γ__(/ Ο ^Ν \Αν )=ο ⁿ H ₃ s n ₃ 513.40 0.85 QC- ACN- TFA- XV 1060 ο-, TOl Α ^Η3 =, AvtmOn )=ο ⁿ H ₃ C sn ₃ 499.10 1.41 QC- ACN- AA-XV 1061 PO H ₃ C QCnvy U ^CHz o, L AAaA zO \u003d - / y ητ 'to __ # ) \u003d ν ΑΑν Υς n ⁿ ₃ s sn ₃ 499.40 0.83 QC- ACN- TFA- XV 1062 /—\ n ₃ s ΥΥθΛ U ^SNz .o \u003d -/ y f +__ / ) \u003d N% a _n uo ⁿ H ₃ C sn ₃ 475.00 1.80 QC- ACN- AA-XV 1063 0-J Oal ^Nz U ^Nz % ΡΑν ) \u003d o ⁿ H ₃ C sn ₃ 499.40 1.02 QC- ACN- TFA- XV 1064 °^η ^H sC Τ 1 - ^CH 3 Ν. / A y G ) \u003d Ν M \u003d N ) \u003d o ⁿ H ₃ C sn ₃ 473.00 1.82 QC- ACN- AA-XV

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1065 NzS Mays M ^CHz a v AM Ά l O y ΊΓ _(/ V?N yOn ρ=\ ^H H ₃ C CH ₃ 499.20 1.61 QC- ACN- AA-XB 1066 ⁿ Asn iM Λ AM Γ ^ν _χ YA'N M( ^H H ₃ C CH ₃ 513.50 0.85 QC- ACN- TFA- XB 1067 /—\ H ₃ C ρΧ/ ^Ν ΆΛ A ^CH3 /°“ ^{CH3 F} \ A^ ^N \A /=( Ao—C An H n 477.20 0.77 QC- ACN- TFA- XB 1068 0-j A—\ H ₃ C / nA Μ ^Η3 /°" ^CH3 o \ Y/N^V =/ ^MLAo—C An ^H 501.30 0.78 QC- ACN- TFA- XB 1069 9~\/\ H ₃ C M?NY--\ A ^CH 3 O-CH ₃ \ a^ ⁿ ^a /=( Ao—C An A^n A ^H N 501.00 0.99 QC- ACN- TFA- XB 1070 ?O _ ^ ^3C \^CH \/\ Nx/7 pCH ₃ o-CH ₃ Ao—C An ^^NA ^H N 501.00 1.00 QC- ACN- TFA- XB 1071 °A A ⁿ ^o ^h a _rH T 1 rsn ₃ o-ch ₃ A^^N^O. /=( X Ao—C An ^H N 475.30 1.52 QC- ACN- AA-XB 1072 A ^Nz Aen Α,νΑ A ^CHz o-sn ₃ ^F \ Ar ^ D / A Ao - C An ⁿ 477.40 0.81 QC- ACN- TFA- XB

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Biological analyzes

The pharmacological properties of the compounds of the present invention can be confirmed using a variety of biological assays. The following exemplary biological assays were performed on the compounds of the present invention.

Assays using the TLR7/8/9 inhibition reporter

HEK-Blue™ cells were used to screen for inhibitors of the human TLR7, TLR8, or TLR9 receptors using an inducible SEAP (Secreted Embryonic Alkaline Phosphatase) reporter driven by a minimal IFN-β gene promoter fused to five NF-kB and AP-1 binding sites. (Invivogen) overexpressing these receptors. Briefly, cells were seeded in 384-well Greiner plates (15,000 cells per well for TLR7, 20,000 for TLR8, and 25,000 for TLR9) and then treated with test compounds in DMSO to produce a final dose-response concentration range, i.e. e. range from 0.05 nM to 50 µM. After a 30 minute compound pretreatment at room temperature, the cells were then stimulated with TLR7 ligand (Gardiquimod at 7.5 μM final concentration), TLR8 ligand (R848 at 15.9 μM final concentration), or TLR9 ligand (ODN2006 at 5 nM final concentration) to activate NF-kB and AP-1, which induce the production of SEAP. After a 22 hour incubation at 37° C., 5% CO ₂ , SEAP levels were determined by adding HEK-Blue™ Detection Reagent (Invivogen), a cell culture medium that allows detection of SEAP, according to the manufacturer's instructions. Percent inhibition was defined as the % reduction in HEK-Blue signal present in agonist plus DMSO treated wells compared to known inhibitor treated wells.

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Table 4 Reporter analysis data for TLR7/8/9 (NT = not tested)

Example No. TLR7 1С ₅₀ (nM) TLR8 1С ₅₀ (nM) TLR9 IC50 (nM) Example No. IC50 TLR7 (nM) IC ₅₀ TLR8 (nM) IC ₅₀ TLR9 (nM) 1 20 3.8 7734 540 1.1 1.4 1951 2 1.7 0.27 7325 541 1.2 0.36 1429 3 0.93 1.1 8542 542 24 17 9235 4 0.60 0.71 1072 543 14 5.3 2279 5 471 4063 37 544 AND 6.4 5660 6 0.30 3.2 625 545 22 7.5 2464 7 4.4 52 8124 546 9.5 1.6 1379 8 4.7 21 8554 547 0.27 0.55 789 9 1.7 8.2 2248 548 0.71 0.98 1090 10 0.42 5.3 1053 549 1.8 18 401 eleven 1.7 21 6794 550 0.87 15 796 12 10 1.6 10102 551 0.94 5.5 582 13 3.2 1.9 5020 552 0.83 2.1 4099 14 eleven 4.2 4331 553 0.63 3.2 537 15 7.3 4.3 1940 554 1.5 2.5 2861 16 0.60 2.1 635 555 0.85 h, o 341 17 3.7 7.7 1097 556 1.7 1.1 5079 18 14 14 1494 557 0.66 1.2 440 19 125 73 6023 558 1.2 5.6 3427 20 2.7 1.3 614 559 0.72 4.6 4923 21 91 46 >50000 560 1.2 1.0 3821 22 56 12 21148 561 0.64 h, o 5653 23 >3125 >3125 >50000 562 1.9 1.1 6484 24 40 2.7 13976 563 0.83 2.4 4257 25 181 117 11662 564 7.9 4.2 1764 26 1769 2131 >50000 565 8.8 6.9 3224 27 >3125 >3125 >50000 566 24 18 18988 28 263 1496 >50000 567 18 18 2325 29 4.6 2.7 2832 568 6.0 3.8 2081 thirty 70 43 22593 569 AND h, o 2183 31 13 19 6059 570 10 57 143 32 7.3 6.9 1883 571 7.5 2.1 813 33 6.5 1.9 1915 572 4.6 25 1197 34 17 6.0 1218 573 0.99 9.1 3234 35 589 282 13783 574 h, o 47 11936 36 >3125 >3125 22084 575 0.44 121 1352 37 1269 465 >50000 576 NT NT NT 38 21 5.2 44362 577 0.69 7.4 1881 39 40 4.8 NT 578 0.53 287 4190 40 24 1.7 7956 579 0.39 79 1838 41 264 177 >50000 580 0.41 8.7 1789 42 178 57 >50000 581 0.30 79 4920 43 2.0 7.8 560 582 0.99 12 7463 44 12 15 3374 583 0.32 5.1 1552 45 22 20 7280 584 0.24 29 2006 46 4.3 4.9 1682 585 0.46 8.6 1839 47 NT NT NT 586 0.75 98 2897 48 7.4 9.3 31274 587 0.31 27 1408 49 1.0 0.62 2673 588 2.3 42 16107 50 0.49 0.39 2839 589 0.25 62 1062 51 5.1 7.0 16309 590 h, o 4.7 3549 52 7.9 20 NT 591 4.8 7.7 2852 53 0.62 0.23 1988 592 2.9 7.4 2244

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54 2.9 2.8 10376 593 1.4 2.6 974 55 2.1 0.39 3340 594 3.9 16 7906 56 2.0 1.1 6340 595 122 >3125 10867 57 7.4 1.3 5070 596 13 67 3204 58 1.3 0.72 1969 597 1.3 1.2 918 59 1.3 1.1 2376 598 0.81 3.1 949 60 5.6 5.9 20242 599 2.7 4.8 3047 61 4.4 1.8 2411 600 0.75 6.2 2051 62 3.8 1.5 11497 601 46 46 >50000 63 7.4 4.0 42357 602 1.2 6.8 1430 64 3.8 1.6 5084 603 1.5 5.2 1190 65 1.9 1.3 25112 604 2.8 2.5 5914 66 1.4 0.98 3870 605 13 17 4244 67 0.98 0.42 963 606 2.3 3.9 1711 68 1.4 0.79 6300 607 2.1 2.6 1142 69 1310 1314 25816 608 1.1 6.1 1713 70 2.3 1.2 2967 609 2.6 23 2718 71 99 31 3897 610 1.5 14 1771 72 2.9 0.90 3416 611 8.4 17 1933 73 29 5.7 24942 612 13 56 3927 74 2468 2562 >50000 613 2.0 3.2 1243 75 18 9.8 >50000 614 1.9 13 1014 76 34 15 >50000 615 2.4 7.9 1958 77 4.8 2.0 11648 616 3.6 1.5 1282 78 3.7 10 3171 617 2219 1325 20509 79 373 355 9724 618 4.8 4.6 3699 80 1.3 1.6 4558 619 0.43 h, o 865 81 1.3 0.95 20099 620 0.73 2.4 223 82 0.77 0.41 6376 621 7.0 7.5 14661 83 3.6 6.9 5445 622 thirty 14 5071 84 2196 >3125 >50000 623 1.6 2.0 3127 85 1.8 5.8 5178 624 h, o 2.0 2568 86 7.5 2.9 >50000 625 0.72 10 978 87 3.5 0.58 >50000 626 29 8.0 13454 88 68 91 3595 627 7.9 18 4504 89 0.51 0.59 3258 628 2.1 3.3 343 90 0.57 4.2 4999 629 2.6 6.5 1920 91 0.68 0.53 6311 630 1.9 14 1284 92 0.87 0.78 3992 631 4.0 1.9 3067 93 5.3 7.2 35043 632 3.1 2.2 439 94 1.0 1.4 9352 633 40 33 25537 95 4.9 3.6 >50000 634 2.0 3.0 2374

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96 1.5 0.28 9430 635 5.7 1.1 1785 97 28 4.1 >50000 636 46 28 21593 98 0.74 0.72 5226 637 3.8 0.53 1359 99 0.51 2.9 4303 638 2.9 7.3 1272 100 3.2 0.55 6146 639 0.98 1.9 1472 101 3.7 0.25 6402 640 4.9 4.9 13508 102 12 5.1 >50000 641 9.2 3.5 3344 103 7.3 2.6 NT 642 14 26 18090 104 2.3 0.75 4161 643 5.4 5.3 3170 105 3.9 0.15 9237 644 2.7 4.5 2690 106 2.2 0.28 7779 645 21 303 4087 107 2.2 0.37 5627 646 2.1 eleven 4140 108 2.5 0.99 3512 647 2.3 26 5888 109 3.6 1.3 8014 648 2.1 40 2073 BY 1.9 0.76 4544 649 6.2 10 3283 111 NT NT NT 650 6.7 18 3125 112 2.2 1.2 6009 651 1.7 24 687 FROM 1.4 0.95 3363 652 3.0 22 1600 114 4.7 1.8 7590 653 5.5 13 13221 115 1.2 0.49 3482 654 6.4 9.6 4917 116 9.7 5.0 35642 655 1.4 eleven 2069 117 1.4 0.81 5643 656 1.4 4.7 1853 118 1.8 0.86 5581 657 2.1 10 842 119 1.8 0.96 14141 658 3.8 8.2 13603 120 2.3 0.60 5487 659 12 24 8538 121 3.4 0.80 6348 660 3.3 15 14410 122 1.7 1.1 7251 661 2.3 5.5 13871 123 1.9 6.3 8648 662 1.8 1.0 9030 124 1.2 4.7 5786 663 3.5 9.9 21144 125 2.6 0.66 6544 664 22 14 38509 126 5.9 1.5 6117 665 34 17 >50000 127 4.6 0.48 5898 666 0.73 1.6 6563 128 5.4 2.6 35374 667 145 711 >50000 129 6.7 1.3 22827 668 1.7 22 17531 130 4.3 4.7 >50000 669 7.4 5.6 31553 131 h, h 0.63 8572 670 56 58 >50000 132 2.8 0.51 7393 671 1.4 2.1 4480 133 4.3 1.4 >50000 672 4.7 90 6244 134 3.7 1.1 26146 673 5.2 6.9 14419 135 4.7 1.6 13167 674 32 48 >50000 136 5.7 0.79 8223 675 9.7 4.6 14462 137 5.6 1.3 8446 676 1.0 2.5 5718

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138 AND 4.6 >50000 677 17 53 >50000 139 37 14 >50000 678 36 29 >50000 140 127 186 >50000 679 16 5.8 20652 141 134 148 >50000 680 12 5.2 1058 142 107 45 >50000 681 104 199 4236 143 7.8 4.5 >50000 682 16 24 1052 144 8.4 1.2 >50000 683 12 13 322 145 1.5 0.49 8201 684 14 13 365 146 5.6 2.5 12892 685 32 39 1576 147 5.0 0.26 18656 686 >3125 >3125 >50000 148 97 16 >50000 687 39 16 5774 149 9.3 0.40 19497 688 8.4 23 177 150 12 2.7 >50000 689 AND 42 433 151 1.2 1.2 11995 690 15 31 288 152 2.7 1.6 5877 691 AND 9.2 315 153 0.87 1.6 7150 692 43 58 1528 154 1919 600 >50000 693 6.5 15 437 155 401 56 >50000 694 2309 2850 14611 156 1.5 0.79 6752 695 42 20 3952 157 2.2 1.2 8844 696 75 36 1311 158 2.3 0.96 8256 697 20 111 919 159 2.4 1.0 7735 698 12 28 1004 160 1.8 1.2 10645 699 12 46 430 161 1.4 0.92 5918 700 26 43 2328 162 2.8 2.8 23098 701 49 15 1748 163 9.7 5.0 24797 702 41 14 2228 164 33 2.0 19767 703 8.9 16 326 165 AND 0.68 22656 704 AND 13 166 166 1.5 18 2189 705 18 15 655 167 0.43 1.7 156 706 8.5 18 1020 168 0.89 3.4 658 707 1.5 5.3 1412 169 3.1 21 1224 708 12 280 >50000 170 2.0 17 1411 709 2330 >3125 >50000 171 0.45 1.8 560 710 2.0 3.2 4665 172 1.9 13 1792 711 2.0 2.9 1699 173 2.0 10 578 712 1.9 AND 3145 174 4.3 37 1468 713 6.2 28 4878 175 0.35 2.0 926 714 1.8 9.3 203 176 5.2 84 16006 715 1.7 AND 8707 177 0.28 2.5 148 716 0.74 6.7 2526 178 0.48 1.8 895 717 1062 1101 2525 179 0.92 7.0 1741 718 9.6 3.6 6211

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180 2.8 AND 1871 719 2.8 7.0 2596 181 1.7 13 561 720 13 94 20336 182 0.48 1.1 301 721 0.41 0.53 982 183 5.6 15 1031 722 6.5 46 18477 184 8.8 18 2054 723 0.99 2.4 4391 185 38 110 10316 724 0.63 2.0 2194 186 2.2 9.3 1011 725 0.62 1.9 2059 187 2.1 20 4221 726 1357 2090 39366 188 0.29 2.5 158 727 3.6 3.2 3352 189 1.6 6.7 313 728 0.74 0.67 3538 190 0.80 2.8 353 729 1.1 1.3 1941 191 0.90 2.7 202 730 3.3 23 10526 192 3.1 19 1106 731 4.6 15 1640 193 1.5 6.0 648 732 10 70 4834 194 8.6 47 3594 733 53 1014 >50000 195 0.80 4.3 530 734 26 252 >50000 196 1.7 10 712 735 25 61 262 197 0.34 1.7 134 736 631 269 >50000 198 ι, ο 7.8 1142 737 0.59 0.55 7774 199 0.16 6.4 1189 738 0.46 0.89 6226 200 1.8 8.5 773 739 0.85 1.6 5324 201 1.5 6.0 570 740 2.2 5.1 623 202 3.8 28 2030 741 1.9 6.5 3034 203 2.0 7.9 537 742 2.9 3.1 4580 204 0.98 2.9 1332 743 3.6 8.4 1881 205 0.42 ι, ο 134 744 2.0 7.1 3058 206 9.5 22 2389 745 2.2 5.8 2446 207 1.9 4.4 253 746 1.1 10 3106 208 2.2 16 1350 747 0.59 4.1 7379 209 0.71 4.0 641 748 7.5 15 37886 210 >3125 >3125 >50000 749 2.9 2.6 14893 211 1.1 6.8 585 750 1.2 3.7 6145 212 3.4 6.8 1192 751 13 7.3 26035 213 9.5 17 706 752 0.38 0.53 10266 214 3.9 6.3 833 753 3.8 12 27862 215 6.0 7.6 2254 754 5.2 1.7 5432 216 5.1 18 416 755 2.8 6.2 3734 217 5.0 8.6 522 756 3.9 6.0 9055 218 8.5 20 389 757 0.70 1.9 5215 219 3.9 8.0 2484 758 0.89 1.7 18200 220 6.7 6.1 1020 759 3.8 14 38197 221 3.7 13 435 760 4.2 27 7629

- 226 041852

222 5.8 21 657 761 9.0 14 8170 223 0.60 1.4 485 762 3.8 8.6 18318 224 1.5 4.2 718 763 3.8 2.6 4579 225 4.0 35 3360 764 1.9 2.8 14428 226 2.7 14 1790 765 5.6 3.5 10263 227 2.0 7.7 926 766 0.86 1.2 3512 228 h, h 23 2387 767 5.4 2.9 8300 229 19 18 1709 768 6.4 9.6 20957 230 38 33 2460 769 1.3 4.5 5569 231 0.61 h, o 365 770 AND 24 18183 232 h, o 9.8 484 771 4.3 9.2 9843 233 AND 24 2662 772 3.2 10 4713 234 1.6 5.0 435 773 3.0 4.6 2706 235 ι, ο 2.0 929 774 3.7 5.7 18596 236 3.9 2.8 376 775 3.8 4.4 8447 237 20 19 18183 776 6.0 5.3 13088 238 0.71 0.97 297 777 9.2 7.4 14795 239 106 181 >50000 778 2.7 2.3 7908 240 5.4 16 5076 779 7.3 AND 34519 241 2.0 2.9 1754 780 1.9 5.4 5225 242 1.5 15 2407 781 AND 18 14380 243 7.6 9.5 999 782 1.3 4.7 5736 244 1.6 8.2 2349 783 1.8 3.9 8377 245 2.7 4.7 343 784 2.9 9.4 4527 246 1.9 2.6 4283 785 8.0 13 4684 247 1.2 1.2 825 786 7.7 12 14676 248 1.5 13 1785 787 9.4 4.9 12254 249 25 7.3 5978 788 2.1 3.2 8302 250 26 57 13721 789 3.2 3.7 13321 251 8.6 13 1754 790 0.42 0.85 8810 252 8.0 10 7255 791 5.3 1.1 18146 253 0.65 0.72 1149 792 4.0 1.0 8555 254 72 27 8734 793 1.4 1.4 7829 255 0.60 0.25 218 794 1.4 1.5 18048 256 1.2 3.7 335 795 12 8.1 >50000 257 35 25 175 796 6.0 15 11322 258 13 3.5 100 797 10 14 17578 259 19 7.1 321 798 4.2 5.7 22334 260 527 173 10867 799 5.0 21 >50000 261 262 90 381 800 20 26 >50000 262 170 19 354 801 0.57 0.56 10960 263 6.2 7.6 338 802 h, o 0.65 17918

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264 55 42 255 803 4.3 4.0 39663 265 0.59 0.91 392 804 1.2 0.56 18116 266 45 13 322 805 2.1 0.57 24156 267 1.9 2.6 453 806 1.1 1.1 29426 268 94 32 578 807 0.95 1.3 16263 269 223 88 670 808 0.19 1.4 8946 270 38 28 322 809 2.2 3.1 35999 271 120 40 228 810 0.64 0.63 7355 272 76 50 398 811 0.36 0.59 5596 273 75 66 1114 812 2.2 3.6 >50000 274 8.5 3.7 474 813 3.7 9.1 >50000 275 14 8.5 684 814 1.9 2.3 >50000 276 8.9 9.0 309 815 1.8 1.4 >50000 277 0.40 1.6 1378 816 1.7 1.7 8723 278 1.5 1.2 837 817 2.1 2.9 >50000 279 0.31 1.4 1817 818 0.78 0.43 12846 280 1.1 7.2 1268 819 2.2 0.58 21064 281 0.48 1.7 880 820 2.7 2.0 9396 282 0.32 0.91 661 821 1.3 1.3 6694 283 0.92 1.4 298 822 1.1 0.24 6914 284 h, o 15 4038 823 0.49 1.2 6932 285 3.6 5.5 2310 824 1.6 2.1 5791 286 5.2 9.2 1566 825 0.53 1.1 6277 287 25 33 2361 826 0.70 1.0 15739 288 28 114 6454 827 0.46 0.34 4852 289 3.5 AND 967 828 0.88 1.4 7157 290 2.1 6.3 425 829 3.7 12 17264 291 2.6 AND 735 830 0.62 0.63 7443 292 99 127 1615 831 1.5 2.3 8550 293 75 208 5641 832 4.0 2.3 16779 294 85 174 2270 833 1.9 4.9 9782 295 AND AND 883 834 0.46 2.5 4367 296 0.59 6.8 600 835 0.70 4.1 5560 297 8.4 15 885 836 2.4 4.1 16449 299 10 6.0 680 837 0.70 1.6 7822 300 48 286 9048 838 0.60 3.5 9891 301 2.0 42 4089 839 0.37 3.2 7869 302 0.74 4.9 739 840 0.38 1.5 7401 303 0.55 6.9 1233 841 5.6 28 14253 304 0.53 1.8 1068 842 0.38 0.47 6919 305 4.0 16 8237 843 0.52 1.4 5479 306 13 61 10058 844 2.0 AND 8817

- 228 041852

307 0.86 2.7 2978 845 7.2 14 21276 308 AND AND 3965 846 0.55 1.2 22620 309 0.31 4.6 268 847 4.9 8.3 22521 310 0.39 4.1 1782 848 1.2 2.2 17494 311 2.8 44 2017 849 0.53 1.6 8120 312 0.26 1.6 577 850 0.72 1.6 6540 313 0.21 7.0 1200 851 5.9 2.2 9978 314 2.4 47 5508 852 5.2 0.82 16163 315 1.8 29 5223 853 0.51 0.66 9571 316 1.4 41 3018 854 AND 5.0 32272 317 4.8 94 3611 855 2.4 4.6 14322 318 0.17 2.1 1060 856 7.3 0.46 27144 319 0.44 4.1 1690 857 0.65 0.40 4396 320 ι, ο 22 1480 858 1.1 1.3 7132 321 NT h, o 1041 859 0.97 1.5 7308 322 1.7 19 7409 860 0.30 0.62 5062 323 1.1 31 1357 861 0.31 4.2 5010 324 6.6 240 20509 862 0.29 2.2 7037 325 1.5 38 3110 863 0.52 17 6065 326 0.13 3.7 988 864 1.5 12 5693 327 >3125 >3125 >50000 865 1.3 72 8891 328 0.08 1.1 576 866 3.2 74 47596 329 1.6 23 2066 867 4.5 AND >50000 330 0.14 4.8 2970 868 12 6.1 >50000 331 1.7 34 1914 869 1.9 34 40301 332 1.3 88 2663 870 0.56 3.3 14448 333 0.60 12 1456 871 1.6 5.1 12728 334 4.6 127 2400 872 0.97 3.8 9539 335 NT 4.0 1927 873 3.1 1.8 12788 336 2.8 48 3439 874 1.2 5.3 15548 337 21 350 >50000 875 6.6 3.2 40475 338 81 1170 >50000 876 644 517 13255 339 0.20 7.1 5888 877 1.5 1.6 12556 340 1.4 51 1869 878 0.48 2.2 9042 341 0.12 0.32 2643 879 ι, ο 3.4 7546 342 0.98 3.9 1906 880 6.4 thirty 19328 343 0.19 0.54 1251 881 25 68 43465 344 0.72 4.8 2789 882 AND 7764 345 0.21 0.68 1675 883 7.4 2.3 12546 346 0.32 6.0 6294 884 0.90 0.17 6501 347 0.27 ι, ο 2466 885 1.6 3.8 7846 348 0.82 8.3 6961 886 2.8 1.7 2568

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349 7.7 63 >50000 887 0.50 0.68 8121 350 0.72 1.0 1155 888 1.2 0.59 12211 351 2.3 4.3 1688 889 1.5 0.76 9839 352 5.4 9.2 2321 890 1.8 1.4 14745 353 0.64 0.96 940 891 0.64 0.93 17965 354 ι, ο 2.3 790 892 0.62 1.4 3285 355 2.6 10 4497 893 0.34 0.74 7440 356 2.8 5.1 2865 894 0.37 0.89 10763 357 3.9 4.4 1050 895 0.74 1.1 7926 358 0.95 2.8 1325 896 0.69 0.37 8435 359 9.1 29 4870 897 0.86 1.5 11982 360 1.3 3.4 1414 898 2.1 3.2 17320 361 0.79 ι, ο 1251 899 ι, ο 1.7 9780 362 1.6 5.1 1634 900 1.1 1.4 15593 363 3.3 6.6 1476 901 0.72 0.15 13255 364 1.5 9.6 2523 902 1.1 1.4 15789 365 4.2 7.9 3197 903 3.0 4.1 35228 366 5.3 15 4693 904 1.0 4.2 14798 367 1.5 3.5 838 905 0.51 0.82 12016 368 1.5 2.5 1612 906 0.39 0.67 7799 369 0.46 1.3 402 907 0.76 0.45 >50000 370 8.6 23 >50000 908 0.89 0.26 6457 371 6.0 14 4358 909 0.54 0.91 6707 372 3.2 7.6 1464 910 0.68 0.86 5398 373 8.6 8.3 1956 911 0.68 1.5 7016 374 36 187 21615 912 0.98 2.2 9330 375 0.87 4.4 2716 913 ι, ο 1.8 8845 376 0.71 1.2 1027 914 0.73 0.94 6046 377 2.1 2.2 767 915 2.3 ι, ο 11137 378 1.6 4.6 1636 916 18 AND 14537 379 2.6 4.7 909 917 5.2 2.9 43171 380 1.4 1.6 1878 918 3.2 6.3 20583 381 3.7 5.5 8062 919 23 ι, ο 13895 382 7.8 22 >50000 920 2.6 5.9 12088 383 33 167 >50000 921 0.61 3.4 5267 384 13 25 1526 922 0.55 2.1 9372 385 22 46 11236 923 1.2 3.6 6556 386 1.5 4.2 1440 924 1.7 4.9 7234 387 7.2 19 5513 925 0.79 9.2 10082 388 0.87 2.2 891 926 3.3 h, o 3040 389 0.45 1.6 923 927 2.9 3.7 4357 390 1.6 7.6 3094 928 1.5 6.9 3640

- 230 041852

391 2.6 14 2451 929 2.6 3.9 5086 392 3.2 6.1 1746 930 22 7.4 24293 393 0.47 1.3 360 931 2.5 3.9 14927 394 1.4 1.5 1412 932 0.66 10 14343 395 7.4 10 1621 933 0.63 18 18442 396 1.7 17 1531 934 0.86 8.6 9746 397 6.3 10 2402 935 0.48 2.9 5613 398 3.8 17 4119 936 0.56 3.5 4638 399 0.83 1.8 988 937 0.52 14 14243 400 0.74 2.9 1549 938 2.6 4.9 8560 401 5.7 6.4 5719 939 1.5 9.8 11863 402 31 43 5146 940 1.7 0.66 8343 403 7.7 44 4281 941 0.66 0.66 7198 404 3.8 9.3 1544 942 0.50 3.4 12005 405 3.6 2.5 1425 943 1.1 1.1 10046 406 1.4 h, o 1466 944 3.1 4.9 17114 407 7.2 8.5 2457 945 4.8 0.94 7846 408 18 43 6440 946 1.4 1.8 8950 409 1.7 1.6 550 947 1.9 0.66 8773 410 5.0 6.5 4925 948 2.8 1.4 12817 411 6.3 8.0 2297 949 2.6 1.6 31028 412 2.2 2.1 727 950 7.2 4.9 36119 413 17 18 4737 951 6.5 1.5 >50000 414 5.1 12 1756 952 1.8 0.70 7862 415 2.5 3.5 1240 953 0.92 5.3 12031 416 0.85 1.2 1622 954 1.9 36 20896 417 5.2 7.1 9504 955 0.76 2.0 20450 418 NT 3.9 2865 956 ι, ο 1.9 9650 419 4.1 2.5 1744 957 0.92 2.9 24415 420 1.2 2.8 3530 958 0.27 2.3 11244 421 1.6 1.8 2058 959 1.4 0.29 7681 422 15 35 6239 960 0.77 0.32 3166 423 175 83 >50000 961 0.35 0.80 8337 424 0.89 0.74 1531 962 3.7 17 >50000 425 0.87 0.50 2915 963 0.84 1.9 35268 426 2.5 2.6 1398 964 0.53 0.25 3095 427 2.4 7.6 4904 965 0.39 1.1 6483 428 7.4 6.4 9858 966 2.4 1.3 6022 429 3.4 5.2 7002 967 7.9 1.2 38697 430 13 14 15105 968 1.9 0.69 16436 431 16 AND 4657 969 1.3 0.12 7175 432 0.37 0.55 584 970 3.1 0.92 10709

- 231 041852

433 42 60 >50000 971 h, o 0.85 9246 434 1.5 2.4 7432 972 3.3 3.1 6915 435 2.7 5.5 2176 973 6.7 1.7 15804 436 8.9 27 8941 974 1.1 0.71 3918 437 5.1 AND 3752 975 12 0.61 6463 438 0.77 0.39 1458 976 2.5 0.96 13425 439 3.5 32 24228 977 1.4 2.1 8600 440 6.4 14 >50000 978 AND 1.8 11451 441 0.79 0.63 1660 979 1.1 0.80 4291 442 3.7 3.5 18317 980 2.2 2.3 6271 443 15 57 NT 981 0.95 0.51 3066 444 16 5.2 39175 982 9.8 20 32827 445 1.5 3.6 4887 983 0.82 0.12 6525 446 0.91 0.91 364 984 ι, ο 0.85 3427 447 1.7 2.3 1637 985 1.6 1.1 3897 448 7.5 24 7692 986 0.63 0.38 2821 449 323 165 17986 987 2.9 0.50 11253 450 0.61 0.71 1193 988 0.36 0.23 3767 451 0.48 0.63 1045 989 0.69 0.31 7098 452 2.7 4.4 3091 990 0.80 4.0 6024 453 4.0 3.3 1440 991 0.27 0.32 5986 454 1.2 0.68 2393 992 0.66 0.72 6311 455 14 12 9203 993 0.82 1.5 7230 456 2.6 8.1 7726 994 13 3.4 11830 457 0.32 0.30 622 995 0.56 0.48 7020 458 5.0 10 9840 996 1.3 0.40 11011 459 6.2 4.3 2790 997 2.4 2.4 13578 460 0.88 0.79 2063 998 1.9 0.44 20008 461 2.6 1.7 8471 999 7.5 2.1 10466 462 6.9 8.4 4538 1000 18 3.2 6438 463 7.4 24 16002 1001 70 40 11739 464 0.68 0.85 1774 1002 10 4.6 1099 465 1.1 1.9 5660 1003 1.8 3.7 3164 466 59 204 5796 1004 2.1 1.3 2794 467 1.2 3.5 413 1005 4.4 7.4 1659 468 46 99 NT 1006 3.6 9.6 339 469 0.98 2.9 1709 1007 3.2 4.0 2337 470 1.3 6.0 7422 1008 15 32 13326 471 2.8 3.2 4706 1009 4.5 7.7 2657 472 0.34 1.1 2511 1010 3.6 4.7 2431 473 7.1 9.6 7373 1011 AND 22 23736 474 0.46 0.43 1450 1012 0.59 1.4 1686

- 232 041852

475 1.4 2.2 3504 1013 eleven 9.2 7677 476 0.81 2.6 9749 1014 21 26 21927 477 8.3 6.0 6162 1015 1.3 7.8 2384 478 13 15 24545 1016 2.9 38 641 479 2.9 10 23712 1017 1.3 16 3302 480 2.0 14 11749 1018 1.7 8.9 2782 481 0.82 3.9 13037 1019 1.7 16 3278 482 96 238 >50000 1020 1.8 17 3863 483 0.94 1.2 5126 1021 4.3 eleven 5329 484 6.1 AND 7071 1022 0.91 1.9 3650 485 1.1 2.2 2516 1023 10 3.6 6939 486 1.2 1.9 2367 1024 1.8 1.2 4538 487 0.75 0.49 2289 1025 3.0 0.86 5861 488 AND 8.4 5364 1026 4.5 6.3 14488 489 20 20 6674 1027 0.60 9.2 3003 490 1.2 3.4 2127 1028 7.6 2.1 16992 491 0.89 8.0 677 1029 1.4 5.0 8378 492 1.4 1.9 1478 1030 3.1 1.9 6278 493 1755 3791 >50000 1031 18 2.0 12671 494 5.2 2.8 14070 1032 1206 196 25365 495 h, h 1.3 3603 1033 1086 974 22372 496 7.5 2.1 2615 1034 1398 >3125 26595 497 52 67 >50000 1035 1.7 21 3666 498 NT NT NT 1036 1.3 2.7 1931 499 607 833 >50000 1037 3.1 6.2 1609 500 19 39 >50000 1038 0.98 1.3 1910 501 6.3 16 9553 1039 7.2 6.4 3068 502 0.79 5.1 2897 1040 0.17 0.66 1106 503 1.4 9.2 2503 1041 0.49 0.85 2424 504 0.55 0.64 3743 1042 2.2 3.3 3316 505 3.5 4.9 7601 1043 2.1 1.6 1749 506 0.41 0.42 3183 1044 4.1 9.2 3595 507 1.1 2.4 8492 1045 4.8 3.6 3236 508 1.1 h, h 6846 1046 0.64 2.4 2502 509 17 thirty 9105 1047 1.3 3.5 4493 510 5.9 28 >50000 1048 4.4 13 9827 511 5.8 4.8 >50000 1049 1.6 5.4 2599 512 1.1 5.6 304 1050 2.8 4.8 2657 513 319 307 545 1051 0.41 1.5 1908 514 38 44 7111 1052 8.9 17 5920 515 7.9 21 223 1053 2.5 4.8 4807 516 0.22 1.9 155 1054 5.4 1.7 1692 517 1.1 6.0 150 1055 4.3 8.3 5471 518 1.6 32 721 1056 2.1 1.2 2992 519 8.3 12 362 1057 0.81 1.7 2698 520 0.80 7.0 285 1058 1.9 3.5 5275 521 0.62 1.3 238 1059 1.6 1.4 2247 522 2.6 495 144 1060 0.50 0.50 2598 523 1.2 147 1470 1061 2.7 4.8 3175 524 0.88 6.7 407 1062 13 25 10182 525 0.18 48 771 1063 10 18 8057 526 8.8 14 666 1064 0.34 0.96 2455 527 7.3 h, o 1157 1065 1.1 1.1 2796 528 NT 23 5701 1066 9.0 eleven 4291 529 2.9 12 1833 1067 1.0 4.5 5396 530 7.1 8.8 4764 1068 0.88 1.8 2957 531 19 21 1289 1069 0.09 0.17 735 532 0.58 4.4 3594 1070 0.54 0.72 845 533 0.50 h, h 1459 1071 3.7 25 5951 534 1.2 8.0 4276 1072 2.9 35 5841 535 2.0 8.6 5717 1073 4.6 28 5832 536 0.66 4.1 2659 1074 0.59 1.9 2126 537 2.1 7.1 2853 1075 1.8 eleven 3354 538 2.0 h, h 8184 1076 1.6 1.8 10583 539 0.47 0.82 3322 1077 18 38 21801 - - - - 1078 9.8 216 >50000

- 233 041852

In vivo mouse model of PD TLR7

Adult male C57BL/6 mice were used for the experiments. Mice (7-10 per group) were randomly assigned to treatment groups based on body weight. Mice from the respective treatment groups were orally administered vehicle formulation or test compound. Thirty minutes after oral administration of the vehicle formulation or test compound, mice were given a challenge intraperitoneal injection of gardiquimod to simulate PD TLR7. Mice were bled under isoflurane anesthesia 90 min after gardiquimod injection and plasma levels of IL-6 and IFN-alpha were assessed using a commercially available ELISA kit (BD Biosciences, PBL Life Sciences). At the end of the experiment, mean cytokine levels were plotted and one-way analysis of variance was performed using Dunnett's test to calculate the significance of the test compound treatment group versus the vehicle control group. Percent inhibition of cytokine induction was calculated for the test compound treatment group compared to the vehicle control group. In table. 5 presents data from several studies with different test compounds.

Table 5. Percent inhibition of IL-6 and IFN-alpha in the PD TLR7 mouse model

Model PD TLR7 Example No. Dose (mg/kg) % inhibition nH6 % inhibition of IFN-alpha 3 0.005 0 29 0.01 24 37 0.05 75 94 0.25 90 99 0.5 91 100 4 0.0015 0 0 0.003 23 33 0.015 75 74 0.075 76 93 0.15 95 99 438 0.003 25 36 0.006 41 57 0.03 56 67 0.15 78 96 0.3 82 98

MRL/lpr model SLE

Male MRL/lpr mice aged 12-14 weeks were screened and randomized for anti-dsDNA antibody titers and urinary NGAL (neutrophil gelatinase-associated lipocalin) levels. Mice were treated orally once a day for 8 weeks with the vehicle formulation or test compound. The effect of test compound on disease severity was assessed by measuring endpoints including proteinuria, urinary NGAL, urinary TIMP1, blood urea nitrogen (BUN), anti-dsDNA antibodies, anti-smRNP antibody titer, and plasma levels of IL10 and IL2p40 blood. At the end of the experiment, all mice were suffocated under CO ₂ and histologically examined with kidney samples. A one-way analysis of variance with Dunnett's test was performed to calculate the significance of the test compound treatment group versus the vehicle control group. Percent reduction in disease severity was calculated for each parameter for the test compound treatment group compared to the vehicle control group. In table. 6 presents the data obtained during the study with the test compound.

Table 6. Inhibition of disease progression by TLR7/8 inhibitors in the MRL/lpr model of lupus

No. pr. Dose (mg/kg) protea nurium NGAL in urine TIMP1 in urine Titer of antibodies to SmRNP Titer of antibodies to dsDNA IL12p40 IL-10 438 0.1 31 34 0 23 0 16 0 0.3 80 58 42 44 28 33 18 1 73 63 54 49 39 26 19 h 82 67 56 43 44 28 21 10 84 67 79 51 37 41 22

CLAIM

Claims (15)

CLAIM 1. Compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein G is - 234 041852 A represents: (i) -OR6 or -O(CR _x R _x )i—2-R6; (ii) -NR ₇ R8; (iii) -C(O)NR9R _w ; (vi) -CH2CH2R11; (v) -CR _x R ₁₂ R ₁₃ where R ₁₂ and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from azetidinyl, C _3-6 cycloalkyl, morpholinyl or piperidinyl, each substituted with 0 to 3 R _12a ; or (vi) pyrazolyl substituted with 0 to 1 R _14a ; R1 is -CH ₃ or -CH(CH ₃ ) ₂ ; each R ₂ is independently Cl, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ OH, -CH ₂ CH ₂ OH, -CH2CN, -OCH3, -CH2OCH3 or -CH2CH2S(O)2CH3; R _2a is C _1-6 alkyl; R _2b is H, halo or C _1-6 alkyl; R5 is F or C _1-3 alkyl; R6 is: (a) -CH ₃ or (b) azetidinyl, cyclohexyl or piperidinyl, each substituted with 0 to 2 R _6a ; each R6a is independently -CH3, -CH2CH2CH3, -C(CH3)2, -CH2C(CH3)2OH, -N(CH3)2, -N(CH2CH2CH3)2, -CH2CH2S(O)2CH3, -CH2C(O )N(CH3)2 or tetrahydropyranyl; R ₇ and R ₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from azetidinyl, diazepanil, diazaspiro[3.5]nonanyl, piperazinonyl, piperazinyl, piperidinyl and pyrrolidinyl, said heterocyclic ring being substituted with 0 to 1 R7b and 0 to 2R7c; R7b is: (a) -NR _x R _x , C _1-6 alkyl, C _2-3 fluoroalkyl, C _1-4 hydroxyalkyl, € _1-2 cyanoalkyl, -CHR _x CH ₂ OCH ₃ , -CH2C(O)NRxRx, -CH2CH2C (O)NRxRx, -(CH ₂ ) ₂ - ₃ S(O) ₂ CH ₃ , -CH2CH2NHS(O)2CH3, -N(CH ₃ )(CH ₂ CH ₃ ), -N(CH2CH3)2, -NH (CH2CN), -N(CH2CN)2, -NRxCH2C(O)N(CH3)2, -NRxC(O)CH2N(CH3)2, -NH (CH ₂ CH ₂ S (O) ₂ CH ₃ ), -N (CH ₂ C (O) N (CH ₃ ) ₂ ) ₂ , -S (O) ₂ CH ₂ CH ₂ N (CH ₃ ) ₂ , -C(O)CH ₂ CH ₂ N(CH ₃ ) ₂ , -C(O)CH2NRxRx, -C(O)CH2N(CD3)2, -C(O)CD2N(CH3)2, -C(O)CD2N(CD3)2, -C(O)CH2NH(CH(CH3 )2), -C(O)CH ₂ NH(CH ₂ CH ₂ OCH ₃ ), -C(O)CH ₂ NH(CH ₂ CH ₂ OH), -CH ₂ (cyclopropyl), -CH ₂ (methyl oxetanyl) , -CH ₂ (tetrahydrofuranyl), -CH ₂ (methyltriazolyl), -CH ₂ CH ₂ (morpholinyl), -NR _x (cyclobutyl), -NR x (oxetanyl), -NR _x (pyrimidinyl), _{-NR x (} tetrahydropyranyl ), -NHCH ₂ (methylsulfonylcyclopropyl), -NHCH ₂ (methyloxetanyl), -NHCH ₂ (methoxypyrimidinyl), -C (O) CH ₂ NH (cyclobutyl), -N (CH ₂ (dimethoxypyrimidinyl)) ₂ , -N (CH ₂ (methoxypyrimidinyl)) ₂ , -N (CH ₂ (triazolyl)) ₂ , -N (CH ₂ (methyltriazolyl)) ₂ , -N (CH ₃ )CH ₂ (cyclopropyl), -N (CH ₃ )CH ₂ ( methylpyrazolyl), -N(CH ₃ )CH ₂ (pyrimidinyl), -N(CH ₃ )CH ₂ (methylpyrimidinyl), -N(CH ₃ )CH ₂ (dimethoxypyrimidinyl), -N(CH ₃ )CH ₂ (methoxypyrimidinyl) , -N (CH ₃ ) CH ₂ (thiadiazolyl), -N (CH ₃ ) CH ₂ (methyltriazolyl), -NH (CH ₂ (methylpyrimidinyl)) ₂ , -NH (CH ₂ (thiadiazolyl), -C (O) CH ₂ (azetidinyl), -C (O) CH ₂ (morpholinyl), -C (O) CH ₂ (hydroxypiperidinyl), -C ( O)CH ₂ (pyrrolidinyl) or -C(O)CH ₂ NHCH ₂ (cyclopropyl); or (b) cyclobutyl, cyclohexyl, dioxothiomorpholinyl, oxetanyl, piperazinyl, piperidinyl, tetrahydrofuranyl or tetrahydropyranyl, each substituted with 0 to 1 R _8a and 0 to 3 R _8b ; each R7c is independently -CH3 or -CH2CN; R8a is -OH, -CH ₃ , -CH2CH3, -CH(CH3 ₎ 2, -C( _CH3 ) ₃ , -CH2CH(CH3)2, -CH2CH2OCH3, -CH2CH2CH2CF3 _, -C ₍ O ) CH ₃ , -C (O) _OCH 3 , -CH ₂ (cyclopropyl), -CH ₂ (methylphenyl), -(CH ₂ ) _2-3 (pyrrolidinyl), -CH ₂ (methylpyrazolyl), -CH ₂ (thiophenyl ), -NR _x R _x , cyclopentyl, methylpiperidinyl or pyridinyl; each R _8b is -CH ₃ ; R9 is -CH2CH2CF3 or -CH2CH2N(CH3)2, - 235 041852 R ₁₀ is H or C ₁ . ₂ alkyl; or R ₉ and R ₁₀ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperidinyl substituted with -C(O)CH3 or -CH(CH3) ₂ ; R11 is azetidinyl or piperidinyl, each substituted with 0 to 1 substituents selected from -CH ₂ (triazolyl), -CH ₂ (methyloxetanyl), -C(O)CH2N(CH3)2, -CH2C(CH3)2OH , -CH2C(O)N(CH3)2, -CH2CH2S(O)2CH3 and oxetanil; each R _12a is independently -OH, -CH3, -CH2CH2CH3, -CH(CH ₃ ) ₂ , -CH ₂ CH(CH ₃ ) ₂ , -CH2CN, -CH2C(CH3)2OH, -CH2C(O)NH( CH3), -CH2C(O)N(CH3)2, -CH2C(O)NH2, -C(CH3)2CH2C(O)N(CH3)2, -CH ₂ CH ₂ S(O) ₂ CH ₃ , - NR _x Ry, -NR _x CH ₂ NR _x R _x , -NR _x (CH ₂ CHF ₂ ), -N(R _x )(CH ₂ CH ₂ CF ₃ ), -NR _x (CH ₂ CH ₂ OCH ₃ ) , -NR _x (C ₁ _ ₂ cyanoalkyl), -NR _x (CH ₂ CH ₂ OH), -N (CH ₂ CH ₂ OH) (CH ₂ C (O) N (CH ₃ ) ₂ ), -N ( CH ₂ CH ₂ OH)(CH2CH2S(O)2CH3), -N(CH2CH2S(O)2CH3)2, -NRxCH2CRxRxS(O)2CH3, -NRxCH2CH2S(O)2CF3, -NRxCH2CH2S(O)2NH2, -NRxC(O)CH3, -NRxC(O)CH2N(CH3)2, -NRx(CRxRxC(O)NRxRx), -NHCH2C(O)NRx(C(CH3)3), -NRx(CRxRxC(O)CH2NRxRx), -NH(CH2C(O)N(CH3)CH2CH2OCH3), - N(CH2CH3)2, -N(CH2CH3)(CH2C(O)N(CH3)2), -N(CH2CH3)(CH2CH2S(O)2CH3), -N(CH2CN)2, - N(CH2CN)(CH2C(O)N(CH3)2), -N(CH2CN)(CH2CH2S(O)2CH3), -N(CH2C(O)NRxRx)2, , -C(O)CH2N(CH3 )2, -C(O)CH2CH2N(CH3)2, R12b, -C^Rnb, -NR.xR.12b, -N(cyclopropyl)R12b, -NRxCHRxR _nb -NHC(O)R _nb -NHCRxRxC(O) R12b, -N(CH2CH3)(CH2R12b), -N(CH2CH2OH)R12b, -N(CH2CH2OH)(CH2R12b), -N(CH2CN)R12b, -N(CH ₂ CN)(CH ₂ R _12b ) or -N (CH ₂ (methyloxetanyl)) ₂ or two R _12a and the carbon atom to which they are attached form C=O; R _12b is azaspiro[3.5]nonanyl, azetidinyl, cyclopropyl, cyclopentyl, dioxotetrahydrothiofuranyl, dioxytetrahydrothiopyranyl, dioxothiaazaspiro[3.3]heptanyl, morpholinyl, oxaazaspiro[3.3]heptanyl, oxazolyl, oxetanyl, phenyl, piperazinonyl, pyridinyl, pyridinyl, pyridinyl, pyrrolidinyl, pyrrolidinonyl, tetrahydrofuranyl, tetrahydropyranyl or triazolyl, each substituted with 0 to 4 substituents independently selected from F, -CN, -CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ CH(CH ₃ ) ₂ , -CH2OH, -CH2CH2OH, C ₁ _ ₂ cyanoalkyl, -OCH3, -CH ₂ C(O)NH(CH ₃ ), -C(O)NRxRx, -S(O)2CH3 and -CH2S(O)2CH3; And R _14a is piperidinyl or —CH ₂ CH ₂ (morpholinyl); each R _x is independently H or -CH ₃ ; Ry is H or C _1-6 alkyl; n is 0 or 1; and p is 0, 1, 2, or 3. 2. The compound according to claim 1 or its pharmaceutically acceptable salt, where G represents A is -CR _x R ₁₂ R ₁₃ where R ₁₂ and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from azetidinyl, C ₄ _ ₆ cycloalkyl or piperidinyl, each substituted with 0 to 3 R12a ; where R2a, R2b, R2, R12a and p have the meanings specified in claim 1. 3. The compound according to claim 1 or its pharmaceutically acceptable salt, where G is (R ₂ ) _p A is -CR _x R ₁₂ R ₁₃ , where R ₁₂ and R ₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl and cyclohexyl, each substituted with 0 to 1 R12a; R ₁ is -CH(CH ₃ ) ₂ ; R12a is -NRxRy, -NRx(CH2CHF2), -N(Rx)(CH2CH2CF3), -NRx(CH2CH2OCH3), -NRχ(C1_2CYAHOALKIL), -NRxCH2NRxRx, -NRx#CH2OH), -NRx(CH2C(O)NRxRx ), -CH2R12b, -NRxR12b or -NRxCHRxR12b and R _12b is cyclopropyl, cyclopentyl, dioxotetrahydrothiofuranyl, dioxytetrahydrothiofuranyl, morpholinyl, oxazaspiro[3.3]heptanyl, oxazolyl, oxetanyl, phenyl, piperidinyl, pyrazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, tetrahydrofuranyl, tetrahydropyranyl, or triazolyl, each substituted with from 0 to 4 independently selected from F, -CN, -CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH, Rhoianoalkyl, -OCH3, -CH2C(O)NH(CH3), -C(O)NRxRx, -S(O)2CH3 and -CH2S(O)2CH3; where R2, Rx, R12, R13 and Ry have the meanings specified in claim 1. 4. The compound according to claim 1 or its pharmaceutically acceptable salt, where - 236 041852 G represents A is -NR ₇ R ₈ ; where R2, R ₇ , R ₈ and p have the meanings specified in claim 1. 5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein G is R ₁ is -CH(CH3) ₂ and A is piperazinil; where R2 and p have the values specified in claim 1. 6. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is 7. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is 8. A compound that is, or a pharmaceutically acceptable salt thereof. - 237 041852 9. Connection representing about o=sn or a pharmaceutically acceptable salt thereof. 10. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is 11. A compound or a pharmaceutically acceptable salt thereof, said compound being selected from 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3- isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)N-(tetrahydro-2H-pyran-4-yl)azetidine-3-amine (1); 6-(3-isopropyl-5-(piperazin-1-yl)-1 H-pyrrolo[3,2b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1, 5-a]pyridine (2); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1one (3); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (4); 2-(3,4-dimethoxyphenyl)-5-(1'isobutyl-[1,4'-bipiperidin]-4-yl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (5); N-(2-(dimethylamino)ethyl)-Nethyl-3-isopropyl-2-(8-methoxy-[1.2.4]triazolo[1,5-a]pyridin-6-yl)-6-methyl- 1H-pyrrolo[3,2-b]pyridine 5-carboxamide (6); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridin-5-yl) cyclopentan-1-one (7-9); 2-((3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclopentyl)amino)-N-methylacetamide (10); 6-(6-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo [1,5-a]pyridine (11); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N,N-dimethylazetidine-3-amine (12); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridin-5-yl )-N,N-dimethylazetidine-3-amine (13); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)azetidine-3-amine (14); N-(1-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-yl)-2-(dimethylamino)acetamide (15); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) azetidin-3-amine (16); 2-(dimethylamino)-N-(1-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)azetidin-3-yl)acetamide (17); 2-((1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1 N-pyrrolo[3,2-b ]pyridin-5yl)azetidin-3-yl)amino)-N,N-dimethylacetamide (18, 27); N-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)azetidin-3-yl)-2-(dimethylamino)-N-methylacetamide (19, 25); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-5- yl)-N-methylazetidine-3-amine (20, 23); 2-((1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-yl)(methyl)amino)-N,N-dimethylacetamide (21); 2-((1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)azetidin-3-yl)amino)-N,N-dimethylacetamide (22, 26); 1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)azetidine-3-amine (24); 2-(dimethylamino)-N-(1-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)azetidin-3-yl)-N-methylacetamide (28); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5- yl) N-(tetrahydro-2H-pyran-4-yl)azetidine-3-amine (29); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) -N-((3-methyloxetan-3-yl)methyl)azetidine-3-amine (30); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5- yl)-N-methylazetidine-3-amine (31); 1-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H - 238 041852 pyrrolo[3,2-b]pyridin-5-yl)azetidine-3-amine (32, 35); 1-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3b]pyridin-3-yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-N-(tetrahydro -2H-pyran-4-yl)azetidine-3-amine (33, 36); 2-((1-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5yl)azetidine -3-yl)amino)-N,N-dimethylacetamide (34, 37); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)azetidin-3-ol (38); 4-(1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-yl)morpholine (39); 1-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine -5-yl)azetidin-3-yl)piperidin-4-ol (40); 4-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin6-yl)-3-isopropyl-1 H-pyrrolo[3,2-b] pyridin-5-yl)azetidin-3-yl)thiomorpholin-1,1-dioxide (41); methyl4-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5yl)azetidin-3-yl)piperazine-1-carboxylate (42); 6-(3-isopropyl-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2 ,4]triazolo[1,5-а]pyridine (43); 2-(2-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-2,7-diazaspiro[3.5]nonan-7-yl)-N,N-dimethylacetamide (44); 6-(3-isopropyl-5-(7-(2-(methylsulfonyl)ethyl)-2,7diazaspiro[3.5]nonan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl) -7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (45); 6-(3-isopropyl-5-(7-isopropyl-2,7-diazaspiro[3.5]nonan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)7,8-dimethyl -[1,2,4]triazolo[1,5-a]pyridine (46); 6-(3-isopropyl-5-(7-(oxetan-3-yl)-2,7-diazaspiro[3.5]nonan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl )-7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine (47); N,N-bis((1H-1,2,3-triazol-4-yl)methyl)-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a ]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidin-4-amine (48); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-4-amine (49); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine-5- yl) piperidine-4-amine (50); 2,2'-((1-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3yl)-1H-pyrrolo[3,2-b]pyridine-5- yl)piperidin-4-yl)azandiyl)diacetonitrile (51-52); 2,2'-((1-(3isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5- yl)piperidin-4yl)azandiyl)diacetonitrile (53); 2,2'-((1-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1Hpyrrolo[3,2-b]pyridin-5- yl)piperidin-4-yl)azandiyl)bis(N,N-dimethylacetamide) (54); 1-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (55); N((1,2,3-thiadiazol-4-yl)methyl)-1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl) -3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-4-amine (56); N-cyclobutyl-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine -5-yl)piperidine-4-amine (57); Na(cyclopropylmethyl)-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)-N-methylpiperidin-4-amine (58); N-cyclobutyl-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-methylpiperidin-4-amine (59); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-(pyrimidin-2-ylmethyl)piperidin-4-amine (60); N-((4,6-dimethoxypyrimidin-5-yl)methyl)-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl) -3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylpiperidin-4-amine (61); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-methyl-N-((1-methyl-1H-pyrazol-5-yl)methyl)piperidin-4-amine (62); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)piperidine-4-amine (63, 68); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine-5- yl)-N-methyl-N-((2-methylpyrimidin-5-yl)methyl)piperidin-4-amine (64); 1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-methyl-N-(oxetan3-yl)piperidin-4-amine (65); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-5- yl)-N-ethyl-N-methylpiperidin-4-amine (66); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-((2-methoxypyrimidin-5-yl)methyl)-N-methylpiperidin-4-amine (67); N-((4,6-dimethoxypyrimidin-5-yl)methyl)-1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)- 3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidin-4-amine (69); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N,N-diethylpiperidin-4-amine (70); N,N-bis((4,6-dimethoxypyrimidin-5-yl)methyl)-1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine-6 -yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidin-4-amine (71); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N-((2-methoxypyrimidin-5-yl)methyl)piperidin-4-amine (72); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N,N-bis((1-methyl-1H-1,2,3-triazol-4yl)methyl)piperidine-4-amine (73, 76); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N,N-bis((2-methylpyrimidin-4-yl)methyl)piperidin-4-amine (74); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)N,N-bis((2-methoxypyrimidin-5-yl)methyl)piperidin-4-amine (75); N-((1,2,3-thiadiazol-4-yl)methyl)-1-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl )-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylpiperidin-4-amine (77); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-(pyrimidin-2-ylmethyl)piperidin-4-amine (78); (6-(5-(4-amino - 239 041852 piperidin-1-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8- yl) methanol (79); (6-(3-isopropyl-5-(4-((tetrahydro-2H-pyran-4-yl)amino)piperidin-1-yl)-1H-pyrrolo[3,2b]pyridin-2-yl)-[ 1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (80); (6-(3-isopropyl-5-(4-(oxetan-3ylamino)piperidin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo [1,5-a]pyridin-8-yl)methanol (81); (6-(3-isopropyl-5-(4-(((3-methyloxetan-3-yl)methyl)amino)piperidin-1-yl)-1 H-pyrrolo[3,2-b]pyrudin-2- yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (82); 2-((1-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2- b]niridin-5-yl)niperidin-4-yl)amino)acetonitrile (83); 2-((1-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b] pyridin-5-yl)piperidin-4-yl)amino)-N,N-dimethylacetamide (84-85); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-(oxetan-3-yl)piperidin-3amine (86); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)piperidin-3-amine (87); 6-(3-isopropyl-5(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5- a]pyridine (88); 6-(3isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a ]pyridine (89); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl)ethan-1-one (90); 6-(3-isopropyl-5-(4-methylpiperazin-1-yl)-1Нpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5 -a]pyridine (91); 6-(3-isopropyl-5-(4-isopropylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1 ,5-a]pyridine (92); 6-(3isopropyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine (93); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperazin-1-yl)acetonitrile (94); 6-(3-isopropyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1 ,2,4]triazolo[1,5-a]pyridine (95); 6-(3-isopropyl-5-(4-methylpiperazin-1-yl)-III-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo [1,5-a]pyridine (96); 6-(3-isopropyl-5-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-1Hn-pyrrolo[3,2-b]n-pyridin-2-yl)-7,8- dimethyl-[1,2,4]triazolo[1,5-a]niridine (97); 1-(4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyrudin-6-ul)-3-isopropyl-III-pyrrolo[3,2-b] pirudin-5-yl)piperazin-1-yl)-3(dimethylamino)propan-1-one (98); 3-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5а]pyridin-6-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)piperazin-1-yl)propan-1-one (99); 6-(3-isopropyl-5-(4isopropylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1 ,5-a]pyridine (100); 6-(3-isopropyl-5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-III-pyrrolo[3,2-b]pyridin-2-yl)7,8- dimethyl-[1,2,4]triazolo[1,5-a]pyridine (101); 6-(3-isopropyl-5-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8- methoxy-[1,2,4]triazolo[1,5-a]pyridine (102); 6-(3isopropyl-5-(4-(tetrahydrofuran-3-yl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy[1,2,4 ]triazolo[1,5-а]pyridine (103); 6-(3-isopropyl-5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy- [1,2,4]triazolo[1,5-a]pyridine (104); 1-(4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)-2methylpropan-2-ol (105); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperazin-1-yl)-2-methylpropan-2-ol (106); 6-(3-isopropyl-5-(4-((tetrahydrofuran-3-yl)methyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy- [1,2,4]triazolo[1,5-a]pyridine (107); 6-(5-(4-cyclobutylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy-[1,2,4]triazolo[1,5 -a]pyridine (108); 6-(5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5 -a]pyridine (109); 6-(5-(4-isopentylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1 ,5-a]pyridine (110); 6-(3-isopropyl-5-(4-neopentylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy[1,2,4]triazolo[1, 5-a]pyridine (111); 6-(3-isopropyl-5-(4-(1-methoxypropan-2-yl)piperazin-1-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1, 2,4]triazolo[1,5-a]pyridine (112); 4-(4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)piperazin-1-yl)cyclohexan-1-ol (113); 6-(5-(4-(3,3-dimethylbutyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine (114); 6-(5-(4-Butylpiperazin-1-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5 -a]pyridine (115); 6-(3-isopropyl-5-(4-(3,3,3trifluoropropyl)ninerazin-1-yl)-1H-n-pyrrolo[3,2-b]niridin-2-yl)-8-methoxy-[1, 2,4]triazolo[1,5-a]niridine (116); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-1H-pyrrolo[3,2b]pyridine-5 -yl)piperazin-1-yl)propan-1-ol (117); 3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)piperazin-1-yl)butan-1-ol (118); 6-(5-(4-ethylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1 ,5-a]pyridine (119); 6-(5-(4-(cyclopropylmethyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy-[1,2,4]triazolo[ 1,5-a]pyridine (120); 1-(4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)piperidin-1-yl)ethan-1-one (121); 5-(3isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (122) ; 2-(dimethylamino)-1-(4-(3-isopropyl-2-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)ethan-1-one (123); 3 -(dimethylamino)-1 -(4-(3-isopropyl-2-(7-methyl7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperazin-1-yl)propan-1-one (124); - 240 041852 5-(3-isopropyl-5-(4-methylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7-methyl-7H-pyrrolo[2,3d]nupuMuguH ( 125); 5-(3-isopropyl-5-(4-isopropylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7methyl-7H-pyrrolo[2,3-d]pyrimidine ( 125); 5-(3-isopropyl-5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7-methyl-7H -pyrrolo[2,3-d]pyrimidine (127); 2-(4-(3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-irrolo[3,2-b]pyridine- 5-yl)piyerazin-1-yl)^^dimethylacetamide (128); 6-(3-isopropyl-5-(4-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)-1Hpyrrolo[3,2-b]pyridine -2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (129); 2-(4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)piperazin-1-yl)acetamide (130); 6-(3-isopropyl-5-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy[1,2,4 ]triazolo[1,5-а]pyridine (131); 6-(3-isopropyl-5-(4-(3-(methylsulfonyl)propyl)piperazin-1-yl)1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1, 2,4]triazolo[1,5-a]pyridine (132); 4-(4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)piperazin-1-yl)tetrahydro-2H-thiopyran-1,1-dioxide (133); N-(2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)ethyl)methanesulfonamide (134); 6-(3-isopropyl-5-(4(4,4,4-trifluorobutyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1 ,2,4]triazolo[1,5а]pyridine (135); 3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine-5 -yl)piperazin-1-yl)-N,N-dimethylpropanamide (136); 3-(4-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperazin-1-yl)propanamide (137); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperazin-1-yl)-N-methylacetamide (138); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperazin-2-one (139); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-4-(oxetan-3-yl)piperazin-2-one (140); 2(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-3oxopiperazin-1-yl-N,N-dimethylacetamide (141), 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine -6-yl)3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-4-methylpiperazin-2-one (142); dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl)- 2-morpholinoethan-1-one (143); isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (144);1-(4-(2-(7,8-dimethyl[1,2 ,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl)-2(pyrrolidin-1 -yl)ethan-1-one (145); a]pyridin6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl)ethan-1-one (146); -(4(3-(methylsulfonyl)propyl)piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[ 1,5-a]pyridine (147), 3-(4- (2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridin-5-yl) piperazin-1-yl)propanenitrile (148); 3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)piperazin-1-yl)propanamide (149); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperazin-2-one (150); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)piperazin-1-yl)sulfonyl)-N,N-dimethylethane-1-amine (151); (S)-6-(3-isopropyl-5-(2-methylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2 ,4]triazolo[1,5-а]pyridine (152); (R)-6-(3-isopropyl-5-(2-methylpiperazin-1-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2, 4]triazolo[1,5-a]pyridine (153); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-5- yl)-1-(2-morpholinoethyl)piperazin-2-one (154-155); 2-(cyclobutylamino)-1(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl)ethan-1-one (156); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine -5-yl)piperazin-1 -yl)-2-(isopropylamino)ethan-1-one (157); 1-(4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)-2-((2hydroxyethyl)amino)ethan-1-one (158); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)piperazin-1-yl)-2-((2-methoxyethyl)amino)ethan-1-one (159); 1-(4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)piperazin-1-yl)-2-(4-hydroxypiperidin-1-yl)ethan-1-one (160); 2-((cyclopropylmethyl)amino)-1-(4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H- pyrrolo[3,2-b]pyridin-5-yl)piperazin-1yl)ethan-1-one (161); 6-(5-(1,4-diazepan-1-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl[1,2,4] triazolo[1,5-a]pyridine (162); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)-1,4-diazepan-1-yl)-N,N-dimethylacetamide (163); 1-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-(oxetan-3-yl)pyrrolidin-3-amine (164); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)pyrrolidin-3-amine (165); 3-((4(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)(methyl)amino)propanenitrile (166, 175); Niisopropyl-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexane-1-amine (167, 193); N-isopropyl4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-III-pyrrolo[3,2-b]pyridine- 5-yl)methylcyclohexane-1-amine (168, 170); 2-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridine-6 - 241 041852 yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)(methyl)amino)ethan-1-ol (169, 191); N-cyclopropyl-4(3-isonronyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-1H-n-pyrrolo[3,2-b]n-yridine- 5-yl)-Nmethylcyclohexane-1-amine (171, 172); -a]niridin6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)pyrrolidin-2-yl)methanol (173, 197); 6-(3-isopropyl5-(4-(pyrrolidin-1-yl)cyclohexyl)-III-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5a]pyridine (174, 192, 195, 199); 4-(3-isonronyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]niridin-6-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl) cyclohexan-1-one (176); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5а]niridin-6-yl)-1H-nirrolo[3,2-b]niridin-5-yl) -N,N-dimethylcyclorexan-1-amine (177, 179, 187); N-(4(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-III-pyrrolo[3,2-b]pyridine- 5-yl)cyclohexyl)oxetan-3-amine (178, 180, 186); 2-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (181, 231, 232); 2-((4-(3izonronyl-2-(1-methyl-1H-n-pyrrolo[2,3-b]n-pyrrolo[3,2-b]n-pyrrolo[3,2-b]n-pyrrolo[2,3-b]n-pyrrolo[3,2-b]n-pyrrolo-5-yl)-cyclohexyl )amino)-N,N-dimethylacetamide (182, 183); N-(4-(3-isonronyl-2-(1-methyl-1H-n-pyrrolo[2,3-b]n-yridin3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) oxetan-3-amine (184, 185); 4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-а]n-yridin-6-yl)-1H-n-pyrrolo[3,2-b]n-yridin-5-yl) -N-methylcyclohexane-1amine (188, 189); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridin-5-yl) -N-((5-methylpyrazin-2-yl)methyl)cyclohexane-1-amine (190, 196); 4-(4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclohexyl)morpholine (194); 4-(3-isonronyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]niridin-6-yl)-1H-nirrolo[3,2-b]niridin-5yl) -N-(2-methoxyethyl)-N-methylcyclohexane-1-amine (198); 2-((4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]n-yridin-3-yl)-1H-n-pyrrolo[3,2-b]n-yridin-5-yl )cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (200, 201); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridin-5-yl) -N-methyl-N-((5-methylpyrazin-2-yl)methyl)cyclohexane-1-amine (202, 203); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5- yl)-N-(oxazol-5ylmethyl)cyclohexane-1-amine (204, 206); 4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1 Hpyrrolo[3,2-b]pyridin-5-yl)-N-( (5-methylpyrazin-2-yl)methyl)cyclohexane-1-amine (205, 207); 4-(3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) -N-methylN-(pyrimidin-2-ylmethyl)cyclohexane-1-amine (208-209); 2-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)-N-methylacetamide (210, 227, 228); 2-((4-(3-isonronyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]niridin-6-yl)-1Hpyrrolo[3,2-b]pyridine- 5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (211, 226); 2-((4-(3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-1H-πirrolo[3,2-b]πiridine- 5-yl)cyclohexyl)(methyl)amino)acetamide (212, 225); 2-((4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (213, 230); N-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b ]pyridin5-yl)cyclohexyl)oxetan-3-amine (214, 229); (6-(3-isopropyl-5-(4-(oxetan-3-ylamino)cyclohexyl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo[1,5 -a]pyridin-8-yl)methanol (215, 220); 2-((4-(2-(8(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (216, 222); (6-(3-isopropyl-5-(4-(((5-methylpyrazin-2yl)methyl)amino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2 ,4]triazolo[1,5-a]pyridin-8-yl)methanol (217); (6-(5-(4-(((1H-1,2,3-triazol-4-yl)methyl)amino)cyclohexyl)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-2-yl )-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (218, 221); 4-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (219); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridin-5-yl )-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (223); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[4,3-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5yl)cyclohexyl)oxetan-3-amine (233-234); (6-(3-isopropyl-5-(4-(oxetan-3-ylamino)cyclohexyl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo[1,5 -a]pyridin-8-yl)methanol (235); 4-(3-isopropyl-2-(1methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-(( 1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (236, 238); N-cyclopropyl-N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[4,3а]n-iridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2 -b]niridin-5-yl)cyclohexyl)oxetan-3-amine (237, 239); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)-N-methyloxetan-3-amine (240); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) -N-methyl-N-(2-(methylsulfonyl)ethyl)cyclohexane-1-amine (241, 242); N-cyclopropyl-4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )cyclohexane-1-amine (243); 6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (244); 6-(4-(3-isopropyl2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) -2-oxa-6azaspiro[3.3]heptane (245); (6-(3-isopropyl-5-(4-(methyl(oxetan-3-yl)amino)cyclohexyl)-1H-pyrrolo[3,2-b]πiridin-2-yl)-[1,2,4 ]triazolo[1,5-a]-pyridin-8-yl)-methanol (246, 252); 4-(3-isopropyl-2-(1methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-(2 -(methylsulfonyl)ethyl)cyclohexane-1-amine (247, 251); 6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridine - 242 041852 6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptan-2,2-dioxide (248); 5-(3isopropyl-5-(4-(methyl(oxetan-3-yl)amino)cyclohexyl)-III-pyrrolo[3,2-b]pyridin-2-yl)-1,3,4-trimethylpyridin-2 (1H)-one (249, 254); 5-(3-isopropyl-5-(4-(methyl(oxetan-3-yl)amino)cyclohexyl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H )-one (250); 6-(4-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptan-2,2-dioxide (253); 6-(4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) -2-thia-6-azaspiro[3.3]heptane-2,2-dioxide (255-256); 2-((4-(3isopropyl-2-(1-(2-(methylsulfonyl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b] pyridin5-yl)cyclohexyl)amino)-MODimethylacetamide (257, 261); 6-(4-(3-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (258); 4-(3-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (259, 262); 4-(3-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)-1 H-pyrrolo[2,3-b]pyridin-3-yl)- 1 H-pyrrolo[3,2b]pyridine- 5-yl)cyclohexan-1-ol (260); 2-(3-(3-isopropyl-5-(4-(methylamino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine- 1-yl)acetonitrile (263, 270); 4-(3-isopropyl-2-(1(2-(methylsulfonyl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-methylcyclohexane-1-amine (264, 269); N-(4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) tetrahydro-2H-pyran-4-amine (265, 267); N-(4-(3-isonronyl-2(1-(2-(methylsulfonyl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (266, 271); 2-(3-(3-isopropyl-5-(4-((tetrahydro-2H-pyran-4yl)amino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-pyrrolo [2,3-b]pyridin-1-yl)acetonitrile (268, 274); 2-((4-(2-(1-(cyanomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-5-yl )cyclohexyl)amino)-N,N-dimethylacetamide (272, 276); 2-(3-(3-isopropyl-5-(4-((2(methylsulfonyl)ethyl)amino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-pyrrolo[2 ,3-b]pyridin-1-yl)acetonitrile (273, 275); 2-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)(oxetan-3-yl)amino)acetonitrile (277); 4-(3-isopropyl-2(1-methyl-III-pyrrolo[2,3-b]pyridin-3-yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-N-( 2-methyl-2-(methylsulfonyl)propyl)cyclohexane-1-amine (278, 285); N-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclohexyl)oxetan-3-amine (279, 284); 2-((4-(3isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (280); 6-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (281, 288); N-(4-(2-(2,6dimethylpyridin-4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)oxetan-3-amine (282, 287) ; 6-(4-(2-(2,6-dimethylpyridin-4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2oxa-6-azaspiro[3.3 ]heptane (283, 286); N-(4-(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) tetrahydro-2H-pyran-4-amine (289); 6-(4-(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropyl-1 H-pyrrolo[3,2-b]pyridin-5-yl )cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (290, 294); 2-((4-(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridin-5-yl)cyclohexyl )amino)-N,N-dimethylacetamide (291); N-(4-(2-(1-ethyl-1H-pyrrolo[2,3b]pyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl) tetrahydro-2H-pyran-4-amine (292); 4-(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1 -ol (293); 2-(3-(3-isopropyl-5-(4-(methylamino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)1H-pyrrolo[2,3-b]pyridine-1 -yl)ethan-1-ol (295, 299); 4-(3-isopropyl-2-(7-methyl-7H-pyrrolo[2,3d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylcyclohexan- 1-amine (296, 301); 4-(3isopropyl-2-(5-methyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylcyclohexane- 1-amine (297, 300); 4-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2b]pyridin-5-yl)-N-methylcyclohexane- 1-amine (302); 2-((4-(3-isopropyl-2-(7-methyl-7H-pyrrolo[2,3d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl )amino)-N,N-dimethylacetamide (303); 4(3-isopropyl-2-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-( 2-(methylsulfonyl)ethyl)cyclohexane-1-amine (304); N-(4-(3-isopropyl-2-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) cyclohexyl)tetrahydro-2H-pyran-4-amine (305); (6-(5-(4((4-fluorobenzyl)(methyl)amino)cyclohexyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2,4] triazolo[1,5-a]pyridin-8-yl)methanol (306); (6-(3-isopropyl-5-(4-((3,3,3-trifluoropropyl)amino)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2, 4]triazolo[1,5-a]pyridin-8-yl)methanol (307, 308); N-(4-(3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b ]pyridin-5yl)cyclohexyl)oxetan-3-amine (309, 316); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)-3-methyloxetan-3-amine (310, 311); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexane-1-amine (312, 315); N-ethyl-4-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2- b]pyridin-5-yl)-N-methylcyclohexan-1-amine (313); 1-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1Hpyrrolo[3,2- b]pyridin-5-yl)cyclohexyl)amino)-2-methylpropan-2-ol (314, 321); 6-(4-(3-isopropyl-2-(8 - 243 041852 methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-III-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)- 2oxa-6-azaspiro[3.3]heptane (317, 319); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)6-methyl-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexane-1-amine (318, 323); Aethyl-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-III-pyrrolo[3,2-b] pyridin-5-yl)-N-methylcyclohexan-1-amine (320); N-(2,2-difluoroethyl)-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-6-methyl-1H- pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-amine (322, 324); 6-(5-(4-(azetidin-1yl)cyclohexyl)-3-isopropyl-6-methyl-III-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5а]pyridine (325, 326); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1Hpyrrolo[3,2-b]pyridine- 5-yl)-N-(2-methoxyethyl)cyclohexane-1-amine (327, 335); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-III-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)tetrahydrofuran-3-amine (328, 329); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6methyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclorexyl)-N-methyloxetan-3-amine (330, 331); 4-(3-isopropyl2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-methyl-N((1-methyl-1H-1,2,4-triazol-3-yl)methyl)cyclohexane-1-amine (332, 333); 4-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b]pyridine -5-yl)-N-methyl-N-neopentylcyclohexan-1-amine (334, 336); 6-(5-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-3-isopropyl-6-methyl-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[ 1,2,4]triazolo[1,5-a]pyridine (337, 338); 3-((4-(3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2 -b]pyridin-5-yl)cyclohexyl)(methyl)amino)propanenitrile (339, 340); 4-(6-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (341, 342); 6-(4-(6-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-III-pyrrolo[3,2b ]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (343, 344); A(4-(6-fluoro-3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)oxetan-3amine (345, 346); 4-(6-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1N-pyrrolo[3,2-b] pyridin-5-yl)-N-methylcyclohexane-1-amine (347, 348); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)cyclohexan-1-one (349); N-(4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)oxetan-3-amine (350, 351); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (352, 354); 4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N,N-dimethylcyclohexane-1-amine (353, 355, 356); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-((5-methylpyrazin-2-yl)methyl)cyclohexane-1-amine (357, 359); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N-isopropylcyclohexane-1-amine (358, 363); 6-(3-isopropyl-5-(4-(pyrrolidin-1-yl)cyclohexyl)1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4 ]triazolo[1,5-a]pyridine (360, 407); 3-((4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)propanenitrile (361); 4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)morpholine (362); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridine- 5-yl)-N-isopropyl-N-methylcyclohexane-1-amine (364); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)cyclohexyl)(methyl)amino)ethan-1-ol (365); 3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)cyclohexyl)(methyl)amino)propanenitrile (366); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]πiridin-5- yl)-N-methylcyclohexane-1-amine (367, 369); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (368); 6-(5-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-3-isopropyl-1 H-pyrrolo[3,2b]niridin-2-yl)-7,8-dimethyl-[1 ,2,4]triazolo[1,5-а]niridine (370, 374); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]πiridine- 5-yl)-N-(πоπ-2-yn-1-yl)cyclohexan-1-amine (371, 375); (R)-(1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3, 2-b]pyridin-5-yl)cyclohexyl)pyrrolidin-2-yl)methanol (372, 377); 4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-(3,3,3-trifluoropropyl)cyclohexane-1-amine (373, 376); (R)-(1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3, 2-b]pyridin-5-yl)cyclohexyl)pyrrolidin-2-yl)methanol (377); 4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N,N-diethylcyclohexane-1-amine (378-411); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)ethan-1-ol (379, 409); N-cyclopropyl-4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-methylcyclohexane-1-amine (380, 387); 6-(5-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-3-isopropyl-1Hn-pyrrolo[3,2-b]niridin-2-yl)-7,8-dimethyl-[1, 2,4]triazolo[1,5-a]niridine (381, 385); 4-(4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-b-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)thiomorpholine-1,1-dioxide (382-383); 3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)propanenitrile (384, 432); 6-(5-(4-(azetidin-1-yl)qi - 244 041852 clohexyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine ( 386); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N-ethyl-N-methylcyclohexane-1-amine (388, 390); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-(2-methoxyethyl)-N-methylcyclohexane-1-amine (389); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N(2-methoxyethyl)-N-methylcyclohexan-1-amine (391); (S)-(1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3, 2-b]pyridin-5-yl)cyclohexyl)pyrrolidin-2-yl)methanol (392-393); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-3-isononyl-1H-n-pyrrolo[3,2-b]n-yridine- 5-yl)-N-methyl-N-((2-methylpyrimidin-5-yl)methyl)cyclohexane-1-amine (394, 402); 4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridine-5 -yl)-N-((2-methoxypyrimidin-5-yl)methyl)-N-methylcyclohexane-1-amine (395, 405); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]n-yridin-6-yl)-3-isononyl-1H-n-pyrrolo[3,2-b]n-yridine -5-yl)cyclohexyl)-2-(dimethylamino)-N-methylacetamide (396, 404); N-((1H-1,2,3-triazol-4-yl)methyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine6- yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylcyclohexan-1-amine (397, 399); 2-((4-(2-(7,8dimethyl-[1,2,4]Ίriazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)acetamide (398, 406); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)-N-methylacetamide (400, 403, 420, 422); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin5-yl)cyclohexyl)-N-methyloxetan-3-amine (401, 424, 430); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b] niridin-5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (408, 410); N-((1H-1,2,3-triazol-4-yl)methyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine6- yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexane-1-amine (412); 4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridine-5 -yl)-N-(oxazol-5-ylmethyl)cyclohexan-1-amine (413, 416); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-((5-methylpyrazin-2-yl)methyl)cyclohexane-1-amine (414415); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-3-isononyl-1H-n-pyrrolo[3,2-b]n-yridine- 5yl)-N-methyl-N-(nirimidin-2-ylmethyl)cyclohexan-1-amine (417, 418); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridine- 5-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (419); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(methyl)amino)-N-methylacetamide (420); N-cyclopropyl-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b] pyridin-5-yl)cyclohexane-1-amine (421, 426); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-(2-((trifluoromethyl)sulfonyl)ethyl)cyclohexane-1-amine (423); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-3-isononyl-1H-n-pyrrolo[3,2-b]n-yridine- 5yl)-N-methyl-N-(2-(methylsulfonyl)ethyl)cyclohexane-1-amine (425, 427); 3-(cyclopropyl(4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b ]niridin-5-yl)cyclohexyl)amino)propanenitrile (428, 433); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b]pyridine-5- yl)-N-(2-methoxyethyl)cyclohexane-1-amine (429, 431); 3-((4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b ]niridin-5-yl)cyclohexyl)amino)propanenitrile (433); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)azetidine-3-carbonitrile (434, 436); 6-(4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]niridin-6-yl)-3-isonronyl-1H-nirrolo[3,2-b] niridin-5-yl)cyclohexyl)-2-oxa6-azaspiro[3.3]heptane (435, 437); 6-((1r,4r)-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-6-yl)-3isopropyl-1H-pyrrolo[ 3,2-b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptan-2,2-dioxide (438); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5yl)cyclohexyl)-N-methylacetamide (439-440); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)(oxetan-3-yl)amino)acetonitrile (441); 4-(4(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b] niridin-5-yl)cyclohexyl)-1-methylpiperazin-2-one (442, 443); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)(oxetan-3-yl)amino)ethan-1-ol (444); 6-(3-isopropyl-5-(4-(3-(methylsulfonyl)azetidin-1-yl)cyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8dimethyl-[1, 2,4]triazolo[1,5-a]pyridine (445, 448); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-3-isonronyl-1H-n-pyrrolo[3,2-b] niridin-5-yl)cyclohexyl)amino)ethane-1-sulfonamide (446-447); 2((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]piridin-6-yl)-3-isopropyl-1H-pirrolo[3,2-b ]πiridin-5yl)cyclohexyl)(oxetan-3-yl)amino)-N-methylacetamide (449); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]niridin-6-yl)-3-isonronyl-1H-nirrolo[3,2-b]niridin-5- yl)-N-(2-(methylsulfonyl)ethyl)cyclohexane-1-amine (450, 452); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (451, 453); 4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)-N-(2-methyl-2-(methylsulfonyl)propyl)cyclohexane-1-amine (454, 455); 2-((cyanomethyl)(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-3-isopropyl-1H-πirrolo[3 ,2-b]piridin-5-yl)cyclohexyl)amino)-N,N-dimethylacetamide (456, 459); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1Н - 245 041852 pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)(2-(methylsulfonyl)ethyl)amino)acetonitrile (457, 458); 4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridine-5 -yl)-N-ethylN-(2-(methylsulfonyl)ethyl)cyclohexane-1-amine (460); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(2-(methylsulfonyl)ethyl)amino)ethan-1-ol (461); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)(ethyl)amino)-N,N-dimethylacetamide (462, 467); 2-((4-(2(7,8-dimethyl-[1,2,4]triαzolo[1,5-α]n-iridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2-b ]niridin-5-yl)cyclohexyl)(2-hydroxyethyl)amino)-N,N-dimethylacetamide (463, 468); 2-(((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2 -b]pyridin-5-yl)cyclohexyl)amino)methyl)tetrahydro-2H-thiopyran-1,1-dioxide (464); 3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)tetrahydrothiophene-1,1-dioxide (465); 4(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclohexane-1-amine (466-469); 3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)tetrahydrothiophene-1,1-dioxide (470); 2-(((4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)amino)methyl)tetrahydro-2H-thiopyran-1,1-dioxide (471); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclohexyl)-3-methyloxetan-3-amine (472-473); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (474, 477); 2-((4-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)((1-(methylsulfonyl)cyclopropyl)methyl)amino)acetonitrile (475, 478); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (476, 479); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-ethyl-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexane-1-amine (480); 2-((4-(2-(7,8-dimethyl-[ 1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-Spirrolo[3,2-b] pyridin-5-yl)cyclohexyl)((1-(methylsulfonyl)cyclopropyl)methyl)amino)ethan-1-ol (481, 482); (3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b ]pyridin-5-yl)cyclohexyl)amino)oxetan-3-yl)methanol (483, 484); Na(tert-butyl)-2-((4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo [3,2-b]pyridin-5-yl)cyclohexyl)amino)acetamide (485); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)-N-(2-methoxyethyl)-N-methylacetamide (486, 488); 2-((4(2-(7,8-dimethyl-[1,2,4]triαzolo[1,5-α]n-yridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2-b ]niridin-5-yl)cyclohexyl)amino)-N,2-dimethylpropanamide (487); N-(tert-butyl)-2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-3-isopropyl- 1H-pyrrolo[3,2-b]piridin-5-yl)cyclohexyl)amino)acetamide (489); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2- b]pyridin5-yl)cyclohexyl)amino)-1-morpholinoethan-1-one (490); 6-(3-isopropyl-5-(2-azaspiro[3.5]nonan-7-yl)1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2, 4]triazolo[1,5-a]pyridine (491); 6-(3-isopropyl-5-(2isopropyl-2-azaspiro[3.5]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1 ,2,4]triazolo[1,5a]pyridine (492-493); 1-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)-N,N-dimethylcyclopentan-1-carboxamide (494, 497); 2((4-(2-(7,8-dimethyl-[1,2,4]triαzolo[1,5-α]n-yridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2-b ]niridin-5yl)cyclohexyl)amino)-N,N,2-trimethylpropanamide (495); 2-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)amino)-2-methyl-1-morpholinopropan-1-one (496, 498); (3-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclohexyl)(2-methoxyethyl)amino)oxetan-3-yl)methanol (499, 500); 2((4-(2-(7,8-dimethyl-[1,2,4]triαzolo[1,5-α]n-iridin-6-yl)-3-isopropyl-1H-n-pyrrolo[3,2-b ]niridin-5yl)cyclohexyl)(methyl)amino)acetamide (501); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)3-isopropyl-6-methyl-1H-pyrrolo[3, 2-b]π-pyridin-5-yl)-cyclohexyl)-oxetan-3-amine (502-503); N-(4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-fluoro-3-isopropyl-1H-pyrrolo[3, 2-b]pyridin-5yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (504, 505); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl)-6-fluoro-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexane-1-amine (506, 507); 2((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-fluoro-3-isopropyl-1H-pyrrolo[3 ,2-b]pyridin5-yl)cyclohexyl)(ethyl)amino)-N,N-dimethylacetamide (508-509); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-6-fluoro-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)-N-ethyl-N-(2-(methylsulfonyl)ethyl)cyclohexane-1-amine (510, 511); 2-(2,6-dimethylpyridin-4-yl)-3-isopropyl-5-(piperidin-4-yl)1H-pyrrolo[3,2-b]pyridine (512); 5-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1methylpyridin-2(1H)-one (513); 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-2,4dimethylpyridazin-3(2H)-one (514); 5-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)1,3-dimethylpyridin-2(1H)-one (515); 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2yl)-8-methyl-[1,2,4]triazolo[1,5-a ]pyridine (516, 518); 6-(3-isopropyl-5-(piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methyltetrazolo[1,5-a]pyridine (517); 5-(3-isopropyl-5-(piperidin-4-yl)1 H-pyrrolo[3,2-b]pyridin-2-yl)- 1,3,4-trimethylpyridin-2(1 H)-one ( 519); 6-(3-isopropyl-5-(piperidine - 246 041852 4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (520); 6-(3-isopropyl-5(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1, 5-a]pyridine (521); 2(2,6-dimethylpyridin-4-yl)-3-isopropyl-6-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (522); 6-(3-isopropyl-6-methyl-5-(piperidin-4-yl)-III-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine (523); 6-(6-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy-[1,2,4]triazolo[1 ,5-a]pyridine (524); 6-(3-isopropyl-6-methyl-5-(piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1 ,5-a]pyridine (525); 2-(3,4-dimethoxyphenyl)-3isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (526); 5-(3-isopropyl-5-(1-(tetrahydro-2Hpyran-4-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridine -2(1H)-one (527); 5-(3isopropyl-5-(1-(oxetαn-3-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridine2(1 H) -on (528); 2-(4-(2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1 H-pyrrolo[3,2b]pyridin-5-yl)piperidine -1-yl)-N,N-dimethylacetamide (529); 2-(4-(2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl) piperidin-1-yl)-N-methylacetamide (530); 5(5-(1-(dimethylglycyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one (531); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b]pyridine-5 -yl)piperidin-1-yl)-N-methylacetamide (532); 2-(4-(3-isopropyl-2-(8-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)piperidin-1-yl)-N,N-dimethylacetamide (533); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methyl-[1,2, 4]triazolo[1,5-a]pyridine (534); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine (535); 2-(4-(3-isopropyl-2-(8methoxy-[1,2,4]triαzolo[1,5-α]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5 -yl)piperidin-1-yl)-N-methylacetamide (536); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine-5 -yl)piperidin-1-yl)-N,N-dimethylacetamide (537); 6-(3-isopropyl-5-(1-(oxetan-3yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1, 2,4]triazolo[1,5-a]pyridine (538); 2-(4-(2-(7,8-dimethyl-[1,2,4]triαzolo[1,5-α]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5yl)piperidin-1-yl)-N-methylacetamide (539); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1-yl)-N,N-dimethylacetamide (540); 1-(4-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1 yl)-2-methylpropan-2-ol (541); 5-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[3,2b]pyridin-2-yl)-1,3,4-trimethylpyridin-2 (1H)-one (542); 5-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3,4 -trimethylpyridin-2(1 H)-one (543); 2-(4-(3isopropyl-2-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) piperidin-1-yl)-N-methylacetamide (544); 2-(4-(3-isopropyl-2-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) piperidin-1-yl)-N,N-dimethylacetamide (545); 5-(5-(1-(2-Hydroxy-2methylpropyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3,4-trimethylpyridine2 (1H)-one (546); 1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine-5 -yl)piperidin-1-yl)-2-methylpropan-2-ol (547); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1-yl)-2-methylpropan-2-ol (548); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3 ,2b]pyridin-5-yl)piperidin-1-yl)ethan-1-one (549-550); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one (551); 6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1 ,2,4]triazolo[1,5-a]pyridine (552); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)piperidin-1-yl)acetonitrile (553); 6-(3-isopropyl-5-(1-(2(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1, 2,4]triazolo[1,5a]pyridine (554); 6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[3,2b]pyridin-2-yl)-7,8-dimethyl-[1 ,2,4]triαzolo[1,5-α]pyridine (556); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)piperidin-1-yl)acetonitrile (557); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triαzolo[1,5-α]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5yl)piperidin-1-yl)acetamide (558); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridine- 5-yl)piperidin-1-yl)acetamide (559); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)piperidin-1-yl)acetamide (560); 3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1-yl)-1-methylpyrrolidin-2-one (561); 3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)piperidin-1-yl)-1-methylpyrrolidin-2-one (562); 3-(4-(2(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)piperidin-1-yl)-1-methylpyrrolidin-2-one (563); 3-chloro-5-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1 ,4-dimethylpyridin-2(1H)-one (564); 2-(4-(2-(5chloro-1,4-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)piperidin-1-yl)-N-methylacetamide (565); 3-chloro-5-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-1,4-dimethylpyridine -2(1H)-one (566); 2-(4-(2-(5-chloro-1,4-dimethyl-6-oxo1,6-dihydropyridin-3-yl)-3-isopropyl-1 H-pyrrolo[3,2-b]pyridine-5 -yl)piperidine-1 -πλ)-N,N-dimethyl - 247 041852 acetamide (567); 3-chloro-5-(3-isoiroyyl-5-(1-iroyyliieridin-4-yl)-1H-yrrolo[3,2-b]iiridin-2-yl)1,4-dimethylpyridin-2(1H)- he (568); 3-chloro-5-(5-(1-isobutyliieridin-4-yl)-3-isoiroyl-1H-uyrrolo[3,2-b]pyridin-2-yl)-1,4-dimethylpyridin-2(1H) -on (569); 3-chloro-5-(5-(1-(dimethylglycyl)piperidin4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,4-dimethylpyridin-2(III )-one (570); 3-chloro-5-(5-(1(2-hydroxy-2-methylpropyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-1, 4-dimethylpyridin-2(1H)-one (571); 1-(4-(3-isoiroyl-6-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]iiridin-6-yl)1H-pyrrolo[3,2- b]pyridin-5-yl)piperidin-1-yl)-2-methylpropan-2-ol (572); 6-(6-Fluoro-3-isoiroyyl-5-(1(2-(methylsulfonyl)ethyl)iiieridin-4-yl)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy -[1,2,4]triazolo[1,5-a]pyridine (573); 6-(6-Fluoro-3-isoiroyyl-5-(1-(oxetan-3-yl)iiieridin-4-yl)-1H-iyrrolo[3,2b]pyridin-2-yl)-8-methoxy-[ 1,2,4]triazolo[1,5-a]pyridine (574); 6-(3-isoiroyyl-6-methyl-5-(1-(tetrahydro-2H-iiran-4-yl)iieridin-4-yl)-1H-iyrrolo[3,2-b]iiridin-2-yl) -8-methyl-[1,2,4]triazolo[1,5-a]iiridine (575); 2-(dimethylamino)-1-(4-(3-isoiroyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-6methyl-1H-pyrrolo [3,2-b]pyridin-5-yl)piperidin-1-yl)ethan-1-one (576); 2-(dimethylamino)-1-(4-(6-fluoro3-isoirooiyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1H-iyrrolo [3,2-b]iiridin-5-yl)iiieridin-1-yl)ethan-1-one (577); 6-(3-isopropyl-6-methyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1 H-pyrrolo[3,2-b]pyridin-2-yl)-8- methyl-[1,2,4]triazolo[1,5-a]pyridine (578); 6-(3-isoiroyl-6-methyl-5-(1(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy- [1,2,4]triazolo[1,5-a]pyridine (579); 2-(4-(6-fluoro-3-isoiroyl-2-(8-methyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1H-iyrrolo[3,2b ]iiridin-5-yl)iieridin-1-yl)-N,N-dimethylacetamide (580); 2-(4-(3-isoiroyl-6-methyl-2-(8-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (581); 6-(6-fluoro-3-isopropyl-5 -(1 -(2-(methylsulfonyl)ethyl)iiieridin-4-yl)-1H-iyrrolo[3,2b]pyridin-2-yl)-8-methyl- [1,2,4]triazolo[1,5-a]pyridine (582); 2-(4-(6-fluoro-3-isoiroyl-2-(8-methoxy[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1H-iyrrolo[3,2- b]iiridin-5-yl)iiieridin-1-yl)-N,N-dimethylacetamide (583); 2-(4-(3-isoiroyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-6-methyl-1Hpyrrolo[3,2-b ]pyridin-5-yl)piperidin-1-rn)-N,N-dimethylacetamide (584); 2-(dimethylamino)-1-(4-(6fluoro-3-isoirooiyl-2-(8-methyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1H-iyrrolo [3,2-b]iiridin-5-yl)iperidin-1-yl)ethan-1-one (585); 2-(dimethylamino)-1 -(4-(3-isopropyl-6-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1H -iyrrolo[3,2-b]iiridin-5-yl)iiieridin-1-yl)ethan-1-one (586); 1-(4-(3isoiroyyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]iiridin-6-yl)-6-methyl-1H-iyrrolo[3,2-b ]iiridin-5yl)iiieridin-1-yl)-2-methyliroan-2-ol (587); 6-(6-Fluoro-3-isoiroyyl-5-(1-(oxetan-3-yl)iiieridin-4yl)-1H-uirrolo[3,2-b]iiridin-2-yl)-8-methyl-[ 1,2,4]triazolo[1,5-a]iiridine (588); 6-(3-isopropyl-6methyl-5-(1-(tetrahydro-2H-iiran-4-yl)iieridin-4-yl)-1H-irrolo[3,2-b]iiridin-2-yl)-8 -methoxy[1,2,4]triazolo[1,5-a]pyridine (589); 6-(3-isoiroyyl-5-((1-methyliiyeridin-4-yl)methoxy)-1H-iyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (590); 6-(3-isopropyl-5-((1-(tetrahydro-2H-iiran-4-yl)iieridin-4-yl)methoxy)-1H-irrolo[3,2-b]iiridin-2-yl)- 8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (591); 6-(3-isoiroyyl-5-((1-isoiroylazetidin-3-yl)methoxy)-1H-yrrolo[3,2b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]pyridine (592); 6-(3-isoirooiyl-5-((1-iroiiyiieridin4-yl)oxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (593); 6-(3isoiroyyl-5-((1-methyliiyeridin-4-yl)oxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methyl-[1,2,4]triazolo[ 1,5-a]pyridine (594); 6-(3-isoiroyl-5-((1-(tetrahydro-2H-iiran-4-yl)azetidin-3-yl)oxy)-1Huyrrolo[3,2-b]iiridin-2-yl)-8- methoxy-[1,2,4]triazolo[1,5-a]iiridine (595); 6-(3-isopropyl-5-((1methylazetidin-3-yl)oxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (596); 1-(4-(((3-isoiroyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]iiridin-6-yl)-1H-irrolo[3,2-b ]iiridin5-yl)oxy)methyl)piperidin-1-yl)-2-methylpropan-2-ol (597); 6-(3-isopropyl-5-((1-isopropylpiperidin4-yl)methoxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (598); 1-(3-(((3isoiroyyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]iiridin-6-yl)-1H-iyrrolo[3,2-b]iiridine -5-yl)oxy)methyl)azetidin-1-yl)-2-methylpropan-2-ol (599); 6-(3-isopropyl-5-((1-methylpiperidin-4-yl)oxy)-1Hiyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (600); 6-(3-isopropyl-5-methoxy1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]iiridine (601); 2-(4-(((3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-a]iiridin-6-yl)-1H-irrolo[3,2-b] iiridin-5-yl)oxy)methyl)iiieridin1-yl)-N,N-dimethylacetamide (602); 6-(3-isopropyl-5-((1-isoirooiyiieridin-4-yl)oxy)-1H-iyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (603); 6-(3-isopropyl-5-((1-(2(methylsulfonyl)ethyl)iieridin-4-yl)methoxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy- [1,2,4]triazolo[1,5-a]pyridine (604); 4-((3-isoiroyyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]iiridin-6-yl)-1Hiyrrolo[3,2-b]iiridin-5-yl )oxy)-N,N-diiroylcyclohexane-1-amine (605, 611); 6-(3-isopropyl-5-((1iroyyliieridin-4-yl)methoxy)-1H-iyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (606); 6-(3-isoiroyl-5-((1-(tetrahydro-2H-iiran-4-yl)iieridin-4-yl)oxy)-1H-iyrrolo[3,2b]iiridin-2-yl)-8- methoxy-[1,2,4]triazolo[1,5-a]iiridine (607); 6-(3-isoiroyl-5-((1-methylazetidin-3yl)methoxy)-1H-uyrrolo[3,2-b]iiridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]iiridine (608); 2-(4-((3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)oxy)pyeridin-1-yl)-N,N-dimethylacetamide (609); 4-((3-isoiroyyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]iiridin6-yl)-1H-iyrrolo[3,2-b]iiridin-5-yl )oxy)-N,N-dimethylcyclohexane-1-amine (610); 6-(3-isopropyl-5-248 041852 ((1-isopropylazetidin-3-yl)oxy)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2, 4]triazolo[1,5-a]pyridine (612); 1-(4-((3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridine- 5-yl)oxy)piperidin-1-yl)-2-methylpropan-2-ol (613); N-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclobutyl)-2-(dimethylamino)N-methylacetamide (615); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5- yl)-N-((3-methyloxetan-3-yl)methyl)cyclobutan-1-amine (616); 3-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-а]niridin-6-yl)-3-isononyl-1H-nirrolo[3,2-b]niridine-5 -yl)cyclobutan-1-amine (617); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5yl)-N,N-dimethylcyclobutan-1-amine (618-623); 2-(dimethylamino)-N-(3-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)cyclobutyl)acetamide (619, 638); 3(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )cyclobutan-1-amine (620); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2b]pyridine-5- yl)-N-methyl-N-(2-(methylsulfonyl)ethyl)cyclobutan-1-amine (621, 636); 2-((3-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]piridin-6-yl)-3-isopropyl-1H-pirrolo[3,2-b] pyridin-5-yl)cyclobutyl)(methyl)amino)-N,N-dimethylacetamide (622); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isonronyl-1H-nirrolo[3,2-b]niridin-5- yl)-N-(2-(methylsulfonyl)ethyl)cyclobutan-1-amine (624); 2(dimethylamino)-N-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-1H-πirrolo[3, 2b]niridin-5-yl)cyclobutyl)-N-methylacetamide (625, 630); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-methyl-N-((3-methyloxetan-3-yl)methyl)cyclobutan-1-amine (626); 2-((3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b]pyridine- 5-yl)cyclobutyl)(methyl)amino)-N,N-dimethylacetamide (627); 2-((3-(3-isopropyl2-(8-methoxy-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-1H-πirrolo[3,2-b]πiridine- 5-yl)cyclobutyl)amino)N-methylacetamide (628); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]niridin-5- yl)-N,N-dimethylcyclobutan-1-amine (629, 639); 2-((3-(2-(7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin-5-yl)cyclobutyl)amino)-Nmethylacetamide (631); N-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclobutyl)tetrahydro-2H-pyran-4-amine (632); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-N,N-bis((3-methyloxetan-3yl)methyl)cyclobutan-1-amine (633); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridin-5-yl )-N-(2-(methylsulfonyl)ethyl)cyclobutan-1-amine (634); N-(3-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclobutyl)tetrahydro-2H-pyran-4-amine (635); 3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-N-((3-methyloxetan-3-yl)methyl)cyclobutan-1-amine (637); 3(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]piridin-6-yl)-1H-pyrrolo[3,2-b]piridin-5-yl )-N-methyl-N-(2-(methylsulfonyl)ethyl)cyclobutan-1-amine (640, 642); 1-((3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5а]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b] pyridin-5-yl)cyclobutyl)(methyl)amino)-2-methylpropan-2-ol (641); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridin-5-yl) -N-methyl-N-((3-methyloxetan-3-yl)methyl)cyclobutan-1-amine (643); N-(3-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-а]πiridin-6-yl)-3-isopropyl-1H-πirrolo[3,2-b]πiridine -5-yl)cyclobutyl)2-(dimethylamino)acetamide (644); 2-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)1H-pyrrolo[3,2-b]pyridine- 5-yl)azetidin-1-yl)acetamide (645); 2-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine -5-yl)azetidin-1-yl)acetamide (646); 6-(3isopropyl-5-(1-(2-(methylsulfonyl)ethyl)azetidin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy[1,2, 4]triazolo[1,5-a]pyridine (647, 653); 6-(5-(azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2yl)-8-methoxy-[1,2,4]triazolo[1,5-a ]pyridine (648); 6-(5-(azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2b]piridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5 -a]piridine (649); 1-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-6-yl)-3-isonronyl-1H-n-pyrrolo[3,2-b ]niridin-5-yl)azetidin-1-yl)-2-(dimethylamino)ethan-1-one (650); 6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)azetidin-3-yl)-3-isopropyl-III-pyrrolo[3,2b]pyridin-2-yl )-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (651); 2-(dimethylamino)-1-(3-(3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)azetidin-1-yl)ethan-1-one (652); 1-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b ]pyridin5-yl)azetidin-1-yl)-2-methylpropan-2-ol (654); 6-(3-isopropyl-5-(1-isopropylazetidin-3-yl)-1Hpyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5 -a]pyridine (655); 6-(3-isopropyl-5-(1isopropylazetidin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1 ,5-a]pyridine (656); 1-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]piridin-6-yl)-1H-pirrolo[3,2-b]piridine -5yl)azetidin-1-yl)-2-methylpropan-2-ol (657); 2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-4-isopropylmorpholine (658); 2-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )-4-(tetrahydro-2H-pyran-4-yl)morpholine (659); 4-isopropyl-2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)morpholine (660); 2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6yl)-1H-pyrrolo[3,2-b]pyridin-5-yl) -4-methylmorpholine (661); 2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl) morpholine (662); 1-(2-(2-(7,8-dimethyl- 249 041852 [1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-III-pyrrolo[3,2-b]pyridin-5-yl)morpholino)-2-(dimethylamino) ethane-1-one (663); 2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1Hpyrrolo[3,2-b]pyridine-5- yl)-4-(tetrahydro-2H-pyran-4-yl)morpholine (664); 5-(3-isopropyl-5-(4-methylmorfolin-2-yl)-1H-pyPROlo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one ( 665); 2-(3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )morpholine (666, 671, 676); 5-(3-isopropyl-5-(4-(oxetan-3-yl)morpholin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2 (1H)-one (667); 2-(dimethylamino)-1-(2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5а]pyridin-6-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)morpholino)ethan-1-one (668); 5-(3-isopropyl-5-(morpholin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one (669, 675 , 679); 2-(2-(2-(1,5dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)morpholino) acetonitrile (670); 3-(dimethylamino)-1-(2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin6-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)morpholino)propan-1-one (672); 2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine- 5-yl)-4-methylmorpholine (673); 2-(2-(7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-5- yl)-4-(2-(methylsulfonyl)ethyl)morpholine (674); 5-(5-(4-(dimethylglycyl)morpholin-2-yl)-3-isopropyl-1Н-pyrrolo[3,2b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one ( 677); 5-(3-isopropyl-5-(4-isopropylmorpholin-2-yl)1 H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1 H)-one ( 678); 6-(3-isopropyl-5-(piperazin-2yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5 -a]pyridine (680); 6-(3-isopropyl-5(2-(piperidin-1-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo [1,5-a]pyridine (681); 6-(3-isopropyl-5-(2-(piperidin-1-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (682); 2-(3-(2-(3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl )ethyl)azetidin-1-yl)-N,N-dimethylacetamide (683); 3-isopropyl-2-(1-methyl1 H-pyrrolo[2,3-b]pyridin-3-yl)-5-(2-(1-(2-(methylsulfonyl)ethyl)azetidin-3-yl)ethyl )-1 H-pyrrolo[3,2b]pyridine (684); 1-(3-(2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3, 2-b]pyridin-5-yl)ethyl)azetidin-1-yl)-2-(dimethylamino)ethan-1-one (685); 6-(3-isopropyl-5-(2-(1(oxetan-3-yl)azetidin-3-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7.8 -dimethyl-[1,2,4]triazolo[1,5a]pyridine (686, 687); 6-(5-(2-(1-((1H-1,2,3-triazol-4-yl)methyl)azetidin-3-yl)ethyl)-3-isopropyl-1Hpyrrolo[3,2-b] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (688); 2-(3-(2-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-а]n-iridin-6-yl)-1H-n-pyrrolo[3,2-b] niridin-5-yl)ethyl)azetidin-1-yl)-N,N-dimethylacetamide (689); 5-(2-(azetidin-3-yl)ethyl)-3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3yl)-1H-pyrrolo[3,2-b ]pyridine (690); 3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-(2-(1((3-methyloxetan-3-yl)methyl)azetidine-3 -yl)ethyl)-1H-pyrrolo[3,2-b]pyridine (691); 6-(5-(2-(azetidin-3 yl)ethyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4 ]triazolo[1,5-a]pyridine (692); 1-(3-(2-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2- b]pyridin-5yl)ethyl)azetidin-1-yl)-2-methylpropan-2-ol (693); 3-isopropyl-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3yl)-5-(2-(1-(oxetan-3-yl)azetidin-3-yl)ethyl)- 1H-pyrrolo[3,2-b]pyridine (694); 6-(3-isopropyl-5-(2-(1(2-(methylsulfonyl)ethyl)azetidin-3-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7, 8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (695); 2-(3-(2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1Hπpyrrolo[3,2- b] π-pyridin-5-yl)-ethyl)-azetidin-1-yl)-N,N-dimethylacetamide (696); 6-(5-(2-(azetidin-3yl)ethyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[ 1,5-a]pyridine (697); 6(3-isopropyl-5-(2-(1-(2-(methylsulfonyl)ethyl)azetidin-3-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8methoxy- [1,2,4]triazolo[1,5-a]pyridine (698); 2-(dimethylamino)-1-(3-(2-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)ethyl)azetidin-1-yl)ethan-1-one (699); 6-(3-isopropyl-5-(2-(1-(oxetan-3-yl)azetidin-3-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8- methoxy[1,2,4]triazolo[1,5-a]pyridine (700); 1-(3-(2-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3isopropyl-1H-pyrrolo[3,2- b]pyridin-5-yl)ethyl)azetidin-1-yl)-2-methylpropan-2-ol (701); 6-(3isopropyl-5-(2-(1-((3-methyloxetan-3-yl)methyl)azetidin-3-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl) 7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (702); 2-(dimethylamino)-1-(3-(2-(3-isopropyl-2-(1-methyl-1Hpyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b ]pyridin-5-yl)ethyl)azetidin-1-yl)ethan-1-one (703); 5-(2(1-((1H-1,2,3-triazol-4-yl)methyl)azetidin-3-yl)ethyl)-3-isopropyl-2-(1-methyl-1H-pyrrolo[2 ,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridine (704); 6-(5-(2-(1-((1H-1,2,3-triazol-4-yl)methyl)azetidin-3yl)ethyl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (705); 6-(3-isopropyl-5-(2-(1-((3-methyloxetan-3-yl)methyl)azetidin-3-yl)ethyl)-1 H-pyrrolo[3,2-b]pyridin-2yl )-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (706); R-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclopentyl)tetrahydro-2H-pyran-4-amine (707, 710, 721, 727); 2,2'-((3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b ]pyridin-5-yl)cyclopentyl)azandiyl)diacetamide (708, 720); 3-(3-isopropyl-2-(8-methoxy[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl )-N-(2-(methylsulfonyl)ethyl)cyclopentan-1-amine (709); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl) -N-((3-methyloxetan-3-yl)methyl)cyclopentan-1-amine (711, 718, 728); 2(dimethylamino)-N-(3-(3-isonronyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]niridin-6-yl)-1H-npyrrolo[3, 2b]pyridin-5-yl)cyclopentyl)acetamide (712); 2,2'-((3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5 - 250 041852 a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentyl)azandiyl)diacetonitrile (713, 730); N-(3(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-III-pyrrolo[3,2-b]pyridine- 5-yl)cyclopentyl)-1-methylpiperidine-4-carboxamide (714); N-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclopentyl)oxetan-3-amine (715); 2-((3-(3-isopropyl2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclopentyl)amino)acetonitrile (716); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2b]pyridin-5-yl) -N,N-bis(2-(methylsulfonyl)ethyl)cyclopentan-1-amine (717, 726); 2-((3-(3-isopropyl-2(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine -5-yl)cyclopentyl)amino)-Nmethylacetamide (719, 725); 2,2'-((3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1Hpyrrolo[3,2-b ]pyridin-5-yl)cyclopentyl)azandiyl)bis(N,N-dimethylacetamide) (722); N-isopropyl-3-(3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine- 5-yl)cyclopentan-1-amine (723); N-(1-cyclopropylethyl)-3-(3-isopropyl-2-(8-methoxy-[1.2.4]triazolo[1.5а]pyridin-6-yl)-1H-pyrrolo[3.2- b]pyridin-5-yl)cyclopentan-1-amine (724); N-(3-(3-isopropyl-2-(8methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)cyclopentyl)-2,2-dimethyltetrahydro-2H-pyran-4-amine (729); 3-isopropyl-N-(1-isopropylpiperidin-4-yl)-2-(8-methoxy[1.2.4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H- pyrrolo[3,2-b]pyridine-5-carboxamide (731); N-(2(dimethylamino)ethyl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N,6-dimethyl-1Hpyrrolo [3,2-b]pyridine-5-carboxamide (732); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5а]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b ]pyridine-5-carbonyl)piperazin-1-yl)ethan-1-one (733); 3isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-N,6-dimethyl-N-(3,3,3-trifluoropropyl)-1Hpyrrolo [3,2-b]pyridine-5-carboxamide (734); 6-(3-isopropyl-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[ 1,2,4]triazolo[1,5-a]pyridine (735); 4-(2-(4-(3-isopropyl-2-(8methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-III-pyrrolo[3,2-b] pyridin-5-yl)-III-pyrazol-1-yl)ethyl)morpholine (736); (2S,5R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl}-3-(iroan-2-yl)- 1Hpyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazine (737); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1yl]-2-(pyrrolidin-1-yl)ethan-1-one (738); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(pyrrolidin-1yl)propan-1-one (739); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl}-3-(iroan-2-yl)-1Hpyrrolo[3,2- b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane (740); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-6-methyl-2,6-diazaspiro[3.3]heptane (741); 2-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]iiridin-6-yl}-3-(iroan-2-yl)-1H-iyrrolo [3,2-b]iiridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-N,N-dimethylacetamide (742); 1-[6-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-(dimethylamino)ethan-1-one (743); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]iiridin-6yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-6-ethyl-2,6-diazaspiro[3.3]heptane (744); 6-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-2-azaspiro[3.3]heptane (745); 1-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)-2-azaspiro[3.3]heptan-2-yl]-3-(dimethylamino)propan-1-one (746); 1[(1R,5S)-8-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-2-(dimethylamino)ethan-1-one (747); (1R,5S)-8-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-3-(2-methanesulfonylethyl)-3,8-diazabicyclo[3.2.1]octane (748); 3-[(1R,5S)-8-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3yl]propanamide (749); 1-[(1R,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl}-3-(iroan-2- yl) 1H-pyrrolo[3,2-b]pyridin-5-yl)-3,9-diazabicyclo[3.3.1]nonan-9-yl]-2-(dimethylamino)ethan-1-one (750); (1R,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-9-(2-methanesulfonylethyl)-3,9-diazabicyclo[3.3.1]nonane (751); l-[(3S,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (752); 3-[(3S,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazin-1-yl]propanamide (753); l-[(1R,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-2-(dimethylamino)ethan-1-one (754); (lR,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-6-(propan-2-yl)-3,6-diazabicyclo[3.1.1]heptane (755); 3-[(1R,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]propanamide (756); (3S,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl}-3-(iroan-2yl)-1Н- pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazine (757); 3-[(2S,6S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]propanamide (758); 2-[(2S,6S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]iiridin-6-yl}-3(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]acetamide (759); 1-[(2S,6S)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl) - 251 041852 2,6-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (760); 1-[(28.68)-4-(2-{7,8-dimethyl-[1.2.4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1yl]-3-(dimethylamino)propan-1-one (761); 2-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]acetamide (762); 3-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]propanamide (763); (1R,4R)-2-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-5-(2methanesulfonylethyl)-2,5-diazabicyclo[2.2.1]heptane (764); (1R,4R)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-5-(3-methanesulfonylpropyl)-2,5-diazabicyclo[2.2.1]heptane (765); 2-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]acetonitrile (766); 3-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-N,N-dimethylpropanamide (767); (1R,4R)-2(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane (768); (1R,4R)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1Н- pyrrolo[3,2-b]pyridin-5-yl)-5-(oxan-4-yl)-2,5-diazabicyclo[2.2.1]heptane (769); 4-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1λ ⁶ -thian-1,1-dione (770); (1R,4R)2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5yl)-5-(oxolan-3-yl)-2,5-diazabicyclo[2.2.1]heptane (771); 1-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-(dimethylamino)ethan-1-one (772) ; l-[(1R,4R)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-(dimethylamino)propan-1-one (773); 2-[(18.48)-5-(2-{7,8-dimethyl-[1.2.4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]acetamide (774); 3-[(18,48)-5-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5diazabicyclo[2.2.1]heptan-2-yl]propanamide (775); 3-[(18.48)-5-(2-{7,8-dimethyl-[1.2.4]triazolo[1.5а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]N,N-dimethylpropanamide (776); (18.48)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-5-(2-methanesulfonylethyl)-2,5-diazabicyclo[2.2.1]heptane (777); (18.48)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2b]pyridin-5-yl)-5-(3-methanesulfonylpropyl)-2,5-diazabicyclo[2.2.1]heptane (778); (18.48)-2-(2-{7,8dimethyl-[1.2.4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane (779); (18.48)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-5-(oxan-4-yl)-2,5-diazabicyclo[2.2.1]heptane (780); 4-[(18.48)-5-(2-{7,8-dimethyl-[1.2.4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1λ ⁶ -thian-1,1-dione (781); (18.48)-2-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)-5-(oxolan-3-yl)2,5-diazabicyclo[2.2.1]heptane (782); (18.48)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-5-(propan-2-yl)-2,5-diazabicyclo[2.2.1]heptane (783); 1[(18,48)-5-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-(dimethylamino)ethan-1-one (784); l-[(18,48)-5-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-(dimethylamino)propan-1-one (785); (1R,4R)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-5-(propan-2-yl)-2,5-diazabicyclo[2.2.1]heptane (786); (18.48)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-5-[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]-2,5-diazabicyclo[2.2.1] heptane (787); 1-[(28.58)-4-(2-{7,8-dimethyl-[1.2.4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl) 1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (788); 1[(28.58)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (789); 1-[(28)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (790); 3-[(28)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]propanamide (791); (28)4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5yl)-2-methyl-1-(propan-2-yl)piperazine (792); (28.58)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethyl-4-(propan-2-yl)piperazine (793); 3[(28.58)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]propanamide (794); (28.58)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-4-(3-methanesulfonylpropyl)-2,5-dimethylpiperazine (795); 1-[(2R,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2 - 252 041852 yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (796); 1[(2R,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (797); 3-[(2R,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]propanamide (798); 2-[(2R,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]acetamide (799); 1-[(3S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3methylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (801); 1-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-III -pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-methylpropan-2-ol (802); 2-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1Hpyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-N,N-dimethylacetamide (803); 3-[(3S)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]propanamide (804); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)-4-(3-methanesulfonylpropyl)-2-methylpiperazine (805); (2R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin5-yl)-4-(3-methanesulfonylpropyl)-2-methylpiperazine (806); 3-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2-yl) -1H-nirrolo[3,2-b]niridin-5-yl)-3-methylninerazin-1-yl]propanamide (807); 1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1Hpyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (808); 2-[(3S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(nponan-2-yl)- 1H-n-pyrrolo[3,2-b]n-pyridin-5-yl)-3methylpiperazin-1-yl]acetamide (809); 2-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]acetonitrile (810); 1-[(3S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3methylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (811); 2-[(3 S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2-yl )-1H-nirrolo[3,2-b]niridin-5-yl)-3-methylninerazin-1-yl]-N-methylacetamide (812); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[ 3,2-b]pyridin-5-yl)-2-methyl-4-(oxetan-3-yl)piperazine (813); (2S)-1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)-2-methyl-4-(oxolan-3-yl)piperazine (814); 4-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-1λ ⁶ -thian-1,1-dione (815); (2S)-1-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2-methyl4-(propan-2-yl)piperazine (816); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(pronan2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-4-(2-methanesulfonylethyl)-2-methylpiperazine (817); 3-[(3S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(nponan-2-yl)- 1H-n-pyrrolo[3,2-b]n-pyridin-5-yl)-3methylpiperazin-1-yl]-N-methylpropanamide (818); 3-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-N,N-dimethylpropanamide (819); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[ 3,2-b]pyridin-5-yl)-2-methyl-4-(oxan-4-yl)piperazine (820); (2S,6S)-1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazine (821); (3R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[ 3,2-b]pyridin-5-yl)-3-methylpiperazine (822); 1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl} -3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (823); 2-(azetidin-1-yl)-1-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-6yl}-3 -(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (824); 1-[(3S)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)3-methylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (825); 2-(cyclopropylamino)-1-[(3S)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan- 2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (826); 1-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-[(propan-2-yl)amino]ethan-1one (827); 1-(2-{7,8-dimethyl-[1,2,4]triazolo[l,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2b]pyridin-5-yl)-4-(1-methylazetidine-3-carbonyl)piperazine (828); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-2-methyl-4-(1-methylazetidine3-carbonyl)piperazine (829); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(methylamino)ethan-1-one (830); 2-[di( ² H ₃ )methylamino]1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3- (propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5yl)piperazin-1-yl]ethan-1-one (831); 2-amino-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (832); (2R)-1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)-2-methyl-4-(propan-2-yl)piperazine (833); 2-(azetidin-1-yl)-1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-6yl}-3 -(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (834); 1-[(3R)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)3-methylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (835); 2-(cyclopropylamino)-1-[(3R)-4-(2-{7.8 - 253 041852 dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridine-5 -yl)-3-methylpiperazin-1-yl]ethan-1-one (836); 1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3(propan-2-yl)- (837); 2-[di( ² H3)methylamino]-1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl }-3(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (838); 1-[(2S,5R)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (839); 1-[(2S,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1yl]-3-(dimethylamino)propan-1-one (840); (2R,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethyl-4-(propan-2-yl)piperazine (841); 1[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (842); 1-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (843); (2S,5R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-III- pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethyl-4-(propan-2-yl)piperazine (844); (2R,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1Hpyrrolo[3,2-b]pyridin-5-yl)-4-(3-methanesulfonylpropyl)-2,5-dimethylpiperazine (845); (2S,5R)-1-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-4(3-methanesulfonylpropyl)-2,5-dimethylpiperazine (846); 3-[(2S,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1yl]propanamide (847); 3-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]propanamide (848); 1-[(2R)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (849); 1-[(2R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-III -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (850); (2R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]nuridin-6-ul}-3-(pronan-2-yl)1H-pyrrolo [3,2-b]pyridin-5-yl)-2-methyl-1-(propan-2-yl)piperazine (851); 3-[(2R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- N-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]propanamide (852); (2S)-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(nponan-2yl)-1Н -pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(dimethylamino)propan-1-one (853); 1-[4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)piperazine-1-carbonyl-K,K-dimethylcyclopropan-1-amine (854); (2R)-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(dimethylamino)propan-1-one (855); (2R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[ 3,2-b]pyridin-5-yl)-1-(3-methanesulfonylpropyl)-2-methylpiperazine (856); 1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)(2,2,3,3,5,5,6,6 ² H8)piperazine (857); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)(2,2,3,3,5,5,6,6-2H8)piperazin-1-yl]-2-(dimethylamino)ethan-1 ^- one (858 ); 2[di( ² H3)methylamino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-( propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)(2,2,3,3,5,5,6,6-2 ^H ₈ )piperazin-1-yl] ethane-1-one (859); 1-[(2R,6S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (860); (2R,6R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazine (861); 1[(2R,6S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (862); 1-[(3R,5R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (863); 1-[(3R,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (864); (2R,6R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethyl-4-(propan-2-yl)piperazine (865); 2-[(3R,5R)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]niridine-6-ul}-3-(nronan-2-ul) -1H-nurrolo[3,2-b]nuridin-5-ul)-3,5dimethylpiperazin-1-yl]acetamide (866); 2-[(2R,6S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]acetamide (867); (2R,6S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-1-(3-methanesulfonylpropyl)-2,6-dimethylpiperazine (868); (2R,6R)-1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-4-(3-methanesulfonylpropyl)-2,6-dimethylpiperazine (869); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2-[ethyl(methyl)amino]ethan-1-one (870); 2(diethylamino)-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (871); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)piperazin-1-yl]-2-[methyl(propan-2-yl)amino]ethan-1-one (872); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H - 254 041852 pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]-2-[methyl(propyl)amino]ethan-1-one (873); 2-[butyl(methyl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-( propan-2-yl)-1H-pyrrolo[3,2b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (874); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6yl}-3-(propan-2-yl)-III-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-[methyl(2-methylpropyl)amino]ethan-1-one (875); 2-[butyl(ethyl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propane -2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (876); 2-(tert-Butylamino)-1[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2 -yl)-III-pyrrolo[3,2-b]pyridin-5yl)piperazin-1-yl]ethan-1-one (877); 2-[tert-butyl(methyl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-( propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (878); 1-[4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[ 3,2-b]pyridin-5yl)piperazin-1-yl]-2-[ethyl(propan-2-yl)amino]ethan-1-one (879); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-[(2-methylpropyl)(propan-2-yl)amino]ethan-1-one (880); 2-[bis(2-methylpropyl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3 -(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (881); 2-[Butyl(propan-2-yl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl} -3-(propan2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (882); 2-[bis(propan-2-yl)amino]-1-[4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}- 3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5yl)piperazin-1-yl]ethan-1-one (883); (3R,5R)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazine (884); 1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (885); 1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl) -III-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-3-(dimethylamino)propan-1-one (886); 1-[(2S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-(dimethylamino)ethan-1-one (887); 2[di( ^2H3 )methylamino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-( propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]( ² H2)ethan-1-one (888); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-(dimethylamino)( ^2H2 )ethan-1-one (889); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)(2,2,3,3,5,5,6,6-2H8)piperazin-1-yl] ^-2- (dimethylamino)( ^2H2 )ethan-1 -one (890); 2-[di( ^2H3 )methylamino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3- (propan-2-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)(2,2,3,3,5,5,6,6-2 ^H8 )piperazin-1-yl]( ² H ₂ )ethan-1-one (891); 3-(azetidin-1-yl)1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl }-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]propan-1-one (892); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2[ethyl(methyl)amino]ethan-1-one (893); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-[methyl(propyl)amino]ethan-1-one (894); 2-(diethylamino)-1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3 (propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]ethan-1-one (895); 1-[(2R,5S)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)2,5-dimethylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethan- 1-one (896); 1-[(2S)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-[ethyl(methyl)amino]ethan-1-one (897); 2-(diethylamino)-1-[(2S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propane -2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]ethan-1-one (898); 1-[(2S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2-yl) 1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (899); 1-[(2S)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)2-methylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethan-1-one ( 900); 1-[(3S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1Н-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethan-1-one (901); 2-(diethylamino)-1-[(3S)-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan- 2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (902); 2-[bis(propan-2-yl)amino]-1-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine -6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1one (903); 2-[tert-Butyl(methyl)amino]-1-[(2S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridine-6- yl}-3(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]ethan-1-one (904); 2-[tert-Butyl(methyl)amino]-1-[(3S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine-6 -yl}-3-(propan-2-yl)-1Hpyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (905); 1-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-[ethyl(methyl)amino]propan-1-one (906); l-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(morpholin-4-yl)propan-1-one (907); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-{2-oxa-6-azaspiro[3.3]heptan-6-yl}propane -1-one (908); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3- 255 041852 (propan- 2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-(3-fluoropyrrolidin-1yl)propan-1-one (909) ; 2-[bis(nponan-2-yl)amino]-1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridine- 6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]ethan-1-one (910) ; 2-[tert-butyl(methyl)amino]-1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridine- 6-yl}-3(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]ethan-1-one (911); 1-[(2R,5S)-4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)2,5-dimethylpiperazin-1-yl]-2-[ethyl(propan-2-yl)amino]ethan-1-one (912) ; 1-[(1R,5S)-8-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-III-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-3-(dimethylamino)propan-1-one (913); 3-[tert-butyl(methyl)amino]-1-[(2R,5S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine-6 -yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5dimethylpiperazin-1-yl]propan-1-one (914); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(3,3-dimethylazetidin-1-yl)ethan-1-one (915); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(3-methoxyazetidin-1-yl)ethan-1-one (916); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(3-fluoropyrrolidin-1-yl)ethan-1-one (917); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-{1-oxa-6-azaspiro[3.3]heptan-6-yl}ethan-1-one (918); 2-(3,3-difluoropyrrolidin-1-yl)-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl} -3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (919); 1-[(1R,5S)-8-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-III-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-2-{2-oxa-6-azaspiro[3.3]heptane -6-yl}ethan-1-one (920); 1-[(1R,5S)-8-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-III-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-2-(pyrrolidin-1-yl)ethan-1-one (921); l-[(1R,5S)-8-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan3-yl]-2-[ethyl(methyl)amino]ethan-1-one ( 922); 1-[(1R,5S)-8-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-2-[methyl(propan-2-yl)amino]ethan- 1-one (923); 2-[tert-Butyl(methyl)amino]-1-[(1R,5S)-8-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridine-6 -yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]ethan-1 -on (924); 2-[tert-Butyl(2-hydroxyethyl)amino]-1-[(1R,5S)-8-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridine -6-yl}-3-(propan-2-yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]ethane -1-one (925); 2-[tert-Butyl(methyl)amino]-1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine- 6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1yl]ethan-1-one (926); 1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-2-[ethyl(methyl)amino]ethan-1-one (927); 1[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (928); 1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl} ethane-1-one (929); 2-[tert-Butyl(2-hydroxyethyl)amino]-1-[(2R,6R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,6-dimethylpiperazin-1-yl]ethan-1-one ( 930); l-[(3R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethan-1-one (931); 1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2[ethyl(methyl)amino]ethan-1-one (932); 1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]-2-[methyl(propan-2-yl)amino]ethan-1-one (933); 2-[tert-Butyl(methyl)amino]-1-[(3R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin6-yl} -3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (934); 1[(2S,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethane -1-one (935); 1-[(2S,5R)4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5yl)-2,5-dimethylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (936); 1-[(2S,5R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-[ethyl(methyl)amino]ethan-1-one (937); 1-[(2S,5R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-2-[methyl(propan-2-yl)amino]ethan-1-one (938) ; 2-[tert-butyl(methyl)amino]-1-[(2S,5R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridine-6 -yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]ethan-1-one (939); 1-[(2R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6yl}ethan-1-one (940) ; 1-[(2K)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1Hpyrrolo[3,24e]pyridin-5-yl)-2-methylpiperazin-1-yl]-2-(pyrrolidin-1-yl)ethan-1-one (941); 1-[(2R)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-2methylpiperazin-1-yl]-2-[ethyl(methyl)amino]ethan-1-one (942); 1-[(2R)-4-(2-{7,8-dimethyl-[1,2,4]tri - 256 041852 azolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1 -yl]-2[methyl(propan-2-yl)amino]ethan-1-one (943); 2-[tert-Butyl(methyl)amino]-1-[(2R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl }-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1-yl]ethan-1-one (944); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-3-methyl-3-{2-oxa-6-azaspiro[3.3]heptan-6-yl}butan-1-one (945); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2b]pyridin-5-yl)piperazin-1-yl]-2-(3-hydroxy-3-methylazetidin-1-yl)ethan-1-one (946); 1-[4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-{2-oxa-7-azaspiro[4.4]nonan-7-yl}ethan-1-one (947); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo [3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(3hydroxy-3-methylpyrrolidin-1-yl)ethan-1-one (948); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin6-yl}-3-(propan-2-yl)-III-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-[(2-hydroxy-2-methylpropyl)(methyl)amino]ethan-1-one (949); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan2-yl)-1Н-pyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-(3,3-dimethylmorpholin-4-yl)ethan-1-one (950); 6{2-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5yl)piperazin-1-yl]-2-oxoethyl}-2λ ⁶ -thia-6-azaspiro[3.3]heptan-2,2-dione (951); 1-[4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2[( ² H3)methylamino]ethan-1-one (952); 2-[tert-Butyl(2-hydroxyethyl)amino]-1-[(3R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridine-6 -yl}-3-(propan-2-yl)-III-pyrrolo[3,2-b]pyridin-5-yl)-3-methylpiperazin-1-yl]ethan-1-one (953); 2-[tert-Butyl(2-hydroxyethyl)amino]-1-[(2S,5R)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridine -6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]ethan-1-one (954 ); 2-[tert-butyl(2-hydroxyethyl)amino]-1-[(2R)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine- 6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2-methylpiperazin-1yl]ethan-1-one (955); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-{6-oxa-2-azaspiro[3.4]octan-2-yl}ethan-1-one (956); 1-[4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5yl)piperazin-1-yl]-2-{2-oxa-6-azaspiro[3.4]octan-6-yl}ethan-1-one (957); 1-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-{1-oxa-6-azaspiro[3.3]heptan-6-yl}propane -1-one (958); 6-{3-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan- 2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-oxopropyl}-2λ ^6- thia-6-azaspiro[3.3]heptane -2,2-dione (959); 1-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1Н-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-{6-oxa-2-azaspiro[3.4]octan-2-yl}propane -1-one (960); 1-[(2R,5S)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3-{2-oxa-6-azaspiro[3.4]octan-6-yl}propane -1-one (961); 3-(3,3-difluoropyrrolidin-1-yl)-1[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine -6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]propan-1-one (962 ); 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2- yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1yl]-3-(3,3-dimethylmorpholin-4-yl)propan-1-one (963) ; 1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1-yl]-3[( ^2H3 )methylamino]propan-1-one (964); 3-[di( ² H ₃ )methylamino]-1-[(2R,5S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridine- 6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazin-1yl]propan-1-one (965); 2-[(cyclopropylmethyl)(methyl)amino]-1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-( propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (966); 1-[4(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[ 3,2-b]pyridin-5yl)piperazin-1-yl]-2-[methyl(oxetan-3-yl)amino]ethan-1-one (967); 2-(cyclopropylamino)-1-[4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl) -1H-pyrrolo[3,2-b]pyridin-5-yl)piperazin-1-yl]ethan-1-one (968); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)piperazin-1-yl]-2-[(2-hydroxyethyl)(methyl)amino]ethan-1-one (969); 1-[4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2-(ethylamino)ethan-1-one (970); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3(propan-2-yl)-III-pyrrolo[ 3,2-b]pyridin-5-yl)piperazin-1-yl]-2-[4-(hydroxymethyl)piperidin-1yl]ethan-1-one (971); 9-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3,2- b]pyridin-5-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane (972); 3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octane (973); (1R,5S)-3-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3,9-diazabicyclo[3.3.1]nonane (974); (3S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-3-(2-methylpropyl)piperazine (975); (3R,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-3,5-dimethylpiperazine (976); 1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-2,3-dimethylpiperazine (977); 6-(2-{7,8-dimethyl- 257 041852 [1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-3 ,6-diazabicyclo[3.1.1]heptane (978); (1R,5S)-8-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2-yl)1H -pyrrolo[3,2-b]pyridin-5-yl)-3,8-diazabicyclo[3.2.1]octane (979); (1R,4R)-2-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-III -pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.2]octane (980); (1R,4R)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)- 1Hpyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptane (981); 4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-4,7-diazaspiro[2.5]octane (982); (3S)1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo [3,2-b]pyridin-5yl)-3-(propan-2-yl)piperazine (983); (1S,4S)-2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)-2,5-diazabicyclo[2.2.1]heptane (984); (1R,5S)-3-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-3,6diazabicyclo[3.1.1]heptane (985); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(pronan2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2-propylpiperazine (986); [(2S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)piperazin-2-yl]methanol (987); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin5-yl)-2-ethylpiperazine (988); (3S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(propan-2yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-3-methylpiperazine (989); (2R,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazine (990); (2S,5S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)- 1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazine (991); (2S)-1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)-2-(propan-2-yl)piperazine (992); (2R,5R)-1-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)-2,5-dimethylpiperazine (993); [(2S)-4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo [3,2-b]pyridin-5-yl)piperazin-2-yl]methanol (994); 1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-N-methylpiperidin-4-amine (995); 1(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)N-methyl-N-[(3-methyloxetan-3-yl)methyl]piperidin-4-amine (996); 2-{[1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]niridin-6-yl}-3-(propan-2-yl)-1H- nirrolo[3,2-b]niridin-5-yl)niperidin-4-yl](methyl)amino}-N,N-dimethylacetamide (997); 1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)1Н-πpyrrolo[3,2 -b] π-pyridin-5-yl)-N-(2-methanesulfonylethyl)-N-methyl π-and-peridin-4-amine (998); 1-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[3,2- b]pyridin-5-yl)-N-(propan-2-yl)azetidine-3-amine (999); 1-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)1H-pyrrolo[3,2 -b]pyridin-5-yl)-N-(2-methoxyethyl)azetidine-3-amine (1000); K1-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridin-6-yl} -3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)ethane-1,2-diamine (1001); N-{2-[(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]niridin-6-yl}-3-(propan-2-yl)-1H- nirrolo[3,2-b]niridin-5-yl)amino]ethyl}-2-(dimethylamino)acetamide (1002); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]πiridin-6-yl}-3-(propan-2-yl)-1Н-πirrolo[3,2- b]piridin-5-yl)-6-(propan-2-yl)-2,6-diazaspiro[3.3]heptane (1003); 1-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol (1004); 3-[6-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]propanamide (1005); 1-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-3-(dimethylamino)propan-1-one (1006); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2b]pyridin-5-yl)-6-(3-methanesulfonylpropyl)-2,6-diazaspiro[3.3]heptane (1007); 2-[6-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]acetonitrile (1008); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-6-(2-methylpropyl)-2,6-diazaspiro[3.3]heptane (1009); 2(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)6-(2,2-dimethylpropyl)-2,6-diazaspiro[3.3]heptane (1010); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)-6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptane (1011); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2b]pyridin-5-yl)-6-(oxan-4-yl)-2,6-diazaspiro[3.3]heptane (1012); 2-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-6-(2-methoxyethyl)-2,6-diazaspiro[3.3]heptane (1013); 3-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]propanenitrile (1014); 2-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-6-propyl-2,6-diazaspiro[3.3]heptane (1015); 2-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-Spyrrolo[3,2-b] pyridin-5-yl)-2,6-diazaspiro[3.3]heptane (1016); 2-(2-{8-methoxy-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)-6-methyl-2,6-diazaspiro[3.3]heptane (1017); 2-ethyl-6-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane (1018); 2-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}3-(propan-2-yl)-1H-pyrrolo[3,2-b ]pyridin-5-yl)-6-propyl-2,6-diazaspiro[3.3]heptane (1019); 2-(2-{8 - 258 041852 methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[3,2-b]pyridin-5 -yl)-6-(propan-2-yl)-2,6-diazaspiro[3.3]heptane (1020); 1-[6-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol (1021); b-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)-2-methyl-2-azaspiro[3.3]heptane (1022); 6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-2-(propan-2-yl)-2-azaspiro[3.3]heptane (1023); 6-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-III-pyrrolo[3,2 -b]pyridin-5-yl)-2(oxan-4-yl)-2-azaspiro[3.3]heptane (1024); 6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-2-[(3-methyloxetan-3-yl)methyl]-2-azaspiro[3.3]heptane (1025); b-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-b-yl}-3-(propan-2-yl)-1H-n-pyrrolo[3, 2-b]niridin-5-yl)-2-(2-methanesulfonylethyl)-2-azaspiro[3.3]heptane (1026); 1-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)-2-azaspiro[3.3]heptan-2-yl]2-(dimethylamino)ethan-1-one (1027); 1-[6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)-2-azaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol (1028); 3-[6-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)-2azaspiro[3.3]heptan-2-yl]propanamide (1029); 6-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)-2-(3-methanesulfonylpropyl)-2-azaspiro[3.3]heptane (1030); b-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]n-yridin-b-yl}-3-(propan-2-yl)-1H-n-pyrrolo[3, 2-b]niridin-5-yl)-2-(2-methoxyethyl)-2-azaspiro[3.3]heptane (1031); 4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2- b]pyridin-5-yl)-1-[2-(dimethylamino)ethyl]piperazin2-one (1032); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2b]pyridin-5-yl)piperazin-1-yl]-2-{2-oxa-6-azaspiro[3.3]heptan-6-yl}ethan-1-one (1033); 1-[(2R,5S)-4-(2{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl )-1H-pyrrolo[3,2-b]pyridin-5-yl)-2,5dimethylpiperazin-1-yl]-3-(methylamino)propan-1-one (1034); 1 -(aminomethyl)-4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl} -3-(propan-2-yl)-1H -pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-ol (1035); 6-[4-(2-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5yl)cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane (1036); 6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2 -b]pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane (1037); N-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-b-yl}-3-(propan-2-yl)-1H-n-pyrrolo [3,2-b]niridin-5-yl)cyclohexyl]-N-ethyloxetan-3-amine (1038); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5a]piridin-6-yl}-3-(propan-2-yl)-1H-pirrolo[3 ,2-b]piridin-5-yl)cyclohexyl]-3,3-dimethylazetidine (1040); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2b]piridin-5-yl)cyclohexyl]-3-methylazetidin-3-ol (1041); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1Н-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-3-methoxyazetidine (1042); 4-{[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2b]pyridin-5-yl)cyclohexyl]amino}-1λ ⁶ -thian-1,1-dione (1043); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]azetidin-3-ol (1046); 1[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]n-yridin-b-yl}-3-(nponan-2-yl)-1H-n-pyrrolo[ 3,2-b]niridin-5yl)cyclohexyl]-N,N-dimethylazetidine-3-carboxamide (1047); 4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]πiridin-6-yl}-3-(πpropan-2-yl)-1H-πirrolo[3,2- b] π-pyridin-5-yl)-N-methyl-N-(π-propan-2-yl)-cyclohexan-1-amine (1048); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]azetidine (1051); 1-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-3,3-dimethylazetidine (1052); 6-((1S,4S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl)-3-isopropyl-1H-pyrrolo [3,2b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptan-2,2-dioxide (1053); N-tert-butyl-4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H- pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-amine (1054); 6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1055); 1-[4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)cyclohexyl]-3fluoropyrrolidine (1058); 7-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-2-oxa-7-azaspiro[4.4]nonane (1059); 6-[4-(2-{7,8-dimethyl[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[ 3,2-b]pyridin-5-yl)cyclohexyl]-2oxa-6-azaspiro[3.4]octane (1060); 2-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1061); 4-[4-(2-{7,8dimethyl-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]morpholine (1064); 3-fluoro-1-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)cyclohexyl]pyrrolidine (1067); 6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3 ,2-b]pyridin-5-yl)cyclohexyl]-2-oxa-6azaspiro[3.4]octane (1068); 2-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1Hpyrrolo[3,2 -b]pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1069); 4-[4-(2-{8-methoxy[1,2,4]triazolo[1,5-а]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3, 2-b]pyridin-5-yl)cyclohexyl]morpholine (1071); b-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]niridin-b-yl}-3-(nponan-2-yl)-1H-npyrrolo[3 ,2- 259 041852 b]pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1074); 6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo [3,2-b]pyridin-5-yl)cyclohexyl]-1X ^b -thia-6azaspiro [3.3]heptan-1,1-dione (1076) and 7H-pyrrolo[2,3-c1]pyrimidin-5-yl}-3(propan-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexan-1-amine (1078 ). 12. A pharmaceutical composition for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease, comprising a compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 13. The use of a compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease. 14. Use according to claim 13, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome. 15. The use of a compound or a pharmaceutically acceptable salt thereof for the treatment of a disease selected from an autoimmune disease or a chronic inflammatory disease, wherein said compound is selected from