WO2014149206A1

WO2014149206A1 - Pyrazolopyrimidine-based insecticidal compositions and related methods

Info

Publication number: WO2014149206A1
Application number: PCT/US2014/014707
Authority: WO
Inventors: William H. DENT; Mark A. Pobanz; Chaoxian Geng; Nick X. WANG
Original assignee: Dow AgroSciences LLC
Current assignee: Corteva Agriscience LLC
Priority date: 2013-03-15
Filing date: 2014-02-04
Publication date: 2014-09-25
Anticipated expiration: 2015-09-15

Abstract

An pesticidal composition comprises a pyrazolopyrimidine compound of general formula (I) or any agriculturally acceptable salt thereof, wherein Ar, W, X, Y, Z and R are as described herein. An pesticidal composition includes a pyrazolopyrimidine compound of general formula (II) or any agriculturally acceptable salt thereof, wherein A, W, R_1, R₂, R₃, R₄ and R₅ are as described herein. Methods of preparing such pesticidal compositions and methods of controlling insects include using such pesticidal compositions.

Description

PYRAZOLOPYRIMIDINE-BASED PESTICIDAL COMPOSITIONS

AND RELATED METHODS

PRIORITY CLAIM

This application claims the benefit of U.S. Provisional Patent Application Serial No. 61/798,550 filed March 15, 2013, the entire disclosure of which is hereby expressly incorporated by reference.

TECHNICAL FIELD

Various aspects and embodiments relate generally to pesticidal compositions and to methods of preparing and using such pesticidal compositions. Particular aspects and embodiments generally relate to pyrazolopyrimidine-based pesticidal compositions and the methods of producing and using the pyrazolopyrimidine-based pesticidal compositions.

BACKGROUND

Controlling insect populations is essential to modern agriculture, food storage, and hygiene. There are more than ten thousand species of insects that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year. Accordingly, there exists a continuous need for new pesticides and for methods of producing and using such pesticides.

DISCLOSURE

Embodiments of the present disclosure include pyrazolopyrimidine compounds, and the pesticidal compositions comprising such pyrazolopyrimidine compounds.

Embodiments of the present disclosure further include methods of producing pyrazolopyrimidine-based pesticidal compositions.

Further embodiments of the present disclosure include methods of controlling insects that include applying an pesticidal composition comprising a pyrazolopyrimidine -based compound near a population of insects.

MODE(S) FOR CARRYING OUT THE INVENTION

As used herein, the term "alkyl" means and includes a saturated, straight, or branched hydrocarbon. Examples may include, but are not limited to, methyl, ethyl, propyl, isopropyl, 1- butyl, isobutyl, t-butyl, 2-methylbutyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, 3-methylpentyl, 2,2-dimethylbutyl, or 2,3-dimethylbutyl.

As used herein the term "cycloalkyl" means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, norbornyl, bicycle[2.2.2]octyl, and decahydronapthyl .

As used herein, the term "alkenyl" means and includes a straight or branched hydrocarbon containing at least one carbon-carbon double bond. Examples may include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, or decenyl.

As used herein the term "cycloalkenyl" means a cyclic hydrocarbon containing at least one carbon-carbon double bond, such as, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and cyclodecenyl.

As used herein, the term "alkynyl" means and includes a straight, branched, or hydrocarbon containing at least one carbon-carbon triple bond. Examples may include, but are not limited to, ethynyl, propargyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, or decynyl.

As used herein the term "cycloalkynyl" means a cyclic hydrocarbon containing at least one carbon-carbon triple bond.

As used herein, the term "aryl" means and includes an aromatic ring compound with or without any substitution, such as, for example, phenyl and naphthyl.

As used herein, the term "alkoxy" means and includes an alkyl group containing at least one carbon-oxygen single bond. Non-limiting examples may include methoxyl, ethoxy, propoxy, or butoxy.

As used herein, the term "alkylthio" means and includes an alkyl group containing at least one carbon-sulfur single bond.

As used herein, the term "haloalkylthio" means and includes an alkyl group containing at least one carbon-sulfur single bond and halogen atom.

As used herein, the terms "halo" and "halogen" mean and include fluorine, chlorine, bromine, or iodine.

As used herein, the terms "haloalkyl" and "haloalkoxy," respectively, mean and include, an alkyl group and an alkoxy group substituted with at least one halogen atom or halothio group. As used herein, the term "heteroatom" means and includes sulfur (S), oxygen (O) or nitrogen (N) atom.

As used herein, the term "heteroaryl" means and includes an aromatic moiety containing at least one sulfur (S), oxygen (O), or nitrogen (N) atom in the aromatic ring. Non-limiting examples may include furyl, pyridyl, pyrimidyl, thienyl, isothiazolyl, imidazolyl, tetrazolyl, pyrazinyl, benzofuranyl, benzothiophenyl, quinolyl, isoquinolyl, benzothienyl, isobenzoiuryl, pyrazolyl, indolyl, isoindolyl, benzimidazolyl, purinyl, carbozolyl, oxazolyl, thiazolyl, isothiazolyl, 1 ,2,4-thiadiazolyl, isooxazolyl, pyrrolyl, pyrazolyl, quinazolinyl, pyridazinyl, pyrazinyl, cinnolinyl, phthalazinyl, quinoxalinyl, xanthinyl, hypoxanthinyl, pteridinyl, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, or pyrazolopyrimidinyl .

As used herein, the term "heteroalkyl" means and includes an alkyl moiety as defined herein containing at least one sulfur (S), oxygen (O), or nitrogen (N) atom.

As used herein, the term "cyano" means and includes a functional group containing a carbon-nitrogen triple bond.

As used herein, the term "nitro" means and includes a functional group containing a nitrogen atom joined to two oxygen atoms.

As used herein the term, "pesticidally effective amount" means and includes an amount of active material that causes an adverse effect to the at least one pest, wherein the adverse effect may include deviations from natural development, killing, regulation, or the like.

As used herein, the term "control" or grammatical variations thereof means and includes regulating the number of living insects or regulating the number of viable eggs of the pests.

The pyrazolopyrimidine-based pesticidal composition may comprise a pyrazolopyrimidine compound of general formula I or any agriculturally acceptable salt thereof:

I wherein,

Ar may be any aryl group including, but are not limited to, phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrazolo, imidazolo, thiophenyl, or any other heteroaromatic rings. Ar may be substituted or unsubstituted. Ar may be substituted at any open position with hydrogen, halogen, alkyl, alkenyl, alkynyl, or combinations thereof. Ar may include one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position. Additionally, Ar may be substituted with alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, sulfoxide, unsubstituted amines, substituted amines, unsubstituted aryloxy, substituted aryloxy group, esters, acetates, amides, or combinations thereof;

X may be nitrogen (N), oxygen (O) or sulfur (S),

where X is nitrogen, it may be substituted with alkyl, cycloalkyl, alkenyl, alkynyl, or combinations thereof, wherein the alkyl, alkenyl or alkynyl may include one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position. Furthermore, N may be substituted directly with N, O or SO_n (n = 1, 2) with each individually substituted with hydrogen and/or an alkyl moiety including one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position. N may also be substituted with C(0)R', C(0)OR', C(0) R', where R' may be a substituted alkyl moiety which may include one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position; an aryl or heteroaryl moiety where substituents may be any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy that may be substituted or unsubstituted,

when X is oxygen, it may be substituted with hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, amino, C(0)R', or C(0)NR' where R' may be substituted alkyl moiety which may include one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position. Additionally, R' may be aryl, heteroalkyl or heteroaryl where substituents may be any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy that may be substituted or unsubstituted,

where X is sulfur, it may be SO_n (n = 0, 1 , 2). It may connect to hydrogen (n=0), alkyl or cycloalkyl group that may include one or more heteroatoms such as N, O, Si, or SO_n (n = 0, 1, 2) at any position. It may connect to aryl or heteroaryl group that may be substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro and sulfone group. It may connect to an amino moiety having at least one substituted alkyl, heteroalkyl, aryl, or heteroaryl group where the substituents may be any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, and sulfone; Y and Z may independently be hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano amine, unsubstituted amine, or substituted amine;

R may be selected from the group consisting of hydrogen, Q-Cg alkyl, C₃-C₈ cycloalkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(C_rC₈ alkyl) (n = 0, 1, 2), C(=0)NR_xR_y, (Ci-C₈ alkyl)NR_xR_y, C(=0)0(C,-C₈ alkyl), C(=0)( C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (C C₈ alkyl)0(Ci-C₈ alkyl), (Ci-C₈ alkyl)OC(=0)(Ci-C₈ alkyl), (C C₈ alkyl)OC(=0)(C₂-C₈ alkenyl), (C,-C₈ alkyl)OC(=0)(C₂-C₈ alkynyl), (Ci-C₈ alkyl)OC(=0)(Ci-C₈ cycloalkyl), (Ci-C₈ alkyl)OC(=0)(C₃-C₈ cycloalkenyl), (d-C₈ alkyl)OC(=0)(C₇-C₈ cycloalkynyl), (C,-C₈ alkyl)S(C C₈ alkyl), C(=0)(C C₈ alkyl)C(=0)0(C₁-C₈ alkyl), wherein each alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl and cycloalkynyl may optionally be substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, Q-C₈ alkyl, C|-C₈ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, Ci-C₈ alkoxy, d-C₈ haloalkoxy, C₂-C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(Ci-C₈ alkyl) (n = 0, 1, 2), S(=0)_n(Ci-C₈ haloalkyl) (n = 0, 1, 2), OS0₂(Ci-C₈ alkyl), OS0₂(C C₈ haloalkyl), C(=0)NR_xR_y, (Ci-C₈ alkyl)NR_xR_y, C(=0)(C C₈ alkyl), C(=0)0(C C₈ alkyl), C(=0)(C!-C₈ haloalkyl), C(=0)0(C C₈ haloalkyl), C(=0)(C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (d-C₈ alkyl)0(C C₈ alkyl), (C,-C₈ alkyl)S(d- C₈ alkyl), C(=0)(Ci-C₈ alkyl)C(=0)0(d-C₈ alkyl), phenyl, and phenoxy, and wherein R_x and R_y each is independently selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy; and

W may be selected from the group consisting of hydrogen, Ci-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, and benzyl, wherein each alkyl, alkenyl, and benzyl may optionally be substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, C]-C₈ alkyl, Q-Q haloalkyl, C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, Cj-Cg alkoxy, Q-Q haloalkoxy, C₂- C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(Ci-C₈ alkyl), S(=0)_n(d-C₈ haloalkyl) (wherein n= 0, 1 , or 2), OS0₂(C,-C₈ alkyl), OS0₂(C,-C₈ haloalkyl), C(=0)NR_xR_y, (C,-C₈ alkyl)NR_xR_y, C(=0)(d-C₈ alkyl), C(=0)0(C C₈ alkyl), C(=0)(C_rC₈ haloalkyl), C(=0)0(C_rC₈ haloalkyl), C(=0)( C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (C,-C₈ alkyl)0(d-C₈ alkyl), (d-C₈ alkyl)S(C,-C₈ alkyl), C(=0)(C,-C₈ alkyl)C(=0)0(C_rC₈ alkyl), phenyl, and phenoxy, wherein R_x and R_y each is independently selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy.

The pyrazolopyrimidine compound of the general formula I may exist in various isomeric forms. Non-limiting examples of such isomeric forms may include, but are not limited to, compounds I-A, I-B and I-C as shown below. The pyrazolopyrimidine compound of the present disclosure may include at least one of these isomeric forms.

I-A I B I-C

In one embodiment, the pyrazolopyrimidine compound may have general formula II or any agriculturally acceptable salt thereof:

wherein,

Ar may be a substituted phenyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, pyrazolo, imidazolo, triazole, thiophenyl, furyl, wherein the substituent group may include at least one of hydrogen, alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, nitro, sulfone, aryloxy, and any combination thereof;

W may be selected from the group consisting of hydrogen, Ci-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, benzyl, wherein each alkyl, alkenyl, and benzyl may optionally be substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, Ci-C₈ alkyl, Q-Q haloalkyl, C3-C8 cycloalkyl, C₃-C₈ halocycloalkyl, C₃-C₈ cycloalkoxy, C₃~C₈ halocycloalkoxy, Cj-Cg alkoxy, C- C₈ haloalkoxy, C₂=C₈ alkenyl, C₂- C₈ alkynyl, S(=0)„(Ci-C₈ alkyl), S(=0)_n(C]-C₈ haloalkyl) (wherein n= 0, 1, or 2), OS0₂(Ci-C₈ alkyl), OS0₂(Ci-C₈ haloalkyl), C(=0)NR_xR_y, (C_rC₈ alkyl)NR_xR_y, C(=0)(Ci-C₈ alkyl), C(=0)0(Ci-C₈ alkyl),

haloalkyl), C(=0)( C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (C_rC₈ alkyl)0(Ci-C₈ alkyl), (Q-Cg alkyl)S(C_rC₈ alkyl), C(=0)(Ci-C₈ alkyl)C(=0)0(Ci-C8 alkyl), phenyl, and phenoxy;

R¹, R² and R⁵ may be independently selected from:

(a) hydrogen, hydroxy, or thiol;

(b) (Ci-C₈) alkyl, C(=0)(Ci-C₈)alkyl, C(=0)0(C_rC₈)aIkyl, 0(C₁-C₈)alkyl,

OC(=0)(Ci-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C C₈)alkyl, S (Q- C₈)alkyl, S(0)(C,-C₈)alkyl, or S(0)₂(C_rCg)alkyl;

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-Cg)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(d) (C₃-Cg)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₃-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃- Cg)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂phenyl;

(f) heterocycyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S- heterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyclyl;

(g) N(R⁸)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, C(=S)N(R⁹)₂, OC(=0)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or

(h) C₃-C₈ cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (h) may independently be substituted with one or more substituents selected from:

(al) F, CI, Br, I, CN, N0₂, OH, or OSi((Ci-C₈)alkyl)₃;

(bl) C(=0)(Ci-C₈)alkyl, C(-0)0(C,-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(C_rC₈)alkyl,

OC(=0)0(C,-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C,-C₈)alkyl, S(0)(C,- C₈)alkyl, or 8(0)₂(€]-€₈)3 1; (cl) C(=0)(C₂-C₈)aIkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(dl) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂phenyl;

(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyclyl;

(gl) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or

(hi) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e) and (f) may independently be substituted with one or more substituents selected from:

(a2) F, CI, Br, I, CN, N0₂, OH, SF₅, or OSi((C_rC₈)alkyl)₃;

(b2) (C_rC₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(d-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(C_!-C₈)alkyl, S(Q- C₈)alkyl, S(0)(C,-C₈)alkyl, or S(0)₂(C,-C₈)alkyl;

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂phenyl;

(Ω) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyclyl;

(g2) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or (h2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) may independently be substituted with one or more substituents selected from:

(a3) F, Cl, Br, I, CN, N0₂, OH, or OSi((C₁-C₈)alkyl)₃;

(b3) C(=0)(Ci-C₈)alkyl, C(=0)0(C C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C C₈)alkyl, C(=S)0(d-C₈)alkyl, S(Ci-C₈)alkyl, S(0)(Ci- C₈)alkyl, or S(0)₂(Ci-C₈)alkyl;

(c3) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(d3) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂phenyl;

(β) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyclyl;

(g3) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)_2, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (β) may independently be substituted with one or more substituents selected from:

(a4) F, Cl, Br, I, CN, N0₂, OH, SF₅, or OSi((C C₈)alkyl)₃;

(b4) (Ci-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(CrC₈)alkyl,

S(C_r Cg)alkyl, S(0)(C_rC₈)alkyl, or S(0)₂(C,-C₈)alkyl;

(c4) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl; (d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl₅ 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂pheny;

(f4) heterocyclyl, C(=0)heterocyelyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyelyl;

(g4) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, or S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; or

(h4) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) may independently be substituted with one or more substituents selected from:

(a5) F, CI, Br, I, CN, N0₂, OH, or OSi((C_rC₈)alkyl)₃;

(b5) C(=0)(CrC₈)alkyl, C(=0)0(C C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(C_!-C₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(d-C₈)alkyl, S(C_!-C₈)alkyl, S(0)(Ci- C₈)alkyl, or S(OMCi-C₈)alkyl;

(c5) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(d5) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

(f5) heterocyclyl, C(=0)heteroeyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heteroeyclyl;

(g5) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or

(h5) (C₃-C₈)cycloalkyl, wherein each of the phenyl and heterocyclyl in (e3), (e4), ( ), and (f4) may independently be substituted with one or more substituents selected from:

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, or OSi((C,-C₈)alkyl)₃;

(b6) (Ci-Cg)alkyl, C(=0)(Ci-C₈)alkyl, C(=0)0(C_!-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(d-C₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(C_rC₈)alkyl , S(C_r C₈)alkyl, S(0)(C,-C₈)alkyl, or S(0)₂(Ci-C₈)alkyl;

(c6) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)O(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, or S(0)₂(C₂-C₈)alkenyl;

(d6) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, C(=0)(C₂-

C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, or S(0)₂(C₂-C₈)alkynyl;

(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, or S(0)₂phenyl;

(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, or S(0)₂heterocyclyl;

(g6) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; or

(h6) (C₃-C₈)cycloalkyl,

wherein R⁸ may be selected from:

(a) H, CN, OH,

(b) (C,-C₈)alkyl, C(=0)(Ci-C₈)alkyl,

C(=0)NH(C,-C₈)alkyl,

S(0)(Ci-C₈)alkyl, S(0)₂(C_r C₈)alkyl,

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, C(=0)NH(C₂- C₈)alkenyl, C(=S)NH(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(0)(C₂- C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d) (C₃-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, C(=0)NH(C₂- C₈)alkynyl, C S)NH(C₂-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(0)(C₃-

C₈)alkynyl, S(0)₂(C₃-C₈)alkynyl,

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=0)NHphenyl, C(=S)NHphenyl, C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)₂phenyl, (f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=0)NH-heterocyclyl, C(=S)NH-heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂ heterocyclyl, and

(h) (C₃-C₈)cycloalkyl,

Q

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of R may independently be substituted with one or more substituents selected from:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((C,-C₈)alkyl)₃,

(bl)

OC(=0)0(C,-C₈)alkyl, C(=S)(C C₈)alkyl, C(=S)0(C_rC₈)alkyl, S(C,-C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C_rC₈)alkyl

(cl) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(dl) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(H) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocycly], S(0)heterocyclyl, S(0)₂heterocyclyl,

(gl) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, C(=S)N(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂, and

(hi) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e) and (f) of R may independently be substituted with one or more substituents selected from:

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃,

(b2) (d-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(C_!-C₈)alkyl, C(=S)0(C_rC₈)alkyl, S(C,- C₈)alkyl, S(0)(d-C₈)alkyl, S(0)₂(Ci-C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, 0C(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl, (d2) (C₂-C₈)alkynyl, C(=OX¾-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)aIkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(g2) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, C(=S)N(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, and S(0)₂N(R⁹)₂, and

(h2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of R⁸ may independently be substituted with one or more substituents selected from:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((Cj-C₈)alkyl)₃,

(b3) C(=0)(C_rC₈)alkyl, C(=0)0(d-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C₁-C₈)alkyl, C(=S)0(d-C₈)alkyl, S(C_rC₈)alkyl, S(0)(C_r C₈)alkyl, S(0)₂(C₁-C₈)alkyl,

(c3) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d3) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(O) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(g3) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R )₂, C(-0)N(R⁹)₂, C(=0)ON(R⁹)₂,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)_2, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂, and

(h3) (C₃-C₈)cycloalkyl, wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of R may independently be substituted with one or more substituents selected from:

(a4) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C₁-C₈)alkyl)₃,

(b4) (Ci-C₈)alkyl, CCOXCrC^alkyl, C(=0)0(d-C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(C_rC₈)alkyl, C(=S)(C₁-C₈)alkyl, C(=S)0(Ci-C₈)alkyl S(C,- C₈)alkyl, S(0)(C_!-C₈)alkyl, S(0)₂(Ci-C₈)alkyl,

(c4) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl,

OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(g4) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂, and

(h4) (C₃-C₈)cycloalkyl,

wherein R⁹ may be selected from:

(a) H, CN, OH, OSi((Cj-C₈)alkyl)₃,

(b) (C,-C₈)alkyl, CCOXQ-Ci alkyl, C(=0)0(C C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(C C₈)alkyl, OC(=0)0(C_rC₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C,- C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(d-C₈)alkyl,

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₃-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₃-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, 0C(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-

C₈)alkynyl, S(0)(C₃-C₈)alkynyl, S(0)₂(C₃-C₈)alkynyl,

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(-0)phenyl, C(-S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)₂phenyl (f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(g) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of R⁹ may independently be substituted with one or more substituents selected from:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((C_rC₈)alkyl)₃,

(bl) C(=0)(C_!-C₈)alkyl, C(=0)0(Cj-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(C C₈)alkyl, OC(=0)0(d-C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(Ci-C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C C₈)alkyl,

(dl) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C3-C8)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(hi) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e) and (f) of R⁹ may independently be substituted with one or more substituents selected from:

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C_rC₈)alkyl)₃,

(b2) (C,-C₈)alkyl, C(=0)(C_!-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C,-C₈)alkyl , S(C,- Q alkyl, S(0)(C₁-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, 0C(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl, (d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, 0C(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(β) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h.2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl),

(d2), (hi), and (hi) of R⁹ may independently be substituted with one or more substituents selected from:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((C_rQ)alkyl)₃,

(b3) C(=0)(C_rC₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C₁-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C_rC₈)alkyl, S(0)(C_r C₈)alkyl, S(0)₂(C_rC₈)alkyl,

(d3) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-

C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of R⁹ may independently be substituted with one or more substituents selected from:

(a4) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃, (b4) (C C₈)alkyl, C(=0)(C C₈)alkyl, C(=0)0(CrC₈)alkyl, 0(C_rC₈)alkyl,

S(C_r Q alkyl, S(0)(C,-C₈)alkyl, S(0)2(Ci-C8)alkyl,

(d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, 0C(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h4) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of R⁹ may independently be substituted with one or more substituents selected from:

(a5) F, CI, Br, I, CN, N0₂, OH, OSi((d-C₈)alkyl)₃,

(b5) C(=0)(C₁-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(C_rC₈)alkyl,

OC(=0)0(C_!-C₈)alkyl, C(=S)(C₁-C₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(C C₈)alkyl, S(0)(Ci- C₈)alkyl, S(0)₂(C_rC₈)alkyl,

(c5) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d5) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(-S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and (h5) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e3), (e4), ( ), and (f4) of R⁹ may independently be substituted with one or more substituents selected from:

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃,

(b6) (Q-Q alkyl, C(=0)(Ci-C₈)alkyl, C(-0)0(C,-C₈)alkyl, 0(C,-C₈)alkyl,

OC(=0)(d-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(Ci-C₈)alkyl , S(Ci- C₈)alkyl, S(0)(C₁-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(c6) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d6) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h6) (C₃-C₈)cycloalkyl.

R³ and R⁴ may independently be hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano amine, unsubstituted amine, or substituted amine.

The pyrazolopyrimidine compound of the general formula II may be produced by reducing the corresponding pyrazolopyrimidine compound of general formula III, as shown in Scheme 1.

Scheme 1

III II The pyrazolopyrimidine compound III may be produced from 4-chloro-2,6-substituted pyrimidine-5-carbonitrile of formula IV- 1. In one embodiment, the compound 4-chloro-2,6- substituted pyrimidine-5-carbonitrile of formula IV-1 may be produced as shown in Scheme 2, wherein each substituent groups R³ and R⁴ is a Ci-C₈ alkyl group substituted with at least two or more halogen atoms. First, two equivalents of the cyanoalkyl compound IV-2 is reacted with ethyl 2-cyanoacetate (IV-3) in a solvent, such as tetrahydrofuran (THF), and a non-nucleophilic base, such as potassium tert-butoxide (KOiBu), at a temperature of approximately 25° C to provide the 4-hydroxy-2,6-substituted pyrimidine-5-carbonitrile salt of formula IV-4. See Parker, M. H. et al. Synth. Commun. 2004, 34, 903-907. Then, the hydroxyl substituent group at the 4-position of the pyrimidine compound IV-4 is converted to a chloride substituent group by reacting with phosphorus oxychloride (POCl₃) in a solvent, such as acetonitrile (MeCN), at a temperature between about 60 °C and about 70 °C to provide the 4-choloro-2,6-substituted pyrimidine-5-carbonitrile of formula IV-1.

Scheme 2

IV-2 IV-3 IV-4 IV-1

X = R³ = R⁴ X = R³ = R⁴ The pyrazolopyrimidine compound V may be synthesized by reacting 4-choloro-2,6- substituted pyrimidine-5-carbonitrile compound IV-1 with a hydrazine-based compound as shown in Scheme 3.

Scheme 3

IV-1 V In one embodiment of the synthetic Scheme 3, compound 4-choloro-2,6-substituted pyrimidine-5-carbonitrile IV-1 may react with a hydrazine-based compound in the presence of a base, such as triethylamine (TEA), and a polar aprotic solvent, such as 1,4-dioxane or N,N- dimethylformamide (DMF), at a temperature from approximately 25° C to about 90° C.

In one embodiment of the synthetic Scheme 3, compound 4-choloro-2,6-substituted pyrimidine-5-carbonitrile IV-1 may react with a feri-butoxycarbonyl (Boc)-protected hydrazine in the presence of a polar, aprotic solvent, such as 1 ,4-dioxane. Then, the resulting Boc- protected compound may react with triethylsilane and an acid, such as trifluoroacetic acid (TFA), in a non-reactive solvent, such as dichloromethane (CH₂Cl₂)_i at a temperature from approximately 25° C to about 50 °C.

In one embodiment of the synthetic Scheme 3, compound 4-choloro-2,6-substituted pyrimidine-5-carbonitrile IV-1 may react with a hydrazine-based compound in the presence of a polar protic solvent, such as ethanol (EtOH), with or without a base, such as TEA, at an ambient temperature i.e. room temperature (RT, about 22 °C).

The amine group of the pyrazolopyrimidine compound V may be substitutented with at least one electrophile to provide the pyrazolopyrimidine compound of general formula VI, as shown in Scheme 4.

Scheme 4

V VI

The pyrazolopyrimidine compound V may be reacted with at least one electrophile in the presence of a base in a polar aprotic solvent at a temperature from approximately 25° C to 60° C to provide the pyrazolopyrimidine compound VI. Non-limiting examples of electrophiles may include: alkyl halides, anhydrides, acid chlorides, isocyanates, isothiocyanate, or sulfonyl chlorides. Examples of suitable bases may include, but are not limited to, TEA, diisopropylethylamine (DIPEA), pyridine, NW-dimethylpyridin-4-amine (DMAP), potassium carbonate (K₂C0₃), or potassium phosphate tribasic ( ₃P0₄). Non-limiting examples of the polar aprotic solvents may include, but are not limited to, MeCN, THF, or CH₂C1₂.

In one embodiment, the pyrazolopyrimidine compound VI may then be reduced by a hydride reducing agent, such as sodium borohydride (NaBH₄), in a polar protic solvent at a temperature from approximately 25° C to about 60° C to provide the pyrazolopyrimidine compound VII, as shown in Scheme 5. Non-limited examples of suitable polar protic solvents may include water, methanol (MeOH) or EtOH. In one embodiment, both R³ and R⁴ groups may be electron withdrawing groups, such as trifluoromethyl and trichloromethyl group.

Scheme 5

VI VII

The internal nitrogen atom of the pyrazolopyrimidine compound VII may be substituted with an electrophile (i.e., R⁵ in Scheme 6) in the presence of a base in a polar aprotic solvent at a temperature from approximately 25° C to about 60° C to produce the pyrazolopyrimidine compound VIII, as shown in Scheme 6.

Scheme 6

VII VIII

Non-limiting examples of electrophiles suitable for Scheme 6 may include alkyl halides, anhydrides, acid chlorides, isocyanates, isothiocyanates, or sulfonyl chlorides. Examples of suitable bases may include, but are not limited to, TEA, DIPEA, pyridine, DMAP, K₂C0₃, or K₃P0₄. Non-limited examples of suitable polar protic solvents may include MeCN, THF, or

1 2

CH₂C1₂. In one embodiment, the R and R groups on the substutited amine of the pyrazolopyrimidine compound VIII may include an electron withdrawing group, such, for example, as carbamates, amides, ureas or sulfonamides. In one embodiment, both R³ and R⁴ groups may be electron withdrawing groups, such as trifluoromethyl. In one embodiment, the R⁵ group on the nitrogen atom of the pyrazolopyrimidine compound VIII may be prepared using the same electrophiles as in R¹ and R² groups.

In one embodiment, the pyrazolopyrimidine compound VI may be converted to the pyrazolopyrimidine compound VIII by Grignard reaction as shown in Scheme 7.

Scheme 7

VI VIII Pyrazolopyrimidine compound VI may react with an alkyl metal such methyl magnesium halide in the presence of metal halide, such as lithium chloride (LiCl), in a polar aprotic solvent, such as THF or ether, at a temperature from approximately -78° C to about 25° C to provide pyrazolopyrimidine compound VIII. In one embodiment, both R³ and R⁴ groups may be electron withdrawing groups, such as trifluoromethyl. In one embodiment, W may be derived from a small alkyl magnesium halide such, for example, as methyl magnesium chloride (MeMgCl), /so-propyl magnesium chloride (z^'PrMgCl) and benzyl magnesium chloride (PhCH₂MgCl).

In one embodiment, the pyrazolopyrimidine compound may have general formula IX or any agriculturally acceptable salt thereof, wherein Ar, R 1 , R2 , R 5 and W may be as previously disclosed.

IX

In one embodiment, the pyrazolopyrimidine compound may have the general formula IX, wherein Ar represents 2,6-dichloro-4-(trifluoromethyl)phenyl group.

In one embodiment, the pyrazolopyrimidine compound may have the general formula

IX, wherein R¹, R², R⁵ and W may independently be hydrogen, alkyl, acyl, or alkylthioalkyl, or

1 2

R may be hydrogen and R may be alkyl, acyl, or alkylthioalkyl.

In one embodiment, the pyrazolopyrimidine compound may have the general formula IX, wherein Ar, R¹, R² and R⁵ may be as previously disclosed, and W is hydrogen.

One embodiment of a method of producing the pyrazolopyrimidine compound IX is shown in Scheme 8, as follows:

Scheme 8

V-2 VI-1 IX-1

Briefly, the method of Scheme 8 includes alkylating the amine substituent group of the pyrazolopyrimidine compound V-2 to produce Ν',Ν'-bis-alkylated pyrazolopyrimidine compound VI-1, and then reducing Compound VI-1 to provide the pyrazolopyrimidine compound IX-1. In one embodiment, the reduction of the pyrazolopyrimidine compound VI-1 may be achieved using ethanolic NaBH₄.

In one embodiment, the pyrazolopyrimidine compound may have general formula X or any agriculturally acceptable salt thereof. One embodiment of a method of producing the pyrazolopyrimidine compound X is shown in Scheme 9. The method of Scheme 9 includes protecting the amine substitution group of the pyrazolopyrimidine compound V-2 with tert- butyloxycarbonyl (BOC) group to provide the bis-BOC protected compound V-3, and reducing Compound V-3 using NaBH₄ in EtOH to produce the pyrazolopyrimidine compound IX-2. The substitution of the nitrogen at the 1 -position of the bis-BOC protected compound IX-2 may be achieved using Procedure A or B, depending on the substituent group. Procedure A may be used when alkyl or benzyl halide is used the alkylating agent. Procedure B may be used when substituted bromomethyl esters, chloroformates, sulfonyl chlorides, or acyl chlorides is employed as the alkylating agent. An external base, such as TEA, DMAP or DIPEA, may be used to affect the substitution of the amine group in an appropriate solvent (e.g., THF, acetone or CH₂C1₂).

Scheme 9

NaBH₄

EtOH

X IX-4 IX-2

Procedure A may be performed as shown in Scheme 10, as follows: Scheme 10

IX-2 IX-4 X

The method of Scheme 10 includes alkylating the internal nitrogen at the 1 -position of the bis-BOC protected compound IX-2 with alkyl halide to provide compound IX-4, and then removing the bis-BOC protecting groups on the amine substituent group of compound IX-4 to provide the pyrazolopyrimidine compound X.

Procedure B may be performed as shown in Scheme 11, as follows:

Scheme 11

The method of Scheme 11 includes substituting the internal nitrogen at the 1 -position of the pyrazolopyrimidine compound IX-5 with bromomethyl ester to provide compound IX-6, and then removing the bis-BOC protecting groups on the amine substituent group at the 3- position of compound IX-6 to provide the pyrazolopyrimidine compound X-l. In some embodiments, the BOC-deprotection of Compound IX-6 may provide compound X-2 in addition to the pyrazolopyrimidine compound X-l in resonance form I-A, I-B or I-C.

The pyrazolopyrimidine compound of the general formula I may be used to control a wide variety of pests. As a non-limiting example, in one or more embodiments, the pyrazolopyrimidine compound I may be used to control one or more members of at least one of Phylum Arthropoda, Phylum Nematoda, Subphylum Chelicerata, Subsphylum Myriapoda, Subphylum Hexapoda, Class Insecta, Class Arachnida, and Class Symphyla. In at least some embodiments, the method of the present disclosure may be used to control one or more members of at least one of Class Insecta and Class Arachnida.

As a non-limiting example, in one or more embodiments, the method of the present disclosure may be used to control one or more members of at least one of Phylum Arthropoda, Phylum Nematoda, Subphylum Chelicerata, Subsphylum Myriapoda, Subphylum Hexapoda, Class Insecta, Class Arachnida, and Class Symphyla. In at least some embodiments, the method of the present disclosure may be used to control one or more members of at least one of Class Insecta and Class Arachnida.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Coleoptera (beetles) including, but not limited to, Acanthoscelides spp. (weevils), Acanthoscelides obtectus (common bean weevil), Agrilus planipennis (emerald ash borer), Agriotes spp. (wireworms), Anoplophora glabripennis (Asian longhorned beetle), Anthonomus spp. (weevils), Anthonomus grandis (boll weevil), Aphidius spp., Apion spp. (weevils), Apogonia spp. (grubs), Ataenius spretulus (Black Turfgrass Ataenius), Atomaria linearis (pygmy mangold beetle), Aulacophore spp., Bothynoderes punctiventris (beet root weevil), Bruchus spp. (weevils), Bruchus pisorum (pea weevil), Cacoesia spp., Callosobruchus maculatus (southern cow pea weevil), Carpophilus hemipteras (dried fruit beetle), Cassida vittata, Cerosterna spp., Cerotoma spp. (chrysomelids), Cerotoma trifurcata (bean leaf beetle), Ceutorhynchus spp. (weevils), Ceutorhynchus assimilis (cabbage seedpod weevil), Ceutorhynchus napi (cabbage curculio), Chaetocnema spp. (chrysomelids), Colaspis spp. (soil beetles), Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar (plum curculio), Cotinus nitidis (Green June beetle), Crioceris asparagi (asparagus beetle), Cryptolestes ferrugineus (rusty grain beetle), Cryptolestes pusillus (flat grain beetle), Cryptolestes turcicus (Turkish grain beetle), Ctenicera spp. (wireworms), Curculio spp. (weevils), Cyclocephala spp. (grubs), Cylindrocpturus adspersus (sunflower stem weevil), Deporaus marginatus (mango leaf-cutting weevil), Dermestes lardarius (larder beetle), Dermestes maculates (hide beetle), Diabrotica spp. (chrysomelids), Epilachna varivestis (Mexican bean beetle), Faustinus cubae, Hylobius pales (pales weevil), Hypera spp. (weevils), Hypera postica (alfalfa weevil), Hyperdoes spp. (Hyperodes weevil), Hypothenemus hampei (coffee berry beetle), Ips spp. (engravers), Lasioderma serricorne (cigarette beetle), Leptinotarsa decemlineata (Colorado potato beetle), Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus (rice water weevil), Lyctus spp. (wood beetles/powder post beetles), Maecolaspis joliveti, Megascelis spp., Melanotus communis, Meligethes spp., Meligethes aeneus (blossom beetle), Melolontha melolontha (common European cockchafer), Oberea brevis, Oberea linearis, Oryctes rhinoceros (date palm beetle), Oryzaephilus mercator (merchant grain beetle), Oryzaephilus surinamensis (sawtoothed grain beetle), Otiorhynchus spp. (weevils), Oulema melanopus (cereal leaf beetle), Oulema oryzae, Pantomorus spp. (weevils), Phyllophaga spp. (May/June beetle), Phyllophaga cuyabana (chrysomelids), Phynchites spp., Popillia japonica (Japanese beetle), Prostephanus truncates (larger grain borer), Rhizopertha dominica (lesser grain borer), Rhizotrogus spp. (European chafer), Rhynchophorus spp. (weevils), Scolytus spp. (wood beetles), Shenophorus spp. (Billbug), Sitona lineatus (pea leaf weevil), Sitophilus spp. (grain weevils), Sitophilus granaries (granary weevil), Sitophilus oryzae (rice weevil), Stegobium paniceum (drugstore beetle), Tribolium spp. (flour beetles), Tribolium castaneum (red flour beetle), Tribolium confusum (confused flour beetle), Trogoderma variabile (warehouse beetle), and Zabrus tenebioides.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Dermaptera (earwigs).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Dictyoptera (cockroaches) including, but is not limited to, Blattella germanica (German cockroach), Blatta orientalis (oriental cockroach), Parcoblatta pennylvanica, Periplaneta americana (American cockroach), Periplaneta australoasiae (Australian cockroach), Periplaneta brunnea (brown cockroach), Periplaneta fuliginosa (smokybrown cockroach), Pyncoselus suninamensis (Surinam cockroach), and Supella longipalpa (brownbanded cockroach). In additional embodiments, the method of the present disclosure may be used to control members of the Order Diptera (true flies) including, but is not limited to, Aedes spp. (mosquitoes), Agromyza frontella (alfalfa blotch leafminer), Agromyza spp. (leaf miner flies), Anastrepha spp. (fruit flies), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies), Bactrocera cucurbitae (melon fly), Bactrocera dorsalis (oriental fruit fly), Ceratitis spp. (fruit flies), Ceratitis capitata (Mediterranea fruit fly), Chrysops spp. (deer flies), Cochliomyia spp. (screwworms), Contarinia spp. (Gall midges), Culex spp. (mosquitoes), Dasineura spp. (gall midges), Dasineura brassicae (cabbage gall midge), Delia spp., Delia platura (seedcorn maggot), Drosophila spp. (vinegar flies), Fannia spp. (filth flies), Fannia canicularis (little house fly), Fannia scalaris (latrine fly), Gasterophilus intestinalis (horse bot fly), Gracillia perseae, Haematobia irritans (horn fly), Hylemyia spp. (root maggots), Hypoderma lineatum (common cattle grub), Liriomyza spp. (leafminer flies), Liriomyza brassica (serpentine leafminer), Melophagus ovinus (sheep ked), Musca spp. (muscid flies), Musca autumnalis (face fly), Musca domestica (house fly), Oestrus ovis (sheep bot fly), Oscinella frit (frit fly), Pegomyia betae (beet leafminer), Phorbia spp., Psila rosae (carrot rust fly), Rhagoletis cerasi (cherry fruit fly), Rhagoletis pomonella (apple maggot), Sitodiplosis mosellana (orange wheat blossom midge), Stomoxys calcitrans (stable fly), Tabanus spp. (horse flies), and Tipula spp. (crane flies).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Hemiptera (true bugs) including, but is not limited to, Acrosternum hilare (green stink bug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed bug), Dagbertus fasciatus, Dichelops furcatus, Dysdercus suturellus (cotton stainer), Edessa meditabunda, Eurygaster maura (cereal bug), Euschistus heros, Euschistus servus (brown stink bug), Helopeltis antonii, Helopeltis theivora (tea blight plantbug), Lagynotomus spp. (stink bugs), Leptocorisa oratorius, Leptocorisa varicornis, Lygus spp. (plant bugs), Lygus hesperus (western tarnished plant bug), Maconellicoccus hirsutus, Neurocolpus longirostris, Nezara viridula (southern green stink bug), Phytocoris spp. (plant bugs), Phytocoris californicus, Phytocoris relativus, Piezodorus guildingi, Poecilocapsus lineatus (fourlined plant bug), Psallus vaccinicola, Pseudacysta perseae, Scaptocoris castanea, and Triatoma spp. (bloodsucking conenose bugs/kissing bugs).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Homoptera (aphids, scales, whiteflies, leaflhoppers) including, but is not limited to, Acrythosiphon pisum (pea aphid), Adelges spp. (adelgids), Aleurodes proletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixus floccosus (woolly whitefly), Aluacaspis spp., Amrasca bigutella bigutella, Aphrophora spp. (leafhoppers), Aonidiella aiirantii (California red scale), Aphis spp. (aphids), Aphis gossypii (cotton aphid), Aphis pomi (apple aphid), Aulacorthum solani (foxglove aphid), Bemisia spp. (whiteflies), Bemisia argentifolii, Bemisia tabaci (sweetpotato whitefly), Brachycolus noxius (Russian aphid), Brachycorynella asparagi (asparagus aphid), Brevennia rehi, Brevicoryne brassicae (cabbage aphid), Ceroplastes spp. (scales), Ceroplastes rubens (red wax scale), Chionaspis .sp/?.(scales), Chrysomphalus spp. (scales), Coccus spp. (scales), Dysaphis plantaginea (rosy apple aphid), Empoasca spp. (leafhoppers), Eriosoma lanigerum (woolly apple aphid), Icerya purchasi (cottony cushion scale), Idioscopus nitidulus (mango leafhopper), Laodelphax striatellus (smaller brown planthopper), Lepidosaphes spp., Macrosiphum spp., Macrosiphum euphorbiae (potato aphid), Macrosiphum granarium (English grain aphid), Macrosiphum rosae (rose aphid), Macrosteles quadrilineatus (aster leafhopper), Mahanarva frimbiolata, Metopolophium dirhodum (rose grain aphid), Mictis longicomis, Myzus spp., Myzus persicae (green peach aphid), Nephotettix spp. (leafhoppers), Nephotettix cinctipes (green leafhopper), Nilaparvata lugens (brown planthopper), Parlatoria pergandii (chaff scale), Parlatoria ziziphi (ebony scale), Peregrinus maidis (corn delphacid), Philaenus spp. (spittlebugs), Phylloxera vitifoliae (grape phylloxera), Physokermes piceae (spruce bud scale), Planococcus spp. (mealybugs), Pseudococcus spp. (mealybugs), Pseudococcus brevipes (pine apple mealybug), Quadraspidiotus perniciosus (San Jose scale), Rhapalosiphum spp. (aphids), Rhapalosiphum maida (corn leaf aphid), Rhapalosiphum padi (oat bird-cherry aphid), Saissetia spp. (scales), Saissetia oleae (black scale), Schizaphis graminum (greenbug), Sitobion avenae (English grain aphid), Sogatella furcifera (white-backed planthopper), Therioaphis spp. (aphids), Toumeyella spp. (scales), Toxoptera spp. (aphids), Trialeurodes spp. (whiteflies), Trialeurodes vaporariorum (greenhouse whitefly), Trialeurodes abutiloneus (bandedwing whitefly), Unaspis spp. (scales), Unaspis yanonensis (arrowhead scale), and Zulia entreriana. In at least some embodiments, the method of the present disclosure may be used to control Myzus persicae.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Hymenoptera (ants, wasps, and bees) including, but not limited to, Acromyrrmex spp., Athalia rosae, Atta spp. (leafcutting ants), Camponotus spp. (carpenter ants), Diprion spp. (sawflies), Formica spp. (ants), Iridomyrmex humilis (Argentine ant), Monomorium ssp., Monomorium minumum (little black ant), Monomorium pharaonis (Pharaoh ant), Neodiprion spp. (sawflies), Pogonomyrmex spp. (harvester ants), Polistes spp. (paper vvasps), So!enopsis spp. (fire ants), Tapoinoma sessile (odorous house ant), Tetranomorium spp. (pavement ants), Vespula spp. (yellow jackets), and Xylocopa spp. (carpenter bees).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Isoptera (termites) including, but not limited to, Coptotermes spp., · Coptotermes curvignathus, Coptotermes frenchii, Coptotermes formosanus (Formosan subterranean termite), Cornitermes spp. (nasute termites), Cryptotermes spp. (drywood termites), Heterotermes spp. (desert subterranean termites), Heterotermes aureus, Kalotermes spp. (drywood termites), Incistitermes spp. (drywood termites), Macrotermes spp. (fungus growing termites), Marginitermes spp. (drywood termites), Microcerotermes spp. (harvester termites), Microtermes obesi, Procornitermes spp., Reticulitermes spp. (subterranean termites), Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes (eastern subterranean termite), Reticulitermes hageni, Reticulitermes hesperus (western subterranean termite), Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, Reticulitermes virginicus, Schedorhinotermes spp., and Zootermopsis spp. (rotten-wood termites).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Lepidoptera (moths and butterflies) including, but not limited to, Achoea janata, Adoxophyes spp., Adoxophyes orana, Agrotis spp. (cutworms), Agrotis ipsilon (black cutworm), Alabama argillacea (cotton leafworm), Amorbia cuneana, Amyelosis transitella (navel orangeworm), Anacamptodes defectaria, Anarsia lineatella (peach twig borer), Anomis sabulifera (jute looper), Anticarsia gemmatalis (velvetbean caterpillar), Archips argyrospila (fruittree leafroller), Archips rosana (rose leaf roller), Argyrotaenia spp. (tortricid moths), Argyrotaenia citrana (orange tortrix), Autographa gamma, Bonagota cranaodes, Borbo cinnara (rice leaf folder), Bucculatrix thurberiella (cotton leafperforator), Caloptilia spp. (leaf miners), Capua reticulana, Carposina niponensis (peach fruit moth), Chilo spp., Chlumetia transversa (mango shoot borer), Choristoneura rosaceana (obliquebanded leafroller), Chrysodeixis spp., Cnaphalocerus medinalis (grass leafroller), Colias spp., Conpomorpha cramerella, Cossus cossus (carpenter moth), Crambus spp. (Sod webworms), Cydiafunebrana (plum fruit moth), Cydia molesta (oriental fruit moth), Cydia nignicana (pea moth), Cydia pomonella (codling moth), Darna diducta, Diaphania spp. (stem borers), Diatraea spp. (stalk borers), Diatraea saccharalis (sugarcane borer), Diatraea graniosella (southw ester corn borer), Earias spp. (bollworms), Earias insulata (Egyptian bollworm), Earias vitella (rough northern bollworm), Ecdytopopha aurantianum, Elasmopalpus lignosellus (lesser cornstalk borer), Epiphysias postruttana (light brown apple moth), Ephestia spp. (flour moths), Ephestia cautella (almond moth), Ephestia elutella (tobbaco moth), Ephestia kuehniella (Mediterranean flour moth), Epimeces spp., Epinotia aporema, Erionota thrax (banana skipper), Eupoecilia ambiguella (grape berry moth), Euxoa auxiliaris (army cutworm), Feltia spp. (cutworms), Gortyna spp. (stemborers), Grapholita molesta (oriental fruit moth), Hedylepta indicata (bean leaf webber), Helicoverpa spp. (noctuid moths), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (bollworm/corn earworm), Heliothis spp. (noctuid moths), Heliothis virescens (tobacco budworm), Hellula undalis (cabbage webworm), Indarbela spp. (root borers), Keiferia lycopersicella (tomato pinworm), Leucinodes orbonalis (eggplant fruit borer), Leucoptera malifoliella, Lithocollectis spp., Lobesia botrana (grape fruit moth), Loxagrotis spp. (noctuid moths), Loxagrotis albicosta (western bean cutworm), Lymantria dispar (gypsy moth), Lyonetia clerkella (apple leaf miner), Mahasena corbetti (oil palm bagworm), Malacosoma spp. (tent caterpillars), Mamestra brassicae (cabbage armyworm), Maruca testulalis (bean pod borer), Metisa plana (bagworm), Mythimna unipuncta (true armyworm), Neoleucinodes elegantalis (small tomato borer), Nymphula depunctalis (rice caseworm), Operophthera brumata (winter moth), Ostrinia nubilalis (European corn borer), Oxydia vesulia, Pandemis cerasana (common currant tortrix), Pandemis heparana (brown apple tortrix), Papilio demodocus, Pectinophora gossypiella (pink bollworm), Peridroma spp. (cutworms), Peridroma saucia (variegated cutworm), Perileucoptera coffeella (white coffee leafminer), Phthorimaea operculella (potato tuber moth), Phyllocnisitis citrella, Phyllonorycter spp. (leafminers), Pieris rapae (imported cabbageworm), Plathypena scabra, Plodia interpunctella (Indian meal moth), Plutella xylostella (diamondback moth), Polychrosis viteana (grape berry moth), Prays endocarpa, Prays oleae (olive moth), Pseudaletia spp. (noctuid moths), Pseudaletia unipunctata (armyworm), Pseudoplusia includens (soybean looper), Rachiplusia nu, Scirpophaga incertulas, Sesamia spp. (stemborers), Sesamia inferens (pink rice stem borer), Sesamia nonagrioides, Setora nitens, Sitotroga cerealella (Angoumois grain moth), Sparganothis pilleriana, Spodoptera spp. (armyworms), Spodoptera exigua (beet armyworm), Spodoptera fugiperda (fall armyworm), Spodoptera oridania (southern armyworm), Synanthedon spp. (root borers), Thecla basilides, Thermisia gemmatalis, Tineola bisselliella (webbing clothes moth), Trichoplusia ni (cabbage looper), Tuta absoluta, Yponomeuta spp., Zeuzera coffeae (red branch borer), and Zeuzera pyrina (leopard moth). In at least some embodiments, the method of the present disclosure may be used to control Spodoptera exigua.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Mallophaga (chewing lice) including, but not limited to, Bovicola ovis (sheep biting louse), Menacanthus stramineus (chicken body louse), and Menopon gallinea (common hen house).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Orthoptera (grasshoppers, locusts, and crickets) including, but not limited to, Anabrus simplex (Mormon cricket), Gryllotalpidae (mole crickets), Locusta migratoria, Melanoplus spp. (grasshoppers), Microcentrum retinerve (angularwinged katydid), Pterophylla spp. (kaydids), chistocerca gregaria, Scudderia furcata (forktailed bush katydid), and Valanga nigricorni.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Phthiraptera (sucking lice) including, but not limited to, Haematopinus spp. (cattle and hog lice), Linognathus ovillus (sheep louse), Pediculus humanus capitis (human body louse), Pediculus humanus humanus (human body lice), and Pthirus pubis (crab louse).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Siphonaptera (fleas) including, but not limited to, Ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea), and Pulex irritans (human flea).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Thysanoptera (thrips) including, but not limited to, Frankliniella fusca (tobacco thrips), Frankliniella occidentalis (western flower thrips), Frankliniella shultzei, Frankliniella williamsi (corn thrips), Heliothrips haemorrhaidalis (greenhouse thrips), Riphiphorothrips cruentatus, Scirtothrips spp., Scirtothrips citri (citrus thrips), Scirtothrips dorsalis (yellow tea thrips), Taeniothrips rhopalantennalis, and Thrips spp.

In additional embodiments, the method of the present disclosure may be used to control members of the Order Thysanura (bristletails) including, but not limited to, Lepisma spp. (silverfish) and Thermobia spp. (firebrats).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Acari (mites and ticks) including, but not limited to, Acarapsis woodi (tracheal mite of honeybees), Acarus spp. (food mites), Acarus siro (grain mite), Aceria mangiferae (mango bud mite), Aculops spp., Aculops lycopersici (tomato russet mite), Aculops pelekasi, Aculus pelekassi, Aculus schlechtendali (apple rust mite), Amblyomma americanum (lone star tick), Boophilus spp. (ticks), Brevipalpus obovatus (privet mite), Brevipalpus phoenicis (red and black flat mite), Demodex spp. (mange mites), Dermacentor spp. (hard ticks), Dermacentor variabilis (american dog tick), Dermatophagoides pteronyssinus (house dust mite), Eotetranycus spp., Eotetranychus carpini (yellow spider mite), Epitimerus spp., Eriophyes spp., Ixodes spp. (ticks), Metatetranycus spp., Notoedres cati, Oligonychus spp., Oligonychus coffee, Oligonychus lcus (southern red mite), Panonychus spp., Panonychus cltrl (citrus red mite), Panonychus ulml (European red mite), Phyllocoptruta olelvora (citrus rust mite), Polyphagotarsonemun latus (broad mite), Rhlpicephalus sanguineus (brown dog tick), Rhlzoglyphus spp. (bulb mites), Sarcoptes scablel (itch mite), Tegolophus perseaflorae, Tetranychus spp., Tetranychus urticae (twospotted spider mite), and Varroa destructor (honey bee mite).

In additional embodiments, the method of the present disclosure may be used to control members of the Order Nematoda (nematodes) including, but not limited to, Aphelenchotdes spp. (bud and leaf& pine wood nematodes), Belonolalmus spp. (sting nematodes), Crlconemella spp. (ring nematodes), Dtrofilaria immltls (dog heartwom), Dltylenchusspp. (stem and bulb nematodes), Heterodera spp. (cyst nematodes), Heterodera zeae (corn cyst nematode), Hirschmanniella spp. (root nematodes), Hoplolalmus spp. (lance nematodes), Meloidogyne spp. (root knot nematodes), Meloidogyne Incognita (root knot nematode), Onchocerca volvulus (hook-tail worm), Pratylenchus spp. (lesion nematodes), Radopholus spp. (burrowing nematodes), and Rotylenchus renlformls (kidney-shaped nematode).

In at least some embodiments, the method of the present disclosure may be used to control at least one insect in one or more of the Orders Lepldoptera, Coleoptera, Homoptera, Hemlptera, Thysanoptera, Isoptera, Orthoptera, Dlptera, Hymenoptera, and Slphonaptera, and at least one mite in the Order Acarl.

Example A: Bioassays on Beet Armyworm ("BAW") and Corn Earworm ("CEW") and Cabbage Looper ("CL")

BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops, hi various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be resistant to certain insecticides. CL feeds on a wide variety of cultivated plants and weeds. It feeds readily on crucifers, and has been reported damaging broccoli, cabbage, cauliflower, Chinese cabbage, collards, kale, mustard, radish, rutabaga, turnip, and watercress. Other vegetable crops injured include beet, cantaloupe, celery, cucumber, lima bean, lettuce, parsnip, pea, pepper, potato, snap bean, spinach, squash, sweet potato, tomato, and watermelon. CL is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.

Certain molecules disclosed in this document were tested against BAW, CEW and CL using procedures described in the following examples. In the reporting of the results, the "Mortality Rating for Beet Armyworm (BAW), Corn Earworm (CEW), and Cabbage Looper (CL) Insects" was used (See Table Section).

BlOASSAYS ON BAW {Spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 xL of 90:10 acetone- water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the tables entitled "Table 1" (See Table Section).

BIOASSAYS ON CEW (Helicoverpa zed)

Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg /cm² of the test compound (dissolved in 50 of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled "Table 1" (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One to five second instar CL larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg /cm² of the test compound (dissolved in 50 Ε of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C, 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled "Table 1" (See Table Section).

Example B: Bioassays on Green Peach Aphid ("GPA") (Myzus persicae).

GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the "Mortality Rating for Green Peach Aphid (GPA) Insects" was used (See Table Section). ,

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/MeOH (1 :1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in H₂0 to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/MeOH (1 : 1 ) solvent. Treated plants were held in a holding room for three days at approximately 25° C and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, "A Method of Computing the Effectiveness of an Insecticide" J. Econ. Entomol. 18 (1925), pp.265-267) follows.

Corrected % Control = 100 * (X - Y) / X

where

X = No. of live aphids on solvent check plants and

Y = No. of live aphids on treated plants

The results are indicated in the tables entitled "Table 1" (See Table Section).

Example C: BlOASSAYS ON Yellow Fever Mosquito "YFM" (Aedes aegypti).

YFM prefers to feed on humans during the daytime and is most frequently found in or near human habitations. YFM is a vector for transmitting several diseases. It is a mosquito that can spread the dengue fever and yellow fever viruses. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and up to 50% of severely affected persons without treatment will die from yellow fever. There are an estimated 200,000 cases of yellow fever, causing 30,000 deaths, worldwide each year. Dengue fever is a nasty, viral disease; it is sometimes called "breakbone fever" or "break- heart fever" because of the intense pain it can produce. Dengue fever kills about 20,000 people annually. Consequently, because of the above factors control of this pest is important. Furthermore, molecules that control this pest (YFM), which is known as a sucking pest, are useful in controlling other pests that cause human and animal suffering.

Certain molecules disclosed in this document were tested against YFM using procedures described in the following paragraph. In the reporting of the results, the "TABLE 4: Mortality Rating for Yellow Fever Mosquitos (YFM)" was used (See Table Section).

Master plates containing 400 μg of a molecule dissolved in 100

of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used. A master plate of assembled molecules contains 15 μΐ, per well. To this plate, 135 xL of a 90:10 watenacetone mixture is added to each well. A robot (Biomek® NXP Laboratory Automation Workstation) is programmed to dispense 15 aspirations from the master plate into an empty 96-well shallow plate ("daughter" plate). There are 6 reps ("daughter" plates) created per master. The created daughter plates are then immediately infested with YFM larvae.

The day before plates are to be treated, mosquito eggs are placed in Millipore water containing liver powder to begin hatching (4 g. into 400 ml). After the daughter plates are created using the robot, they are infested with 220 of the liver powder/larval mosquito mixture (about 1 day-old larvae). After plates are infested with mosquito larvae, a non- evaporative lid is used to cover the plate to reduce drying. Plates are held at RT for 3 days prior to grading. After 3 days, each well is observed and scored based on mortality.

The results are indicated in Table 1 (See Table Section).

TABLE 1 shows the pesticidal activities of the pyrazolopyrimidine compounds against several insects: beet armyworm (BAW), corn earworm (CEW), cabbage looper (CL), green peach aphid (GPA), and yellow fever mosquitos (YFM). The mortality efficiency of the pyrazolopyrimidine compounds against BAW, CEW, CL and GPA insects is determined after five days of treatment. The mortality efficiency against YFM is determined after three days of treatment. The mortality efficiency is rated as shown in TABLES 2-4.

TABLE 1 shows the mortality study results of the pyrazolopyrimidine compounds 1-96 against several insects: beet armyworm (BAW), corn earworm (CEW), cabbage looper (CL), green peach aphid (GPA), and yellow fever mosquitos (YFM).

TABLE 1

Compound BAW CEW CL GPA YFM

No. Results Results Results Results Results

1 A A C D A

2 A A C D B

3 A A C C C

4 A A C C C

5 A A C C C

6 A A C C C

7 A A C C C

8 A A C C C

9 A D C C C

10 A A C C C

1 1 C C C C D

12 D D C C C

13 A B C D C

14 A A C D D

15 A A C D D

16 D B C C C

17 A A C C D

18 A A C B D Compound BAW CEW CL GPA YFM No. Results Results Results Results Results

19 A A C C D

20 A A C B A

21 A D C D D

22 A A C C C

23 A A C B D

24 D D C C C

25 D D C C C

26 A D C B D

27 A A C B B

28 A A C C C

29 A D C C C

30 D D C C D

31 D D C C C

32 A B C D D

33 A A C C C

34 B D C C C

35 A A C B B

36 D A C C D

37 A C A C B

38 A C D C C

39 C C C C C

40 A A C C C

41 A A C D D

42 C C C C D

43 A A C B A

44 A A C C C

45 D A C C D

46 A A C C C

47 B D C C D

48 A A C B D

49 A A C C C

50 D D C D C

51 C C C B C

52 A A C C C

53 A A C B D Compound BAW CEW CL CPA YFM No. Results Results Results Results Results

54 D D C C C

55 A D C C C

56 A A C C C

57 C C C C D

58 C C C C D

59 C C C C C

60 A A C B D

61 D D C C C

62 D D C C C

63 A A C B A

64 A A C D A

65 A D C C C

66 A A C C C

67 A A C B D

68 A A C B A

69 D D C C D

70 A A C C D

71 A A C C C

72 C C C C C

73 A A C C D

74 C C C C D

75 A A C C C

76 A A C C C

77 A D C C C

78 D D C C C

79 D D C C C

80 C C C C D

81 C C c C D

82 A A c C C

83 A D c C D

84 A D c D C

85 D D c C D

86 A B C C C

87 D D C C D

88 A A c C C Compound BAW CEW CL GPA YFM

No. Results Results Results Results Results

89 D D C C C

90 D A C C C

91 D D C C C

92 D D C C D

93 D D C C C

94 C C C C C

95 C C C C C

96 A A C C C

TABLE 2: Mortality Rating for Beet Armyworm (BAW), Corn Earworm (CEW), and Cabbage Looper (CL) Insects

TABLE 3 : Mortality Rating for Green Peach Aphid (GPA) Insects

TABLE 4: Mortality Rating for Yellow Fever Mosquitos (YFM)

% Control (or Mortality) Rating

> 80 A

More than 0 - Less than 80 B

Not Tested C

No activity noticed in this bioassay D Embodiments of the present disclosure further include methods of controlling pests that comprises applying an pesticidal composition comprising a pyrazolopyrimidine compound of the general formula I near a population of pests.

In some embodiments, the pesticidal composition may comprise a pyrazolopyrimidine compound of the general formula I in a phytologically-acceptable inert carrier (e.g., solid carrier or liquid carrier), and may be applied near a population of pests.

The control of insects may be achieved by applying an pesticidally effective amount of the pyrazolopyrimidine-based composition in form of sprays, topical treatment, gels, seed coatings, microcapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants aerosols, dusts, or the like.

In some embodiments, the pyrazolopyrimidine-based pesticidal compositions may be in the form of solid. Non-limiting examples of the solid forms may include power, dust or granular formulations.

In some embodiments, the pyrazolopyrimidine-based pesticidal compositions may be in the form of liquid formulation. Examples of the liquid forms may include, but not limited to, dispersion, suspension, emulsion or solution in appropriate liquid carrier.

In some embodiments, the pyrazolopyrimidine-based pesticidal compositions may be in the form of liquid dispersion, wherein the pyrazolopyrimidine compound may be dispersed in water or other agriculturally suitable liquid carrier.

In some embodiments, the pyrazolopyrimidine-based pesticidal compositions may be in the form of solution in an appropriate organic solvent. In one embodiment, the spray oils, which are widely used in agricultural chemistry, may be used as the organic solvent for the pyrazolopyrimidine-based pesticidal compositions.

When desired, the pyrazolopyrimidine-based pesticidal compositions may be used in conjunction with at least one of other insecticides, fungicides and herbicides to obtain control of a wider variety of pests, diseases and weeds. When used in conjunction with other insecticides or fungicides or herbicides, the pyrazolopyrimidine-based pesticidal compositions may be formulated with the other insecticides or fungicides or herbicide, or applied sequentially with the other insecticides or fungicides or herbicides.

The following examples serve to explain embodiments of the present disclosure in more detail. These examples are not to be construed as being exhaustive or exclusive as to the scope of the disclosure. EXAMPLES

Example 1

Preparation of 4-chloro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile

[Compound IV-1]

IV-1 To a solution of 5-cyano-4-oxo-2,6-bis(trifluoromethyl)-4H-pyrimidin-3-ide potassium salt (prepared as in Parker, M. Η. et al. Synth. Commun. 2004, 34, 903-907; 23 g, 78 mmol) in MeCN (250 mL) was added POCl₃ (10.89 mL, 117 mmol), which formed an off-white suspension. The mixture was heated at 65° C for two hours (h) and then was cooled to RT. The mixture was filtered over a Buchner funnel, and the white solid material was washed with MeCN (4 x 25 mL). The filtrate was concentrated under vacuum at 35° C to give golden oil which was diluted with CH₂C1₂ (300 mL) and washed with warm distilled water (35° C) and brine. The organic layer was dried over magnesium sulfate (MgS0₄), filtered and concentrated under vacuum to give golden oil residue. The oil was Kugelrohr distilled at a temperature of 95° C and a pressure of about five mbar to provide Compound IV-1 as light yellow oil (18.36 g, 81%): ¹³C NMR (101 MHz, CDC1₃) δ 167.48, 160.80, 160.41, 160.03, 159.64, 158.77, 157.87, 157.45, 157.06, 122.58, 121.89, 119.87, 119.14, 1 17.10, 116.38, 1 14.33, 1 13.63, 109.69, 108.85; ^,9F NMR (376 MHz, CDC1₃) δ -67.25 (s), -70.54 (s); EIMS: m/z 275 ([M]⁺). Example 2

Preparation of 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-^pyrimidin-3-amines

[Compound V-l]

V-l

To a solution of 4-c oro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile IV-1 (1 equivalent) in 1,4-dioxane (3 mL) was added an appropriate solution of hydrazine (1 equivalent) dissolved in 1 ,4-dioxane (2-5 mL). When hydrazine hydrochlorides were used, they were pre- treated with TEA (1 equivalent). The mixture was stirred at RT from 30 minutes (min) to 24 h. The resulting suspension was then treated with TEA (2 equivalents) and heated at 95° C from two h to 24 h. After cooling, the mixture was purified by column chromatography to give 4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-c ]pyrimidin-3-amines as Compounds V-2 to V-11.

The hydrazines may include: (2,6-dichloro-4-(trifluoromethyl)phenyl)hydrazine, (2- chloro-6-fluoro-4-(trifluoromethyl)phenyl)hydrazine, (2,4-dichlorophenyl)hydrazine, (3,5- dichlorophenyl)hydrazine hydrochloride, 3-chloro-2-hydrazinyl-5-(trifluoromethyl)pyridine, (2,4,6-trichlorophenyl)hydrazine, (2,6-dichloro-4-((trifluoromethyl)thio)phenyl)hydrazine (as prepared in WO 2005/090313 by Critcher, D. J. et al), (2,6-dichloro-4- (trifluoromethoxy)phenyl)hydrazine (as prepared in WO 2005/090313 by Critcher, D. J. et al.), (3,4,5-trichlorophenyl)hydrazine hydrochloride, or (2-phenoxyphenyl) hydrazine hydrochloride.

Compounds V-2 to V-11 in TABLE 5 were made in accordance with the procedure disclosed in Example 2. TABLE 5

Example 3

Preparation of bis-terf-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-yl)carbamate [Compound V-12] and

tert-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H- pyrazolo[3,4-d]pyrimidin-3-yl)carbamate

[Compound V-13]

V-2 V-12 V-13

To a stirred solution of Compound V-2 (100 mg, 0.207 mmol) in CH₂C1₂ (2.1 mL) was added di-tert-butyl carbonate (54 mg, 0.248 mmol) followed by DMAP (25 mg, 0.207 mmol). The reaction mixture was stirred at RT for 3 h. Then, hydrochloric acid (HCl, 1 N, 4 mL) was added and the mixture was stirred for an additional 15 min. The solution was extracted with ethyl acetate (EtOAc) and washed with water and brine. The organic phase was dried with MgS0₄, filtered and concentrated under vacuum. The residue was purified via radial chromatography (6:1 hexane-EtOAc). The first isolated fraction (Rf = 0.41) afforded Compound V-12 as a yellow solid (97 mg; 69%): Ή NMR (400 MHz, CDC1₃) δ 7.82 (s, 2H), 1.43 (s, 18H). ESIMS: m/z 684 ([M+H]⁺). The second isolated fraction

0.30) afforded Compound V-13 as a yellow solid (32 mg; 27%): Ή NMR (400 MHz, CDC1₃) δ 7.85 (s, 2H), 6.51 (s, 1H), 1.36 (s, 9H); ESIMS: m/z 584 ([M+H]⁺). Examp!e 4

Preparation of iV-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H- pyrazolo[3,4-i/Jpyrimidin-3-yl)pentanamide

-14]

V-2 V-14

To a solution of Compound V-2 (100 mg, 0.21 mmol) and TEA (60 mg, 0.59 mmol) in anhydrous CH₂C1₂ (2.5 mL) was added DMAP (61 mg, 0.49 mmol) and pentanoyl chloride (30.4 mg, 0.25 mmol). The reaction mixture was stirred for two h under nitrogen (N₂) at RT. The mixture was diluted with distilled water (10 mL) and extracted with EtOAc (2 x 15 mL). The combined organic phase was concentrated under vacuum to give a residue, which was purified by preparative thin layer chromatography to afford Compound V-14 as a yellow solid (60 mg, 51.1%): mp 169.4° C -171.8° C; ^]H NMR (300 MHz, OMSO-d₆) δ 11.00 (s, 1H), 8.44 (s, 2H), 2.31 (t, J= 7.2 Hz, 2H), 1.43-1.38 (m, 2H), 1.1 1-1.03 (m, 2H), 0.79 (t, J= 7.2 Hz, 3H); ESIMS: m/z 566 ([M-H]^").

Electrophiles for the above reaction were: 4-chlorobutyryl chloride, dichloroacetyl chloride, isopropyl chloroformate, 3-cyanopropanoyl chloride, or 3-methylbutanoyl chloride.

Compounds V-15 to V-19 in TABLE 6 were made in accordance with the procedure disclosed in Example 4. TABLE 6

Example 5

Preparation of bis-2,2,2-trichloroethyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo [3,4-</] pyrimidin-3-yl)carbamate

[Compound V-20]

V-2 V-20 To a 0° C solution of Compound V-2 (107 mg, 0.221 mmol) and N-ethyl-N- isopropylpropan-2-amine (96 iL, 0.553 mmol) in THF (2.2 mL), 2,2,2-trichloroethyl carbonochloridate (38 μL, 0.276 mmol) was added dropwisely. The mixture was stirred at RT for three h. Then, one equivalent of N-ethyl-N-isopropylpropan-2-aniine and one equivalent of chloroformate were added, and the mixture was heated at 50° C for three h. The mixture was diluted with EtOAc (10 mL). The organic layer was washed with water and brine, dried over MgS0₄ and evaporated. The residue was triturated with hexane-EtOAc solution (6:1), filtered and dried to afford Compound V-20 as a tan solid (103 mg, 56%): 1H NMR (400 MHz, CDC1₃) δ 7.83 (s, 2H), 4.98 (d, J= 11.8 Hz, 2H), 4.71 (d, J= 11.8 Hz, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.32, -66.71, -70.03; ESIMS: m/z 835 ([M+H]⁺).

Example 6

Preparation of methyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-

2H-pyrazolo [3,4-rf] pyrimidin-3-yl)carbamate

[Compound V-21]

V-2 V-21

To a stirred solution of Compound V-2 (1 10 mg, 0.227 mmol) in CH₂C1₂ (2.3 mL) was added methyl chloroformate (18 μί, 0.227 mmol) followed by DMAP (28 mg, 0.227 mmol). The reaction mixture was stirred at RT overnight. The mixture was diluted with CH₂C1₂ (20 mL) and washed with 1 N HCl, saturated aqueous sodium bicarbonate (NaHC0₃) solution, water and brine. The solution was dried over MgS0₄, filtered and concentrated under vacuum. The residue was purified via radial chromatography (4:1 hexane-EtOAc; Rf= 0.25) to afford Compound V-21 as a tan solid (57 mg, 46%): 1H NMR (400 MHz, CDC1₃) δ 7.86 (s, 2H), 7.25 (br, 1H), 3.69 (s, 3H); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.30, -67.17, -70.14; ESIMS: m/z 542 ([M+H]⁺).

Example 7

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-7V-(3,3-dimethylbutyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine

-22]

V-2 V-22

To a mixture of Compound V-2 (100 mg, 0.21 mmol, 1 equivalent), l-bromo-3,3- dimethylbutane (69.3 mg, 0.42 mmol, 2 equivalents) in MeCN (3.0 mL) was added potassium iodide (KI, 34.9 mg, 0.21 mmol, 1 equivalent) and K₃P0₄ (89.2 mg, 0.42 mmol, 2 equivalents). The dark mixture was heated at 60° C for five h. The cooled mixture was diluted with EtOAc and washed with water (10 mL). The organic phase was concentrated under vacuum to give a residue, which was purified by preparative thin layer chromatography to afford Compound V-22 as a yellow solid (23 mg, 19.6%): Ή NMR (300 MHz, CDC1₃) δ 7.84 (s, 2H), 5.20 (br, 1H), 2.92.84 (m, 2H), 1.46-1.41 (m, 2H), 0.77 (s, 9H); ESIMS: m/z 568 [(M+H)]⁺.

Electrophiles used in the above reaction may include: 5-bromopentanenitrile, 1 -bromo-

4-methoxybutane, 5-bromopentan-l-ol, 4-bromobut-l-ene, l-bromopent-2-yne, l-bromo-3- (ethylsulfanyl)propane, l-bromo-2-methylpentane, 4-bromo-2-methyl-2-butene, 2- (bromomethyl)thiazole, or 2-[(2-bromoethyl)sulfanyl]propane.

Compounds V-23 to V-32 in TABLE 7 were made in accordance with the procedure disclosed in Example 7. ABLE 7

s,

Example 8

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-N-pentyl-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyriimdin-3-amine

-33]

V-2 V-33

To a solution of Compound V-2 (0.1 g, 0.21 mmol, 1 equivalent) and 1 -iodopentane (83.2 mg, 0.42 mmol) in MeCN (3.0 mL) was added K₃P0₄ (89.2 mg, 0.42 mmol). The dark mixture was heated to 60° C for 8 h. The cooled mixture was diluted with EtOAc (50 mL) and washed with water (10 mL). The organic phase was dried over sodium sulfate ( a₂S0₄), filtered and concentrated under vacuum to give a yellow/orange solid residue which was purified by Preparative thin layer chromatography to afford Compound V-33 as a yellow solid (70 mg, 61.1%): mp 98° C-101° C; Ή NMR (300 MHz, CDC1₃) 7.82 (s, 2H), 5.26 (br, 1H), 2.91- 2.81 (m, 2H), 1.56-1.49 (m, 2H), 1.25-1.18 (m, 4H), 0.86 (t, J= 6.9 Hz, 3H); ESIMS: m/z 554 ([M+H]⁺).

Electrophiles used (1-9 equivalents) may include the following: (iodomethyl)cyclopentane, l-iodo-4-methylpentane, or 2-(3-iodopropyl)-2-methyl-l,3- dioxolane.

Compounds V-34 to V-36 in TABLE 8 were made in accordance with the procedure disclosed in Example 8.

TABLE 8

Example 9

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyI)-N-((3,3-dimethyloxiran-2- yl)methyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidm-3-amine

[Compound V-37]

To a stirred solution of Compound V-30 (65 mg, 0.12 mmol) in CH₂C1₂ (3.0 mL) was added NaHC0₃ (20.2 mg, 0.24 mmol) and meto-chloroperoxybenzoic acid (m-CPBA, 31 mg, 0.18 mmol). The mixture was stirred at RT for one h, and then treated with saturated sodium sulfite aqueous solution (Na₂S0₃, 10 mL) and extracted with CH₂C1₂ (2 x 10 mL). The organic phase was dried over Na₂S0₄, filtered and concentrated under vacuum. The resulting residue was purified by preparative thin layer chromatography to afford Compound V-37 as a yellow solid (30 mg, 45%): Ή NMR (300 MHz, CDC1₃) δ 7.84 (s, 2H), 5.54 (s, 1H), 3.22-3.10 (m, 1 H), 3.00-2.88 (m, 2H), 1.32 (s, 3H), 1.20 (s, 3H); ESIMS: m/z 568 [(M+H)f . Ex ample 10

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-N-(2-(methylsulfonyl)ethyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo [3,4-d] pyrimidin-3-amine

-38]

V-2 V-38

Procedure was adapted from Yeom, C-E, et. al. Tetrahedron, 2006, 63, 904. A solution of Compound V-2 (100 mg, 0.21 mmol), methyl vinyl sulfone (20 μί, 0.22 mmol) and 1,8- diazabicycloundec-7-ene (DBU, 3 drops) in DMF (3 mL) was heated to 100 °C for 1 h. The cooled mixture was diluted with water and extracted with EtOAc (2 x 10 mL). The combined organic phase was washed with brine (10 mL), dried over anhydrous Na₂S0₄ and concentrated to give a residue that was purified by preparative thin layer chromatography to afford Compound V-38 as a yellow solid (55 mg, 44%): 1H NMR (300 MHz, CDC1₃) δ 7.87 (s, 2H), 5.96 (s, 1H), 3.55 (q, J = 5.9 Hz, 2H), 3.17 (dd, J= 6.8, 4.6 Hz, 2H), 2.98 (s, 3H); ESIMS: m/z 590 [(M+H)]⁺.

Example 11

Preparation of ethyl 3-((2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifIuoromethyl)-2H-pyrazolo [3,4-d] pyrimidin-3-yl)amin o)pr opan oate

-39]

V-2 V-39 Procedure was adapted from Yeom, C-E, et. al. Tetrahedron, 2006, 63, 904. A solution of Compound V-2 (100 mg, 0.21 mmol), ethyl acrylate (22 mg, 0.22 mmol) and DBU (3 drops) in DMF (3 mL) was heated to 100 °C for 1 h. The cooled mixture was diluted with water and extracted with EtOAc (2 x 10 mL). The combined organic phase was washed with brine (10 mL), dried over Na₂S0₄ and concentrated under vacuum to give a residue that was purified by preparative thin layer chromatography to afford Compound V-39 as a yellow solid (55 mg, 44%): Ή NMR(300 MHz, CDC1₃) δ 7.84 (s, 2H), 6.03 (s, 1H), 4.18 (q, J= 7.2 Hz, 2H), 3.18 (q, J= 5.9 Hz, 2H), 2.48 (t, J= 5.8 Hz, 2H), 1.27 (t, J= 7.1 Hz, 3H); ESIMS: m/z 584

[(M+H)]⁺.

Example 12

Preparation of Preparation of 2-(2,6-dichloro-4-(trifluoroniethyl)phenyl)-N-(2- (isopropylsulmiyl)ethyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyruTudin-3-amine

[Compound V-40]

V-32 V-40

Procedure adapted from Alder, C. M. et al, WO 2010/106016, a solution of Compound V-32 (120 mg, 0.206 mmoL) in MeOH/water (2:1 , 10.0 mL) was treated with oxone (potassium peroxymonosulfate, 192 mg, 0.312 mmol) and stirred at 0 °C for six h under nitrogen atmosphere. The mixture was extracted with EtOAc (2 x 10 mL), and the combined organic phase was dried over Na₂S0₄, filtered and concentrated to give a residue, which was purified by column chromatography to afford Compound V-40 as a yellow solid (50 mg, 41 %): mp 139° C -140° C; Ή NMR (300 MHz, CDC1₃) δ 7.85 (s, 2H), 6.52 (s, 1H), 3.63-3.51 (m, 2H), 2.92- 2.68 (m, 3H), 1.28 (dd, J = 17.8, 6.7 Hz, 6H); ESIMS: m/z 602 [(M+H)]⁺. Example 13

Preparation of 5-((2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H- pyrazolo[3,4-d]pyrimidin-3-yl)amino)pentan-2-one

-41)

Procedure adapted from Sterzycki, R. Synthesis, 1979, 724, a solution of Compound V- 36 (100 mg, 0.16 mmol) dissolved in acetone/water (1 :1 , 3 mL) was treated with concentrated HCl (2-3 drops). The mixture was stirred at RT for 1 h and then extracted with EtOAc (2 x 10 mL), dried over Na₂SC¼, filtered, and concentrated under vacuum to give a residue which was purified by column chromatography to afford Compound V-41 as a yellow solid (40 mg, 43%): 1H NMR (CDCI₃) 51.765-1.808 (m, 2H), 2.1 10 (s, 3H), 2.467 (t, 2H, J = 6.6 Hz), 2.898-2.961 (m, 2H), 5.576 (br, 1H), 7.812 (s, 2H). ESIMS m/z 568 [(M+H)]⁺.

Preparation of N-(5-(ter/-butyldimethylsilyloxy)pentyl)-2-(2,6-dichIoro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3

-42]

V-25 V-42

A solution of Compound V-25 (100 mg, 0.18 mmol) in CH₂C1₂ (5 mL) was treated with imidazole (12 mg, 0.18 mmol) and tert-butylchlorodimethylsilane (33 mg, 0.22 mmol). The mixture was stirred at RT for six h and concentrated under vacuum to give a residue, which was purified by column chromatography to afford Compound V-42 as a yellow solid (60 mg, 49%): mp 98.6° C-99.9° C; ^!H NMR (300 MHz, CDC1₃) δ 7.82 (s, 2H), 5.26 (br, 1H), 3.57 (t, J= 6.6 Hz, 2H), 2.90-2.84 (m, 2H), 1.60-1.55 (m, 2H), 1.46-1.39 (m, 2H), 1.35-1.26 (m, 2H), 0.87 (s, 9H), 0.02 (s, 6H); ESMS m/z 684 ([M+H]⁺).

Example 15

Preparation of 5-(2-(2,6-dichloro-4-(trifIuoromethyl)phenyl)-4,6-bis (trifiuoromethyl)-2H- pyr azolo [3,4-i/] pyrimidin-3-ylamino)pentyl acetate

[Compound V-43]

V-25 V-43

A solution of Compound V-25 (100 mg, 0.18 mmol) in CH₂C1₂ (5 mL) was treated with TEA (36 mg, 0.35 mmol) and acetyl chloride (21 mg, 0.26 mmol). The mixture was stirred at 0° C for 30 min, and concentrated under vacuum to give a residue that was purified by column chromatography to afford Compound V-43 as a yellow oil (90 mg, 82%); ^lU NMR (300 MHz, CDC1₃) δ 7.84 (s, 2H), 5.21 (br, 1H), 4.03 (t, J = 6.6 Hz, 2H), 2.89-2.87 (m, 2H), 2.04 (s, 3H), 1.61-1.55 (m, 4H), 1.34-1.29 (m, 2H); ESIMS m/z 612 ([M+H]⁺).

Example 16

Preparation of 2-(2,6-dichIoro-4-(trifluoromethyl)phenyl)-7V-(2,6-difluorobenzyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine [Compound V-44]

and

(_JE -N-(2-(2,6-dichloro-4-(trifiuoromethyl)phenyl)-l-(2,6-difluorobenzyl)-4,6- bis(trifluoromethyl)-lH-pyrazolo[3,4-d]pyrimidin-3(2H)-ylidene)-l-(2,6- difIuoropheny])methanamine [Compound V-45]

V-2 V-44 V-45 To a stirred solution of Compound V-2 (200 mg, 0.413 mmol) in MeCN (4.1 mL) was added 2,6-difluorobenzyl bromide (103 mg, 0.496 mmol) followed by K₃P0₄ (88 mg, 0.413 mmol). The mixture was heated at 70° C for 5 h. The mixture was diluted with EtOAc (20 mL), and the organic solution was washed with water and brine. The solution was dried over MgSC"4, filtered and concentrated. The residue was purified via radial chromatography (6:1—1 :1 hexane- EtOAc). The first fraction

0.36) afforded the bis-alkylated compound V.45 as a yellow solid (78 mg, 26%): Ή NMR (400 MHz, CDC1₃) δ 7.55 (s, 2H), 7.21-7.] 1 ₍m, 2H), 6.80 (t, J = 7.8 Hz, 2H), 6.72 (t, J= 8.1 Hz, 2H), 5.19 (s, 2H), 4.15 (s, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ - 63.29, -66.51 , -70.59, -1 15.53; ESIMS: m/z 736 ([M+H] ⁺). The second fraction isolated at

0.25 afforded the mono-alkylated compound V-44, as a yellow solid (137 mg, 54%): Ή NMR (400 MHz, CDC1₃) δ 7.83 (s, 2H_}, 7.32 (ddd, J= 75.0, 8.4, 6.6 Hz, 1H), 6.59 (t, J= 8.0 Hz, 2H), 5.31 (s, 1H)' 4.22 (d, J = 6.2 Hz 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.25, -66.45, -70.58, - 1 15.55; ESIMS m/z 610 ([M+H]⁺).

Electrophiles used in th_e ^above reaction may in_clude: 2-fluorobenzyl bromide, 4- trifluoromethylbenzyl bromide and 1 -(bromomethyl)-4-₍trifluoromethoxy)benzene.

The following compounds V-46 to V-50 were made in accordance with the procedures disclosed in Example 16. Preparation of 2-(2,6-diehIoro-4-(lrifluoromethyl)phenyl)-N-(2-/luorobenzyl⁾-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-aniine [Compound V-46]

Compound V-46 was obtained when 2-fluorobenzyl bromide was used as the electrophile, and was isolated as a yellow solid (60 mg, 33%): Ή NMR (400 MHz, CDC1₃) δ 7.70 (s, 2H), 7.36-7.25 (m, IH), 7.20-7.07 (m, 2H), 7.04-6.94 (m, IH), 5.55 (br, IH), 4.25 (d, J = 6.2 Hz, 2H); ¹⁹F NMR (376 MHz, CDC1₃): δ -63.26, -66.26, -70.63, -118.63; ESIMS m/z 592 ([M+H]⁺).

Preparation of (E)- -(2-(2,6-dich!oro-4-(irif!uoroniethyI)phenyl)-l-(2-f!uoro benzyl)-4,6-bis(trifluoromethyl)-lH-pyrazolo[3,4-d]pyriniidin-3(2H)-ylidene)-l-(2 fluorophenyl)methanamine [Compound V-47]

V-2 V-47

Compound V-47 was obtained when 2-fluorobenzyl bromide was used as the electrophile, and was isolated as a yellow solid (49 mg, 23%): 1H NMR (400 MHz, CDC1₃) δ 7.57 (t, J = 7.0 Hz, 1H), 7.35 (s, 2H), 7.20-7.02 (m, 4H), 6.95-6.74 (m, 3H), 5.18 (s, 2H), 4.32 (s, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.55, -67.54, -70.58, -117.14, -120.08; ESIMS: m/z 700 ([M+H]⁺).

Preparation of 2-(2,6-Dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- N-(4-(trifluorometh l)-benzyl)-2H-pyrazolo[3,4-d]pyrimidm-3-amine [Compound V-48]

V-2 V-48

Compound V-48 was obtained when 4-tri fluromethylben/.yl bromide was used as the electrophile, and was isolated as a yellow solid (103 mg, 39%): Ή NMR (400 MHz, CDC1₃) δ 7.63 (s, 2H), 7.54 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.62 (br, 1H), 4.31 (d, J= 6.4 Hz, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -62.88, -63.35, -66.09, -70.62; ESIMS: m/z 642 ([M+H]⁺). Preparation of (iS)-N-(2-(2,6-dichIoro-4-(irifluoroinethyI)phenyI)-4,6-bis(tri fluoromethyl)-l-(4-(trifluoromethyl)benzyl)-lH-pyrazolo[3,4-d]pyrimidin-3(2H)-ylidene)- l-(4-(trifluoromethyl)phenyl)methanamine [Compound V-49]

V-2 V-49

Compound V-49 was obtained when 4-trifluromethylbenzyl bromide was used as the electrophile, and was isolated as a yellow solid (61 mg, 18%): ^!H NMR (400 MHz, CDC1₃) δ 7.44 (d, J= 8.0 Hz, 2H), 7.38 (d, J= 8.0 Hz, 2H), 7.31 (s, 2H), 7.27-7.19 (m, 4H), 5.19 (s, 2H), 4.32 (s, 2H); ¹⁹F NMR (376 MHz, CDC1₃) 5 -62.53, -63.16, -63.77, -67.53, -70.52; ESIMS m/z 800 ([M+H] ⁺).

Preparation of 2-(2,6-dichloro-4-(trifluoroniethy!)pheny!)-N-(4-(trifluoro methoxy)benzyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine

[Compoun -50]

Compound V-50 was obtained when l-(bromomethyl)-4-(trifluoromethoxy) benzene was used as the electrophile, and was isolated as a yellow solid (72 mg, 35%): Ή NMR (400 MHz, CDC1₃) δ 7.67 (s, 2H), 7.16-7.1 1 (m, 2H), 7.09-7.05 (m, 2H), 5.63 (br, 1H), 4.22 (d, J = 6.2 Hz, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -58.03, -63.35, -66.13, -70.65; ESIMS m/z 658 ([M+H]⁺).

Example 17

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2,7a- dihydro- lH-pyr azolo [3,4-d] pyriniidin-3-amine

[Compound 1]

The pyrazolo[3,4-d]pyrimidin-3-amine compound V-2 was reduced to provide Com ound 1 as shown below:

V-2 Compound 1

To a solution of Compound V-2 (110 mg, 0.227 mmol) in EtOH (2.5 mL, 42.8 mmol) was added NaBH₄ (18.91 mg, 0.500 mmol), causing the mixture to turn a deep red color and then a very pale tan color. The reaction mixture was allowed to stir at RT for 1 h, followed by the addition of 4-5 drops of glacial acetic acid (AcOH) that caused gas evolution and the mixture to turn a pale clear yellow. After the solvent was removed under vacuum, the residue was diluted in EtOAc (50 mL) and washed with distilled water (3 x 20 mL), then brine (1 x 25mL), aqueous NaHC0₃ solution (2 x lOmL) and finally aqueous ammonium chloride (NH₄C1, 1 x 15mL). The organic phase was dried over Na₂S0₄, filtered and concentrated under vacuum to give a light tan solid residue that was purified by column chromatography (Hexane-EtOAc; gradient 40 g column) to afford Compound 1 as a white solid (0.094 g, 86%): mp 257° C- 259° C; Ή NMR (400 MHz, DMSO- ₆) δ 9.19 (d, J = 3.4 Hz, 1H), 8.15 (d, J = 1.8 Hz, 2H), 5.89-5.74 (m, 2H), 5.59-5.38 (m, 1H); ESIMS m/z 486.6 ([M+l]⁺).

Compounds 2-10 in TABLE 9 were prepared from compounds V-2 to V-ll in accordance with the procedure disclosed in Example 17.

Example 18

Preparation of bis-teri-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4-d]pyriniidin-3-yl)carbamate

[Compound 11]

V-12 Compound 11

To a solution containing Compound V-12 (44 mg, 0.064 mmol) dissolved in EtOH (1.1 mL, 0.06 M) was added NaBH₄ (5 mg, 0.129 mmol), and the reaction stirred at RT for 3 h. AcOH was added (10 equivalents), and the mixture was stirred for an additional 10 min, followed by dilution with water (5 mL) and mixture was extracted with EtOAc (3 x 5 mL). The organic layer was washed with water (5 mL) and brine (5 mL), dried over MgS0₄, filtered and concentrate under vacuum. The residue was purified by silica chromatography using a 3:1 hexane/EtOAc mixture as the eluent to afford Compound 11 as a white solid (42 mg, 94%): Ή NMR (400 MHz, CDC1₃) δ 7.72 (s, 2H), 5.63-5.35 (m, 2H), 1.60-1.40 (m, 18H); ESIMS m/z 686 ([M+H]⁺). Example 19

Preparation of tert-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyi)-4,6- bis(trifluoromethyl)-2,7a-di ydro-lH-pyrazolo[3,4-d]pyrimidin-3-yl)carbamate

[Compound 12]

V-13 Compound 12

To a solution containing Compound V-13 (239 mg, 0.409 mmol) dissolved in EtOH (1.1 mL, 0.06 M) was added NaBH₄ (31 mg, 0.818 mmol), and the reaction was stirred at RT for overnight. Then, glacial AcOH (10 equivalents) was added, and the mixture was stirred for 10 min. T he reaction mixture was diluted with water (5 mL), and the solution was extracted with EtOAc (3 x 5 mL). The organic layer was washed with water (5 mL) and brine (5 mL), dried over MgS0₄, filtered and concentrated under vacuum to afford Compound 12 as a white solid (220 mg, 92%): 1H NMR (400 MHz, CDC1₃) δ 7.77 (s, 2H), 6.08 (s, 1H), 5.87-5.74 (m, 2H), 1.45 (s, 9H); ESIMS m/z 586 ([M+H]⁺).

Compounds 13— 9 in TABLE 9 were prepared from Compounds V-14 to V-50 in accordance with the procedure disclosed in Example 19.

Example 20

Preparation of (3-((bis-te i-butoxycarbonyl)amino)-2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4- d] pyrimidin- 1 -yl) methyl cyclopentanecar boxylate

[Compound 50]

Compound 11 Compound 50

To a stirred solution of Compound 11 (27 mg, 0.039 mmol) dissolved in acetone (1 mL, 0.04 M) was added bromomethyl cyclopentanecarboxylate (12 mg, 0.059 mmol, 1.5 equivalents) followed by K₂C0₃ (16 mg, 0.118 mmol, 3 equivalents). The reaction mixture was stirred at RT overnight. Then, the mixture was diluted with water ( 5 mL) and extracted with EtOAc (3 x 5 mL). The organic solution was washed with brine (5 mL), dried over MgS0₄, filtered and concentrated under vacuum. The residue was purified via radial chromatography using a 6:1 hexane/EtOAc mixture as the eluent to afford Compound 50 (19 mg, 59%): Ή NMR (400 MHz, CDC1₃) δ 7.70 (s, 2H), 5.95-5.85 (m, 2H), 5.61 (q, J= 6.6 Hz, 1H), 2.81-2.69 (m, 1H), 1.92-1.24 (m, 26H); ESIMS m/z 812 ([M+H]⁺).

The electrophiles used may include: bromomethylisobutyrate, bromomEtOAc, bromomethyl 2-ethoxyacetate.

Compounds 51-54 in TABLE 9 were made in accordance with the procedure disclosed in Example 20. Example 21

Preparation of tert-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-l-methyl-4,6- bis(trifluoromethyl)-2,7a-dmydro-lH-pyrazolo[3,4-d]pyrimidin-3-yl)(methyl)carbamate

[Compound 55]

Compound 12 Compound 55

To a stirred solution of Compound 12 (87 mg, 0.148 mmol) in THF (1.5 mL, 0.1M) cooled to 0° C was added sodium hydride (NaH, 60% dispersion in mineral oil, 13 mg, 0.326 mmol, 2.2 eq.), and the reaction mixture was stirred at 0° C for 20 min. Methyl iodide (CH₃I, 46 μί, 0.742 mmol, 5 eq.) was then added. The reaction was allowed to warm to RT, and stirred overnight. Water was added (5 mL), and the mixture was extracted with EtOAc (3 5 mL). The solution was washed with water (5 mL) and brine (5 mL). The organic phase was dried over MgS0₄, filtered and concentrated under vaccum. The residue was purified via silica chromatography using a 5:1 hexane/EtOAc mixture as the eluent (R/ = 0.25) to afford Compound 55 as a purple oil (44 mg, 48%): 1H NMR (400 MHz, CDC1₃) δ 7.75 (d, J = 16.7 Hz, 2H), 5.31 (s, 1H), 3.37 (s, 3H), 2.78 (s, 3H), 1.49 (s, 9H); ESIMS: m/z 614 ([M+H]⁺).

Example 22

Preparation of tert-butyl (l-(cyclopropylmethyl)-2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4- d] pyrimidin-3-yl)carbamate

[Compound 56]

Compound 12 Compound 56

To a stirred solution of Compound 12 (51 mg, 0.087 mmol) dissolved in DMF (0.9 mL, 0.1 M) was added (bromomethyl)cyclopropane (10 μΙ>, 0.104 mmol, 1.2 eq.) followed by cesium carbonate (Cs₂C0₃, 85 mg, 0.261 mmol, 3 eq.). The reaction was stirred at RT overnight, diluted with a saturated sodium chloride (NaCl) solution (10 mL) and extracted with EtOAc (4 x 10 mL). The combined organic layers were washed with water (10 mL) and brine (10 mL). The organic phase was dried over MgS0₄, filtered and concentrated under vaccum. The residue was purified by silica chromatography using a 6:1 hexane/EtOAc mixture as the eluent

0.25) to afford Compound 56 as a white solid (27 mg, 49%): Ή NMR (400 MHz, CDC1₃) δ 7.76 (d, J = 7.1 Hz, 2H), 6.02 (s, 1H), 5.81 (br, 1H), 3.86-3.71 (m, 2H), 1.43 (s, 9H), 0.93-0.77 (m, 1H), 0.52-0.38 (m,4H); ESIMS m/z 640 ([M+H]⁺).

The electrophiles used may include: 2-(bromomethyl)-l ,l-difluorocyclopropane. Compound 57 in TABLE 9 was made in accordance with the procedure disclosed in Example 22. Example 23

Preparation of bis-teri-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-l-methyl-4,6- bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4-d]pyrimidin-3-yl)carbamate

[Compound 58]

Compound 11 Compound 58

To a solution containing Compound 11 (56 mg, 0.082 mmol) dissolved in MeCN (0.8 mL, 0.1 M) was added potassium phosphate (17.3 mg, 0.082 mmol, 1 equivalent) followed by CH₃I (26 μί, 0.408 mmol, 5 equivalents). The reaction was heated at 70° C for 5 h. The mixture was cooled to RT and was diluted with EtOAc (20 mL). The organic solution was washed with water (10 mL) and brine (10 mL). The organic phase was dried over MgS0₄, filtered and concentrated under vacuum to afford Compound 58 as a yellow solid (55 mg, 96%): mp 54° C-56° C; 1H NMR (400 MHz, CDC1₃) δ 7.71 (s, 2H), 5.58 (q, J = 6.6 Hz, 1H), 3.49 (s, 3H), 1.60-1.09 (m, 18H); ESIMS: m/z 700 ([M+H]⁺).

The electrophiles used may include: ethyl iodide, isopropyl iodide, l-(bromomethyl)-2- fiuorobenzene, l-(bromomethyl)-4-(trifluoromethoxy)benzene, 5-bromopentane nitrile, 1- bromopent-2-yne, 3-(iodomethyl)heptane.

Compounds 59-65 in TABLE 9 were made in accordance with the procedure disclosed in Example 23. Example 24

Preparation of tert-butyl (l-acetyl-2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4-d]pyrimidin-3-yl)carbamate

[Compound 66]

Compound 12 Compound 66

To a stirred solution containing Compound 12 (85 mg, 0.145 mmol) dissolved in THF (1.5 mL, 0.1 M) was added acetic anhydride (27 μί, 0.290 mmol, 2 eq.), DMAP (1 mg, 0.008 mmol, 0.05 eq.) and pyridine (2.5 μί, 0.029 mmol, 0.2 eq.). The reaction was allowed to stir at RT overnight. The solution was diluted with EtOAc (20 mL) and washed with water (10 mL) and brine (10 mL). The orgainc phase was dried over MgS0₄, filtered and concentrated under vaccum. The residue was purified by silica chromatography using a 5:1 hexane mixture as the eluent to afford Compound 66 as a white solid in a 4:1 mixture of isomers (87 mg, 95%): H NMR (400 MHz, CDC1₃) δ 7.78-7.65 (m, 2H, a mixture of isomers 1 and 2), 6.43 (be, 1H, isomer 1), 6.21 (br, 1H, isomer 2), 5.84 (br, 1H, isomer 2), 5.50 (br, 1H, isomer 1), 2.51 (s, 3H, isomer 1), 2.32 (s, 3H, isomer 2), 1.42 (s, 9H, isomer 1), 1.32 (s, 9H, isomer 2); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.27, -63.31, -72.93, -73.04, -79.15; ESIMS m/z 628 ([M+H]⁺).

Example 25

Preparation of bis-terf-butyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-l- (methylsulfonyl)-4,6-bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4-d]pyrimidin-3- yl)carbamate

Compound 67]

Compound 11 Compound 67

To a stirred solution of Compound 11 (100 mg, 0.146 mmol) dissolved in CH₂Cl₂ (1.5 mL, 0.1 M) was added methanesulfonyl chloride (14 μί, 0.175 mmol, 1.2 eq) followed by N- ethyl-N-isopropylpropan-2-amine (53 μί, 0.306 mmol, 2.1 eq), and the reaction was stirred at RT overnight. Additional methanesulfonyl chloride (15 μΐ.) and N-ethyl- V-isopropyl propan-2- amine (30 μί) were added to the reaction and heated at 50° C for 5 h. The cooled reaction mixture was diluted with EtOAc (20 mL) and washed with water (10 mL), 0.1 N HC1 (10 mL) and brine (10 mL). The solution was dried over MgS0₄, filtered and concentrated under vacuum. The residue was purified by silica chromatography using a 6:1 hexane/EtOac mixture as the eluent (R = 0.20) to afford Compound 67 as a clear oil (23 mg, 21%): 1H NMR (300 MHz, CDC1₃) 6 7.72 (d, J = 6.4 Hz, 2H), 6.14 (q, J = 7.1 Hz, 1H), 3.31 (s, 3H), 1.42 (s, 18H); ESIMS m/z 764 ([M+H]⁺).

Examp!e 26

Preparation of tert-butyl 7V-[2-[2,6-dichloro-4-(trifIuoromethyl)phenyl]-7a-methyl-4,6- bis(trifluoromethyl)-lH-pyrazolo[3,4-d]pyrimidin-3-yl]carbamate

[Compound 68]

Compound 11 Compound 68

To a stirred solution of Compound 11 (103 mg, 0.151 mmol) and LiCl (7 mg, 0.166 mmol, 1.1 eq) dissolved in THF (1.5 mL, 0.1 M) was added CH₃MgCl (3.0 M in THF, 56 μΐ,, 0.166 mmol, 1.1 eq), and the reaction was stirred at RT for 3 h. The reaction was quenched by the addition of saturated NH₄C1 solution (5 mL) and then extracted with EtOAc (3 x 5 mL). The organic phase was dried over MgS0₄, filtered and concentrated under vacuum. The residue was purified by silica chromatography using a 4:1 hexane/EtOAc mixture as the eluent

0.17) to afford Compound 68 as a white solid (54 mg, 60%): Ή NMR (400 MHz, CDC1₃) δ 7.73 (d, J = 9.4 Hz, 2H), 6.04 (s, 1H), 5.77 (s, 1H), 1.87 (s, 3H), 1.30 (s, 9H); ¹⁹F NMR (376 MHz, CDC1₃) δ -63.25, -72.76, -80.55; ESIMS m/z 600 ([M+H]⁺).

The Grignard reagents used may include: isopropylmagnesium chloride, ethylmagnesium chloride, n-propylmagnesium chloride, benzylmagnesium chloride.

Compounds 69-74 in TABLE 9 were made in accordance with the procedure disclosed in Example 26. Example 27

Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-N,l-dimethyl-4,6- bis(trifluoromethyl)-2,7a-dihydro-lH-pyrazolo[3,4-d]pyrimidin-3-amine

[Compound 75]

Compound 55 Compound 75

To a stirred solution of Compound 55 (35 mg, 0.057 mmol) dissolved in CH₂C1₂ (1 mL, 0.06 M) was added TFA (0.13 mL, 1.709 mmol), and the reaction was stirred at RT for 2 h. Saturated NaHC03 was added carefully (10 mL), and the mixture was stirred for an additional 15 min. The layers were separated, and the aqueous layer was extracted with CH₂C1₂ (3 x 10 mL). The combined organic layers were washed with brine, dried over MgS04, filtered and concentrated under vacuum to afford Compound 75 as a yellow solid (24 mg, 82%): Ή NMR (400 MHz, CDC1₃) δ 7.73 (s, 2H), 5.30 (s, 1H), 5.02 (q, J= 5.4 Hz, 1H), 3.38 (s, 3H), 2.85 (d, J = 5.4 Hz, 3H); ESIMS m/z 514 ([M+H]⁺).

Compounds 76-96 in TABLE 9 were made in accordance with the procedure disclosed in Example 27.

TART O

J=

5.91

5.90 (dd,

5.78

δ

5.82

δ (m,

(s,

5.46

5.46 1.13

While the present disclosure may be susceptible to various modifications and alternative forms, specific embodiments have been described by way of example in detail herein. However, it should be understood that the present disclosure is not intended to be limited to the particular forms disclosed. Rather, the present disclosure is to cover all modifications, equivalents, and alternatives falling within the scope of the present disclosure as defined by the following appended claims and their legal equivalents.

Claims

Wliat is claimed is:

1. A pyrazolopyrimidine compound of formula I or a salt thereof:

I

wherein,

Ar is an aryl group,

X is nitrogen, oxygen or sufur,

Y and Z are independently hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano amine, or amine,

W is selected from the group consisting of hydrogen, C]-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, and benzyl, and

R is selected from the group consisting of:

(a) hydrogen,

(b) Ci-Cs alkyl, C₃-C₈ cycloalkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl,

(c) S(=O)_n(C,-C₈ alkyl) (n = 0, l, 2),

(d) C(=0)NR_xR_y,

(e) (C,-C₈ alkyl)NR_xR_y,

(f) C(=0)0(C C₈ alkyl), C(=0)(C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)(C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl),

(g) (C,-C₈ alkyl)0(C_rC₈ alkyl),

(h) (Ci-Cg alkyl)OC(=0)(C|-C₈ alkyl), (C,-C₈ alkyl)OC(=0)(C₂-C₈ alkenyl), (Q-Q alkyl)OC(=0)(C₂-C₈ alkynyl), (C,-C₈ alkyl)OC(=0)(C₃-C₈ cycloalkyl), (C,-C₈ alkyl)OC(=0)(C₃-C₈ cycloalkenyl), (Cj-C₈ alkyl)0C(O)(C₇-C₈ cycloalkynyl), (i) (C,-C₈ alkyl)S(C,-C₈ alkyl), C(=0)(C,-C₈ alkyl)C(=0)0(C,-C₈ alkyl), wherein each of the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl and cycloalkynyl in (b), (c), (f), (g), (h) is independently substituted with one or more substituents selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, Ci-C alkyl, Ci-C₈ haloalkyl, C₃- C cycloalkyl, C₃-C₈ halocycloalkyl, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, Ci-C₈ alkoxy, d-Cs haloalkoxy, C₂-C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(d-C₈ alkyl) (n = 0, 1, 2), S(=0)_n(C_rC₈ haloalkyl) (n = 0, 1 , 2), OS0₂(Ci-C₈ alkyl), OS0₂(C₁-C₈ haloalkyl), C(=0)NR_xR_y, (C_rC₈ alkyl)NR_xR_y, C(=0)(C,-C₈ alkyl), C(=0)0(d-C₈ alkyl), C(=0)(C C₈ haloalkyl), C(=0)0(C,- C₈ haloalkyl), C(=0)(C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)(C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (Ci-Cg alkyl)0(d-C₈ alkyl), (d-C₈ alkyl)S(C C₈ alkyl), C(=0)(C_rC₈ alkyl)C(=0)0(Ci-C₈ alkyl), phenyl, and phenoxy, and

wherein each R_x and R_y in (d) and (e) is independently selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy; and

2. The compound of claim 1, wherein the aryl or heteroaryl group is selected from the group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrazolo, imidazolo, and thiophenyl, and wherein the aryl or heteroaryl group is substituted at any open position with at least one of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, sulfoxide, amines, aryloxy, esters, acetates, amides, and combinations thereof.

3. The compound of claim 1, wherein each of the alkyl, alkenyl, alkynyl, and benzyl of W is substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, d-C₈ alkyl, Ci-C₈ haloalkyl, C₃-C₈ cycloalkyl, C₃-Cg halocycloalkyl, C₃-Cg cycloalkoxy, C₃-C₈ halocycloalkoxy, Ci-C₈ alkoxy, Cj- C₈ haloalkoxy, C₂-C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(C C₈ alkyl) (n = 0, 1, 2), S(=0)_n(d-C₈ haloalkyl) (n = 0, 1 , 2), OS0₂(C C₈ alkyl), OS0₂(C_rC₈ haloalkyl), C(=0)NR_xR_y, (d-C₈ alkyl)NR_xR_y, C(=0)(Ci-C₈ alkyl), C(=0)0(d-C₈ alkyl), C(=0)(C C₈ haloalkyl), C(=0)0(C C₈ haloalkyl), C(=0)( C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-Q alkenyl), (d-C₈ alkyl)0(d-C₈ alkyl), (d-C₈ alkyl)S(Ci-C₈ alkyl), C(=0)(d-C₈ alkyl)C(=0)0(Ci-C₈ alkyl), phenyl, and phenoxy, wherein R_x and R_y each is independently selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy. 4. The compound of claim 1 , wherein X is nitrogen and substituted with at least one of alkyl, cycloalkyl, alkenyl, alkynyl, heteroatom, C(0)R', C(0)OR', C(0)NR', where R' is selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy.

5. The compound of claim 1, wherein X is oxygen and substituted with at least one of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, amino, C(0)R', or C(0)NR' where R' is selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy.

6. The compound of claim 1, wherein X is SO_n where n is 0, 1 or 2, and wherein sulfur is substituted with at least one of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, amino, C(0)R', and C(0)NR' where R' is selected from the group consisting of alkyl moiety including one or more heteroatoms, aryl and heteroaryl substituted with any combination of halo, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano, nitro, sulfone, and aryloxy. The compound of claim 1 having formula II or a salt thereof:

wherein,

Ar is selected from the group consisting of substituted phenyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, pyrazolo, imidazolo, triazole, thiophenyl, and furyl, wherein the substituent group includes at least one of hydrogen, alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, nitro, sulfone, aryloxy, and any combination thereof;

W is selected from the group consisting of hydrogen, -Q alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, and benzyl;

R¹, R² and R⁵ are independently selected from the group consisting of:

(a) hydrogen, hydroxy, thiol;

(b) (C,-C₈) alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(d-C₈)alkyl, 0(C C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(Ci-C₈)alkyl, S-(C C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)2(Ci-C₈)alkyl;

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₃-C₈)alkynyl, OC(=0)(C₃-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-

C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(f) heterocycyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S- heterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl

(g) N(R⁸)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, C(=S)N(R⁹)₂, OC(=0)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; and (h) C₃-C₈ cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) is independently substituted with one or more substituents selected from the group consisting of:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃;

(bl) C(=0)(Ci-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(d-C₈)alkyl, OC(=0)(C,-C₈)alkyl,

OC(=0)0(Ci-C₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(C C₈)alkyl, S(0)(C_r C₈)alkyl, or S(0)₂(C₁-C₈)alkyl;C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(dl) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-

C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(gl) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(hi) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e) and (f) is independently substituted with one or more substituents selected from the group consisting of:

(a2) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃;

(b2) (d-C^alkyl, CCOXd-QOalkyl, C(=0)0(C_rC₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C_rC₈)alkyl, C(=S)(C]-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C,- C₈)alkyl, S(0)(C₁-C₈)alkyl, S(0)₂(d-C₈)alkyl;

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, 0C(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl,

OC(=0)(C₂-C₈)alkynyl, 0C(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl; - I l l -

(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g2) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) is independently substituted with one or more substituents selected from the group consisting of:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((C_rC₈)alkyl)₃;

(b3) C(=0)(C C₈)alkyl, C(=0)0(d-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(C_!-C₈)alkyl, S(C C₈)alkyl, S(0)(C C₈)alkyl, SiOHd-C^alkyl;

(c3) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d3) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(β) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g3) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)0N(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)_2; SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (β) is independently substituted with one or more substituents selected from the group consisting of::

(a4) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃; (b4) (Ci-C₈)alkyl, C(=0)(C_rC₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-Q)alkyl, C(=S)0(C,-Q)alkyl S(C_r C₈)alkyl, S(0)(Ci-C₈)alkyl, SiOMQ-Q alkyl;

(c4) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g4) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, or S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h4) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) is independently substituted with one or more substituents selected from the group consisting of:

(a5) F, CI, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃;

(b5) C(=0)(C,-C₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl,

S(d-C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(C,-C₈)alkyl;

(c5) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-

C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d5) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(-0)Ophenyl, C(-S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl; (f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g5) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R )₂, S(0)₂N(R⁹)₂; and

(h5) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e3), (e4), (O), and (f4) is independently substituted with one or more substituents selected from the group consisting of:

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃;

(b6) (C C₈)alkyl, C(=0)(d-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(Cj-C₈)alkyl,

C₈)alkyl, S(0)(Cj-C₈)alkyl, S(0)₂(d-C₈)alkyl;

(c6) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C -C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d6) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, C(=0)(C₂- C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g6) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂;

(h6) (C₃-C₈)cycloalkyl,

wherein R⁸ is selected from the group consisting of:

(a) H, CN, OH,

(b) (C-CiOalkyl,

C(=S)NH(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C C₈)alkyl, S(0)(C]-C₈)alkyl, S(0)₂(C_r

C₈)alkyl, (c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, C(=0)NH(C₂- C₈)alkenyl, C(=S)NH(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(0)(C₂- C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, C(=0)NH(C₂- C₈)alkynyl, C(=S)NH(C₂-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(0)(C₃-

C₈)alkynyl, S(0)₂(C₃-C₈)alkynyl,

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=0)NHphenyl, C(=S)NHphenyl, C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)₂phenyl,

(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=0)NH-heterocyclyl, C(=S)NH-heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂ heterocyclyl, and

(h) (C₃-C₈)cycloalkyl,

wherein R⁹ is selected from the group consisting of:

(a) H, CN, OH, OSi((d-C₈)alkyl)₃,

(b) (C_rC₈)alkyl, C(=0)(C_rC₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(d-C₈)alkyl,

OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(d-C₈)alkyl, S(C C₈)alkyl, S(0)(d-C₈)alkyl, S(0)₂(C C₈)alkyl,

(d) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₃-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃- C₈)alkynyl, S(0)(C₃-C₈)alkynyl, S(0)₂(C₃-C₈)alkynyl,

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)₂phenyl,

(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(g) (C₃-C₈)cycloalkyl; and

R³ and R⁴ are independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, cyano amine, and amine.

8. The compound of claim 7, wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of R is independently substituted with one or more substituents selected from the group consisting of:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((C_rC₈)alkyl)₃,

(bl) C(=0)(Ci-C₈)alkyl, C(=0)0(C_!-C₈)alkyl, 0(d-C₈)alkyl, OC(=0)(Ci-C₈)alkyl,

OC(=0)0(C,-C₈)alkyl, C(=S)(C C₈)alkyl, C(=S)0(C C₈)alkyl, S(d-C₈)alkyl, S(0)(Ci- C₈)alkyl, S(0)₂(C,-C₈)alkyl

(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(hi) (C₃-C₈)cycloalkyl, and

wherein each of the phenyl and heterocyclyl in (e) and (f) of R⁸ is independently substituted with one or more substituents selected from the group consisting of:

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃,

(b2) (C,-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(d-C₈)alkyl,

OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(C C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(C C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, 0C(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, 0C(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl, (e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(h2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of R⁸ is independently be substituted with one or more substituents selected from the group consisting of:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((C,-C₈)alkyl)₃,

(b3) C(=0)(Ci-C₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(C C₈)alkyl, OC(=0)0(d-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(Ci-C₈)alkyl, S(0)(d- C₈)alkyl, S(0)₂(Ci-C₈)alkyl,

(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(g3) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)_2, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂, and

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (O) of R is independently substituted with one or more substituents selected from the group consisting of:

(a4) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃, (b4) (C,-C₈)alkyL C(=0)(C,-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(C C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(C,-C₈)alkyl S(d- C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-Cg)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂, and

(h4) (C₃-C₈)cycloalkyl.

9. The compound of claim 7, wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of R⁹ is independently be substituted with one or more substituents selected from the group consisting of:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((d-C₈)alkyl)₃,

(bl) C(=0)(C,-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(d-C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C_rC₈)alkyl, S(0)(d- C₈)alkyl, S(0)₂(C C₈)alkyl,

(dl) C(=0)(C₂-C₈)alkynyl, C(-0)0(C₃-C₈)alkynyl, 0(C3-C8)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, 0C(=O)phenyl, OC(=0)Ophenyl, C(-S)Ophenyl, C(-S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl, (fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(hi) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e) and (f) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C_rC₈)alkyl)₃,

(b2) (C,-C₈)alkyl, C(=0)(CrC₈)alkyl, C(=0)0(C₁-C₈)alkyl, Oid-Ci alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(Ci-C₈)alkyl , S(C_r C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(O) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h2) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((C_rC₈)alkyl)₃,

(b3)

OC(=0)0(C,-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C,-C₈)alkyl, S(0)(d- C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(c3) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-

C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl, (d3) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(D) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a4) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((d-C₈)alkyl)₃,

(b4) (Ci-Cg)alkyl, C(=0)(C_rC₈)alkyl, C(=0)0(C C₈)alkyl, 0(C_!-C₈)alkyl,

S(C_r C₈)alkyl, S(0)(Ci-C₈)alkyl, S(0)₂(d-C₈)alkyl,

(d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(h4) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a5) F, CI, Br, I, CN, N0₂, OH, OSi((C,-C₈)alkyl)₃, (b5) C(=0)(C,-C₈)alkyl, C(=0)0(C C₈)alkyl, 0(C_!-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C C₈)alkyl, S(C,-C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h5) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e3), (e4), (O), and (f4) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃,

(b6) (C,-C₈)alkyl, C(=0)(C C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(C,-C₈)alkyl , S(C_r C₈)alkyl, S(0)(Ci-C₈)alkyl, S(0)₂(C_rC₈)alkyl,

(d6) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl,

(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

(h6) (C₃-C₈)cycloalkyl.

10. The compound of claim 7, wherein R³ and R⁴ each is trifluoromethyl group.

11. The compound of claim 1 , wherein Ar is 2,6-dichloro-4-(trifluoromethyl)phenyl group.

12. The compound of claim 1 selected from the group consisting of Compounds 1- 96 as specified in TABLE 9. 13. A method of producing a pyrazolopyrimidine compound, the method comprising:

reacting a 2-R⁴-4-choloro-6-R³-pyrimidine-5-carbonitrile compound IV-1 with a hydrazine compound to produce a pyrazolopyrimidine compound V;

reacting the pyrazolopyrimidine compound V with at least one first electrophile in a presence of base to provide a pyrazolopyrimidine compound VI,

selected from the group consisting of substituted phenyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, pyrazolo, imidazolo, triazole, thiophenyl, and furyl, wherein the substituent group includes at least one of hydrogen, alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, halothio, nitro, sulfone, aryloxy, and any combination thereof;

R' and R^z are independently selected from the group consisting of:

(a) hydrogen, hydroxy, thiol;

(b) (C,-C₈) alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(C C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(d-C₈)alkyl, S-(C_r C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(C,-C₈)alkyl;

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl; (d) (C₃-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₃-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃- Cg)alkynyl, S(C₂-Cg)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(f) heterocycyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S- heterocyclyl, S(0)heterocyclyl, S(0)₂heteroeyclyl

(g) N(R⁸)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, C(=S)N(R⁹)₂, OC(=0)N(R )₂, SN(R⁹)₂, S(0)N(R⁹)₂, or S(0)₂N(R⁹)₂; and

(h) C₃-C₈ cycloalkyl,

(al) F, CI, Br, I, CN, N0₂, OH, OSi((C_rC₈)alkyl)₃;

(bl)

0(d-C₈)alkyl, OC(=0)(Ci-C₈)alkyl,

OC(=0)0(Ci-C₈)alkyl, C(=S)(C_rC₈)alkyl, C(=S)0(C₁-C₈)alkyl, S(Ci-C₈)alkyl, S(0)(Ci- C₈)alkyl, or S(0)₂(Ci-C₈)alkyl;C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-Q)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

(hi) (C₃-C₈)cycloalkyl,

(a2) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C C₈)alkyl)₃; (b2) (C,-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(C,-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C,- C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(C₁-C₈)alkyl;

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl;

(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(12) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heteroeyclyl;

(g2) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂,

ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h2) (C₃-C₈)cycloalkyl,

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃;

(b3) C(=0)(d-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C₁-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(d-C₈)alkyl, S(Ci-C₈)alkyl, S(0)(d- C₈)alkyl, S(0)₂(C,-C₈)alkyl;

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl; (O) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g3) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)_2> SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (el), (fl), and (f2) is independently substituted with one or more substituents selected from the group consisting of:

(a4) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃;

(b4) (C,-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(C,-C₈)alkyl,

C₈)alkyl, S(0)(C_!-C₈)alkyl, S OMQ-Q alkyl;

(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(g4) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, or S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h4) (C₃-C₈)cycloalkyl,

(a5) F, CI, Br, I, CN, N0₂, OH, OSi((C C₈)alkyl)₃;

(b5) C(=0)(CrC₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(C C₈)alkyl,

C(=S)0(C,-C₈)alkyl, S(C,-C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C,-C₈)alkyl; (c5) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂- C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl;

(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g5) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; and

(h5) (C₃-C₈)cycloalkyl,

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃;

(b6) (C_rC₈)alkyl,

0(C,-C₈)alkyl, OC(=0)(C C₈)alkyl, OCi^Oid-Cs)^, C(=S)(C C₈)alkyl, C(=S)0(C,-C₈)alkyl , S(Ci- C₈)alkyl, SiOXd-Cs)^, S(0)₂(Ci-C₈)alkyl;

(c6) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl;

(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(-0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl;

(g6) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R⁹)₂, C(=0)ON(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, C(=S)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, S(0)₂N(R⁹)₂; (h6) (C₃-C₈)cycloalkyl,

wherein R⁸ is selected from the group consisting of:

(a) H, CN, OH,

(b) (d-C₈)alkyl,

C(=0)NH(Ci-C₈)alkyl, C(=S)NH(C,-C₈)alkyl, C(=S)(C C₈)alkyl, C(=S)0(C C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(d-

C₈)alkyl,

(d) (C₃-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, C(=0)NH(C₂-

C₈)alkynyl, C(=S)NH(C₂-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(0)(C₃- C₈)alkynyl, S(0)₂(C₃-C₈)alkynyl,

(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=0)NH-heterocyclyl,

C(=S)NH-heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂ heterocyclyl, and

(h) (C₃-C₈)cycloalkyl,

wherein R⁹ is selected from the group consisting of:

(a) H, CN, OH, OSi((C C₈)alkyl)₃,

(b) (Ci-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(d-C₈)alkyl, OC(=0)(C,-C₈)alkyl, OC(=0)0(C C₈)alkyl, C(=S)(d-C₈)alkyl, C(=S)0(C,-C₈)alkyl, S(C C₈)alkyl, S(0)(C_!-C₈)alkyl, SiO^id-Cs)^,

(c) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₃-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, 0C(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl,

S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, C(=S)phenyl,

C(=S)Ophenyl, S(0)phenyl, S(0)₂phenyl, (f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(g) (C₃-C₈)cycloalkyl; and

14. The method of claim 13, wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of R⁸ is independently substituted with one or more substituents selected from the group consisting of:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃,

(bl)

S(C,-C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C_!-C₈)alkyl

(cl) C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-

C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂- C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(hi) (C₃-C₈)cycloalkyl, and

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((C,-Q)alkyl)₃, (b2) (C,-C₈)alkyl, C(=0)(C₁-C₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C_rC₈)alkyl, S(d- Q alkyl, S(0)(C_rC₈)alkyl, S(0)₂(d-C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, 0C(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(g2) N(R⁹)₂, NHC(=0)N(R⁹)₂, NHC(=S)N(R⁹)₂, C(=0)N(R )₂, C(=0)ON(R⁹)₂,

C(=S)N(R⁹)₂, ON(R⁹)₂, OC(=0)N(R⁹)₂, SN(R⁹)₂, S(0)N(R⁹)₂, and S(0)₂N(R⁹)₂, and

(h2) (C₃-C₈)cycloalkyl,

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃,

(b3) C(=0)(C₁-C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C_rC₈)alkyl, OC(=0)(C_rC₈)alkyl, OC(=0)0(Ci-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(d-C₈)alkyl, S(C C₈)alkyl, S(0)(C,- C₈)alkyl, S(0)₂(C C₈)alkyl,

(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl, (f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl,

(h3) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (el), (e2), (fl), and (β) of R is independently substituted with one or more substituents selected from the group consisting of:

(a4) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃,

(b4) (Ci-C₈)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C₁-C₈)alkyl, 0(C!-C₈)alkyl,

OC(=0)(C_rC₈)alkyl, OC(=0)0(C_rC₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(C_rC₈)alkyl S(C,- C₈)alkyl, S(0)(Ci-C₈)alkyl, S(0)₂(Ci-C₈)alkyl,

(h4) (C₃-C₈)cycloalkyl.

15. The method of claim 13, wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of R⁹ is independently be substituted with one or more substituents selected from the group consisting of:

(al) F, CI, Br, I, CN, N0₂, OH, OSi((C,-C₈)alkyl)₃,

(bl) C(=0)(d-C₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(C,-C₈)alkyl, 0C(O)(C_rC₈)alkyl,

OC(=0)0(d-C₈)alkyl, C(=S)(C C₈)alkyl, C(=S)0(Ci-C₈)alkyl, S(d-C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(dl) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C3-C8)alkynyl, OC(=0)(C₂- C₈)alkynyl, OC(0)0(C₃-C₈)alkynyl, C(=S)(C₂-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂- C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(hi) (C₃-C₈)cycloalkyl,

(a2) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃,

(b2) (Ci-C₈)alkyl, C(=0)(C_rC₈)alkyl, C(=0)0(C,-C₈)alkyl, 0(C C₈)alkyl, OC(=0)(Ci-C₈)alkyl, OC(=0)0(C,-C₈)alkyl, C(=S)(C_!-C₈)alkyl, C(=S)0(C_rC₈)alkyl , S(C,- C₈)alkyl, S(0)(C₁-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(c2) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl, OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-Q)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl,

(d2) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(-0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(e2) phenyl, C(=0)phenyl, , C(-0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(-S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl, (Ω) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)₂heterocyclyl, and

(h2) (C₃-C₈)cycloalkyl,

(d2), (hi), and (h2) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a3) F, Cl, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃,

(b3) C(=0)(C_rC₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(Ci-C₈)alkyl, OC(=0)(d-C₈)alkyl, OC(=0)0(d-C₈)alkyl, C(=S)(C,-C₈)alkyl, C(=S)0(d-C₈)alkyl, S(C_rC₈)alkyl, S(0)(d- C₈)alkyl, S(0)₂(d-C₈)alkyl,

(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

(h3) (C₃-C₈)cycloalkyl,

(a4) F, Cl, Br, I, CN, N0₂, OH, SF₅, OSi((Ci-C₈)alkyl)₃,

(b4) (Ci-Cg)alkyl, C(=0)(C,-C₈)alkyl, C(=0)0(C_rC₈)alkyl, 0(0,-0₈)_& 1,

C₈)alkyl, S(0)(Ci-C₈)alkyl, S(0)₂(C C₈)alkyl,

(c4) (C₂-C₈)alkenyl, C(=0)(C₂-C₈)alkenyl, C(=0)0(C₂-C₈)alkenyl, 0(C₂-C₈)alkenyl,

OC(=0)(C₂-C₈)alkenyl, OC(=0)0(C₂-C₈)alkenyl, C(=S)(C₂-C₈)alkenyl, C(=S)0(C₂-C₈)alkenyl, S(C₂-C₈)alkenyl, S(0)(C₂-C₈)alkenyl, S(0)₂(C₂-C₈)alkenyl, (d4) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂(C₂-C₈)alkynyl,

(h4) (C₃-C₈)cycloalkyl,

wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3),

(d4), (h3), and (h4) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a5) F, CI, Br, I, CN, N0₂, OH, OSi((Ci-C₈)alkyl)₃,

(b5) C(=0)(C C₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(Ci-C₈)alkyl, OC OXd-Q alkyl, OC(=0)0(C_rC₈)alkyl, C(=S)(Ci-C₈)alkyl, C(=S)0(C_!-C₈)alkyl, S(C_!-C₈)alkyl, S(0)(C_r C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(d5) C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-

(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,

(h5) (C₃-C₈)cycloalkyl,

wherein each of the phenyl and heterocyclyl in (e3), (e4), (D), and (f4) of R⁹ is independently substituted with one or more substituents selected from the group consisting of:

(a6) F, CI, Br, I, CN, N0₂, OH, SF₅, OSi((C,-C₈)alkyl)₃, (b6) (C,-C₈)alkyl, C(=0)(C_rC₈)alkyl, C(=0)0(Ci-C₈)alkyl, 0(C_rC₈)alkyl,

C₈)alkyl, S(0)(C,-C₈)alkyl, S(0)₂(C,-C₈)alkyl,

(d6) (C₂-C₈)alkynyl, C(=0)(C₂-C₈)alkynyl, C(=0)0(C₃-C₈)alkynyl, 0(C₂-C₈)alkynyl, OC(=0)(C₂-C₈)alkynyl, OC(=0)0(C₃-C₈)alkynyl, C(=S)0(C₃-C₈)alkynyl, S(C₂-C₈)alkynyl, S(0)(C₂-C₈)alkynyl, S(0)₂ ^r(C₂-C₈)alkynyl,

(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,

OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)₂phenyl,

(h6) (C₃-C₈)cycloalkyl.

16. The method of claim 13, wherein the first electrophile is a member selected from the group consisting of alkyl halides, anhydrides, acid chlorides, isocyanates, isothiocyanate, and sulfonyl chlorides.

17. The method of claim 13, further comprising reducing the pyrazolopyrimidine compound VI to produce a pyrazolopyrimidine compound VII.

vn-i

18. The method of claim 17, wherein reducing the pyrazolopyrimidine compound VI comprises reducing the pyrazolopyrimidine compound VI with a hydride reducing agent to produce a pyrazolopyrimidine compound VII-1. 19. The method of claim 18, wherein the hydride reducing agent includes sodium borohydride.

20. The method of claim 18, wherein R₃ and R₄ is independently selected from the group consisting of trifluoromethyl and trichloromethyl groups.

21. The method of claim 13, further comprising reacting the pyrazolopyrimidine compound VII-1 with a second electrophile in a presence of base to provide a pyrazolopyrimidine compound VII, wherein R⁵ is selected from the group consisting of members described for R and R in claim 13.

VII-1 VII

22. The method of claim 21, wherein the second electrophile is a member selected from the group consisting of alkyl halides, anhydrides, acid chlorides, isocyanates, isothiocyanate, and sulfonyl chlorides.

23. The method of claim 13, further comprising reacting the pyrazolopyrimidine compound VI with a Grignard reagent to provide a pyrazolopyrimidine compound VIII,

VIII

wherein W is selected from the group consisting of hydrogen, Q-Q alkyl, C₂-C₈ alkenyl, C₂-C alkynyl, and benzyl.

24. The method of claim 23, wherein each of the alkyl, alkenyl, and benzyl of W is substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, oxo, Q-C₈ alkyl, Q-C₈ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C C₈ alkoxy, Q-Cs haloalkoxy, C₂- C₈ alkenyl, C₂-C₈ alkynyl, S(=0)_n(Ci-C₈ alkyl), S(=0)_n(C]-C₈ haloalkyl), OS0₂(C]-C₈ alkyl), OS0₂(Ci-C₈ haloalkyl), C(=0)NR_xR_y, (C C₈ alkyl)NR_xR_y, C(=0)(C₁-C₈ alkyl), C(=0)0(C C₈ alkyl),

haloalkyl), C(=0)( C₃-C₈ cycloalkyl), C(=0)0(C₃-C₈ cycloalkyl), C(=0)( C₂-C₈ alkenyl), C(=0)0(C₂-C₈ alkenyl), (C C₈ alkyl)0(d- C₈ alkyl), (C C₈ alkyl)S(d-C₈ alkyl),

alkyl), phenyl, and phenoxy.

25. The method of claim 13, wherein reacting a 2-R⁴-4-chloro-6-R³-pyrimidine-5- carbonitrile compound IV-1 with a hydrazine compound comprises: reacting the 2-R⁴-4- choloro-6-R -pyrimidine-5-carbonitrile compound IV-1 with a hydrazine compound in a presence of a base in a polar aprotic solvent to produce a pyrazolopyrimidine compound V.

26. The method of claim 13, wherein reacting a 2-R⁴-4-choloro-6-R³-pyrimidine-5- carbonitrile compound IV-1 with a hydrazine compound comprises:

reacting the 2-R⁴-4-choloro-6-R³-pyrimidine-5-carbonitrile compound IV-1 with a tert- butoxycarbonyl (Boc)-protected hydrazine in a polar aprotic solvent to produce a Boc- protected compound; and

reacting the Boc-protected compound with triethylsilane and an acid in a non-reactive solvent to produce a pyrazolopyrimidine compound V.

27. The method of claim 13, wherein reacting a 2-R⁴-4-choloro-6-R³-pyrimidine-5- carbonitrile compound IV-1 with a hydrazine compound comprises: reacting the 2-R⁴-4- choloro-6-R³-pyrimidine-5-carbonitrile compound IV-1 with a hydrazine in a presence of a polar protic solvent with or without a base at an ambient temperature to produce a pyrazolopyrimidine compound V.

28. An pesticidal composition, comprising a pyrazolopyrimidine compound of claim 1.

29. An pesticidal composition, comprising a pyrazolopyrimidine compound of claim 7.

30. An pesticidal composition, comprising a pyrazolopyrimidine compound of claim 12.

31. A method of controlling insect, comprising applying an pesticidal composition near a population of insects, wherein the pesticidal composition comprises a pyrazolopyrimidine compound of claim 1.

32. A method of controlling insect, comprising applying an pesticidal composition near a population of insects, wherein the pesticidal composition comprises a pyrazolopyrimidine compound of claim 7.

33. A method of controlling insect, comprising applying an pesticidal composition near a population of insects, wherein the pesticidal composition comprises a pyrazolopyrimidine compound of claim 12.