WO2022040157A1

WO2022040157A1 - Boron containing compounds and their uses

Info

Publication number: WO2022040157A1
Application number: PCT/US2021/046260
Authority: WO
Inventors: Yong-Kang Zhang; Chunliang Liu; Christopher Michael HAHNE; Gregory Luke Steere; Chun Yu Liu
Original assignee: 5Metis, Inc.
Priority date: 2020-08-18
Filing date: 2021-08-17
Publication date: 2022-02-24
Also published as: AR123277A1

Abstract

The present disclosure relates to novel boron-containing compounds and their novel uses, e.g., as active ingredients that have pesticidal activity. The disclosure also relates to agrochemical compositions and their use in agriculture or horticulture for the control or prevention of infestation of plants, plant parts, plant propagation materials, harvested food crops, or seeds by pests, specifically fungi and nematodes. The disclosure further relates to methods for promoting plant performance and/or curatively or preventively controlling phytopathogens, (particularly fungi and nematodes) on or in a plant, plant parts, plant propagation materials, seeds, harvested fruits, or vegetables.

Description

BORON CONTAINING COMPOUNDS AND THEIR USES Cross-Reference to Related Applications [0001] The present application claims the benefit of and priority to United States Provisional Application Serial No.63/067,060, filed 18 August 2020, which is herein incorporated by reference in its entirety. Technical Field [0002] The present disclosure relates to novel boron-containing compounds and their novel uses, e.g., as active ingredients that have pesticidal activity. The disclosure also relates to agrochemical compositions and their use in agriculture or horticulture for the control or prevention of infestation of plants, plant parts, plant propagation materials, harvested food crops, or seeds by pests, specifically fungi and nematodes. The disclosure further relates to methods for promoting plant performance and/or curatively or preventively controlling phytopathogens, (particularly fungi and nematodes) on or in a plant, plant parts, plant propagation materials, seeds, harvested fruits, or vegetables. Background [0003] Boron is a unique element due to its capacity to create powerfully effective compounds. While the use of boron in simple, naturally occurring borates is well known, the construction and characterization of more complex, rationally designed boron-containing synthetic compounds that have low toxicity and are effective has been relatively under- investigated. [0004] The creation and development of such boron-containing compounds is unpredictable, even in the hands of experts. Additionally, boron is challenging to work with due to its ability to covalently bond with other molecules. Boron-containing molecules have traditionally been stymied from becoming commercially viable products due to these synthetic and pharmacological uncertainties. [0005] Further complicating matters, the charge and geometry of benzoxaborole compounds are often dynamic depending on the environment of the compound; benzoxaboroles often exist in a dynamic equilibrium. Moreover, substitutions on the benzoxaborole may have profound effects on this dynamic equilibrium. Additionally, the boron atom’s empty p-orbital readily forms covalent bonds with Lewis bases, which potentially affects biological activity. These characteristics together make the development of benzoxaborole compounds that display biological activity an unpredictable and challenging endeavor. [0006] Within the field of plant health, fungal and nematode plant pathogens lead to a wide range of diseases across all crops, resulting in massive losses (e.g., rusts, spots, blights, downy mildews, blasts, blotches, powdery mildews, stripes, rots, smuts, wilt, galling, damping-off, girdling, stunting, root knot nematode disease, etc.). Current solutions are limited; currently available, conventional, and outdated chemical pesticides provide only a partial level of control (as with resistant cultivars), or add significant cost. While breeding for resistance traits to specific crop/pathogen combinations in germplasm offers some hope in circumventing these problems, it is widely recognized that novel fungicidal and/or nematicidal compounds must be discovered. [0007] Current fungicidal and/or nematicidal compounds are costly to both purchase and use, and are often toxic and may be otherwise detrimental to off-target animals and/or vegetation near the site of application including runoff and affecting the watershed. Moreover, many fungicidal and/or nematicidal compounds lose efficacy over time, concomitantly with the rise of respective pathogens becoming resistant to treatment. Nonetheless, agrochemical fungicidal and/or nematicidal compounds are important to control various diseases and minimize crop loss. [0008] In agriculture and horticulture, some nematodes are considered beneficial; however, predatory nematodes such as cutworms, root-knot nematodes, and cyst nematodes attack and damage various plant parts including leaves, stems and roots, inflicting significant economic losses to this industry as well. Despite the relatively well-understood model, C. elegans, a very limited number of nematicidal compounds have been developed recently that address some of these shortcomings. Accordingly, there is still a pressing need for additional nematicidal compounds with superior and/or varying attributes in terms of spectrum and activity, physical- chemical properties and drug-ability profile, mammalian safety, and more diverse and convenient treatment options to ensure long-term viability. [0009] Accordingly, there is a need for fungicidal and/or nematicidal compounds and compositions for plant health. Compounds that have both nematicidal and fungicidal properties have several benefits and advantages. For example, combination fungicide and nematicide products applied to seed allow end users to protect against severe losses caused by soilborne pests during the first 30 days of growth, when the plant is more susceptible. Such a combination is also advantageous for seed treatment applications since seeds have a small surface area, and a combination product maximizes the available application surface area. Additionally, treatment of a plant, plant part, or plant propagation material with two separate active ingredients, one being a fungicide, and the second being a nematicide, may cause antagonistic effects that may have a negative overall effect on plant health. Additionally, the cost for two plant protection products is higher than for a single active ingredient combination product. [0010] Accordingly there is a need for compounds and compositions that have both fungicidal and nematicidal properties for plant health. Brief Summary [0011] One embodiment of the present disclosure includes a compound of formula (I):

wherein: A is an aryl or heteroaryl; each occurrence of X is independently selected from the group consisting of: fluorine, chlorine, bromine, and iodine; n is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when n is 0, X is absent; R¹ is selected from the group consisting of: hydrogen, C₁-C₄ hydrocarbyl, and C₃-C₄ cyclohydrocarbyl; and R² is selected from the group consisting of: aryl, heteroaryl, C₁-C₆ hydrocarbyl, and C₃-C₆ cyclohydrocarbyl, where each R² is substituted with (Y)_m; wherein: each occurrence of Y is independently selected from the group consisting of: fluorine, chlorine, bromine, iodine, C₁-C₆ hydrocarbyl, C₁-C₆ halohydrocarbyl, O(C₁-C₆ hydrocarbyl), S(C₁-C₆ hydrocarbyl), O(C₁-C₆ halohydrocarbyl), S(C₁-C₆ halohydrocarbyl), S(O)_w(C₁-C₆ hydrocarbyl), S(O)_w(C₁-C₆ halohydrocarbyl), O(C₃-C₆ cyclohydrocarbyl), S(C₃-C₆ cyclohydrocarbyl), O(C₃-C₆ heterocyclohydrocarbyl), S(C₃-C₆ heterocyclohydrocarbyl), NO₂, CN, C(O)O(C₁-C₆ hydrocarbyl); m is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when m is 0, Y is absent, and w is number selected from the group consisting of 1 and 2; wherein when A is a heterorayl, the heteroaryl contains 1 ring or 2 fused rings and includes 1, 2, or 3 ring heteroatoms that are the same or different and wherein each is selected from one or more of nitrogen, oxygen, and sulfur, or a salt, stereoisomer, enantiomer, or tautomer thereof. [0012] One embodiment of the present disclosure includes a compound of formula (I’):

wherein: A is an aryl or heteroaryl; each occurrence of X is independently selected from the group consisting of: fluorine, chlorine, bromine, and iodine; n is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when n is 0, X is absent; R¹ is selected from the group consisting of: hydrogen, C₁-C₄ hydrocarbyl, and C₃-C₄ cyclohydrocarbyl; and R² is selected from the group consisting of: aryl, C₁-C₆ hydrocarbyl, and C₃-C₆ cyclohydrocarbyl, where each R² is substituted with (Y)_m; wherein: each occurrence of Y is independently selected from the group consisting of: fluorine, chlorine, bromine, iodine, C₁-C₆ hydrocarbyl, C₁-C₆ partially of fully fluorinated hydrocarbyl, O(C₁-C₆ hydrocarbyl), and S(C₁-C₆ hydrocarbyl); and m is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when m is 0, Y is absent, wherein when A is a heterorayl , the heteroaryl contains 1 ring or 2 fused rings and includes 1, 2, or 3 ring heteroatoms that are the same or different and wherein each is selected from one or more of nitrogen, oxygen, and sulfur, or a salt, stereoisomer, enantiomer, or tautomer thereof. [0013] In one aspect, at least one of m or n is not 0. In one aspect, A is phenyl or pyridine. In one aspect, the compound is a compound of formula Ia:

In one aspect, the compound is a compound of formula Ib:

In one aspect, R¹ is hydrogen, methyl, or ethyl. In one aspect, R² is phenyl or substituted phenyl. In one aspect, the sum of m and n is 1, 2, or 3. In one aspect, m is 1 and n is 1. In one aspect, m is 1 and n is 2. In one aspect, each X is independently selected from the group consisting of fluorine and chlorine. In one aspect, each Y is independently selected from the group consisting of: fluorine, chlorine, SCH₃, OCH₃, CH₃, and CF₃. [0014] Compound List A: one embodiment of the present disclosure includes a compound selected from the group consisting of:

or a salt thereof. [0015] Compound List B: one embodiment of the present disclosure includes a compound selected from the group consisting of:

or a salt thereof [0016] Compound List C: one embodiment of the present disclosure includes a compound selected from

or a salt thereof. [0017] Compound List D: one embodiment of the present disclosure includes a compound selected from:

or a salt thereof. [0018] Compound List E: one embodiment of the present disclosure includes a compound selected from the group consisting of:

or a salt thereof. [0019] One embodiment of the present disclosure includes a method for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen by applying a compound or a composition according to the present disclosure. In one aspect, the pathogen is phytopathogenic. In one aspect, the pathogen is a soil-borne pathogen. In other words, the pathogen is any pest that causes damage to a plant below the surface of the soil, and may be a pathogen that infects one or more of the roots and the seed. In one aspect, the pathogen is a fungus. In one aspect, the pathogen is a nematode. In one aspect, the pathogen includes both a fungus and a nematode. In one aspect, the pathogen is selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, Phoma, Plasmodiophora, and Spongospora. In one aspect, the pathogen is a nematode from the class Chromodorea, Rhabditida, or Enoplea. In one aspect, the pathogen is a nematode from the genera Xiphinema, Roylenchulus, Tylenchulus, Helicotylenchus, Pratylenchus, Radopholus, Hirschmanniella, Heterodera, Globodera, Meloidogyne, Ditylenchus, Bursaphelencus, Anguina, Aphelenchoides. Longidorus, or Paratrichodorus. In one aspect, the pathogen is a fungus selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, and Phoma; and a nematode selected from the class consisting of: Chromodorea, Rhabditida, or Enoplea. In one aspect: the fungus is Fusarium and the nematode is soybean cyst nematode, or the fungus is Verticillium and the nematode is Pratylenchus, or the fungus is Fusarium (oxy) and the nematode is root knot nematode. [0020] In one embodiment, the microbial infection is fungal. In one aspect, the fungal infection is a True Fungal infection or a fungal-like infection. In one aspect, the fungal infection is caused by an organism characterized as Ascomycota, Basidiomycota, Cercozoa, Chytridiomycota, Deuteromycota (fungi imperfecti), Glomeromycota, Oomycota, or Zygomycota. In one aspect, the fungal infection is caused by a fungal organism characterized as Ascomycota. In one aspect, the Ascomycota is further characterized as Pzizomycotina, Saccharomycotina, Taphrinomycotina, Arthoniomycetes, Coniocybomycetes, Dothideomycetes, Eurotiomycetes, Geoglossomycetes, Laboulbeniomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes, Omnivoromycetes, Orbiliomycetes, Pezizomycetes, Sordariomycetes, Xylonomycetes, Lahmiales, Itchiclahmadion, Triblidiales, Saccharomycetes, Archaeorhizomyces, Neolectomycetes, Pneumocystidomycetes, Schizosaccharomycetes, or Taphrinomycetes. In one aspect, wherein the fungal infection is caused by a fungal organism characterized as Basidiomycota. In one aspect, the Basidiomycota is further characterized as Pucciniomycotina, Ustilaginomycotina, or Agaricomycotina. In one aspect, the fungal infection is caused by a fungal organism characterized as Cercozoa. In one aspect, the Cercozoa is further chracterized as Endomyxa, Phytomyxea, Plasmodiophoromycota, or Phagomyxida. In one aspect, the fungal infection is caused by a fungal organism characterized as Chytridiomycota. In one aspect, the Chytridiomycota is further characterized as Synchytriales. In one aspect, the fungal infection is caused by a fungal organism characterized as Glomeromycota. In one aspect, the Glomerocycota is further characterized as Achaeosporales, Diversisporales, Glomerales, Paraglomerales, or Nematophytales. In one aspect, the fungal infection is caused by a fungal organism characterized as Oomycota. In one aspect, the Oomycota is further characteriezed as Lagenidiales, Leptomitales, Peronosporales, Phipidiales, or Saprolegniales. In one aspect, the fungal infection is caused by a fungal organism characterized as Zygomycota. In one aspect, the Zygomycota is further characterized as Mucoromycotina, Kickxellomycotina, Entomophthoromycotina, Zoopagomycotina; Endogonales, Mucorales, Mortierellales, Asellariales, Kickxellales, Dimargaritales, Harpellales, Entomophthorales, and Zoopagales. In one aspect, the fungal infection is selected from one or more of the group consisting of Alternaria, Aspergillus, Bipolaris, Blumeria, Botrytis, Candida, Cercospora, Cercosporidium, Claviceps, Cochliobolus, Colletotrichum, Corynespora, Dybotryon, Dilophospora, Erysiphe, Exserohilum, Fusarium, Leveillula, Magnaporthe, Melampsora, Microsphaera, Microsphaeropsis, Monilia, Monilinia, Mycosphaerella, Oidiopsis, Peronospora, Phaeosphaeria, Phakopsora, Phomopsis, Phymatotrichum, Phytophthora, Plasmopora, Podosphaera, Pseudoperonospora, Puccinia, Pyrenophora, Pyricularia, Pythium, Rhizoctonia, Sclerophthora, Sclerotinia, Septoria, Setosphaeria, Stangospora, Uncinula, Ustilago, Venturia, Verticillium, and Zymoseptoria. In one aspect, the fungal infection is selected from one or more of the group consisting of Alternaria, Aspergillus, Bipolaris, Blumeria, Botrytis, Candida, Cercospora, Cercosporidium, Colletotrichum, Corynespora, Erysiphe, Fusarium, Magnaporthe, Mycosphaerella, Peronospora, Phaeosphaeria, Phakopsora, Phytophthora, Plasmopora, Podosphaera, Pseudoperonospora, Puccinia, Pyricularia, Pythium, Rhizoctonia, Sclerotinia, Septoria, Stangospora, Verticillium, and Zymoseptoria. [0021] In one embodiment, the plants or plant propagation material is agricultrual, horticultural, or ornamental. In one aspect, the plant propagation materials is seed. In one aspect, the plants or plant propagation materials are one or more of maize, soya bean, alfalfa, cotton, sunflower, Brassica oil seeds, Brassica napus, Brassica rapa, B. juncea, Brassica carinata, Arecaceae sp., Rosaceae sp., Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp., Rubiaceae sp., Theaceae sp., Sterculiceae sp., Rutaceae sp., Solanaceae sp., Liliaceae sp., Compositae sp., Umbelliferae sp., Cucurbitaceae sp., Alliaceae sp., Cruciferae sp., Leguminosae sp., Chenopodiaceae sp., Linaceae sp., Cannabeacea sp., Malvaceae sp., Papaveraceae, Asparagaceae, Stevia rebaudiana, and genetically modifed versions thereof. In one aspect, the plants or plant propagation materials are one or more of a variety of soybean. In one aspect, the plants or plant propagation materials are one or more of the family Solanaceae sp. In one aspect, the plants or plant propagation materials are one or more of tomatoes, potatoes, peppers, tomatillo, aubergines, and tobacco. In one aspect, the plants or plant propagation materials are one or more of: (a) Fabaceae: soybean, dry beans, peanuts; (b) Poaceae: grasses including maize, wheat, rice, barley, and millet; (c) Solanaceae: tomato, potato, eggplant, peppers; (d) Cucurbitaceae: squash, pumpkin, zucchini, gourds, watermelon, melons, cucumber; (e) Rosaceae: apple, pear, quinces, apricots, plums, cherries, peaches, raspberries, strawberries, almonds; (f) Brassicaceae: broccoli, cabbage, cauliflower, kale, collards, turnips, rapeseed, radish; (g) Asteraceae or Compositae: lettuces, sunflower, artichoke; (h) Amaranthaceae: spinach, beets, chard, quinoa; (i) Convolvulaceae: sweet potato; (j) Amaryllidaceae: onion, chive, leek, garlic; (k) Ubelliferae: carrots, celery, cilantro, parsley, dill, fennel; (l) Rutaceae: citrus fruit; (m) Juglandaceae: walnut, pecan; (n) Fagaceae: oak, beeches, chesnut; (o) Pinaceae: cedar, fir, hemlock, spruce, pine; and (p) Anacardiacea: cashew, mango, pistachio. [0022] In one aspect, the compound is applied to one or more of a plant, a plant part, plant propagation material, and soil. In one aspect, the application of the compound or the composition is selected from the group consisting of: topical, to the soil, foliar, a foliar spray, a seed coating, a seed treatment, a soil drench, directly in-furrow dipping, drenching, soil drenching, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, overhead chemigation, watering (drenching), and drip irrigating, or any combinations thereof. In one aspect, the application of the compound or the composition is a seed treatment. [0023] One embodiment of the present disclosure provides a compound of the present disclosure is administered to one or more of an animal, a plant, a plant part, plant propagation material, and harvested fruits or vegetables. [0024] One embodiment of the present disclosure includes a composition comprising a compound according to the present disclosure, and one or more carrier. In one aspect, the composition is in the form of a powder. In one aspect, the composition is in the form of a liquid. In one aspect, the liquid is at least 50 percent water. In one aspect, the composition has a pH value of about 5 to about 10. [0025] One embodiment of the present disclosure includes a composition comprising a compound of the present disclosure and one or more additional active agent. In one aspect, the one or more additional active agent is selected from the group consisting of: a fungicide, a nematicide, an insecticide, and a bactericide, or any combination thereof. In one aspect, the one or more additional active agent is a fungicide. In one aspect, the fungicide has a mode as action as described by a FRAC target site code. In one aspect, the FRAC target site code is selected from the group consisting of: B1, B3, C2, C3, C4, C6, D1, E1, E2, E3, G1, H5, M4, and M5. In one aspect, the additional active agent is a fungicide selected from the group consisting of: carbendazim, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, zoxamide, ethaboxam, pencycuron, fluopicolide, metrafenone, pyriofenone, flutolanil, fluopyram, fluxapyroxad, penthiopyrad, benodanil, mepronil, isofetamid, fenfuram, carboxin, oxycarboxin, thifluzamide, benzovindiflupyr, bixafen, furametpyr, inpyrfluxam, isopyrazam, penflufen, sedaxane, isoflucypram, pydiflumetofen, pyraziflumid, boscalid, benomyl, fuberidazole, diflumetorim, tolfenpyrad, fenazaquin, azoxystrobin, coumaxystrobin, enoxastrobin, flufenoxystrobin, picoxystrobin, pyraoxystrobin, mandestrobin, pyraclostrobin, pyrametostrobin, triclopyricarb, kresoxim-methyl, trifloxystrobin, dimoxystrobin, fenamistrobin, methominostrobin, orysastrobin, famoxadone, fluoxastrobin, fenamidone, pyribencarb, cyazofamid, amisulbrom, fenpicoxamid, binapacryl, meptyldinocap, dinocap, fluazinam, ferimzone, fentin chloride, fentin acetate, fentin hydroxide, silthiofam, ametoctradin, cyprodinil, mepanipyrim, pyrimethanil, kasugamycin, blasticidin-s, quinoxyfen, proquinazid, fenpiclonil, fludioxonil, nuarimol, imazalil, oxpoconazole, pefurazoate, prochloraz, triflumizole, azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, prothioconazole, aldimorph, dodemorph, fenpropimorph, tridemorph, fenpropidin, spiroxamine, fenhexamid, fenpyrazamine, piperalin, pyributicarb, naftifine, terbinafine, validamycin, polyoxin, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, valifenalate, mandipropamid, copper, sulphur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, zinc thiazole, ziram, captan, captafol, folpet, dichlofluanid, tolylfluanid, chlorothalonil, chlozolinate, dimethachlone, anilazine, iprodione, procymidone, vinclozolin, triforine, pyrifenox, pyrisoxazole, fenarimol, guazatine, iminoctadine, dithianon, chinomethionat, quinomethionate, fluoroimide, methasulfocarb, and phenamacril. [0026] In another aspect, is a method of reducing, ameliorating, or controlling a plant fungal infestation. That method comprises administering a composition comprising a fungicidally effective amount of a compound of the present disclosure, preferably dissolved or dispersed in a carrier medium to a plant, a plant part, plant propagation material, and/or harvested fruits or vegetables in need thereof. [0027] In one embodiment, the present disclosure includes compositions suitable for treatment of a locus that may be infected with pests, such as a plant, an animal, such as a mammal, or a building, or for the prevention of infection or infestation of such a locus with pests. [0028] In some embodiments of the disclosure, a contemplated compound or a composition containing a contemplated compound is administered locally to an animal or a part of an animal, a plant, a plant parts plant propagation material, and/or harvested fruits or vegetables. In some embodiments, the administration is systemic. [0029] In some embodiments, the administration of a compound or a composition of the disclosure is topical, to the soil, foliar, a foliar spray, systemic, a seed coating, a seed treatment, a soil drench, directly in-furrow dipping, drenching, soil drenching, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, watering (drenching), or drip irrigating, or any combinations thereof. [0030] The formulations/agrochemical compositions described herein may comprise a carrier and may be conveniently formulated in a known manner into emulsifiable concentrates, suspension concentrates, coatable pastes, directly sprayable or dilutable solutions, emulsions, wettable powders, soluble powders, dusts, granulates, and/or encapsulations in polymeric substances. The carrier can be any solid carrier or a liquid carrier known in the art suitable for agrochemical compositions. The type of the compositions and the methods of applications such as spraying, atomizing, dusting, scattering, coating or pouring, are chosen based on objectives and the circumstances. A contemplated composition can contain adjuvants such as stabilizers, antifoams, viscosity regulators, binders, or tackifiers, fertilizers, micronutrient donors, additives that enhance plant uptake, spreaders, stickers, or other compositions for obtaining special effects. Such adjuvants can be included in the agrochemical composition/formulation or tank mixed with the agrochemical composition/formulation prior to application. [0031] The preceding is a simplified summary to provide an introduction and understanding of some embodiments of the present disclosure. This summary is neither an extensive nor exhaustive over-view of the present disclosure and its various embodiments. The summary presents selected concepts of the embodiments of the present disclosure in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other embodiments of the present disclosure are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below. [0032] The headings used herein are for organizational purposes only and are not meant to be used to limit the scope of the description or the claims. The words “include”, “including”, and “includes” mean including but not limited to the recited description. Brief Description of the Drawings [0033] Figure 1 is a Table, providing results of biological testing for compounds of the present disclosure, including activity against several pests, including fungi and bacteria. In light of taxonomical updating, reference to Alternaria solani may also be considered as a reference to Alternaria linariae. In some embodiments of the present disclosure, a compound is useful as a fungicide. In some embodiments of the present disclosure, a compound is useful as a nematocide. In some embodiments of the present disclosure, a compound is useful as an antibacterial. In some embodiments of the present disclosure, a compound is useful as a dual fungicide-nematocide, a dual fungicide-antibacterial, or a dual nematocide-antibacterial. In some embodiments of the present disclosure, a compound is useful as a triple fungicide- nematocide-antibacterial. Detailed Description [0034] The description set forth below is intended as a description of various embodiments of the described subject matter and is not necessarily intended to represent the only embodiment(s). In certain instances, the description includes specific details for the purpose of providing an understanding of the described subject matter. However, it will be apparent to those skilled in the art that embodiments may be practiced without the specific details as described. Definitions [0035] Any reference in the specification to “one embodiment” or “an embodiment” or “another embodiment” means that a particular feature, structure, characteristic, operation, or function described in connection with an embodiment is included in at least one embodiment. Thus, any appearance of the phrases “in one embodiment” or “in an embodiment” in the specification is not necessarily referring to the same embodiment. Further, the particular features, structures, characteristics, operations, or functions may be combined in any suitable manner in one or more embodiments, and it is intended that embodiments of the described subject matter may and do cover modifications and variations of the described embodiments. [0036] The phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C”, “at least one of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B, or C” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together. [0037] The term “a” or “an” entity refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, and “having” may be used interchangeably. [0038] Compounds of this disclosure include those described generally above, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry", 5th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, Plant Pathology, 5^th Ed., Gore N Agrios, Elsevier Academic Press: 2005, the entire contents of which are hereby incorporated by reference. [0039] The term “hydrocarbon”, used herein refers to paraffinic and naphthenic compounds, or any mixtures of paraffin, naphthenic, or paraffin and naphthenic compounds. Paraffinic compounds may either be linear (n-paraffins) or branched (i-paraffins). Examples of linear paraffins are pentane, hexane, heptane, etc. Examples of branched paraffins are isooctane, isobutane, isopentane, etc. Naphthenic compounds are cyclic saturated hydrocarbons, i.e. cycloparaffins. Such hydrocarbons with cyclic structure are typically derived from cyclopentane or cyclohexane. A naphthenic compound may comprise a single ring structure (mononaphthene) or two isolated ring structures (isolated dinaphthene), or two fused ring structures (fused dinaphthene) or three or more fused ring structures (polycyclic naphthenes or polynaphthenes). [0040] The term "hydrocarbon solvent" refers to one or more hydrocarbons which have solvency for mineral oil. Typically, the hydrocarbon solvent comprises at least one of normal or branched chain paraffins or olefins, cyclic hydrocarbons and aromatic hydrocarbons. Often, the hydrocarbon solvent is comprised of at least 50 wt. %, preferably at least 75 wt. % and most preferably at least 90 wt. % of normal or branched chain paraffins or olefins based on the weight of the hydrocarbon solvent. In some embodiments, the hydrocarbon solvent is selected from the group consisting of isoparaffins and normal paraffins. In other embodiments, the hydrocarbon solvent is a normal paraffin. In one embodiment, the hydrocarbon solvent is petroleum ether. In still other embodiments, the hydrocarbon solvent comprises from 5 to 15 carbon atoms per molecule. In other embodiments, the hydrocarbon solvent comprises 7 to 10 carbon atoms per molecule. In addition, the hydrocarbon solvent does not require the presence of functional groups such as, for example, esters, alcohols or adds. In another embodiment, the hydrocarbon solvent is a mixture of petroleum ether and ethyl acetate. In yet other embodiments, that the hydrocarbon solvent contain less than about 5 wt. % and more preferably less than about 1 wt. % of oxygen-containing functional groups such as, for examples, esters, alcohols, acids, or mixtures thereof, based on the weight of the hydrocarbon solvent. [0041] The term “hydrocarbyl” refers to a monovalent moiety formed by removing a hydrogen atom from a hydrocarbon. The term ‘hydrocarbyl’ includes alkyl groups, alkenyl groups, and alkynyl groups. A preferred “hydrocarbyl” group is an “alkyl” group. Representative hydrocarbyl groups are alkyl groups having 1 to 25 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, undecyl, decyl, dodecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, docosyl, tricosyl, and the isomeric forms thereof; alkenyl groups having 2 to 25 carbon atoms, such as methenyl, ethenyl, 1-propenyl, 2-propenyl, iso-propenyl, 1-butenyl, 2- butenyl, 3-butenyl, iso-butenyl, sec-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, hexenyl, heptenyl, octenyl and the isomeric forms thereof; alkynyl groups having 2 to 25 carbon atoms, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2- pentynyl, 3-pentynyl, 4-pentynyl, hexynyl, pentynyl, and octynyl, and the isomeric forms thereof. [0042] In some embodiment, a “hydrocarbyl radical” (or “hydrocarbyl group”) contains 1 to 5 members (C₁-C₅). In other embodiment, the hydrocarbyl radical contains 1 to 3 members (C₁- C₃). In yet other embodiment, the hydrocarbyl radical may contain from 1 to 17 substitutions, or in another embodiment from 1 to 5 substitutions. The hydrocarbyl or hydrocarbyl radical group may also contain one or more substitutents. [0043] The term “cyclohydrocarbyl”, by itself or part of another substituent, unless otherwise stated, refers to a cyclic hydrocarbyl radical which may be fully saturated, monounsaturated or polyunsaturated and includes C₃-C₁₅ hydrocarbons in a ring system. The cyclohydrocarbyl ring may contain one or more substitutents. In one embodiment, the ring contains 3 to 6 members (C₃-C₆). In another embodiment, the ring system may have from 1 to 11 substitutions, or in another embodiment from 2 to 6 substitutions. Examples of cyclohydrocarbyl include, but are not limited to cyclopropyl, cyclopentyl, cyclohexyl, cyclohex-1-enyl, cyclohex-3-enyl, cycloheptyl, cyclooctyl, norbornyl, decalinyl, adamant¬-1-yl, adamant-2-yl, bicyclo[2.1.0]pentyl, bicyclo[3.1.0]hexyl, spiro[2.4]heptyl, spiro[2.5]octyl, bicyclo[5.1.0]octyl, spiro[2.6]nonyl, bicyclo[2.2.0]hexyl, spiro[3.3]heptyl, bicyclo[4.2.0]octyl, and spiro[3.5]nonyl, and the like. [0044] Similarly, the term “heterocyclohydrocarbyl,” by itself or part of another substituent, unless otherwise stated, refers to a heterocyclic hydrocarbyl radical which may be fully saturated, monounsaturated, or polyunsaturated and includes C₃-C₁₅ hydrocarbons in a ring system along with one or more heteroatoms selected from N, O, or S. The heterocyclohydrocarbyl ring may contain one or more substitutents. In one embodiment, the ring contains 3 to 6 members, including at least one heteroatom. In another embodiment, the ring system may have from 1 to 11 substitutions, or in another embodiment from 2 to 6 substitutions. Examples include, but are not limited to, ethylene oxide, tetrahydrofuran, tetrahydropyran, 1,4- dioxane, ethylene imine, pyrrolidine, piperidine, ethylene sulfide, tetrahydrothiophene, tetrahydrothiopyran, morpholine, piperazine, and the like. [0045] The term "alkyl", by itself or as part of another substituent, unless otherwise stated, refers to a straight chain or branched chain, or cyclic hydrocarbon radical, or combination thereof, which is fully saturated, having the number of not more than 15 carbon atoms. Exemplary “alkyl” groups include, but are not limited to groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclopropyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl, 2-(cyclopropyl)ethyl, cyclohexylmethyl, cyclopropylethyl, cyclohexyl, cyclopropylmethyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1- dimethylpropyl, 1,2- dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1- methylpentyl, 2- methylpentyl, 3- methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2- dimethylbutyl, 1,3- dimethylbutyl, 2,2- dimethylbutyl, 2,3- dimethylbutyl, 3,3-dimethylbutyl, ethylmethylpropyl, trimethylpropyl, methylhexyl, dimethylpentyl, ethylpentyl, ethylmethylbutyl, dimethylbutyl, spiropentyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. [0046] An “unsaturated alkyl” group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to vinyl, prop-2-enyl, crotyl, isopent-2-enyl, butadien-2-yl, penta-2,4-dienyl, penta-1,4-dien-3-yl, ethynyl, prop-1-ynyl, prop-3- ynyl, but-3-ynyl, and the higher homologs and isomers, and the like. [0047] The term "alkenyl", by itself or as part of another substituent, unless otherwise stated, refers to a straight chain or branched chain radical, or combination thereof, which may be monounsaturated or polyunsaturated and may include divalent and multivalent radicals, having the number of not more than 15 carbon atoms and containing at least one double bond. An “alkenyl radical” may contain 1 to 5 members (C₁-C₅). [0048] The term "heteroalkyl", by itself or as part of another substituent, unless otherwise stated, refers to a straight or branched chain, or cyclic hydrocarbyl radical, or combinations thereof, consisting of one to fourteen carbon atoms and from one to six heteroatoms selected from oxygen, nitrogen, sulfur, and silicon, and where the nitrogen, sulfur and silicon atoms may optionally be oxidized and the nitrogen atom may optionally be quaternized. The heteroatoms O, N and S may be placed at any interior position of the heteroalkyl group. The heteroatom Si may be placed at any position of the heteroalkyl group, including the position at which the heteroalkyl group is attached to the remainder of the molecule. Examples include, but are not limited to 2-methoxyethyl, 2-(methylamino)ethyl, 2-(dimethylamino)ethyl, 2-(ethylthio)methyl, 2- (methylsulfinyl)ethyl, 2-(methylsulfonyl)ethyl, 2-methoxyvinyl, trimethylsilyl, dimethyl(vinyl)silyl, 2-(cyclopropylthio)ethyl, and 2-(methoxyimino)ethyl. Up to two heteroatoms may be consecutive, such as, for example, (methoxyamino)methyl and trimethylsilyloxy. [0049] The terms "alkoxy" refers to those groups attached to the remainder of the molecule via an oxygen atom. Suitable examples of alkoxy groups include, but are not limited to methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, pentoxy, hexoxy, heptoxy, and the like. [0050] The term "heterocyclyl", by itself or as part of another substituent, represents, unless otherwise stated, cyclic version of "heteroalkyl". Additionally, for heterocyclyl, a heteroatom may occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of heterocyclyl include, but are not limited to piperidinyl, piperidin-2-yl, piperidin-3-yl, morpholin-4-yl, morpholin-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, piperazinyl, piperazin-2-yl, and the like. In some embodiments, the heterocyclyl radical contains 3 to 6 members (C₃-C₆). In other embodiments, the radical may contain from 1 to 6 substitutions, or in another embodiment from 1 to 5 substitutions. [0051] The term "aryl", unless otherwise stated, used alone or as part of a larger moiety as in “arylalkyl”, is a polyunsaturated, aromatic, hydrocarbyl substituent which is mono- or bicyclic. In one embodiment, the monocyclic ring system comprises 6 carbon atoms, namely phenyl. Suitable examples of aryl groups include, but are not limited to phenyl, substituted phenyl, nalhthyl, and substituted naphtyl groups. The term aryl refers to rings that may contain one or more substituents. In one embodiment, a monocyclic aryl may have from 1 to 5 substitutions, or in another embodiment from 2 to 3 substitutions. [0052] The term “phenyl” as used herein is an aromatic 6 carbon ring system. The term “phenyl” may be abbreviated herein as “Ph”. A “phenyl” group is an example of an “aryl” group. [0053] The term "heteroaryl", unless otherwise stated, used alone or as part of a larger or smaller moiety as in “aryl”, contain from one to four heteroatoms selected from nitrogen, oxygen, and sulfur, where the nitrogen and sulfur atoms are optionally oxidized, and one or several nitrogen atoms are optionally quaternized. A heteroaryl group may be attached to the remainder of the molecule through a heteroatom. Non-limiting examples of heteroaryl groups include phenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 1-imidizoyl, 2-imidazolyl, 4- imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2- pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. [0054] The terms "arylalkyl," "heteroarylalkyl," and “heterocyclylalkyl” refers to those radicals in which an aryl, heteroaryl, or heterocyclyl group is linked through an alkyl group. Examples includes benzyl, phenethyl, pyridylmethyl, and the like. The terms also include alkyl linking groups in which a carbon atom, for example, a methylene group, has been replaced by, for example, an oxygen atom. Examples include phenoxymethyl, pyrid-2-yloxymethyl, 3-(naphth-1- yloxy)propyl, and the like. Similarly, the term “benzyl” as used herein is a radical in which a phenyl group is attached to a CH₂ group, thus, a CH₂Ph group. Benzyl groups may be substituted or unsubstituted. The term substituted benzyl refers to radicals in which the phenyl group or CH₂ contains one or more substituents. In one embodiment, the phenyl group may have 1 to 5 substituents, or in another embodiment 2 to 3 substituents. [0055] As used herein “optionally substituted” refers to a substitution of a hydrogen atom, which would otherwise be present for the substituent. When discussing ring systems, the optional substitution is typically with 1, 2, or 3 substituents replacing the normally-present hydrogen. When referencing straight and branched moieties, however, the number of substitutions may be more, occurring wherever hydrogen is present. The substitutions may be the same or different. [0056] Illustrative substituents, which with multiple substituents may be the same or different, include halogen, haloalkyl, R', OR', OH, SH, SR', NO₂, CN, C(O)R', C(O)(alkyl substituted with one or more of halogen, haloalkyl, NH₂, OH, SH, CN, and NO₂), C(O)OR', OC(O)R', CON(R')₂, OC(O)N(R')₂, NH₂, NHR', N(R')₂, NHCOR', NHCOH, NHCONH₂, NHCONHR', NHCON(R')₂, NRCOR', NRCOH, NHCO₂H, NHCO₂R', NHC(S)NH₂, NHC(S)NHR', NHC(S)N(R')₂, CO₂R',CO₂H, CHO, CONH₂, CONHR', CON(R')₂, S(O)₂H, S(O)₂R', SO₂NH2, S(O)H, S(O)R', SO₂NHR', SO₂N(R')₂, NHS(O)₂H, NR'S(O)₂H, NHS(O)₂R', NR'S(O)₂R', Si(R')₃, where each of the preceding may be linked through a divalent alkylene linker, (CH₂)x, where x is 1, 2, or 3. In embodiments where a saturated carbon atom is optionally substituted with one or more substituent groups, the substituents may be the same or different and also include =O, =S, =NNHR', =NNH₂, =NN(R')₂, =N-OR', =N-OH, =NNHCOR', =NNHCOH, =NNHCO₂R', =NNHCO₂H, =NNHSO₂R', =NNHSO₂H, =N-CN, =NH, or =NR'. For each of the preceding, each may be linked through an alkylene linker, (CH₂)_x, where x is 1, 2, or 3, Each occurrence of R’ is the same or different and represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl, or when two R’ are each attached to a nitrogen atom, they may form a saturated or unsaturated heterocyclic ring containing from 4 to 6 ring atoms. [0057] As used herein, the term "heteroatom" includes oxygen (O), nitrogen (N), and sulfur (S). [0058] The phrases “independently selected”, “independently” and their variants, when used in reference to two or more of the same substituent group are used herein to mean that that two or more groups may be the same or different. [0059] The term "halogen" or “halo” means fluorine, chlorine, bromine, or iodine. The term "halohydrocarbyl" means a hydrocarbyl radical as defined above wherein one or more hydrogens are replaced with a halogen. A halohydrocarbyl radical (group or substituent) is typically a substituted alkyl substituent. Examples of such haloalkyl radicals include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and the like. A haloalkyl is a alkyl radical as defined above wherein one or more hydrogen is replaced with a halogen. [0060] The term “perfluorohydrocarbyl” means an alkyl radical (group or substituent) wherein each hydrogen has been replaced by a fluorine atom. Examples of such perfluorohydrocarbyl groups, in addition to trifluoromethyl above, are perfluorobutyl, perfluoroisopropyl, and perfluorohexyl. [0061] The term “pathogen” includes any organism that may cause infection or disease. The term is typically used to describe an infectious microorganisms such as, for example, fungi and nematodes. “Phytopathogen” as used herein, is a pathogen affecting a seed, plant, plant part, plant propagation material, or harvested fruits and/or vegetables. Plant parasitic nematodes form a particular aspect of pathogen of the present disclosure. [0062] The phrase “True Fungi” is used herein means all members of the kingdom Fungi, including, but not limited to, yeasts, rusts, smuts, mildews, molds, and mushrooms, excepting members of Oomycota (Phytophthora infestens and Plasmopara viticola). The uncapitalized term “fungi” or “fungus” is used to include all of the fungal organisms discussed herein, including the Oomycota. The uncapitalized term “fungi” or “fungus” is also used to include all of the fungal organisms discussed herein, including plasmodiophoromycetes. [0063] The term “plant health” generally describes various sorts of characteristics of plants. For example, properties that may be mentioned are crop characteristics including: emergence, crop yields, protein content, oil content, starch content, root system, root growth, root size maintenance, stress tolerance (e.g. against drought, heat, salt, UV, water, cold), ethylene (production and/or reception), tillering, plant height, leaf blade size, number of basal leaves, tillers strength, leaf color, pigment content, photosynthetic activity, amount of input needed (such as fertilizers or water), seeds needed, tiller productivity, time to flowering, time to grain maturity, plant verse (lodging), shoot growth, plant vigor, plant stand, tolerance to biotic and abiotic stresses, natural defense mechanisms, and time to germination. [0064] Improved plant health refers to improved plant characteristics including: crop yield, more developed root system (improved root growth), improved root size maintenance, improved root effectiveness, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf color, photosynthetic activity, more productive tillers, enhanced plant vigor, and increased plant stand. [0065] In general, “pesticidal” means the ability of a substance to increase mortality or inhibit the growth rate of plant pests. The term is used herein, to describe the property of a substance to exhibit activity against pests such as fungi and nematodes. The term “pests” include phytopathogens, as hereinabove described, including nematodes and fungi. A substance that demonstrates pesticidal activity may be referred to as a “pesticide”. [0066] By “effective” amount of a formulation, active ingredient, fungicide, or nematicide, is meant a sufficient amount of an active agent to provide the desired local or systemic effect. A(n) “effective”, “fungicidally effective”, or “nematicidally effective” amount refers to the amount of active ingredient needed to effect the desired biological result. [0067] The term “control” or “controlling” refers to an active agent or composition that provides a curative, inhibitive, ameliorative, reduction in, and/or preventative activity for phytopathogens such as fungi and/or nematodes. [0068] The term “agricultural compositions” includes optical isomers, enantiomers, diastereomers, or agriculturally acceptable salts of the active agents disclosed herein. The compound of the disclosure included in the agrochemical composition may be covalently attached to a carrier moiety, as described below. Alternatively, the any of the compounds of the disclosure included in the agricultural composition is not covalently linked to a carrier moiety. [0069] The term “acceptable salt” and “agriculturally acceptable salt” is meant to include a salt of a compound of the disclosure which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the disclosure contain relatively acidic functionalities, base addition salts may be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert carrier. Examples of agriculturally acceptable base addition salts include sodium, potassium, zinc, calcium, ammonium, organic amino (such as choline or diethylamine or amino acids such as d-arginine, l-arginine, d-lysine, or l-lysine), or magnesium salt, or a similar salt. When compounds of the disclosure contain relatively basic functionalities, acid addition salts may be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science 66: 1-19 (1977), herein incorporated by reference regarding selection of a salt form for an intended commercial use, including agricultural, pharmaceutical, or veterinary uses, having characteristics for synthesis and storage. Certain specific compounds of the disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. [0070] The term “agriculturally acceptable carrier” or “agriculturally acceptable vehicle” refers to any medium that provides the appropriate delivery of an effective amount of an active agent(s), fungicide, nematicide, formulation, or permeant, as defined herein, does not negatively interfere with the effectiveness of the biological activity of the active agent, fungicide, nematicide, formulation, or permeant, and that is sufficiently non-toxic to the host. Representative carriers include water, oils, both vegetable and mineral, emulsion bases, and the like. These bases include suspending agents, thickeners, penetration enhancers, and the like. Additional information concerning carriers may be found in Remington: The Science and Practice of Pharmacy, 21st Ed., Lippincott, Williams & Wilkins (2005), which is incorporated herein by reference, regarding selection of a carrier or carrier system for an intended commercial use, including agricultural, pharmaceutical, or veterinary uses, having characteristics for delivery of an active ingredient for an intended use. [0071] The term "carrier" is used herein to denote a natural or synthetic, organic, or inorganic material that constitutes a portion of the diluent medium in which the active agent, fungicide, nematicide, formulation, or permeant, is dispersed or dissolved. This carrier is inert. In some embodiments, this carrier is inert and agriculturally acceptable, in particular to the plant being treated. The phrase “agriculturally acceptable” is utilized herein to be analogous to “pharmaceutically acceptable” as used in pharmaceutical products to describe diluent media. A carrier may be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, dusts and dispersible powders such as kaolinite, lactose, calcite, talc, kaolin, bentonite, or other absorptive polymers, and the like) or liquid (water, alcohols, ketones, petroleum fractions, aromatic or paraffinic hydrocarbons, chlorinated hydrocarbons, liquefied gases, and the like). [0072] The term “agriculturally acceptable excipient” is conventionally known to mean agriculturally acceptable carriers, agriculturally acceptable diluents and/or agriculturally acceptable vehicles used in formulating compositions effective for the desired use. [0073] The term “active agent” or “active ingredient” means an active compound, as well as any prodrugs thereof and acceptable salts, hydrates, and solvates of the compound and the prodrugs [0074] The term “vigor” is the measure of the increase in plant growth or foliage volume through time after planting. [0075] “Nematicides” and “nematicidal” refers to the ability of a substance to increase mortality or inhibit the growth rate of nematodes. In general, the term “nematode” comprises eggs, larvae, juvenile, and mature forms of said organism. [0076] “Fungicide” and “fungicidal” refers to the ability of a substance to increase mortality, control, or inhibit growth rate of fungi. [0077] “Biological medium,” as used herein refers to both in vitro and in vivo biological milieus. In vivo applications may be performed on, in, or in the area surrounding plants, plant parts, or plant propagation material. [0078] Chemical structures represented herein may be determined by those of skill in the art. [0079] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the disclosure. Unless otherwise stated, all tautomeric forms of the compounds of the disclosure are within the scope of the disclosure (e.g., keto-enol tautomerism). Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a 13C- or 14C-enriched carbon are within the scope of this disclosure. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present disclosure. [0080] The presence of one or more possible asymmetric carbon atoms in a compound of the disclosure means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also, atropisomers may occur as a result of restricted rotation about a single bond. Additionally, cis-trans amide bond rotomers may exist in an equilibria that may favor one rotomer over the other. The disclosed compound formulae are intended to include all those possible isomeric forms and mixtures thereof. The disclosed compounds are intended to include all possible tautomers (e.g. keto-enol tautomerism) where present. Accordingly, the present disclosure includes all possible tautomeric forms for the disclosed compounds. Compounds of the Disclosure [0081] One embodiment of the present disclosure includes a method for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen by applying a compound or a composition according to the present disclosure. In one aspect, the pathogen is phytopathogenic. In one aspect, the pathogen is a soil-borne pathogen. In other words, the pathogen is any pest that causes damage to a plant below the surface of the soil, and may be a pathogen that infects one or more of the roots and the seed. In one aspect, the pathogen is a fungus. In one aspect, the pathogen is a nematode. In one aspect, the pathogen includes both a fungus and a nematode. In one aspect, the pathogen is selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, Phoma, Plasmodiophora, and Spongospora. In one aspect, the pathogen is a nematode from the class Chromodorea, Rhabditida, or Enoplea. In one aspect, the pathogen is a nematode from the genera Xiphinema, Roylenchulus, Tylenchulus, Helicotylenchus, Pratylenchus, Radopholus, Hirschmanniella, Heterodera, Globodera, Meloidogyne, Ditylenchus, Bursaphelencus, Anguina, Aphelenchoides. Longidorus, or Paratrichodorus. In one aspect, the pathogen is a fungus selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, and Phoma; and a nematode selected from the class consisting of: Chromodorea, Rhabditida, or Enoplea. In one aspect: the fungus is Fusarium and the nematode is soybean cyst nematode, or the fungus is Verticillium and the nematode is Pratylenchus, or the fungus is Fusarium (oxy) and the nematode is root knot nematode. In one aspect, the compound is applied to one or more of a plant, a plant part, plant propagation material, and soil. In one aspect, the application of the compound or the composition is selected from the group consisting of: topical, to the soil, foliar, a foliar spray, a seed coating, a seed treatment, a soil drench, directly in-furrow dipping, drenching, soil drenching, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, overhead chemigation, watering (drenching), and drip irrigating, or any combinations thereof. In one aspect, the application of the compound or the composition is a seed treatment. [0082] In each case, the compounds of the disclosed disclosure are may be present in free form, as a hydrate, as a salt, as a stereoisomer, as an enantiomer, or a tautomeric form; e.g., as a agriculturally acceptable salt form. [0083] The active compound(s) of the presently disclosed subject matter, or compositions thereof, will generally be used in an amount effective to achieve the intended result, for example in an amount effective to treat a phytopathogen. The amount of compound applied will depend upon a variety of factors, including, for example, the particular phytopathogen, the method of administration, whether the desired benefit is curative or preventative , the level of disease pressure, plant maturity, the bioavailability of the particular active compound, and the like. [0084] Effective application rates may be estimated initially from in vitro assays. Preferably, the compound(s) will provide the intended effect without causing substantial phytotoxicity. Phytotoxicity of the compound(s) may be determined using standard procedures. Compounds(s) that are not phytotoxic at the intended application rate are preferred. Agrochemical Compositions [0085] The agrochemical compositions may be selected form the following types of formulations: emulsifiable concentrates, coatable pastes, dilute emulsions, wettable powders, soluble powders, dusts, granulates, concentrated aqueous emulsions, suspension concentrates, oil dispersions, water dispersible granules, seed treatments, and also encapsulations/microencapsulations e.g. in substances. The agrochemical compositions described herein may be directly sprayable. The agrochemical compositions may also be further diluted to produce an applied formulation prior to being applied on plants or plant propagation materials. In some instances, the agrochemical composition is mixed with water to obtain the applied formulation. As with the type of the agrochemical compositions, the methods of application, such as spraying, atomizing, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. A contemplated agrochemical composition may also contain further components such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors, or other formulations or active ingredients for obtaining special effects. [0086] The compounds disclosed herein may be used in unmodified form or together with inerts conventionally employed in the art of formulation. The compounds disclosed herein may be prepared as a formulation that is an agrochemical composition. They may be formulated into emulsifiable concentrates, suspension concentrates, water dispersible concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, water-dispersible granules, soluble powders, dusts, granulates, seed treatments, and also encapsulations e.g. in polymeric substances. The methods of application, such as spraying, atomizing, dusting, scattering, coating, or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. Also contemplated in the present disclosure are conventional slow release formulations. [0087] The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining the intended effect(s). They may also contain surfactants (also known as surface-active agents). Exemplary surfactants include wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g., the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, an ethoxylated alkylphenol, a trisiloxane ethoxylate, and an ethoxylated fatty alcohol. [0088] Suitable diluent media, carriers and adjuvants (auxiliaries) may be solid or liquid and are substances useful in formulation technology, e.g., natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders, or fertilizers. Such diluent media are for example described in WO 97/33890, which is hereby incorporated by reference. Water-based (more than 50 weight percent water) diluent media are used illustratively herein. [0089] Suitable carriers and adjuvants may be solid or liquid and are substances useful in formulation technology, for example: mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders, surfactants, and/or fertilizers. [0090] Solid, particulate carriers that may be used, for example for dusts and dispersible powders, are calcite, talc, kaolin, diatomaceous earth, montmorillonite or attapulgite, and highly- disperse silica or absorptive polymers. Illustrative particulate, adsorptive carriers for granules include pumice, crushed brick, sepiolite or bentonite, montmorillonite-type clay, and exemplary nonsorbent carrier materials are calcite or dolomite. A particulate solid formulation may also be prepared by encapsulation of a compound of the disclosure or by a granulation process that utilizes one or more of the above diluents or an organic diluent such as microcrystalline cellulose, rice hulls, wheat middlings, saw dust and the like. Illustrative granules may be prepared as discussed in US Patents No.4,936,901, No.3,708,573 and No.4,672,065. [0091] Suitable liquid carriers include: aromatic hydrocarbons, in particular the fractions C₈-C₁₂, such as xylene mixtures or substituted naphthalenes, phthalic esters such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane, paraffins or limonene, alcohols and glycols as well as their ethers and esters, such as ethylene glycol monomethyl ether, ketones such as cyclohexanone or isophorone, strongly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, and, if appropriate, epoxidized vegetable oils such as soybean oil, and water. If appropriate, the liquid carrier may be a naturally occurring essential oil, such as oils from citronella and lemon grass. [0092] Suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting properties, depending on the water solubility of the compound of the disclosure. The term “surfactants” is also to be understood as meaning mixtures of two or more surface-active compounds. [0093] The surfactants customarily employed in formulation technology are described, inter alia, in the following publications: McCutcheon’s Detergents and Emulsifiers Annual, MC Publishing Corp., Glen Rock, N.J., 1988; M. and J. Ash, Encyclopedia of Surfactants, Vol. I-III, Chemical Publishing Co., New York, 1980-1981. [0094] Among the suitable illustrative surfactants there may be mentioned, e.g., high molecular weight polymers, polyacrylic acid salts, lignosulphonic acid salts, phenolsulphonic or (mono- or di-alkyl)naphthalenesulphonic acid salts, laurylsulfate salts, polycondensates of ethylene oxide with lignosulphonic acid salts, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (in particular alkylphenols or arylphenols such as mono- and di-(polyoxyalkylene alkylphenol) phosphates, polyoxyalkylene alkylphenol carboxylates or polyoxyalkylene alkylphenol sulfates), salts of sulphosuccinic acid esters, taurine derivatives (in particular alkyltaurides), polycondensates of ethylene oxide with phosphated tristyrylphenols and polycondensates of ethylene oxide with phosphoric esters of alcohols or phenols. Additional suitable surfactants include: amine ethoxylates, alkylaryl sulphonates, alkylbenzene sulphonates, castor oil ethoxylates and polyethylene glycol derivatives of hydrogenated castor oil, sorbitan fatty acid ester ethoxylates, sorbitan fatty acid esters, non-ionic ethoxylates, branched and unbranched secondary alcohol ethoxylates, nonylphenol ethoxylates, and octylphenol ethoxylates. The presence of at least one surfactant is often where the inert vehicles are not readily soluble in water and the composition of the disclosure used for the administration is aqueous. [0095] Furthermore, useful adjuvants which enhance application are natural or synthetic phospholipids from the series of the cephalins and lecithins, for example phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerine, or lysolecithin. [0096] In general, a concentrated formulation comprising a compound of the disclosure includes about 0.01 to about 90% by weight compound of the disclosure, about 0 to about 20% agriculturally acceptable surfactant and 5 to 99.99% solid or liquid carriers and adjuvant(s). [0097] The formulations preferably comprise between 0.00000001% and 98% by weight compound of the disclosure or, with particular preference, between 0.01% and 95% by weight compound of the disclosure, more preferably between 0.5% and 90% by weight compound of the disclosure . Application takes place in a customary manner adapted to the application forms. [0098] Suitable penetrants in the present context include all those substances which are typically used in order to enhance the penetration of active agrochemical compounds into plants. Penetrants in this context are defined in that, from the (generally aqueous) application liquor and/or from the spray coating, they are able to penetrate the cuticle of the plant and thereby increase the mobility of the active compounds in the cuticle. This property may be determined using the method described in the literature (Baur et al., 1997, Pesticide Science 51, 131-152). Examples include alcohol alkoxylates such as coconut fatty ethoxylate or isotridecyl ethoxylate, fatty acid esters such as rapeseed or soybean oil methyl esters, fatty amine alkoxylates such as tallowamine ethoxylate, or ammonium and/or phosphonium salts such as ammonium sulphate or diammonium hydrogen phosphate, for example. [0099] A contemplated formulation may also include at least one polymer that is a water-soluble or water-dispersible film-forming polymer that improves the adherence of the compound of the disclosure to plant propagation material. [00100] In some embodiments, a coloring agent, such as a dye or pigment, is included in the agrochemical composition so that an observer may immediately determine that the plant or plant propagation material has been treated. An agrochemical composition that includes a coloring agent is an embodiment of the disclosure, as such a composition may improve user and consumer safety. The coloring agent is also useful to indicate to the user the degree of uniformity of application of a composition. Generally, the coloring agent tends to have a melting point above 30 °C., and therefore, is suspended in the composition. The coloring agent may also be a soluble compound. [00101] As examples of coloring agents may be mentioned pigment red 48-2 (CAS-7023- 61-2), pigment blue 15 (CAS-147-14-8), pigment green 7 (CAS-1328-53-6), pigment violet 23 (CAS-6358-30-1), pigment red 53-1 (CAS-5160-02-1), pigment red 57-1 (CAS 5281-04-9), pigment red 112 (CAS 6535-46-2) or similar coloring agents. A coloring agent is typically present at about 0.01% to about 0.10% by weight, although potentially greater amounts may be useful, of an agrochemical formulation. [00102] In typical use, a compound of the disclosure is formulated as a concentrate also known as a pre-mix composition (or concentrate, formulated compound, agrochemical composition), and the end user normally employs a diluted formulation for administration to the plants of interest. Such a diluted composition is often referred to as a tank-mix composition. A tank-mix composition is generally prepared by diluting a pre-mix agrochemical composition (concentrate) with a solvent such as water that may optionally also contain further auxiliaries. Generally, an aqueous tank-mix is used. [00103] Particularly, formulations for crop protection may be applied as a spray, e.g., foliar, soil, etc . [00104] The compounds of the disclosed disclosure are may be present in free form, as a hydrate, as a salt, as a stereoisomer, as an enantiomer, or a tautomeric form; e.g., as an agronomically usable or an agrochemically acceptable salt form. [00105] The compounds of the disclosure may be used in fungicidal and/or nematicidal compositions for controlling or protecting against phytopathogenic pests, where the composition comprises as an active ingredient of at least one compound of the present disclosure in either the free form, as a hydrate, as a salt, as a stereoisomer, as an enantiomer, or a tautomeric form. Seed Treatment [00106] In another aspect of the present disclosure is a seed treated with a compound or composition described herein. [00107] The control of phytopathogens and pests such as fungi or nematodes, or a combination thereof, by treating the seed of plants has been known for a long time and is a subject of continual improvements. Nevertheless, the treatment of seed entails a series of problems which maynot always be solved in a satisfactory manner. Thus, it is desirable to develop compounds and compositions for protecting the seed and the germinating plant that remove the need for, or at least significantly reduce, the additional application of crop protection compositions in the course of storage, after sowing or after the emergence of the plants. It is desirable, furthermore, to optimize the amount of active ingredient employed in such a way as to provide the best-possible protection to the seed and the germinating plant from attack by phytopathogens such as fungi or nematodes, or a combination thereof, but without causing damage to the plant itself by the active ingredient employed. In particular, compounds and compositions for treating seed ought also to take into consideration the intrinsic pesticidal properties of pest-resistant or pest-tolerant transgenic plants, in order to achieve optimum protection of the seed and of the germinating plant with a minimal use of crop protection compositions. [00108] The disclosure likewise relates to compounds and compositions of the disclosure for treating seed for the purpose of protecting the seed and the resultant plant against phytopathogens such as fungi or nematodes or combinations thereof. [00109] Furthermore, the disclosure relates to seed which, following treatment with the compound or composition of the disclosure, is subjected to a film-coating process in order to prevent dust abrasion of the seed. [00110] One of the advantages of the present disclosure is that, owing to the particular systemic properties of the compounds and compositions of the disclosure, the treatment of the seed with these compounds and compositions provides protection from phytopathogens such as fungi or nematodes or a combination thereof, not only to the seed itself but also to the plants originating from the seed, after they have emerged. In this way, it may not be necessary to treat the crop directly at the time of sowing or shortly thereafter. [00111] A further advantage is to be seen in the fact that, through the treatment of the seed with a compound or composition of the disclosure, germination and emergence of the treated seed may be greater relative to the untreated control in the presence of a pathogen. [00112] It is likewise considered to be advantageous that the formulation of the disclosure may also be used, in particular, on transgenic seed. [00113] The disclosure further relates to seed treatment formulations that comprise a compound of the present disclosure, and optionally one or more additional fungicides, nematicides, insecticides, biologic, or mixtures thereof. [00114] The compounds and compositions of the disclosure are suitable for protecting seed of any variety of plant which is used in agriculture, in greenhouses, in forestry or in horticulture. More particularly, the seed in question is that of cereals (e.g., wheat, barley, rye, oats and millet), maize, cotton, soybeans, rice, potatoes, sunflower, coffee, tobacco, canola, oilseed rape, beets (e.g., sugar beet and fodder beet), peanuts, vegetables (e.g., tomato, cucumber, bean, brassicas, onions and lettuce), fruit plants, lawns and ornamentals. Particularly important is the treatment of the seed of cereals (e.g., wheat, barley, rye and oats) maize, soybeans, cotton, canola, oilseed rape and rice. [00115] As already mentioned above, the treatment of transgenic seed with the compounds and compositions of the disclosure forms one embodiment of the present disclosure. [00116] For the purposes of the present disclosure, the compounds or compositions of the disclosure are applied to the seed. The seed is preferably treated in a condition in which its stability is such that no damage occurs in the course of the treatment. Generally speaking, the seed may be treated at any point in time between harvesting and sowing. Typically, seed is used which has been separated from the plant and has had cobs, hulls, stems, husks, hair or pulp removed. Thus, for example, seed may be used that has been harvested, cleaned and dried to a moisture content of less than 15% by weight. Alternatively, seed may also be used that after drying has been treated with water, for example, and then dried again. [00117] When treating seed it is necessary, generally speaking, to ensure that the amount of the compounds and compositions of the disclosure, and/or of other additives, that is applied to the seed is selected such that the germination of the seed is not adversely affected, and/or that the plant which emerges from the seed is not damaged. This is the case in particular with active ingredients which may exhibit phytotoxic effects at certain application rates. [00118] The compounds and compositions of the disclosure may be applied directly, in other words without comprising further components, and without having been diluted. As a general rule, it is preferable to apply the compounds and compositions in the form of a suitable formulation to the seed. [00119] The compounds and compositions which may be used in accordance with the disclosure may be converted into the customary seed-dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other coating compositions for seed, and also ultra-low-volume (ULV) formulations. [00120] These seed treatments may be prepared by mixing the compounds and compositions with customary adjuvants, such as, for example, customary extenders and also solvents or diluents, colorants, wetters, dispersants, emulsifiers, antifoams, antioxidants, preservatives, secondary thickeners, antifreezes, stickers, gibberellins, and also water. [00121] Colorants which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include all colorants which are customary for such purposes. In this context, it is possible to use not only pigments, which are of low solubility in water, but also water-soluble dyes. Examples include the colorants known under the designations Rhodamin B, C.I. Pigment Red 112 and C.I. Solvent Red 1. [00122] Wetters, which may be present in the seed-dressing formulations and may be used in accordance with the disclosure, include all of the substances which promote wetting and which are customary in the formulation of active agrochemical ingredients. Use may be made preferably of alkylnaphthalenesulphonates, such as diisopropyl- or diisobutyl- naphthalenesulphonates. [00123] Dispersants and/or emulsifiers which may be present in the seed-dressing formulations that may be used in accordance with the disclosure include all of the nonionic, anionic, and cationic dispersants that are customary in the formulation of active agrochemical ingredients. Use may be made preferably of nonionic or anionic dispersants or of mixtures of nonionic or anionic dispersants. Suitable nonionic dispersants are, in particular, ethylene oxide- propylene oxide block polymers, alkylphenol polyglycol ethers, polyalkylene oxide block co- polymers, acrylic co-polymers and also tristryrylphenol polyglycol ethers, and the phosphate or sulphated derivatives of these. Suitable anionic dispersants are, in particular, lignosulphonates, salts of polyacrylic acid, and arylsulphonate-formaldehyde condensates. [00124] Antifoams which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include the foam inhibitors that are customary in the formulation of active agrochemical ingredients. Use may be made preferably of silicone antifoams and magnesium stearate. [00125] Antioxidants which may be present in the seed- dressing formulation are preferably those that have a low level of phytotoxicity. It is also preferred that the antioxidant that is used in the present method and formulations be one that is approved for use in food, feed, or cosmetics. Examples of such approval are approval by a regulatory body, such as the U.S. Food and Drug Administration for use in food or cosmetics, or approval by the U.S. Department of Agriculture for use. Antioxidants that have GRAS (Generally Recognized As Safe) status are examples of preferred antioxidants. In some embodiments of the present disclosure, it is preferred that the antioxidant is one that is added to the seed, as opposed to an antioxidant that is a natural component of the seed. However, such preferred antioxidants may include natural antioxidants that are added to the seed during the present treatment process. [00126] Examples of materials that may serve as the antioxidant of the present disclosure include: glycine, glycinebetaine, choline salts, in particular choline chloride, 2(3)-tert-butyl-4- hydroxyanisole (BHA), tert-butylhydroxyquinone (TBHQ), dilauryl thiodipropionate (DLTDP), tris(nonylphenyl))phosphite (TNPP), 2,6-dihydroxybenzoic acid (DHBA), acetylsalicylic acid (ASA), salicylic acid (SA), Irganox 1076 (Ciba Geigy), Ethanox 330 (Ethyl Corp.), Tinuvin 144 (Ciba Geigy), Ambiol (2-methyl-4-[dimethylaminomethyl]-5-hydroxybenzimidazole), propyl gallate, trihydroxybutyrophenone (THBP), thiodipropionic acid and dilauryl thiodipropionate, betaines (see, AU-B-27071/95 to Bodapati, and EO 0493670 A1 to Lunkenheimer et al.), amines (aromatic amines and hindered amines), methionine, cysteine, proline, mannitol, phosphites, thioesters, lecithin, gum or resin guiac, Vitamin E, polyphenols, Vitamin A, carotenoids (beta-carotene), Vitamin B, Vitamin C, tocopherols, alpha-lipoic acid, coenzyme Q10 CoQ10), grape seed extract, green tea, lutein, N-acetyl Cysteine (NAC), OPCs (pycnogenols), selenium, zinc, 2,6-di-tert-para-benzoquinone, abscisic acid, bioflavonoids, DMAE (N,N-Dimethylethanolamine, precursor of choline), metronidazole, 2-methyl-5- nitroimidazole, glyoxal, polymerized 2,2,4-trimethyl-1,2-dihydroquinoline, 2- mercaptobenzimidazol, 5-tert-butyl-4-hydroxy-2-methyl-phenyl sulfide (CAS RN 96-69-5), 4-tert- butylphenol (CAS RN 98-54-4), catechol (CAS RN 120-80-9), 2-naphthol (2- hydroxynaphthalene) (CAS RN 135-19-3), octadecyl-3-(3′,5′-di-tert-butyl-4- hydroxyphenyl)propionate (CAS RN 2082-79-3), 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4- hydroxybenzyl)benzene (CAS RN 1709-70-2), and tris-(2,4,-di-tert-butylphenyl)phosphite (CAS RN 31570-04-4). [00127] In some embodiments, hindered phenol antioxidants are preferred. Examples of hindered phenol antioxidants include: 2,6-di-tert-butyl-p-cresol (BHT) (CAS RN 128-37-0), 2(3)- tert-butyl-4-hydroxyanisole (BHA), isobutylenated methylstyrenated phenol (CAS RN 68457-74- 9), styrenated phenol (CAS RN 61788-44-1), 2,6-di-tert-butyl-4- (octadecanoxycarbonylethyl)phenol (CAS RN 2082-79-3), 4,4′-thiobis-6-(t-butyl-m-cresol) (CAS RN 96-69-5), 4,4′-butylidenebis(6-t-butyl-m-cresol) (CAS RN 85-60-9), 4,4′-(1- methylethylidene)bis[2-(1,1-dimethylethyl)]phenol (CAS RN 79-96-9), 2,2′-methylenebis(4- methyl-6-nonyl)phenol (CAS RN 7786-17-6), 4-methyl-phenol reaction products with dicyclopentadiene and isobutylene (CAS RN 68610-51-5), tetrakis-(methylene-(3,5-di-tertbutyl- 4-hydrocinnamate)methane (CAS RN 6683-19-8), tert-butylhydroxyquinone (TBHQ), Irganox 1076, Ethanox 330, and 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl-)-1,3,5-triazine- 2,4,6(1H,3H,5H)-trione (CAS RN 27676-62-6). [00128] Preservatives which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include substances which may be employed for such purposes in agrochemical compositions. Examples include dichlorophen and benzyl alcohol hemiformal. [00129] Secondary thickeners which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include substances which may be used for such purposes in agrochemical compositions. Those contemplated with preference include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and highly disperse silica. [00130] Stickers which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include customary binders which may be used in seed- dressing products. Preferred mention may be made of polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, styrene acrylic emulsion polymers, polyethylene wax, and tylose. [00131] Gibberellins which may be present in the seed-dressing formulations which may be used in accordance with the disclosure include preferably the gibberellins A1, A3 (=gibberellic acid), A4 and A7, with gibberellic acid being used with particular preference. The gibberellins are known (cf. R. Wegler, “Chemie der Pflanzenschutz-und Schädlingsbekämpfungsmittel”, Volume 2, Springer Verlag, 1970, pp.401-412). [00132] The seed-dressing formulations, which may be used in accordance with the disclosure may be used, either directly or after prior dilution with water, to treat seed of any of a wide variety of types. Accordingly, the concentrates or the preparations obtainable from them by dilution with water may be employed to dress the seed of cereals, such as wheat, barley, rye, oats and triticale, and also the seed of maize, rice, oilseed rape, peas, beans, cotton, sunflowers and beets, or else the seed of any of a very wide variety of vegetables. The seed- dressing formulations, which may be used in accordance with the disclosure, or their diluted preparations, may also be used to dress seed of transgenic plants. [00133] For the treatment of seed with the seed-dressing formulations which may be used in accordance with the disclosure, or with the preparations produced from them by addition of water, suitable mixing equipment includes all such equipment which may typically be employed for seed dressing. More particularly, the procedure when carrying out seed dressing is to place the seed in a mixer, to add the particular desired amount of seed-dressing formulations, either as such or following dilution with water beforehand, and to carry out mixing until the distribution of the formulation on the seed is uniform. This may be followed by a drying operation. [00134] The application rate of the seed-dressing formulations which may be used in accordance with the disclosure may be varied within a relatively wide range. The application rates in the case of the composition are situated generally at between 0.001 and 50 g per kilogram of seed, preferably between 0.01 and 15 g per kilogram of seed. [00135] The disclosure also relates to a method for controlling unwanted pathogens, characterized in that the compounds and compositions are applied to the phytopathogenic fungi or nematodes, or mixture thereof, and/or their habitat. [00136] The formulations, according to the disclosure, may be used to treat all plants, plant propagation material, and plant parts. Plants means all plants and plant populations, such as desirable and undesirable wild plants, cultivars and plant varieties (whether or not protectable by plant variety or plant breeder's rights). Cultivars and plant varieties may be plants obtained by conventional propagation and breeding methods which may be assisted or supplemented by one or more biotechnological methods such as by use of double haploids, protoplast fusion, random and directed mutagenesis, molecular or genetic markers or by bioengineering and genetic engineering methods. By plant parts is meant all above ground and below ground parts and organs of plants such as shoot, leaf, blossom and root, whereby for example leaves, needles, stems, branches, blossoms, fruiting bodies, fruits and seed as well as roots, corms and rhizomes are listed. Crops and vegetative and generative propagating material, for example cuttings, corms, rhizomes, runners, and seeds also belong to plant parts. [00137] The compounds and compositions, when it is well-tolerated by plants, have low toxicity and are well tolerated by the environment, are suitable for protecting plants and plant organs, enhances harvest yields and improves the quality of the harvested material. It may preferably be used as crop protection composition. It is active against normally sensitive and tolerant species and against all or some stages of development. Agricultural Activity [00138] In one aspect, the disclosure includes a compounds and methods for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen by applying an effective amount of a compound described herein. [00139] In one aspect, the disclosure includes a compounds and methods for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen by applying an effective amount of a compound described herein, wherein the pathogen is a nematode ora fungus, or a combination thereof. [00140] The good pesticidal activity of the compounds of the present disclosure corresponds to a mortality rate of at least 50-60% of the pests mentioned, more preferably to a mortality rate over 90%, most preferably to 95-100%. The compounds of the disclosure are preferably in unmodified form or preferably together with the adjuvants conventionally used in the art of formulation and may therefore be processed in a known manner to give, for example, liquid or solid formulations (e.g. spot-on, pour-on, spray-on, emulsions, suspensions, solutions, emulsifiable concentrates, solution concentrates, powders, granules, coatings). As with the compositions, the methods of application are selected in accordance with the intended objectives and the prevailing circumstances. [00141] In yet another aspect, the disclosure includes a method for controlling or preventing an infestation of the pathogen by treating a plant, plant part, or plant propagation material with an effective amount of a compound according to the compounds of the disclosure. [00142] In another aspect, the present disclosure provides agrochemical compositions comprising a compound according to compounds of the disclosure in combination with an agrochemically acceptable carrier. [00143] In some embodiments, a compound of the present disclosure is applied to a plant, a plant part, or plant propagation material or a combination thereof. Once applied, the compounds of the present disclosure are useful for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen. In some embodiments the pathogen is selected from a group consisting of: fungi and nematodes, or a combination thereof. [00144] In some embodiments, an effective amount of a compound of the present disclosure is applied to a plant, a plant part, or plant propagation material or a combination thereof. Once applied, the compounds of the present disclosure are useful for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen. In some embodiments the pathogen is selected from a group consisting of: fungi and nematodes, or a combination thereof. [00145] In one embodiment of the disclosure, there is provided a composition comprising a compound of the present disclosure. According to another embodiment of the disclosure, there is provided an agrochemical composition comprising a compound of the present disclosure. [00146] Another embodiment of the present disclosure includes an agrochemical composition comprising a compound of the present disclosure and an agrochemically- acceptable diluent or carrier. [00147] In yet another embodiment, the agrochemical composition comprising the compound of the present disclosure is applied to a plant, a plant part, or plant propagation material. [00148] The compounds and compositions disclosed herein provide a method for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen. The pathogen is selected from a group consisting of: fungi and nematodes, or a combination thereof. [00149] It is an object of the present disclosure to provide compounds exhibiting control (e.g., curative, inhibitive, ameliorative, and/or preventative activity) of phytopathogens such as fungi or nematodes, or a combination thereof. [00150] Surprisingly, the compounds described herein, when applied to plants, plant parts, plant propagation material such as seeds, harvested fruits, vegetables, and/or plant’s locus of growth allows for effective control of pathogens including fungi, or nematodes, or a combination thereof. [00151] A method of reducing growth of a target pathogen such as a fungus or nematode, or combination thereof is contemplated. In accordance with that method, a target fungus, or nematode, or combination thereof is contacted with an effective amount of a compound described herein, or a compound described herein, or a prodrug of a compound described herein and that contact is maintained for a period of time sufficient to control and/or inhibit growth of the target pathogen such as a fungus, or nematode, or combination thereof. For example, that contact is carried out by administering the compounds described herein to the target pathogen such as a fungus, or nematode, or combination thereof, where the administration is topical, applied to the soil, in-furrow, a seed treatment, foliar, or systemic. In some embodiments, the administration is repeated. [00152] In another aspect of the present disclosure, the compounds described herein are used for reducing overall damage of plants and plant parts as well as losses in harvested fruits or vegetables caused by fungi or nematodes, or a combination thereof. [00153] Furthermore, in another aspect, the compounds described herein, increase the overall plant health. [00154] Furthermore, the compounds described herein, have potent activity and may be used for control of unwanted pathogens, such as fungi and nematodes, in crop protection and in the protection of plant materials, a plant, a plant part, seeds, or plant propagation material. [00155] Wherein the compound of the disclosure is a fungicide, the compound may be used in crop protection for control of phytopathogenic fungi. They may include an outstanding efficacy against a broad spectrum of phytopathogenic fungi, including soil borne pathogens, which are in particular members of the classes Plasmodiophoromycetes, Peronosporomycetes (Syn. Oomycetes), Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, and Deuteromycetes (Syn. Fungi imperfecti). Some fungicides are systemically active and may be used in plant protection as foliar, seed dressing or soil fungicide. Furthermore, they are suitable for combating fungi, which inter alia infest wood or roots of plant. [00156] Wherein the compound of the disclosure is a nematocide, the compound may be used in crop protection for control of phytopathogenic nematodes. They may include an outstanding efficacy against a broad spectrum of phytopathogenic nematodes, including soil borne plant parasitic nematodes. The compounds of the disclosure also include compounds that have efficacy against plant-parasitic nematodes selected from the group consisting of: root- knot nematodes (abbreviated herein as RKN, Meloidogyne spp.), soybean cyst nematodes (abbreviated herein as SCN, Heterodera glycines) the cyst nematodes (Heterodera spp.), reniform nematodes (Rotylenchulus reniformis); the lesion nematodes (Pratylenchus spp.) and sting nematodes (Belonolaimus spp.). Some nematicides are systemically active and may be used in plant protection as foliar, seed dressing or soil-applied nematicide. Furthermore, they are suitable for combating nematodes, which inter alia infest roots, seed gall, seeds, stems, foliar parts of plants. [00157] The compounds disclosed herein are active against a wide spectrum of nematodes; there are 16 to 20 different orders within the phylum Nematoda according to various authorities. Ten of these orders regularly occur in soil, and four orders, including Rhabditida, Tylenchida, Aphelenchida, and Dorylaimid, are particularly common in soil. Further, plant parasites include many members of the order Tylenchida, and a few genera in the orders Aphelenchida and Dorylaimida. [00158] In a preferred embodiment, the compounds disclosed herein are active against the Nematode classes of Chromodorea, Rhabditida, Enoplea. In another preferred embodiment, the compounds disclosed herein are active against the nematodes of the genera: Xiphinema, Roylenchulus, Tylenchulus, Helicotylenchus, Pratylenchus, Radopholus, Hirschman niella, Heterodera, Globodera, Meloidogyne, Ditylenchus, Bursaphelencus, Anguina, Aphelenchoides, Longidorus, Paratrichodorus; Phytoparasitic pests from the phylum Nematoda, for example, Aphelenchoides spp., Bursaphelenchus spp., Ditylenchus spp., Globodera spp., Heterodera spp., Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radopholus spp., Trichodorus spp., Tylenchulus spp., Xiphinema spp., Helicotylenchus spp., Tylenchorhynchus spp., Scutellonema spp., Paratrichodorus spp., Meloinema spp., Paraphelenchus spp., Aglenchus spp., Belonolaimus spp., Nacobbus spp., Rotylenchulus spp., Rotylenchus spp., Neotylenchus spp., Paraphelenchus spp., Dolichodorus spp., Hoplolaimus spp., Punctodera spp., Criconemella spp., Quinisulcius spp., Hemicycliophora spp., Anguina spp., Subanguina spp., Hemicriconemoides spp., Psilenchus spp., Pseudohalenchus spp., Criconemoides spp., Cacopaurus spp., Hirschmaniella spp, and Tetylenchus spp.. [00159] Chemical treatment with nematicides is the main methods for controlling plant- parasitic nematodes. Application methods include fumigation, in furrow, seed treatment, post planting application through irrigation systems, granules, and broadcast sprays, and bare root dipping in the case of transplanted seedlings. Such application methods are considered an aspect of the disclosure. [00160] The nematocides of the disclosure are particularly effective against eggs and juvenile/infective stages of nematodes. The compounds of the disclosure may also inhibit egg hatch rate. [00161] Examples of fungi include: one or more members of the phyla of Ascomycota, Oomycota, Basidiomycota, and the subphylum Mucoromycotina. [00162] The target fungi of the division Ascomycota include, for example, subdivision Pezizomycotina and Taphrinomycotina which include Dothideomycetes, Leotiomycetes, Sordariomycetes and Taphrinomycetes classes. [00163] The target fungi of the phylum Ascomycota include , for example, subphylum selected from the group consisting of Dothideomycetes, Leotiomycetes, and Sordariomycetes. [00164] The target fungi of the division Basidiomycota include, for example, subdivisions Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina. [00165] In some embodiments, the one or more target fungi whose growth is to be controlled or prevented is selected from one or more of the group consisting of Zymoseptoria, Phaeosphaeria, Erysiphe, Blumeria, Sclerotinia, Botrytis, Cercospora, Alternaria, Verticillium, Fu sarium, Magnaporthe, Colletotrichum, Phakopsora, Puccinia, Rhizoctonia, Pythium, Plasmopara , Phytophthora, Aspergillus, Bipolaris, Candida, Cochliobolus, Dilophospora, Exserohilum, Mycosphaeralla, Sclerophthora, Ustiligo, Melampsora, Oidiopsis, Phymatotrichum, Pyrenophora, Uncinula, Peronospora, Monolinia, Venturia, Phomopsis, Claviceps, Aspergillus, Dibotryon, Pseudoperonospora, Setosphaeria, and Podosphaera. [00166] In some embodiments, the one or more target fungi whose growth is to be controlled or prevented is selected from one or more of the group consisting of Zymoseptoria, Phaeosphaeria, Erysiphe, Blumeria, Sclerotinia, Botrytis, Cercospora, Alternaria, Verticillium, Fusarium, Magnaporthe, Colletotrichum, Phakopsora, Puccinia, Rhizoctonia, Pythium, Plasmopara, Phytophthora, Aspergillus, Bipolaris, Candida, Cochliobolus, Dilophospora, Exserohilum, Mycosphaeralla, Sclerophthora, Ustiligo, Melampsora, Oidiopsis, Phymatotrichum, Pyrenophora, Uncinula, and Peronospora. [00167] The compounds of the disclosure may exhibit outstanding efficacy against a broad spectrum of phytopathogenic fungi, including soil borne pathogens, which are in particular members of the classes Plasmodiophoromycetes, Peronosporomycetes (Syn. Oomycetes), Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, and Deuteromycetes (Syn. Fungi imperfecti). Some fungicides are systemically active and may be used in plant protection as foliar, seed dressing or soil fungicide. Furthermore, they are suitable for combating fungi, which, inter alia, infest wood or roots of plant. The compounds of the disclosure may be used to control one or more target fungi or prevent the growth of one or more target fungi. Accordingly, the agrochemical compositions of the disclosure may be used to control one or more target fungi or prevent the growth of one or more target fungi. [00168] Examples of fungi include: one or more members of the phyla of Ascomycota, Oomycota, Basidiomycota, and the subphylum Mucoromycotina. [00169] The target fungi of the division Ascomycota include, for example, subdivision Pezizomycotina and Taphrinomycotina which include Dothideomycetes, Leotiomycetes, Sordariomycetes and Taphrinomycetes classes. [00170] The target fungi of the division Basidiomycota include, for example, subdivisions Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina. [00171] In a preferred embodiment, the compounds of the disclosure are active against fungi including: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, and Phoma. [00172] In another preferred emobidment, the compounds of the disclosure are active against Plasmodiophoromycetes, including the genera Plasmodiophora and Spongospora. [00173] The compositions according to the disclosure demonstrate antipathogenic activity, good plant tolerance, low toxicity to plants and animals, while exhibiting low environmental impact. The compositions are suitable for protecting seeds, plants, plant organs, and plant propagation material, for increasing harvest yields, for improving the quality and/or vigor of the harvested material and for controlling pathogens such as fungi or nematodes, or a combination thereof, that are encountered in agriculture, in horticulture, in forests, in gardens and leisure facilities, and in protection of stored products. They may be employed as plant protection agents. [00174] The compositions herein disclosed, in some embodiments, are active against normally sensitive and resistant species and against all or some stages of development. Examples Section I: Experimental Procedures for Syntheses of Exemplary Compounds [00175] In the schemes, general substituent groups are represented with assignments that may not align with the formulae of the present disclosure. The following schemes and examples provide variables that should be followed for these schemes and not necessarily applied to the formulae of the present disclosure. [00176] Although the chemical nomenclature used throughout this specification and in the appended claims is intended to conform with the International Union of Pure and Applied Chemistry (IUPAC) naming conventions, the application of these nomenclature rules is oftentimes complex, with the result that those of ordinary skill in the art may apply the rules differently and different names may be used to identify a specific compound. Notwithstanding, in the event of any discrepancy between a chemical structure shown in the specification or in the appended claims and the name assigned to it in the specification, the chemical structure shall take precedence and be deemed correct. General Scheme A:

General Synthetic Procedure A: [00177] 2-Formylphenylboronic acid, substituted 2-formylphenylboronic acid, 2- ketonephenylboronic acid, or substituted 2-ketonephenylboronic acid was reacted with phenylhydrazine or substituted phenylhydrazine in a suitable solvent, such as a mixed solvent of water and DMSO, at an appropriate temperature, such as room temperature or 100 °C, for a period of time to drive the reaction to completion giving the desired product as shown in General Scheme A. The product, generally as solid form, could be purified by treating with a suitable solvent, such as water/DMSO, acetonitrile or water/acetonitrile, or by recrystallization from a suitable solvent such as water and DMSO, acetonitrile or water/acetonitrile, or by column chromatography. The product chemical structure and purity were determined by NMR, HPLC and LC-MS. General Scheme B:

General Synthetic Procedure B: Preparation of Common Intermediate [00178] As shown in General Scheme B above, a boron-containing common intermediate used in several of the syntheses described herein—namely, 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3- pyridyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [also known as 2-chloro-4-(1,3-dioxolan-2-yl)-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine]—was synthesized from 3-bromo-2- chloropyridine (SM) by a formylation procedure giving 3-bromo-2-chloroisonicotinaldehyde (SM- CHO), which was protected using ethylene glycol to generate 3-bromo-2-chloro-4-(1,3-dioxolan- 2-yl)pyridine [SM-CH(EG)], followed by a boronylation step to replace bromo with a boron group. The boron intermediate was then reacted with alkylhydrazine, phenylhydrazine or substituted phenylhydrazine in a suitable solvent, such as a mixed solvent of water and DMSO, at an appropriate temperature, such as room temperature or 100 °C, for a period of time to drive the reaction to completion giving the desired product as shown in General Scheme B. The product, generally as solid form, could be purified by treating with a suitable solvent, such as water/DMSO, acetonitrile or water/acetonitrile, or by recrystallization from a suitable solvent such as water and DMSO, acetonitrile or water/acetonitrile, or by column chromatography. The product chemical structure and purity were determined by NMR, HPLC and LC-MS. [00179] A specific example of a representative synthetic procedure for preparing the common intermediate 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane is shown in the scheme and procedures below:

[00180] Step 1: To a solution of 2-chloro-3-bromo pyridine (5.0 g, 26.2 mmol) in THF (50 mL) was added LDA (7.3 mL, 31.4 mmol, 2 M in THF) dropwise at – 78 °C under nitrogen atmosphere. The reaction was stirred at – 78 °C for 1 hour, then ethyl formate (7.8g, 104.8 mmol) was carefully added dropwise. The reaction was stirred at -78 °C for 1 h, then allowed to warm to room temperature and quenched with 50 mL of sat. NaHCO₃. The aqueous phase was extracted with EtOAc (2 × 50 mL). T he combined organic phases were dried and evaporated under reduced pressure. The crude was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the compound 2-chloro-3-bromo-4-formyl pyridine (1.0 g, yield 17.4%) as a light yellow solid. MS: (M+H)⁺: m/z = 219.9. ¹H NMR (300 MHz, DMSO-d₆): δ 10.23 (s, 1H), 8.44 (d, J = 5.2 Hz, 1H), 7.94 (d, J = 5.2 Hz, 1H) ppm. [00181] Step 2: To a solution of 2-chloro-3-bromo-4-formyl pyridine (1.0 g, 4.6 mmol) in toluene (20 mL) was added ethylene glycol (1.43 g, 23.0 mmol) and pyridinium p- toluenesulfonate (226 mg, 0.9 mmol) at room temperature. The mixture was heated to reflux and stirred for 4h. The solvent was removed under reduced pressure, and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give 2-(3-bromo-2- chloro-4-pyridyl)-1,3-dioxolane (800 mg, yield 66.7%). ¹H NMR (300 MHz, DMSO-d₆): δ 8.32 (t, J = 10.5 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.82 (d, J = 4.0 Hz, 1H), 6.26 (s, 1H), 4.32 – 3.96 (m, 4H) ppm. [00182] Step 3: To a solution of 2-(3-bromo-2-chloro-4-pyridyl)-1,3-dioxolane (526 mg, 2.0 mmol) in dioxane (10 mL) was added KOAc (294 mg, 3.0 mmol), bis(pinacolato)diboron (762 mg, 3.0 mmol), and (dppf)PdCl₂ (326 mg, 0.4 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to reflux and stirred for 3h, then the solid was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 30/1) to give the common intermediate 2-[2- chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (380 mg, yield 61.1%) as a light yellow solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.39 (d, J = 4.4 Hz, 1H), 7.38 (d, J = 3.9 Hz, 1H), 5.97 (s, 1H), 4.02 (m, 4H), 1.30 (s, 12H) ppm. [00183] EXAMPLE 1 [00184] 2-(4-chlorophenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00185] The title compound was prepared by using the scheme and procedures shown below:

[00186] A mixture of (2-formylphenyl)boronic acid (1 g, 6.6 mmol) and (4- chlorophenyl)hydrazine (937 mg, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h, and the reaction was monitored by TLC. After completely disappearance of (2-formylphenyl)boronic acid by TLC, the mixture was filtered. The filter cake was washed with hexane and dried in high vacuum to give the title compound 2-(4- chlorophenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (590 mg, yield 34%) as a white solid.¹HNMR (400 MHz, DMSO-d₆): δ 9.13 (s, 1H), 8.41 (d, J = 7.5 Hz, 1H), 8.22 (s, 1H), 7.84-7.81 (m, 2H), 7.72-7.58 (m, 3H), 7.46 (d, J = 8.6 Hz, 2H) ppm. HPLC purity: 97.51% at 210 nm and 99.27% at 254 nm. MS (ESI+): m/z = 257.1 (M+H)⁺. [00187] EXAMPLE 2 [00188] 5-fluoro-2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00189] The title compound was prepared by using the scheme and procedures shown below:

[00190] To a solution of 3-(methylthio)aniline (17.0 g, 123 mmol) in 6N HCl (150 mL) was added NaNO₂ (9.3 g, 135 mmol) in H₂O (30 mL) at 0 °C. The reaction was stirred at 0 °C for 30 min, and then SnCl₂·2H₂O (55.5 g, 246 mmol) in 6N HCl (200 mL) was added. The reaction was stirred at room temperature for 2 h and poured into water. The mixture pH was adjusted to 7-8 by adding 5N NaOH solution (about 300 mL) and extracted with EtOAc (500 mL x 2). The organic was concentrated and the residue was purified by column chromatography to give (3- (methylthio)phenyl)hydrazine (5.1 g, yield 27%) as a yellow oil.¹H NMR (400 MHz, CDCl₃): δ 7.13 (t, J = 7.9 Hz, 1H), 6.79-6.64 (m, 2H), 6.56 (dd, J = 8.1, 1.6 Hz, 1H), 4.10-3.75 (br s, 3H), 2.45 (s, 3H) ppm. [00191] To a solution of (3-(methylthio)phenyl)hydrazine (5.1 g, 33.1 mmol) in DMSO/MeOH (1:4, 80 mL) was added (3-fluoro-2-formylphenyl)boronic acid (5.6 g, 33.1 mmol) at rt. The reaction was stirred at room temperature for 2 h, poured into water and extracted with EtOAc. The organic was concentrated and the residue was triturated with water and DMSO to give the product 5-fluoro-2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (7.2 g, yield 76%) as a yellow solid.¹H NMR (400 MHz, DMSO-d₆): δ 9.23 (s, 1H), 8.35 (s, 1H), 8.22 (d, J = 7.5 Hz, 1H), 7.77-7.66 (m, 1H), 7.66 -7.55 (m, 1H), 7.47 (s, 1H), 7.43-7.31 (m, 2H), 7.16 (d, J = 2.8 Hz, 1H), 2.51 (s, 3H) ppm. HPLC purity: 97.24% at 210 nm and 98.04% at 254 nm. MS (ESI+): m/z =286.9 (M+H)⁺. [00192] EXAMPLE 3 [00193] 8-chloro-2-(3-chlorophenyl)pyrido[3,4-d][1,2,3]diazaborinin-1(2H)-ol

[00194] The title compound was prepared by using the scheme and procedures shown below:

[00195] A solution of NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooling suspension of 3-chloroaniline (2.55 g, 20.0 mmol) in 6N HCl (30 mL) with stirring. After an additional 30 min, a suspension of SnCl₂·2H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The mixture pH was adjusted to 9-10 by adding 30% NaOH solution and extracted with EtOAc (30 mL × 2). The combined organic phases were dried, filtered and evaporated under reduced pressure to give (3-chlorophenyl)hydrazine (2.6 g, yield 91.5%) as a yellow oil. n-BuLi (2 M in hexane, 312 mL, 624 mmol) was added dropwise to a solution of 3-bromo-2-chloropyridine (100 g, 520 mmol) in anhydrous THF (1 L) under N₂ at -78 °C over 30 min. After stirring at -78 °C for an additional 1 h, anhydrous ethyl formate (37 mL, 624 mmol) was added over 30 min and the mixture stirred at -40 °C for 1 h. The reaction was quenched with saturated aqueous NH₄Cl and warmed up to rt. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned into EtOAc (500 mL) and water (500 mL). The aqueous layer was further extracted with EtOAc (3 × 200 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The residue was purified by chromatography (PE / EtOAc = 10:1) to give 3-bromo-2-chloroisonicotinaldehyde (11.4 g, yield 11%).¹HNMR (400 MHz, DMSO-d₆): δ 10.18 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 7.70 (d, J = 4.8 Hz, 1H) ppm. [00196] A mixture of 3-bromo-2-chloroisonicotinaldehyde (11.4 g, 52 mmol), ethylene glycol (6.5 g, 104 mmol), p-toluene sulfonic acid (9.9 g, 58 mmol) in toluene (150 mL) was refluxed overnight to remove H₂O with a Dean-Stark apparatus. The reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure. The residue was partitioned into EtOAc (100 mL) and water (100 mL). The aqueous layer was further extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to give 3-bromo-2-chloro-4-(1,3-dioxolan- 2-yl)pyridine (11.1 g, yield 81%).¹HNMR (400 MHz, DMSO-d₆): δ 8.46 (d, J = 4.9 Hz, 1H), 7.53 (d, J = 4.9 Hz, 1H), 6.01 (s, 1H), 4.11–4.00 (m, 4H) ppm. MS (ESI+): m/z = 263.9 (M+H)⁺. [00197] A mixture of 3-bromo-2-chloro-4-(1,3-dioxolan-2-yl)pyridine (11.1 g, 41 mmol), B₂(Pin)2 (12.8 g, 50 mmol), Pd(dppf)Cl₂ (3.3 g, 4.5 mmol), KOAc (12.1 g, 123 mmol) in 1,4- dioxane (500 mL) was stirred at 80 °C for 8 h under N2. The reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure. The result solid was purified by flash column chromatography (PE / EtOAc = 10:1) to give 2-chloro- 4-(1,3-dioxolan-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (8.1 g, yield 69%). MS (ESI+): m/z = 312.0 (M+H)⁺. To a solution of 2-chloro-4-(1,3-dioxolan-2-yl)-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3- chlorophenylhydrazine (126 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 h. The solid was collected by filtration and triturated with MeCN and water (10 mL, v/v = 1:1) to give the desired product 8-chloro-2-(3-chlorophenyl)pyrido[3,4-d][1,2,3]diazaborinin-1(2H)-ol (71 mg, yield 24.4%) as a white solid.¹H NMR (400 MHz, DMSO-d₆): δ 9.80 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 8.32 (d, J = 5.0 Hz, 1H), 7.68 (t, J = 2.0 Hz, 1H), 7.60 (dd, J = 7.3 & 2.0 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.35 (dd, J = 9.8 & 1.6 Hz, 1H) ppm. HPLC purity: 96.32% at 210 nm and 94.08% at 254 nm. MS (ESI+): m/z = 292.0 (M+H)⁺. [00198] EXAMPLE 4 [00199] 2-Phenyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00200] The title compound was prepared by using the scheme and procedures shown below:

[00201] A mixture of 2-formylphenylboronic acid (1.0 g, 6.6 mmol) and phenylhydrazine (712 mg, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After completely disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-phenyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (1370 mg, yield 93%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.96 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.20 (s, 1H), 7.85- 7.74 (m, 2H), 7.67 (t, J = 7.0 Hz, 1H), 7.58 (d, J = 7.7 Hz, 2H), 7.42 (t, J = 7.7 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H) ppm. HPLC purity: 99.55% at 210 nm and 99.47% at 254 nm. MS (M+H)⁺: m/z = 223.1. [00202] EXAMPLE 5 [00203] 2-(m-Fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00204] The title compound was prepared by using the scheme and procedures shown below:

[00205] Step 1: To a suspension of 3-fluoroaniline (2 g, 18 mmol) in water (20 mL) was added concentrated hydrochloric acid (5 mL). The mixture was cooled to -10 °C under nitrogen. A solution of sodium nitrite (1.2 g, 18 mmol) in water (5 mL) was added dropwise. After addition was completed, the mixture was stirred for an additional 30 min at -10 °C. Tin(II) chloride dehydrate (9.8 g, 44 mmol) was dissolved in 6 N hydrochloric acid (10 mL) and the diazotization mixture was poured into this solution. The mixture was stirred for 3.5 h at -10 °C. The solids were filtered and dried overnight to give crude 3-fluorophenylhydrazine (1.9 g, crude) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 7.18-6.88 (m, 2H), 6.56-6.52 (m, 1H), 6.41-6.19 (m, 2H), 4.02 (s, 2H). [00206] Step 2: A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and 3- fluorophenylhydrazine (831 mg, 6.6 mmol) in DMSO / H₂O (10 mL, v/v = 4:1) was stirred at room temperature for 2h. The reaction was monitored by TLC. After completely disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-(m-fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1- ol (500 mg, yield 32%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.24 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.23 (s, 1H), 7.81 (dt, J = 14.7, 7.5 Hz, 2H), 7.69 (t, J = 7.2 Hz, 1H), 7.56-7.38 (m, 3H), 7.05 (td, J = 8.3, 1.9 Hz, 1H) ppm. HPLC purity: 96.21% at 210 nm and 98.56% at 254 nm. MS (M+H)⁺: m/z = 241.1. [00207] EXAMPLE 6 [00208] 2-(o-Chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00209] The title compound was prepared by using the scheme and procedures shown below:

[00210] Step 1: To a suspension of 2-chloroaniline (2 g, 16 mmol) in water (20 mL) was added concentrated hydrochloric acid (5 mL). The mixture was cooled to -10 °C under nitrogen. A solution of sodium nitrite (1.2 g, 18 mmol) in water (5 mL) was added dropwise. After addition was complete, the mixture was stirred for an additional 30 min at -10 °C. Tin(II) chloride dehydrate (9.8 g, 44 mmol) was dissolved in 6 M hydrochloric acid (10 mL) and the diazotization mixture was poured into this solution. The mixture was stirred for 3.5 h at -10 °C. The solids were then filtered off and dried overnight to give 2-chlorophenylhydrazine (1.9 g, crude) as a red solid. It was not purified further but carried over into the next step. ¹HNMR (300 MHz, DMSO- d₆): δ 7.25-7.10 (m, 3H), 6.68-6.55 (m, 1H), 6.47 (s, 1H), 4.12 (s, 2H). [00211] Step 2: A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and 2- chlorophenylhydrazine (950 mg, 6.6 mmol) in DMSO / H₂O (10 mL, v/v = 1:4) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After completely disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE: EtOAc = 30/1 to 5/1) to give the title compound 2-(o-chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (146 mg, yield 7%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.76 (s, 1H), 8.35 (d, J = 7.5 Hz, 1H), 8.15 (s, 1H), 7.81 (dt, J = 14.8, 7.4 Hz, 2H), 7.68 (t, J = 7.2 Hz, 1H), 7.59 (d, J = 7.3 Hz, 1H), 7.47-7.36 (m, 3H) ppm. HPLC purity: 99.96% at 210 nm and 98.99% at 254 nm. MS (M+H)⁺: m/z = 257.0. [00212] EXAMPLE 7 [00213] 2-(3,4-Dichlorophenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00214] The title compound was prepared by using the scheme and procedures shown below:

[00215] A mixture of 2-formylphenylboronic acid (1.0 g, 6.6 mmol) and 3,4- dichlorophenylhydrazine (1.1 g, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After completely disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-(3,4- dichlorophenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (410 mg, yield 21%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.40 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.25 (s, 1H), 7.91 (d, J = 2.0 Hz, 1H), 7.87-7.75 (m, 2H), 7.69-7.65 (m, 3H) ppm. MS (M+H)⁺: m/z = 291.0. HPLC purity: 96.93% at 210 nm and 98.44% at 254 nm. [00216] EXAMPLE 8 [00217] p-(1-Hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzonitrile

[00218] The title compound was prepared by using the scheme and procedures shown below:

[00219] Step 1: To a suspension of 4-aminobenzonitrile (2.0 g, 15 mmol) in water (20 mL) was added concentrated hydrochloric acid (5 mL). The mixture was cooled to -10 °C under nitrogen. A solution of sodium nitrite (1.2 g, 18 mmol) in water (5 mL) was added dropwise. After addition was complete, the mixture was stirred for an additional 30 min at -10 °C. Tin(II) chloride dehydrate (9.8 g, 44 mmol) was dissolved in 6 M hydrochloric acid (10 mL) and the diazotization mixture was poured into this solution. The mixture was stirred for 3.5 h at -10 °C. The solids were then filtered off and dried overnight to give crude 4-cyanophenylhydrazine (1.8 g, crude) as a red solid. It was not purified further but carried over into the next step. ¹HNMR (400 MHz, DMSO-d₆): δ7.70 (d, J = 35.2 Hz, 1H), 7.43 (t, J = 10.2 Hz, 2H), 6.79 (d, J = 8.6 Hz, 2H), 4.25 (s, 2H). [00220] Step 2: A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and 4- cyanophenylhydrazine (880 mg, 6.6 mmol) in DMSO / H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2h. The reaction was monitored by TLC. After completely disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE / EtOAc = 30/1 to 5/1) to give the title compound p-(1-Hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzonitrile (179 mg, yield 11%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.51 (s, 1H), 8.43 (d, J = 7.6 Hz, 1H), 8.29 (s, 1H), 7.94-7.78 (m, 6H), 7.70 (t, J = 7.3 Hz, 1H) ppm. HPLC purity: 98.23% at 210 nm and 98.82% at 254 nm. MS (M+H)⁺: m/z = 248.1.0. [00221] EXAMPLE 9 [00222] 2-(m-Bromophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol [00223] The title compound was prepared by using the scheme and procedures shown below:

[00224] A mixture of 2-formylphenylboronic acid (250 mg, 1.6 mmol) and 3- bromophenylhydrazine (260 mg, 1.6 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2h. The reaction was monitored by TLC. After completely disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE/EtOAc = 30/1 to 5/1) to give the title compound 2-(m- bromophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (240 mg, yield 51%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.25 (s, 1H), 8.41 (d, J = 7.5 Hz, 1H), 8.23 (s, 1H), 7.80 (dd, J = 15.1, 7.1 Hz, 3H), 7.68 (dd, J = 12.2, 7.4 Hz, 2H), 7.44-7.33 (m, 2H) ppm. HPLC purity: 95.01% at 210 nm and 97.55% at 254 nm. MS (M+H)⁺: m/z = 301. [00225] EXAMPLE 10 [00226] Ethyl m-(1-hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzoate

[00227] The title compound was prepared by using the scheme and procedures shown below:

[00228] Step 1: To a solution of m-amino benzoic acid ethyl ester (1.65 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 1.0.0 mmol) at 0 °C. the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield ethyl 3-hydrazinobenzoate hydrogen chloride (2.1 g, yield 100%) as a white solid, which was used for the next reaction without further purification. ¹H NMR (400 MHz, DMSO-d6): δ 9.09 (s, 1H), 7.68 (dd, J = 13.9, 8.2 Hz, 2H), 7.27 (d, J = 31.6 Hz, 2H), 4.97 (s, 3H), 3.92 (d, J = 5.5 Hz, 1H), 3.35 (s, 5H), 2.36 (s, 3H), 1.23 (s, 3H) ppm. MS: (M+H)⁺: m/z = 181.1. [00229] Step 2: A solution of 3-hydrazinobenzoate hydrogen chloride (347 mg, 2.3 mmol) and 2-formylphenylboronic acid (500 mg, 2.3 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted by water (25 mL), extracted by EtOAc (2 x 25 mL), washed with brine (2 x 10 mL), dried over Na2SO4, filtered and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) to afford the desired product ethyl m-(1-hydroxy-1,2-dihydro-2,3,1- benzodiazaborinin-2-yl)benzoate (117 mg, yield 17%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.22 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.25 (d, J = 3.5 Hz, 2H), 7.92 (dd, J = 8.1, 1.1 Hz, 1H), 7.87-7.76 (m, 3H), 7.69 (t, J = 7.3 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H) ppm. HPLC purity: 98.54% at 210 nm and 91.45% at 254 nm. MS: (M+H)⁺: m/z = 295.1. [00230] EXAMPLE 11 [00231] 2-(3-(Trifluoromethyl)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00232] The title compound was prepared by using the scheme and procedures shown below:

[00233] A solution of 2-formylphenylboronic acid (300 mg, 2.0 mmol) and (3- (trifluoromethyl)phenyl)hydrazine (352 mg, 2.0 mmol) in DMSO/H₂O (1/4, 10 mL) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted by water (25 mL), extracted by EtOAc (2 x 25 mL), washed with brine (2 x 10 mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) to afford the desired product 2- (3-(Trifluoromethyl)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (203 mg, yield 33%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.35 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.27 (s, 1H), 8.05- 7.95 (m, 2H), 7.91-7.77 (m, 2H), 7.76-7.63 (m, 2H), 7.57 (d, J = 7.7 Hz, 1H) ppm. HPLC purity: 97.17% at 210 nm and 97.59% at 254 nm. MS: (M+H)⁺: m/z = 291.1. [00234] EXAMPLE 12 [00235] 2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00236] The title compound was prepared by using the scheme and procedures shown below:

[00237] Step 1: To a solution of m-thioanisidine (1.39 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C. The reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield (3- (methylthio)phenyl)hydrazine hydrogen chloride (1.1 g, yield 58%) as a white solid, which was used for the next reaction without further purification. ¹H NMR (400 MHz, DMSO-d₆): δ 10.20 (s, 3H), 7.21 (t, J = 7.4 Hz, 1H), 6.89 (s, 1H), 6.83 (d, J = 7.7 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 2.46 (s, 3H) ppm. MS: (M+H)⁺: m/z = 155.1. [00238] Step 2: A solution of 2-formylphenylboronic acid (868 mg, 5.79 mmol) and (3- (methylthio)phenyl)hydrazine hydrogen chloride (1.1 g, 5.79 mmol) in DMSO/H₂O (25 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted by water (50 mL), extracted by EtOAc (2 × 50 mL), washed with brine (2 × 50 mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (20 mL, v/v = 1/1) to afford the desired product 2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (582 mg, yield 38%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.05 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.21 (s, 1H), 7.87-7.74 (m, 2H), 7.68 (t, J = 6.8 Hz, 1H), 7.49 (s, 1H), 7.44 -7.32 (m, 2H), 7.13 (d, J = 7.0 Hz, 1H) ppm. HPLC purity: 98.6% at 210 nm and 98.68% at 254 nm. MS: (M+Na)⁺: m/z = 291.1. [00239] EXAMPLE 13 [00240] 2-(3-methoxyphenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00241] The title compound was prepared by using the scheme and procedures shown below:

[00242] Step 1: To a solution of m-anisidine (1.23 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C. and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield 3- methoxyphenylhydrazine hydrogen chloride (1.1 g, yield 63%) as a white solid, which was used for the next reaction without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 3H), 7.17 (t, J = 8.1 Hz, 1H), 6.61 (d, J = 1.9 Hz, 1H), 6.53 (ddd, J = 16.6, 8.1, 1.6 Hz, 2H), 3.71 (s, 3H) ppm. MS: (M+H)⁺: m/z = 139.1. [00243] Step 2: A solution of 2-formylphenylboronic acid (431 mg, 2.9 mmol) and 3- methoxyphenylhydrazine hydrogen gchloride (500 mg, 2.9 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted by water (25 mL), extracted by EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) to afford the desired product 2-(3-methoxyphenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (104 mg, yield 14%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.98 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.20 (s, 1H), 7.85-7.74 (m, 2H), 7.71-7.63 (m, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.17 (dd, J = 7.5, 5.3 Hz, 2H), 6.81 (dd, J = 8.1, 2.1 Hz, 1H), 3.79 (s, 3H) ppm. HPLC purity: 99.45% at 210 nm and 99.50% at 254 nm. MS: (M+H)⁺: m/z = 253.0. [00244] EXAMPLE 14 [00245] 8-Chloro-2-(m-fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00246] The title compound was prepared by using the scheme and procedures shown below:

[00247] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 3-fluoroaniline (2.22 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2 h. The mixture pH was adjusted to 9-10 by 30% NaOH solution and extracted with EtOAc (300 mL × 2). The combined organic phases were dried and evaporated under reduced pressure to give 3- fluorophenylhydrazine product (2.0 g, yield 79.4%) as a yellow oil. ¹HNMR (400 MHz, DMSO- d₆): δ 7.26-6.90 (m, 2H), 6.67-6.46 (m, 2H), 6.44-6.20 (m, 1H), 4.04 (s, 2H) ppm. [00248] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol; prepared as described above in reference to General Synthetic Procedure B) in DMSO (6 mL) was added 3-fluorophenylhydrazine (126 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-(m- fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (107 mg, yield 38.9%) as a white solid. 1H NMR (400 MHz, DMSO-d₆): δ 9.80 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 8.33 (d, J = 5.0 Hz, 1H), 7.54-7.43 (m, 3H), 7.17-7.09 (m, 1H) ppm. HPLC purity: 96.48% at 210 nm and 93.66% at 254 nm. MS: (M+H)⁺: m/z = 276.0. [00249] EXAMPLE 15 [00250] 6-Fluoro-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00251] The title compound was prepared by using the scheme and procedures shown below:

[00252] Step 1: To a mixture of m-thioanisidine (1.00 g, 7.18 mmol) in conc.HCl (15 mL) was added NaNO₂ (950 mg, 14.36 mmol) in water (2 mL) dropwise at -15 °C. The resulting mixture was stirred for 20 min. The reaction mixture was added SnCl₂.6H₂O (6.67 g, 28.72 mmol) in conc.HCl (10 mL) dropwise. The reaction mixture was heated to room temperature and stirred for 1 h. The reaction mixture was cooled to 0 °C, basified with 10 M aqueous NaOH and extracted with chloroform. The combined organic phases was washed with water, dried over Na₂SO₄ and concentrated in vacuo. The product was column chromatography (SiO₂, petroleum ether/ethyl acetate=10/1 to 4:1) to give [m-(methylthio)phenyl]hydrazine (810 mg, 73.10% yield) as a yellow solid. ¹H NMR (300 MHz, DMSO-d₆): δ 7.01 (t, J = 7.9 Hz, 1H), 6.70 (dd, J = 6.5, 4.5 Hz, 2H), 6.52 (m 1H), 6.47 – 6.39 (m, 1H), 3.95 (s, 2H), 2.40 (s, 3H). [00253] Step 2: A solution of [m-(methylthio)phenyl]hydrazine (656 mg, 4.26 mmol) and 2-(dihydroxyboryl)-5-fluorobenzaldehyde (698 mg, 4.26 mmol, 1 eq) in EtOH (4 mL) was stirred for 2 h. The reaction mixture was filtered and the solid was triturated with methanol to give 6- fluoro-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (600 mg, 52.6% yield) as a yellow solid.¹H NMR (300 MHz, DMSO-d₆): δ 9.12 (s, 1H), 8.46 (dd, J = 8.5, 6.1 Hz, 1H), 8.20 (s, 1H), 7.65 (dd, J = 9.8, 2.5 Hz, 1H), 7.59 – 7.49 (m, 1H), 7.46 (s, 1H), 7.36 (dd, J = 3.9, 1.3 Hz, 2H), 7.19 – 7.03 (m, 1H), 2.48(s, 3H) ppm. MS: (M+H)⁺: m/z = 287.0. HPLC purity: 97.79% at 210 nm and 98.41% at 254 nm. [00254] EXAMPLE 16 [00255] 5-chloro-2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00256] The title compound was prepared by using the scheme and procedures shown below:

[00257] Step 1: To a stirred solution of 2-bromo-6-chlorobenzaldehyde (7.0 g, 36.5 mmol) in MeOH (10 mL) was added trimethyl orthoformate (4.7 g, 43.8 mmol) and a drop of conc. H₂SO₄. The reaction mixture was heated at 95 °C for 1 hour. Then the reaction mixture was neutralized with sodium methoxide and the volatiles were removed under reduced pressure. The mixture was purified by column chromatography on silica gel (petroleum ether/EtOAc- 100/1) to give 1-bromo-3-chloro-2-(dimethoxymethyl)benzene (5.4 g, yield 55.7%）. ¹H NMR (300 MHz, DMSO) δ 7.65 (dd, J = 8.0, 1.1 Hz, 1H), 7.51 (dd, J = 8.1, 1.1 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 5.77 (s, 1H), 3.37 (s, 6H) ppm. [00258] Step 2: To a solution of n-BuLi (8.0 mL, 19.58 mmol, 2.4 M in diethyl ether) in diethyl ether (20 mL) was added a solution of 1-bromo-3-chloro-2-(dimethoxymethyl)benzene (4 g, 15.06 mmol) in diethyl ether (30 mL) at -78 °C. Then to the reaction mixture was added B(OMe)3 (3.14 g, 30.2 mmol) at -78 °C after 15 min stirring. The mixture was stirred for 30 minutes and allowed to warm to -50 °C, quenched with 2 M aq. HCl (10 mL), and the organic layer was separated. The solvent was evaporated under reduced pressure. To the mixture was added water (20 mL) and a drop of conc. aq. HCl (5 mL) to an oily residue. The mixture was heated shortly to ca.70 °C to cleave the acetal moiety and methanol was removed in vacuo. The crude solid product was filtered off and washed with water and toluene to obtain 3-chloro-2- formylphenyl) boronic acid (2.3 g, yield 71.28%）. ¹H NMR (300 MHz, DMSO): δ 10.24 (s, 1H), 7.77 (dd, J = 8.0, 0.9 Hz, 1H), 7.63 (dd, J = 8.0, 0.8 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H) ppm. [00259] Step 3: A solution of 3-chloro-2-formylphenyl) boronic acid (2.3 g, 6.51 mmol) and [m-(methylthio)phenyl]hydrazine (603 mg, 3.91 mmol) in DMSO/H₂O (12 mL/3 mL) was stirred at room temperature for 1 h. LCMS indicated no starting materials left. The mixture was poured into water and extracted with EtOAc (25 mL x 2). The organic layer was concentrated in vacuo to dryness. The resulting residue was purified by pre-HPLC (0.1% TFA as additive) to give the product 5-chloro-2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (450 mg, yield 22.96%) as a yellow solid. ¹H NMR (300 MHz, DMSO) δ 9.25 (s, 1H), 8.45 (s, 1H), 8.37 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.47 (s, 1H), 7.36 (d, J = 4.9 Hz, 2H), 7.15 (s, 1H), 2.49 – 2.48 (m, 3H) ppm. HPLC purity: 97.16% at 210 nm and 97.95% at 254 nm. MS (ESI⁺): m/z =303.0(M+H)⁺. [00260] EXAMPLE 17 [00261] 8-chloro-2-(p-tolyl)pyrido[3,4-d][1,2,3]diazaborinin-1(2H)-ol

[00262] The title compound was prepared by using the scheme and procedures shown below:

[00263] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 4-methylbenzenamine (2.14 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9~10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give 4-methylphenylhydrazine (2.2 g, yield 90.2%) as a yellow solid. ¹HNMR (300 MHz, DMSO-d₆): δ 6.90 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.2 Hz, 2H), 6.42 (s, 1H), 3.83 (s, 2H), 2.16 (s, 3H) ppm. [00264] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4- methylphenylhydrazine (122 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-(p-tolyl)pyrido[3,4-d][1,2,3]diazaborinin-1(2H)-ol (55 mg, yield 20.3%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.48 (s, 1H), 8.60 (d, J = 5.0 Hz, 1H), 8.44 (s, 1H), 8.30 (d, J = 5.0 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 2.35 (s, 3H) ppm. HPLC purity: 99.36% at 210 nm and 98.37% at 254 nm. MS: (M+H)⁺: m/z = 272.0. [00265] EXAMPLE 18 [00266] 8-chloro-2-propylpyrido[3,4-d][1,2,3]diazaborinin-1(2H)-ol

[00267] The title compound was prepared by using the scheme and procedures shown below:

[00268] Step 1: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (622 mg, 2.0 mmol) in Et₂OH (10 mL) was added hydrazine hydrate (80% in H₂O, 1 mL) at room temperature. The mixture was stirred for 20 min and 6N HCl (5 mL) was added. The reaction mixture was stirred for another 2h, then solvent was removed under reduced pressure and the residue was washed with EtOAc. The organic layer was evaporated under reduced pressure to give the product 8-chloro-1,2-dihydro-2,3,7-triaza-1- bora-1-naphthol (320 mg, yield 88.4%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 10.65 (s, 1H), 8.90 (s, 1H), 8.52 (d, J = 4.9 Hz, 1H), 8.30 (s, 1H), 8.11 (d, J = 4.9 Hz, 1H) ppm. [00269] Step 2: To a solution of 8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (181 mg, 1.0 mmol) in DMF (5 mL) was added 1-iodopropane (340 mg, 2.0 mmol) and K₂CO₃ (276 mg, 2.0 mmol). The reaction was stirred at 60 °C for 2h, poured into water, and extracted with EtOAc. The organic layer was washed with water, brine, concentrated under reduced pressure, and the residue was purified by pre-HPLC to give the product 8-chloro-2-propylpyrido[3,4- d][1,2,3]diazaborinin-1(2H)-ol (14.4 mg, yield 18.4%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.11 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 8.19 (d, J = 4.9 Hz, 1H), 3.83 (t, J = 7.1 Hz, 2H), 1.80-1.60 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H) ppm. HPLC purity: 99.60% at 210 nm and 99.81% at 254 nm. MS: (M+H)⁺: m/z =224.0. [00270] EXAMPLE 19 [00271] 1-Hydroxy-2-(3-methylsulfanylphenyl)-7-(trifluoromethyl)-2,3,1 - benzodiazaborinine

[00272] The title compound was prepared by using the scheme and procedures shown below:

[00273] Step 1: To an ice-cold aqueous solution of 3-methylsulfanylaniline (2.00 g, 14.37 mmol, 1.77 mL, 1 eq) in HCl (12 N, 10 mL) was added a solution of NaNO₂ (991 mg, 14.37 mmol, 1 eq) in H₂O (3 mL), the reaction mixture was stirred for 30 min at 0 °C. To the resulting mixture was added drop-wise a solution of SnCl₂.2H₂O (9.72 g, 43.10 mmol, 3 eq) in HCl (12 N, 20 mL), the reaction mixture was stirred for 4 h at 0 °C. The mixture was filtered and the filtrate was diluted with ice water (w/w = 1/1) (50 mL). The aqueous phase was adjusted pH to 6-7 with 1 N NaOH and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 5/1) to give (3-methylsulfanylphenyl)hydrazine (1.20 g, 7.78 mmol, 54.16% yield) as yellow oil. ¹H NMR (DMSO-d₆, 400 MHz) δ 7.01 (t, J = 8.0 Hz, 1H), 6.73 (s, 1H), 6.69 (s, 1H), 6.52 (d, J = 8.0 Hz, 1H), 8.45 (d, J = 7.6 Hz, 1H), 3.95 (s, 2H), 2.40 (s, 3H). [00274] Step 2: To a mixture of (3-methylsulfanylphenyl)hydrazine (100 mg, 648.37 umol, 1 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzaldehyde (200 mg, 666.49 umol, 1.03 eq) in EtOH (3 mL) was added NH₃.H₂O (182 mg, 1.30 mmol, 0.2 mL, 25% purity, 2.00 eq) in one portion at 25 °C, the mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Nano-micro Kromasil C18100*30mm 5um;mobile phase: [water(0.1%TFA)-ACN];B%: 55%-80%,10 min) to give 1-hydroxy-2-(3-methyl sulfanylphenyl)-7- (trifluoromethyl)-2,3,1-benzodiazaborinine (106 mg, 303.52 umol, 46.81% yield, 96.25% purity) as a gray solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.36 (s, 1H), 8.85 (s, 1H), 8.35 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.47 (s, 1H), 7.37 (d, J = 4.8 Hz, 2H), 7.16-7.14 (m, 1H), 2.50 (s, 3H). MS (ESI): mass calcd. For C15H12BF3N2OS 336.07, m/z found 337.1 [M+H]⁺. HPLC: 96.25% (220 nm), 97.85% (254 nm). [00275] EXAMPLE 20 [00276] 4-ethyl-2-(3-(methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol

[00277] The title compound was prepared by using the scheme and procedures shown below:

[00278] Step 1: To a solution of a 2-bromobenzaldehyde (10 g, 54 mmol) in THF (80 mL) was added ethylmagnesium bromide (22 mL, 65 mmol) at 0 °C under an inert nitrogen atmosphere. After addition, the reaction was allowed to warm to room temperature and stirred for 1h, then quenched by sat. NH₄Cl and extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give o-bromo(sec- butyl)benzene (7.5 g, yield 64.6%) as a light oil. ¹H NMR (400 MHz, DMSO-d₆): δ 7.64-7.49 (m, 2H), 7.39 (m, 1H), 7.17 (m, 1H), 5.36 (d, J = 4.5 Hz, 1H), 4.75 (dt, J = 8.3, 4.3 Hz, 1H), 1.65 (m, 1H), 1.56-1.42 (m, 1H), 0.91 (t, J = 7.4 Hz, 3H) ppm. [00279] Step 2: To a solution of o-bromo(sec-butyl)benzene (7.5 g, 34.9 mmol) in DCM (30 mL) was added Dess-Martin reagent (14.7 g, 34.9 mmol) in small portions at 0 °C. The reaction was stirred at room temperature for 1 h, then the solid was filtered and washed with DCM. The organic layer was concentrated under reduced pressure and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 50/1) to give 1-(o- bromophenyl)-1-propanone (5.2 g, yield 70.7%) as a colorless oil. ¹H NMR (400 MHz, DMSO- d₆): δ 7.70 (dd, J = 7.9, 1.0 Hz, 1H), 7.58 (dd, J = 7.6, 1.7 Hz, 1H), 7.48 (m, 1H), 7.41 (td, J = 7.7, 1.8 Hz, 1H), 2.91 (q, J = 7.2 Hz, 2H), 1.08 (t, J = 7.2 Hz, 3H) ppm. [00280] Step 3: To a solution of 1-(o-bromophenyl)-1-propanone (5.26 g, 24.7 mmol) in dioxane (80 mL) was added KOAc (7.27 g, 74.1 mmol), bis(pinacolato)diboron (9.4 g, 37.05 mmol), and Pd(dppf)Cl₂ (2 g, 2.47 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 80 °C and stirred for 2 h, then the solid was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/0 to 50/1) to give 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-propanone (4.8 g, yield 74.7%) as a yellow oil. ¹H NMR (400 MHz, DMSO-d₆): δ 7.97 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 7.0 Hz, 1H), 7.52 (t, J = 5.9 Hz, 1H), 7.44 (d, J = 7.1 Hz, 1H), 3.04 (q, J = 7.1 Hz, 2H), 1.33 (s, 11H), 1.09 (d, J = 7.2 Hz, 3H) ppm. [00281] Step 4: To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]- 1-propanone (500 mg, 1.92 mmol) in DMSO (5 mL) was added 3-(methylthio)phenylhydrazine (343 mg, 1.92 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-ethyl-2-(3- (methylthio)phenyl)benzo[d][1,2,3]diazaborinin-1(2H)-ol (89 mg, yield 15.7%) as a white powder. 1H NMR (400 MHz, DMSO-d₆): δ 8.43 (d, J = 6.9 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.3 Hz, 1H), 7.56 (s, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.10 (d, J = 7.7 Hz, 1H), 2.99 (q, J = 7.3 Hz, 2H), 1.29 (t, J = 7.3 Hz, 3H) ppm. MS: (M+H)⁺: m/z = 297.1. HPLC purity: 97.83% at 210 nm and 98.33% at 254 nm. [00282] EXAMPLE 21 [00283] 1-Hydroxy-7-(trifluoromethyl)-2-[3-(trifluoromethylsulfanyl)phenyl] -2,3,1- benzodiazaborinine

[00284] The title compound was prepared by using the scheme and procedures shown below:

[00285] Step 1: To a mixture of 2-bromo-4-(trifluoromethyl)benzaldehyde (1.00 g, 3.95 mmol, 1 eq) in dioxane (15 mL) was added B₂Pin₂ (1.51 g, 5.93 mmol, 1.5 eq), KOAc (969 mg, 9.88 mmol, 2.5 eq) and Pd(dppf)Cl₂ (289 mg, 395.23 umol, 0.1 eq) in one portion at 25 °C under N₂, then the mixture was heated to 80 °C and stirred for 16 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, petroleum ether/ethyl acetate=10/1 to 3/1) to give 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzaldehyde (1.00 g, 3.33 mmol, 84.32% yield) as a yellow solid. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 10.65 (s, 1H), 8.15 (s, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 1.41 (s, 12H). [00286] Step 2: To a mixture of N-hydroperoxy-3-[(3-nitrophenyl)disulfanyl]aniline (4.50 g, 14.50 mmol, 1 eq) in THF (70 mL) was added NaBH4 (1.92 g, 50.75 mmol, 3.5 eq) in portions at 0 °C, the reaction mixture was stirred at 20 °C for 2 h. The reaction mixture was poured into ice-water (w/w = 1/1) (150 mL) and adjusted pH to 3-4 with HCl (2 N). Then the aqueous layer was extracted with EtOAc (30 mL x 3). The combined organic phase was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered and concentrated in vacuum. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=5/1 to 3/1) to give 3- nitrobenzenethiol (3.80 g, crude) as yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 8.13 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 8.4 Hz, 1H), 3.72 (s, 1H). [00287] Step 3: To a solution of 3-nitrobenzenethiol (3.80 g, 24.49 mmol, 819.67 uL, 1 eq) in DMF (70 mL) was added NaH (1.47 g, 36.73 mmol, 60% purity, 1.5 eq) portionwise at 0 °C, the mixture was stirred at this temperature for 10 min. Then trifluoro(iodo)methane (28.79 g, 36.73 mmol, 1.5 eq) was added dropwise and the resulting reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was poured into ice-water (w/w = 1/1) (150 mL), adjusted pH to 3-4 with HCl (2 N) and extracted with EtOAc (40 mL x 3). The combined organic phases was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 1-nitro-3-(trifluoromethylsulfanyl)benzene (5.00 g, 22.40 mmol, 91.49% yield) as yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 8.54 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H). [00288] Step 4: To a mixture of 1-nitro-3-(trifluoromethylsulfanyl)benzene (4.7 g, 21.06 mmol, 1 eq) and NH₄Cl (4.51 g, 84.24 mmol, 4 eq) in EtOH (55 mL)/H₂O (15 mL) was added Fe (4.70 g, 84.24 mmol, 4 eq) in 4 portions at 25 °C under N2, the mixture was heated to 80 °C and stirred for 2 h. The reaction mixture was filtered through a pad of CELITE and the filtrate was concentrated under reduced pressure to remove the solvents. The residue was suspended in EtOAc (300 mL) and filtered. The filter cake was discarded to remove the inorganic salt. The filtrate was dried over Na₂SO₄, filtered and concentrated in vacuo to give 3- (trifluoromethylsulfanyl)aniline (4.00 g, 20.71 mmol, 98.31% yield) as yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 7.19 (t, J = 8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.97 (s, 1H), 6.78 (dd, J = 8.0, 2.4 Hz, 1H), 3.77 (s, 2H). [00289] Step 5: To an ice-cold solution of 3-(trifluoromethylsulfanyl)aniline (1.00 g, 5.18 mmol, 884.96 uL, 1 eq) in HCl (12 N, 10 mL) was added drop-wise a solution of NaNO₂ (357 mg, 5.18 mmol, 1 eq) in H₂O (1 mL), the reaction was stirred for 30 min at 0 °C. To the mixture above was added drop-wise a solution of SnCl₂.2H₂O (3.50 g, 15.53 mmol, 3 eq) in HCl (12 N, 10 mL), the reaction mixture was stirred for 4 h at 0 °C. The mixture was filtered and the filtrate was diluted with ice-water (w/w = 1/1) (20 mL). The aqueous phase adjusted pH to 6-7 with 1 N NaOH and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 3/1) to give [3-(trifluoromethylsulfanyl)phenyl]hydrazine (1.00 g, 4.80 mmol, 92.79% yield) as a brown solid. ¹H NMR (DMSO-d_6, 400 MHz) δ 10.12 (s, 2H), 8.54 (s, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.16 (d, J = 3.2 Hz, 1H). [00290] Step 6: To a mixture of [3-(trifluoromethylsulfanyl)phenyl]hydrazine (200 mg, 960.60 umol, 1.06 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4- (trifluoromethyl)benzaldehyde (300 mg, 999.73 umol, 1.1 eq) in EtOH (5 mL) was added NH₃.H₂O (273 mg, 1.95 mmol, 0.3 mL, 25% purity, 2.14 eq) in one portion at 25 °C, the mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18 150*25mm*5um;mobile phase: [water(10mM NH4HCO3)-ACN];B%: 75%-95%,10.5min) to give 1-hydroxy-7- (trifluoromethyl)-2-[3-(trifluoromethylsulfanyl)phenyl]-2,3,1-benzodiazaborinine (48 mg, 121.91 umol, 13.41% yield, 99.08% purity) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.61 (s, 1H), 8.86 (s, 1H), 8.40 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.90-7.88 (m, 1H), 7.60(d, J = 6.4 Hz, 2H). MS (ESI): mass calcd. For C₁₅H₉BF₆N₂OS 390.04, m/z found 391.0 [M+H]⁺. HPLC: 99.08% (220 nm), 98.64% (254 nm). [00291] EXAMPLE 22 [00292] 8-Chloro-2-phenyl-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00293] The title compound was prepared by using the scheme and procedures shown below:

[00294] Step 1: n-BuLi (2 M in hexane, 312 mL, 624 mmol) was added dropwise to a solution of 3-bromo-2-chloropyridine (100 g.520 mmol) in anhydrous THF (1 L) under N₂ at -78 °C over 30 min. After stirring an additional 1 h at -78 °C, anhydrous methyl formate (37 mL, 624 mmol) was added over 30 min and the mixture stirred at -40 °C for 1 h. The reaction was quenched with saturated aqueous NH₄Cl and warmed up to room temperature. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned into EtOAc (500 mL) and water (500 mL). The aqueous layer was further extracted with EtOAc (3 × 200 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The residue was purified by chromatography (PE / EtOAc = 10:1) to give 3-bromo-2-chloroisonicotinaldehyde (11.4 g, yield 11%). ¹HNMR (400 MHz, DMSO- d₆):δ10.18 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 7.70 (d, J = 4.8 Hz, 1H) ppm. [00295] Step 2: A mixture of 3-bromo-2-chloroisonicotinaldehyde (11.4 g, 52 mmol), ethylene glycol (6.5 g, 104 mmol), and p-toluenesulfonic acid (9.9 g, 58 mmol) in toluene (150 mL) was refluxed overnight to remove H₂O in a Dean-Stark apparatus. The reaction was monitored by TLC. After the reaction mixture was completed, the solvent was evaporated under reduced pressure. The residue was partitioned into EtOAc (100 mL) and water (100 mL). The aqueous layer was further extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated in vacuo to give 3-bromo-2- chloro-4-(1,3-dioxolan-2-yl)pyridine (11.1 g, yield 81%). ¹HNMR (400 MHz, DMSO-d₆):δ8.46 (d, J = 4.9 Hz, 1H), 7.53 (d, J = 4.9 Hz, 1H), 6.01 (s, 1H), 4.11–4.00 (m, 4H)ppm. MS (M+H)⁺: m/z = 263.9. [00296] Step 3: A mixture of 3-bromo-2-chloro-4-(1,3-dioxolan-2-yl)pyridine (11.1 g, 41 mmol), B2(Pin)2 (12.8 g, 50 mmol), Pd(dppf)2Cl₂ (3.3 g, 4.5 mmol), KOAc(12.1 g, 123 mmol) in dioxane(500 mL) was heated to 80 °C for 8h, the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure. The result solid was purified by flash column chromatography (PE / EtOAc = 10:1) to give 2-[2-chloro-4-(1,3- dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.1 g, yield 69%). MS (M+H)⁺: m/z = 312.0. [00297] Step 4: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (1 g, 3.2 mmol) and phenylhydrazine (421 mg, 3.9 mmol) in DMSO (3 mL) at room temperature was added sequentially HCl (2 mL, 6 N), H₂O (8 mL). The acidic mixture was stirred for 2 h and extracted with EtOAc (2 × 25 mL). Combined organics were washed with H₂O, brine, dried over Na₂SO₄ and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with PE/EtOAc (30:1 to 10:1) to give the title compound 8-chloro-2-phenyl-1,2-dihydro-2,3,7-triaza-1- bora-1-naphthol (156 mg, yield 19%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.56 (s, 1H), 8.62 (d, J = 4.9 Hz, 1H), 8.46 (s, 1H), 8.32 (d, J = 4.9 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.29 (t, J = 7.3 Hz, 1H) ppm. HPLC purity: 96.43% at 210 nm and 93.40% at 254 nm. MS (M-H)-: m/z = 256.0. [00298] EXAMPLE 23 [00299] 2-(p-Fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00300] The title compound was prepared by using the scheme and procedures shown below:

[00301] A mixture of 2-formylphenylboronic acid (1.0 g, 6.6 mmol) and (p- fluorophenyl)hydrazine (831 mg, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-(p-Fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (840 mg, yield 53%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.01 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.20 (s, 1H), 7.87-7.73 (m, 2H), 7.68 (t, J = 7.3 Hz, 1H), 7.59 (dd, J = 8.4, 5.3 Hz, 2H), 7.24 (t, J = 8.8 Hz, 2H) ppm. HPLC purity: 99.92% at 210 nm and 99.97% at 254 nm. MS (M+H)⁺: m/z = 241.1. [00302] EXAMPLE 24 [00303] 2-(o-Fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00304] The title compound was prepared by using the scheme and procedures shown below:

[00305] A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and 2- fluorophenylhydrazine (831 mg, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-(o-Fluorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (635 mg, yield 41%) as an off-white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.87 (s, 1H), 8.36 (d, J = 7.5 Hz, 1H), 8.17 (s, 1H), 7.84-7.81 (m, 2H), 7.69 (t, J = 7.1 Hz, 1H), 7.46 (t, J = 7.4 Hz, 1H), 7.43-7.24 (m, 3H). HPLC purity: 98.03% at 210 nm and 97.05% at 254 nm. MS (M+H)⁺: m/z = 241.1. [00306] EXAMPLE 25 [00307] 2-(p-Bromophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00308] The title compound was prepared by using the scheme and procedures shown below:

[00309] A mixture of 2-formylphenylboronic acid (1.0 g, 6.6 mmol) and 4- bromophenylhydrazine (1.2 g, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane to give a crude product, which was purified by silica gel chromatography (EtOAc: PE from 1:30 to 1:5) to give the title compound 2-(p-bromophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (100 mg, yield 6%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.14 (s, 1H), 8.40 (d, J = 7.6 Hz, 1H), 8.22 (s, 1H), 7.84-7.79 (m, 2H), 7.68 (t, J = 7.1 Hz, 1H), 7.62-7.58 (m, 4H) ppm. HPLC purity: 98.45% at 210 nm and 99.09% at 254 nm. MS (M+H)⁺: m/z = 301.0. [00310] EXAMPLE 26 [00311] 2-(o-Bromophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00312] The title compound was prepared by using the scheme and procedures shown below:

[00313] A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and 2- bromophenylhydrazine (1.2 g, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-(o-bromophenyl)-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (787 mg, yield 40%) as an off-white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.74 (s, 1H), 8.35 (d, J = 7.5 Hz, 1H), 8.14 (s, 1H), 7.90-7.72 (m, 3H), 7.68 (t, J = 7.2 Hz, 1H), 7.54-7.39 (m, 2H), 7.32 (t, J = 7.5 Hz, 1H) ppm. HPLC purity: 96.67% at 210 nm and 98.30% at 254 nm. MS (M+H)⁺: m/z = 301.0. [00314] EXAMPLE 27 [00315] m-(1-Hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzonitrile

[00316] The title compound was prepared by using the scheme and procedures shown below:

[00317] Step 1: To a suspension of m-aminobenzonitrile (2 g, 16 mmol) in water (20 mL) was added concentrated hydrochloric acid (5 mL). The mixture was cooled to -10 °C under nitrogen. A solution of sodium nitrite (1.2 g, 18 mmol) in water (5 mL) was added dropwise. After addition was complete, the mixture was stirred for an additional 30 min at -10 °C. Tin(II) chloride dehydrate (9.8 g, 44 mmol) was dissolved in 6 M hydrochloric acid (10 mL) and the diazotization mixture was poured into this solution. The mixture was stirred for 3.5 h at -10 °C. The solids were then filtered off and dried overnight. The m-hydrazinobenzonitrile product (2.2 g, yellow liquid) was not purified further but carried over into the next step. MS (M+H)⁺: m/z = 134.0. [00318] Step 2: A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and m- hydrazinobenzonitrile (850 mg, 6.6 mmol) in DMSO/H₂0(2 mL/8 mL) was stirred at room temperature for 2h. The reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE/EtOAc = 30/1 to 5/1) to give the title compound m-(1- hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzonitrile (240 mg, yield 14%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.37 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.26 (s, 1H), 8.06 (s, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.89-7.76 (m, 2H), 7.67 (tt, J = 15.6, 8.0 Hz, 3H) ppm. HPLC purity: 97.40% at 210 nm and 97.63% at 254 nm. MS (M+H)⁺: m/z = 248.1. [00319] EXAMPLE 28 [00320] 2-(m-Trifluoromethoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00321] The title compound was prepared by using the scheme and procedures shown below:

[00322] A solution of 2-formylphenylboronic acid (300 mg, 2.0 mmol) and (3- (trifluoromethoxy)phenyl)hydrazine (384 mg, 2.0 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) to afford the desired product 2-(m-trifluoromethoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (424 mg, yield 69%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.34 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.26 (s, 1H), 7.87-7.77 (m, 2H), 7.75-7.63 (m, 3H), 7.54 (t, J = 8.2 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H) ppm. HPLC purity: 98.33% at 210 nm and 99.03% at 254 nm. MS: (M+H)⁺: m/z = 307.1. [00323] EXAMPLE 29 [00324] Ethyl p-(1-hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)benzoate

[00325] The title compound was prepared by using the scheme and procedures shown below:

[00326] Step 1: To a solution of 4-carboxyphenyl hydrazine (1.0 g, 6.55 mmol) in ethanol (10 mL) and HCl (10 %, 20 mL) in a sealed-tube was heated at 80 °C for 10 h. After completion, the reaction mixture was allowed to cool to room temperature and the solid so obtained was filtered at pump. The solid was washed with diethyl ether and dried to afford the compound ethyl 4-hydrazinylbenzoate (730 mg, yield 62%) as white shiny crystals. ¹HNMR (400 MHz, DMSO-d₆): δ 10.21 (s, 1H), 9.38 (s, 1H), 8.25 (d, J = 1.7 Hz, 1H), 7.76 (d, J = 7.2 Hz, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.46-7.30 (m, 2H), 7.25-7.12 (m, 3H), 6.13 (s, 1H) ppm. MS: (M+H)⁺: m/z = 181.1. [00327] Step 2: A solution of 2-formylphenylboronic acid (347 mg, 2.3 mmol) and ethyl 4- hydrazineylbenzoate (500 mg, 2.3 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 x 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H2O (10 mL, v/v = 1/1) afforded the desired product BN100395 (336 mg, yield 50%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.35 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.27 (s, 1H), 8.01 (d, J = 8.7 Hz, 2H), 7.87-7.76 (m, 4H), 7.69 (t, J = 7.2 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H) ppm. HPLC purity: 98.87% at 210 nm and 98.03% at 254 nm. MS: (M+H)⁺: m/z = 295.1. [00328] EXAMPLE 30 [00329] 2-[p-(Trifluoromethyl)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00330] The title compound was prepared by using the scheme and procedures shown below:

[00331] A solution of 2-formylphenylboronic acid (360 mg, 2.4 mmol) and (4- (trifluoromethyl)phenyl)hydrazine (4 mg, 2.4 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 x 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-[p-(Trifluoromethyl)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (552 mg, yield 79%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.37 (s, 1H), 8.44 (d, J = 7.5 Hz, 1H), 8.27 (s, 1H), 7.92-7.76 (m, 6H), 7.70 (dd, J = 10.6, 3.9 Hz, 1H) ppm. HPLC purity: 99.06% at 210 nm and 98.44% at 254 nm. MS: (M+H)⁺: m/z = 291.1. [00332] EXAMPLE 31 [00333] 2-[p-(Trifluoromethyl)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00334] The title compound was prepared by using the scheme and procedures shown below:

[00335] A solution of 2-formylphenylboronic acid (360 mg, 2.4 mmol) and (4- (trifluoromethyl)phenyl)hydrazine (422 mg, 2.4 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-[p-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (254 mg, yield 36%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.74 (s, 1H), 8.34 (d, J = 7.5 Hz, 1H), 8.10 (s, 1H), 7.79 (dt, J = 17.5, 7.9 Hz, 4H), 7.68 (dd, J = 10.5, 4.0 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H) ppm. HPLC purity: 99.57% at 210 nm and 99.30% at 254 nm. MS: (M+H)⁺: m/z = 291.0. [00336] EXAMPLE 32 [00337] 2-Methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00338] The title compound was prepared by using the scheme and procedures shown below:

[00339] A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and methylhydrazine (5 mL, 40% in water) in EtOH (10 mL) was stirred at room temperature for 2 hours. The reaction was monitored by TLC. After complete disappearance of compound 1, the mixture was filtered. The filter cake was washed with hexane and dried to give the title compound 2-methyl-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (417 mg, yield 40%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.54 (s, 1H), 8.26 (d, J = 7.5 Hz, 1H), 8.00 (s, 1H), 7.80-7.65 (m, 2H), 7.64-7.53 (m, 1H), 3.52 (s, 3H) ppm. HPLC purity: 98.36% at 210 nm and 98.60% at 254 nm. MS (M+H)⁺: m/z = 161.1. [00340] EXAMPLE 33 [00341] 2-[o-(Methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00342] The title compound was prepared by using the scheme and procedures shown below:

[00343] Step 1: To a solution of 2-(methylthio)aniline (1.39 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C, and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield (2- (methylthio)phenyl)hydrazine hydrogen chloride (910 mg, yield 48%) as a white solid, which was used for the next reaction without further purification. ¹HNMR (400 MHz, DMSO-d₆): δ 10.21 (s, 3H), 7.35 (d, J = 7.7 Hz, 1H), 7.24 (t, J = 7.7 Hz, 1H), 7.02 (t, J = 8.1 Hz, 2H), 2.42 (s, 3H) ppm. [00344] Step 2: A solution of 2-formylphenylboronic acid (720 mg, 4.8 mmol) and (2- (methylthio)phenyl)hydrazine hydrogen chloride (910 mg, 4.8 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) to afford the desired product 2-[o-(Methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (136 mg, yield 11%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.57 (s, 1H), 8.33 (d, J = 7.5 Hz, 1H), 8.11 (s, 1H), 7.79 (dt, J = 14.6, 7.5 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.37 (d, J = 3.5 Hz, 2H), 7.24 (d, J = 3.2 Hz, 2H), 2.33 (s, 3H) ppm. HPLC purity: 99.52% at 210 nm and 99.30% at 254 nm. MS: (M+H)⁺: m/z = 269.0. [00345] EXAMPLE 34 [00346] 2-Isopropyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00347] The title compound was prepared by using the scheme and procedures shown below:

[00348] A mixture of 1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (500 mg, 3.5 mmol), 2- iodopropane (1 mL), and K₂CO₃ (690 mg, 5 mmol) in DMF (10 mL) was stirred at 80 °C for 6 h. The reaction was monitored by TLC. After complete disappearance of 1,2-dihydro-2,3,1- benzodiazaborinin-1-ol, the solvent was evoprated under reduced pressure. The resulting solid was purified through silica chromatography eluting with PE/EtOAc (30:1 to 10:1) and further purified by prep-HPLC (0.5% TFA in MeCN) to afford the title compound 2-isopropyl-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (24 mg, yield 4%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.37 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.59-7.41 (m, 2H), 4.61 (dt, J = 13.2, 6.5 Hz, 1H), 1.34 (dd, J = 16.9, 6.3 Hz, 6H) ppm. HPLC purity: 99.77% at 210 nm and 99.58% at 254 nm. MS (M+H)⁺: m/z = 189.1. [00349] EXAMPLE 35 [00350] 8-Chloro-2-(p-fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00351] The title compound was prepared by using the scheme and procedures shown below:

[00352] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.6 mmol) in DMSO (10 mL) was added 4-fluorophenylhydrazine (202 mg, 1.6 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (6 mL) was added. The reaction mixture was stirred for another 2h and the solid was filtered to give the title compound 8-chloro-2-(p-fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (178 mg, yield 40.5%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.61 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.45 (s, 1H), 8.32 (d, J = 13.1 Hz, 1H), 7.59 (m, 2H), 7.28 (m, 2H) ppm. HPLC purity: 97.29% at 210 nm and 94.66% at 254 nm. MS: (M+H)⁺: m/z = 276.0. [00353] EXAMPLE 36 [00354] 8-Chloro-2-(o-fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00355] The title compound was prepared by using the scheme and procedures shown below:

[00356] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.6 mmol) in DMSO (10 mL) was added 2-fluorophenylhydrazine (202 mg, 1.6 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (6 mL) was added. The reaction mixture was stirred for another 2 hours and the solid was filtered to give the title compound 8-Chloro-2-(o-fluorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol (165 mg, yield 37.5%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.52 (s, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.45 (s, 1H), 8.28 (d, J = 4.8 Hz, 1H), 7.54-7.27 (m, 4H) ppm. HPLC purity: 97.43% at 210 nm and 95.07% at 254 nm. MS: (M+H)⁺: m/z = 276.0. [00357] EXAMPLE 37 [00358] 8-Chloro-2-(p-chlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00359] The title compound was prepared by using the scheme and procedures shown below:

[00360] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) at room temperature was added 4- chlorophenylhydrazine (142 mg, 1.0 mmol). The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8- chloro-2-(p-chlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (118 mg, yield 40.5%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.72 (s, 1H), 8.62 (d, J = 4.9 Hz, 1H), 8.46 (s, 1H), 8.31 (d, J = 4.8 Hz, 1H), 7.62 (d, J = 6.9 Hz, 2H), 7.50 (d, J = 8.6 Hz, 2H) ppm. HPLC purity: 97.63% at 210 nm and 94.12% at 254 nm. MS: (M+H)⁺: m/z = 291.9. [00361] EXAMPLE 38 [00362] 8-Chloro-2-(3,4-dichlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol structure [00363] The title compound was prepared by using the scheme and procedures shown below:

[00364] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) at room temperature was added 2,4- dichlorophenylhydrazine (176 mg, 1.0 mmol). The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 hours, the solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8- chloro-2-(3,4-dichlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (75 mg, yield 23.0%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.89 (s, 1H), 8.63 (d, J = 6.9 Hz, 1H), 8.48 (s, 1H), 8.31 (d, J = 4.4 Hz, 1H), 7.89 (s, 1H), 7.68 (m, 2H) ppm. HPLC purity: 98.21% at 210 nm and 97.01% at 254 nm. MS: (M+H)⁺: m/z = 324.0. [00365] EXAMPLE 39 [00366] 8-Chloro-2-(o-chlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00367] The title compound was prepared by using the scheme and procedures shown below:

[00368] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 2-chloroaniline (2.55 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the product 2-chlorophenylhydrazine (2.5 g, yield 88.0%) as a yellow oil. ¹HNMR (300 MHz, DMSO-d₆): δ 7.22-7.14 (m, 1H), 6.66-6.53 (m, 1H), 6.44 (s, 1H), 4.11 (s, 1H) ppm. [00369] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2- chlorophenylhydrazine (126 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-(o-chlorophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (55 mg, yield 18.9%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.44 (s, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.44 (s, 1H), 8.28 (d, J = 4.9 Hz, 1H), 7.67-7.59 (m, 1H), 7.53-7.40 (m, 3H) ppm. HPLC purity: 96.24% at 210 nm and 95.06% at 254 nm. MS: (M+H)⁺: m/z = 292.0. [00370] EXAMPLE 40 [00371] p-(8-Chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2- naphthyl)benzonitrile

[00372] The title compound was prepared by using the scheme and procedures shown below:

[00373] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 4-aminobenzonitrile (2.36 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the product 4-cyanophenylhydrazine (2.1 g, yield 79%) as a yellow solid. ¹HNMR (300 MHz, DMSO-d₆): δ 7.72 (s, 1H), 7.44 (d, J = 8.7 Hz, 2H), 6.79 (d, J = 8.7 Hz, 2H), 4.25 (s, 2H) ppm. [00374] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4- cyanophenylhydrazine (133 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product p-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2-naphthyl)benzonitrile (91 mg, yield 32.3%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.99 (s, 1H), 8.65 (d, J = 5.0 Hz, 1H), 8.51 (s, 1H), 8.33 (d, J = 5.0 Hz, 1H), 7.94-7.86 (m, 4H) ppm. HPLC purity: 99.51% at 210 nm and 92.75% at 254 nm. MS: (M+H)⁺: m/z = 283.1. [00375] EXAMPLE 41 [00376] Ethyl p-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2- naphthyl)benzoate

[00377] The title compound was prepared by using the scheme and procedures shown below:

[00378] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4-hydrazino-benzoic acid ethyl ester (180 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 hours, the solid was filtered and triturated with DMF and H₂O (8 mL, v/v = 1:3), then filtered to give the desired product ethyl p-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2-naphthyl)benzoate (41 mg, yield 12.5%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.91 (s, 1H), 8.64 (d, J = 5.0 Hz, 1H), 8.51 (s, 1H), 8.33 (d, J = 5.0 Hz, 1H), 8.04 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 4.34 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H) ppm. HPLC purity: 97.75% at 210 nm and 96.72% at 254 nm. MS: (M+H)⁺: m/z = 330.1. [00379] EXAMPLE 42 [00380] 8-Chloro-2-(m-tolyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00381] The title compound was prepared by using the scheme and procedures shown below:

[00382] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3-methylphenylhydrazine (122 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8- chloro-2-(m-tolyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (25 mg, yield 9.2%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.51 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.46 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.41-7.28 (m, 3H), 7.12 (d, J = 7.0 Hz, 1H), 2.37 (s, 3H) ppm. HPLC purity: 96.82% at 210 nm and 93.86% at 254 nm. MS: (M+H)⁺: m/z = 272.1. [00383] EXAMPLE 43 [00384] 2-(p-Bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00385] The title compound was prepared by using the scheme and procedures shown below:

[00386] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5-trimethyl-1,3,2- dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4-bromophenylhydrazine (187 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 hours, the solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 2-(p- bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (102 mg, yield 30%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.72 (s, 1H), 8.62 (d, J = 4.8 Hz, 1H), 8.47 (s, 1H), 8.31 (d, J = 3.7 Hz, 1H), 7.60 (m, 4H) ppm. HPLC purity: 97.04% at 210 nm and 95.15% at 254 nm. MS: (M+H)⁺: m/z = 335.9. [00387] EXAMPLE 44 [00388] 2-(m-Bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00389] The title compound was prepared by using the scheme and procedures shown below:

[00390] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 2-bromoaniline (3.44 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the 3- bromophenylhydrazine product (3.0 g, yield 80.6%) as a yellow oil. ¹HNMR (400 MHz, DMSO- d₆): δ 7.07-6.89 (m, 2H), 6.72-6.65 (m, 2H), 4.03 (s, 2H) ppm. [00391] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3- bromophenylhydrazine (186 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 2-(m-bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (113 mg, yield 33.7%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.79 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.47 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.81 (t, J = 1.8 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.49-7.40 (m, 2H) ppm. HPLC purity: 96.94% at 210 nm and 94.68% at 254 nm. MS: (M-H)-: m/z = 335.9. [00392] EXAMPLE 45 [00393] 8-Chloro-2-(o-trifluoromethoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00394] The title compound was prepared by using the scheme and procedures shown below:

[00395] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3- (trifluoromethoxy)phenylhydrazine (192 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and purified by pre-HPLC to give the desired product 8-chloro-2-(o- trifluoromethoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (49 mg, yield 14.4%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.54 (s, 1H), 8.65 (d, J = 4.9 Hz, 1H), 8.44 (s, 1H), 8.29 (d, J = 4.9 Hz, 1H), 7.62-7.46 (m, 4H) ppm. HPLC purity: 97.49% at 210 nm and 92.52% at 254 nm. MS: (M+H)⁺: m/z = 342.0. [00396] EXAMPLE 46 [00397] Ethyl m-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2- naphthyl)benzoate

[00398] The title compound was prepared by using the scheme and procedures shown below:

[00399] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of ethyl 3-aminobenzoate (3.30 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution and the mixture was extracted with EtOAc (2 × 300 mL). The mixture was filtered and the solid was dried under reduced pressure to give the ethyl- 3-hydrazinobenzoate product (3.30 g, yield 91.7%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 10.30 (s, 2H), 7.58-7.50 (m, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.22 (d, J = 7.6 Hz, 1H), 4.30 (q, J = 14.2, 7.1 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H) ppm. [00400] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added ethyl-3- hydrazinobenzoate (180 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product ethyl m-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2- naphthyl)benzoate (18 mg, yield 5.5%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.77 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 8.32 (d, J = 5.0 Hz, 1H), 8.22 (s, 1H), 7.88 (t, J = 9.1 Hz, 2H), 7.60 (t, J = 7.9 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H) ppm. HPLC purity: 99.66% at 210 nm and 98.99% at 254 nm. MS: (M+H)⁺: m/z =330.0. [00401] EXAMPLE 47 [00402] m-(8-Chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2- naphthyl)benzonitrile

[00403] The title compound was prepared by using the scheme and procedures shown below:

[00404] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3-cyanophenylhydrazine (133 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product m-(8- chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2-naphthyl)benzonitrile (93 mg, yield 33.0%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.90 (s, 1H), 8.64 (d, J = 5.0 Hz, 1H), 8.49 (s, 1H), 8.32 (d, J = 4.9 Hz, 1H), 8.05 (s, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.67 (t, J = 7.9 Hz, 1H) ppm. HPLC purity: 96.64% at 210 nm and 93.18% at 254 nm. MS: (M+H)⁺: m/z = 283.0. [00405] EXAMPLE 48 [00406] 8-Chloro-2-(p-trifluoromethoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00407] The title compound was prepared by using the scheme and procedures shown below:

[00408] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 2-(trifluoromethoxy)aniline (3.54 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure, and the residue was purified by column chromatography (PE/EA = 2/1) to give the (p- trifluoromethoxyphenyl)hydrazine product (0.60 g, yield 15.6%) as a yellow oil. ¹HNMR (400 MHz, DMSO-d₆): δ 7.06 (d, J = 8.5 Hz, 2H), 6.92 (s, 1H), 6.79 (d, J = 9.0 Hz, 2H), 4.02 (s, 2H) ppm. [00409] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2- (trifluoromethoxy)phenylhydrazine (192 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired 8-Chloro-2-(p-trifluoromethoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol product (63 mg, yield 18.5%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.76 (s, 1H), 8.64 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 8.33 (d, J = 5.0 Hz, 1H), 7.72 (dd, J = 9.6, 2.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H) ppm. HPLC purity: 96.54% at 210 nm and 94.77% at 254 nm. MS: (M-H)-: m/z =339.9. [00410] EXAMPLE 49 [00411] 1-Hydroxy-2-(3-methyl sulfanylphenyl)-7-(trifluoromethyl)-2,3,1- benzodiazaborinine

[00412] The title compound was prepared by using the scheme and procedures shown below:

[00413] Step 1: To an ice-cold aqueous solution of 3-methylsulfanylaniline (2.00 g, 14.37 mmol, 1.77 mL, 1 eq) in HCl (12 N, 10 mL) was added a solution of NaNO₂ (991 mg, 14.37 mmol, 1 eq) in H₂O (3 mL). The reaction mixture was stirred for 30 min at 0 °C. To the resulting mixture was added drop-wise a solution of SnCl₂.2H₂O (9.72 g, 43.10 mmol, 3 eq) in HCl (12 N, 20 mL). The reaction mixture was stirred for 4 h at 0 °C. The mixture was filtered and the filtrate was diluted with ice-water (w/w = 1/1) (50 mL). The aqueous phase pH was adjusted to 6-7 with 1 N NaOH and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 5/1) to give (3-methylsulfanylphenyl)hydrazine (1.20 g, 7.78 mmol, 54.16% yield) as a yellow oil. ¹H NMR (DMSO-d_6, 400 MHz) δ 7.01 (t, J = 8.0 Hz, 1H), 6.73 (s, 1H), 6.69 (s, 1H), 6.52 (d, J = 8.0 Hz, 1H), 8.45 (d, J = 7.6 Hz, 1H), 3.95 (s, 2H), 2.40 (s, 3H). [00414] Step 2: To a mixture of (3-methylsulfanylphenyl)hydrazine (100 mg, 648.37 umol, 1 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzaldehyde (200 mg, 666.49 umol, 1.03 eq) in EtOH (3 mL) was added NH₃.H₂O (182 mg, 1.30 mmol, 0.2 mL, 25% purity, 2.00 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Nano-micro Kromasil C18100*30mm 5um;mobile phase: [water(0.1%TFA)-ACN];B%: 55%-80%,10min) to give 1-hydroxy-2-(3-methyl sulfanylphenyl)-7-(trifluoromethyl)-2,3,1-benzodiazaborinine (106 mg, 303.52 umol, 46.81% yield, 96.25% purity) as a gray solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.36 (s, 1H), 8.85 (s, 1H), 8.35 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.47 (s, 1H), 7.37 (d, J = 4.8 Hz, 2H), 7.16-7.14 (m, 1H), 2.50 (s, 3H). MS (ESI): mass calcd. For C15H12BF3N2OS 336.07, m/z found 337.1 [M+H]⁺. HPLC: 96.25% (220 nm), 97.85% (254 nm). [00415] EXAMPLE 50 [00416] 8-Chloro-2-[m-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00417] The title compound was prepared by using the scheme and procedures shown below:

[00418] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 3-(trifluoromethyl)aniline (3.22 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the 3-(trifluoromethyl)phenylhydrazine product (2.8 g, yield 79.5%) as a yellow oil. ¹HNMR (300 MHz, DMSO-d₆): δ 7.26 (t, J = 7.9 Hz, 1H), 7.15 (s, 1H), 7.07 (s, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 7.5 Hz, 1H), 4.11 (s, 2H) ppm. [00419] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3- (trifluoromethyl)phenylhydrazine (176 mg, 1.0 mmol) at room temperature. The mixture was stirred at room temperature for 20 min. 6N HCl (3 mL) was added to the mixture. The reaction mixture was stirred for another 2 h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-[m-(trifluoromethyl)phenyl]- 1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (114 mg, yield 35.1%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.89 (s, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.51 (d, J = 0.5 Hz, 1H), 8.32 (d, J = 4.9 Hz, 1H), 8.02-7.90 (m, 2H), 7.70 (t, J = 7.9 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H) ppm. HPLC purity: 97.34% at 210 nm and 99.68% at 254 nm. MS: (M+H)⁺: m/z = 326.0. [00420] EXAMPLE 51 [00421] 8-Chloro-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00422] The title compound was prepared by using the scheme and procedures shown below:

[00423] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5-trimethyl-1,3,2- dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4-(methylthio)-phenylhydrazine (154 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was purified by pre- HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 8-chloro-2-[m- (methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (35 mg, yield 11.6%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.62 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.46 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.42-7.32 (m, 2H), 7.21-7.15 (m, 1H), 2.46 (s, 3H) ppm. HPLC purity: 96.81% at 210 nm and 96.90% at 254 nm. MS: (M+H)⁺: m/z = 304.1. [00424] EXAMPLE 52 [00425] 8-Chloro-2-(2-thienyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00426] The title compound was prepared by using the scheme and procedures shown below:

[00427] Step 1: To a solution of CuI (190 mg, 1.0 mmol) in DMF (10 mL) was added 1,10- phenanthroline (216 mg, 1.2 mmol), 2-iodothiophene (1.0 g, 5.0 mmol), tert-butyl hydrazinecarboxylate (792 mg, 6.0 mmol) and Cs2CO3 (3.3 g, 10.0 mmol) under N2. The mixture was heated at 70 °C overnight and then cooled to r.t and poured into water. The mixture was extracted with EtOAc (x 2). The organic layer was washed with brine, water, dried over Na₂SO₄, and concentrated to give the crude product (tert-Butyl )2-(2-thienyl)carbazate (1.2 g, contain DMF) as a brown solution. ¹H NMR (400 MHz, DMSO-d₆): δ 6.90 (dd, J = 5.3, 1.6 Hz, 1H), 6.87 – 6.76 (m, 2H), 5.38 (s, 2H), 1.51 (s, 9H) ppm. [00428] Step 2: Crude (tert-butyl )2-(2-thienyl)carbazate (1.2 g, crude) was dissolved in HCl/dioxane (10 mL, 4 N) and stirred for 4 h at room temperature. The mixture was concentrated and the residue was dissolved in DMSO (5 mL). 2-[2-Chloro-4-(1,3-dioxolan-2-yl)- 3-pyridyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (300 mg) was added and the reaction was stirred for 1 h. 6 N HCl (2 mL) was added and the mixture was stirred for another 30 min, poured into water, and extracted with EtOAc. The organic layer was washed with brine, water and concentrated. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 8-chloro-2-(2-thienyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (22 mg, yield 1.7%) as a green solid. ¹H NMR (400 MHz, DMSO-d₆): δ 10.32 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.47 (s, 1H), 8.34 (d, J = 4.7 Hz, 1H), 7.43 (dd, J = 3.8, 1.3 Hz, 1H), 7.17 (dd, J = 5.5, 1.3 Hz, 1H), 6.98 (dd, J = 5.5, 3.8 Hz, 1H) ppm. HPLC purity: 95.27% at 210 nm and 98.70% at 254 nm. MS: (M+H)⁺: m/z = 264.0. [00429] EXAMPLE 53 [00430] 8-Chloro-2-(p-nitrophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00431] The title compound was prepared by using the scheme and procedures shown below:

[00432] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.6 mmol) in DMSO (10 mL) was added 4-nitrophenylhydrazine (245 mg, 1.6 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (6 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with DMF and H₂O (10 mL, v/v = 8:2), then filtered to give the title compound 8-chloro- 2-(p-nitrophenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (86 mg, yield 17.8%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 10.03 (s, 1H), 8.65 (d, J = 5.0 Hz, 1H), 8.52 (s, 1H), 8.35-8.29 (m, 3H), 8.00-7.94 (m, 2H) ppm. MS: (M+H)⁺: m/z = 303.0. [00433] EXAMPLE 54 [00434] 8-Chloro-2-[p-(methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00435] The title compound was prepared by using the scheme and procedures shown below:

[00436] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.6 mmol) in DMSO (10 mL) was added (4- (methylthio)phenyl)hydrazine (245 mg, 1.6 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (6 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and it was purified by pre-HPLC (0.1% TFA) to give the desired product 8- chloro-2-[p-(methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (53 mg, yield 11.0%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.58 (s, 1H), 8.61 (d, J = 5.0 Hz, 1H), 8.45 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.53 (d, J = 8.6 Hz, 2H), 7.34 (d, J = 8.6 Hz, 2H), 2.52 (s, 3H) ppm. HPLC purity: 97.05% at 210 nm and 95.84% at 254 nm. MS: (M+H)⁺: m/z = 303.9. [00437] EXAMPLE 55 [00438] 2-(p-Chlorophenyl)-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00439] The title compound was prepared by using the scheme and procedures shown below:

[00440] To a solution of a 2-acetylphenylboronic acid (328 mg, 2.0 mmol) in DMSO (10 mL) was added 4-chlorophenylhydrazine (284 mg, 2.0 mmol) at room temperature. The reaction was stirred for 30 min and poured into water. The solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 2-(p-chlorophenyl)-4- methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (309 mg, yield 61.3%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.98 (s, 1H), 8.42 (d, J = 7.2 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.83-7.76 (m, 1H), 7.72-7.61 (m, 3H), 7.49-7.40 (m, 2H), 2.55 (s, 3H). HPLC purity: 97.92% at 210 nm and 98.74% at 254 nm. MS: (M+H)⁺: m/z = 271.1. [00441] EXAMPLE 56 [00442] 2-(p-Chlorophenyl)-6-fluoro-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol

[00443] The title compound was prepared by using the scheme and procedures shown below:

[00444] Step 1: To a solution of 2-bromo-5-fluoroacetophenone (2.0 g, 9.2 mmol) in dioxane (30 mL) was added KOAc (1.35 g, 13.8 mmol), bis(pinacolato)diboron (3.51 g, 13.8 mmol) and (dppf)PdCl₂ (1.47 g, 1.8 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to reflux and stirred for 3 h, then the solid was filtered and the filtrate was concentrated under reduce pressure. The residue was was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the 1-[5-fluoro-2-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-ethanone product (1.1 g, yield 45.3%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 7.85 (d, J = 9.3 Hz, 1H), 7.53-7.40 (m, 2H), 2.60 (s, 3H), 1.32 (s, 12H) ppm. [00445] Step 2: To a solution of 1-[5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-ethanone (500 mg, 1.9 mmol) in DMSO (10 mL) was added 4- chlorophenylhydrazine (270 mg, 1.9 mmol) at room temperature and the mixture was stirred for 20 min. 6N HCl (5 mL) was added and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 2-(p-chlorophenyl)-6-fluoro-4-methyl-1,2-dihydro- 2,3,1-benzodiazaborinin-1-ol (74 mg, yield 13.5%) as a white solid. ¹H NMR (400 MHz, DMSO- d₆): δ 9.04 (s, 1H), 8.48 (dd, J = 8.3, 6.5 Hz, 1H), 7.70-7.52 (m, 4H), 7.45 (d, J = 8.8 Hz, 2H), 2.53 (s, 3H) ppm. HPLC purity: 98.73% at 210 nm and 98.73% at 254 nm. MS: (M+H)⁺: m/z = 289.0. [00446] EXAMPLE 57 [00447] 2-(p-Chlorophenyl)-4-ethyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00448] The title compound was prepared by using the scheme and procedures shown below:

[00449] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- propanone (500 mg, 1.92 mmol) in DMSO (5 mL) was added (4-chlorophenyl)hydrazine hydrochloride (343 mg, 1.92 mmol) at room temperature, and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN) to give the desired product 2-(p-chlorophenyl)-4-ethyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (96 mg, yield 17.8%) as a white powder. ¹H NMR (400 MHz, DMSO-d₆): δ 8.98 (s, 1H), 8.42 (d, J = 7.6 Hz, 1H), 8.01-7.82 (m, 2H), 7.70-7.67 (m, 1H), 7.58 (t, J = 7.3 Hz, 1H), 7.29 (q, J = 8.9 Hz, 3H), 3.01-2.96 (m, 2H), 1.31-1.26 (m, 3H) ppm. MS: (M+H)⁺: m/z = 285.1. HPLC: Purity at 210 nm = 98.94% and purity at 254 nm = 98.44%. [00450] EXAMPLE 58 [00451] 8-Chloro-2-(m-trifluoromethoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00452] The title compound was prepared by using the scheme and procedures shown below:

[00453] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3-trifluoromethoxy- phenylhydrazine (192 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 h, then it was poured into water and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the product 8-chloro-2-(m-trifluoromethoxyphenyl)-1,2-dihydro- 2,3,7-triaza-1-bora-1-naphthol (39.5 mg, yield 11.5%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.87 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.49 (s, 1H), 8.32 (d, J = 5.0 Hz, 1H), 7.70 (d, J = 9.2 Hz, 1H), 7.64 (s, 1H), 7.58 (t, J = 8.2 Hz, 1H), 7.28 (d, J = 7.9 Hz, 1H) ppm. HPLC purity: 99.02% at 210 nm and 97.22% at 254 nm. MS: (M+H)⁺: m/z = 342.0. [00454] EXAMPLE 59 [00455] 8-Chloro-2-[p-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00456] The title compound was prepared by using the scheme and procedures shown below:

[00457] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2-trifluoromethyl- phenylhydrazine (176 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 h, then it was poured into water and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the product 8-chloro-2-[p-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (44.4 mg, yield 13.7%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.90 (s, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.51 (s, 1H), 8.34 (d, J = 5.0 Hz, 1H), 7.88-7.81 (m, 4H) ppm. HPLC purity: 95.15% at 210 nm and 91.62% at 254 nm. MS: (M+H)⁺: m/z = 326.0. [00458] EXAMPLE 60 [00459] 6-Fluoro-4-methyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00460] The title compound was prepared by using the scheme and procedures shown below:

[00461] To a solution of 1-[5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-ethanone (500 mg, 1.9 mmol) in DMSO (10 mL) was added 3- (methylthio)phenylhydrazine (293 mg, 1.9 mmol) at room temperature, and the mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 6-fluoro-4-methyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (49 mg, yield 8.6%) as a light yellow solid. ¹H NMR (400 MHz, DMSO- d₆): δ 8.94 (s, 1H), 8.51-8.43 (m, 1H), 7.66 (d, J = 10.5 Hz, 1H), 7.56 (t, J = 8.8 Hz, 1H), 7.47 (s, 1H), 7.39-7.29 (m, 2H), 7.11 (d, J = 6.8 Hz, 1H), 2.53 (s, 3H), 2.47 (s, 3H) ppm. HPLC purity: 96.93% at 210 nm and 97.18% at 254 nm. MS: (M+H)⁺: m/z = 301.1. [00462] EXAMPLE 61 [00463] 2-(p-Chlorophenyl)-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00464] The title compound was prepared by using the scheme and procedures shown below:

[00465] To a solution of 1-[o-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- butanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added (4-chlorophenyl) hydrazine hydrochloride (325 mg, 1.82 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 2- (p-chlorophenyl)-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (92 mg, yield 17.8%) as a white powder. ¹H NMR (400 MHz, DMSO-d₆): δ 8.98 (s, 1H), 8.42 (d, J = 7.4 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.79 (t, J = 7.7 Hz, 1H), 7.66 (t, J = 6.9 Hz, 2H), 7.45 (d, J = 8.7 Hz, 2H), 7.26 (d, J = 3.4 Hz, 1H), 3.00-2.79 (m, 2H), 1.74 (dd, J = 14.9, 7.4 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H) ppm. MS: (M+H)⁺: m/z = 299.1. HPLC purity: 99.48% at 210 nm and 98.67% at 254 nm. [00466] EXAMPLE 62 [00467] 2-(p-Chlorophenyl)-4-isopropyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00468] The title compound was prepared by using the scheme and procedures shown below:

[00469] To a solution of 2-methyl-1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-propanone (500 mg, 1.8 mmol) in DMSO (10 mL) was added 4- chlorophenylhydrazine (256 mg, 1.8 mmol) at room temperature, and the mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H2O) to give the desired product 2-(p-chlorophenyl)-4-isopropyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (23 mg, yield 4.3%) as a white solid. ¹H NMR (300 MHz, DMSO-d₆): δ 9.01 (s, 1H), 8.43 (d, J = 7.5 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.87-7.60 (m, 4H), 7.46 (d, J = 8.8 Hz, 2H), 3.79-3.51 (m, 1H), 1.30 (d, J = 6.6 Hz, 6H) ppm. HPLC purity: 99.10% at 210 nm and 99.16% at 254 nm. MS: (M+H)⁺: m/z = 299.1. [00470] EXAMPLE 63 [00471] 2-[m-(Methylthio)phenyl]-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00472] The title compound was prepared by using the scheme and procedures shown below:

[00473] Step 1: To a solution of a 2-bromobenzaldehyde (10 g, 54 mmol) in THF (80 mL) was added ethylmagnesium bromide (22 mL, 65 mmol) at 0 °C under an inert nitrogen atmosphere. After addition, the reaction was allowed to warm to room temperature and stirred for 1h, then quenched with sat. NH₄Cl and extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 50/1) to give the product o-bromo(1- methylbutyl)benzene (6 g, yield 78.5%) as a light oil. ¹H NMR (400 MHz, DMSO-d₆): δ 7.55 (m, 2H), 7.38 (dd, J = 11.0, 4.0 Hz, 1H), 7.17 (td, J = 7.8, 1.7 Hz, 1H), 5.34 (d, J = 4.6 Hz, 1H), 4.89- 4.74 (m, 1H), 1.63-1.52 (m, 1H), 1.51-1.29 (m, 3H), 0.90 (t, J = 7.2 Hz, 3H) ppm. [00474] Step 2: To a solution of o-bromo(1-methylbutyl)benzene (6 g, 26 mmol) in DCM (30 mL) was added Dess-Martin reagent (11 g, 26 mmol) in small portions at 0 °C. The reaction was stirred at room temperature for 1h, then the solid was filtered and washed with DCM. The organic layer was concentrated under reduced pressure, and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 50/1) to give the product 1-(o-bromophenyl)-1- butanone (5.44 g, yield 92%) as a colorless oil. ¹H NMR (400 MHz, DMSO-d₆):) δ 7.74 (dd, J = 7.9, 0.8 Hz, 1H), 7.62 (dd, J = 7.5, 1.7 Hz, 1H), 7.53 (td, J = 7.5, 1.1 Hz, 1H), 7.46 (td, J = 7.7, 1.8 Hz, 1H), 2.92 (t, J = 7.1 Hz, 2H), 1.66 (h, J = 7.3 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H) ppm. [00475] Step 3: To a solution of 1-(o-bromophenyl)-1-butanone (5.44 g, 24 mmol) in dioxane (80 mL) was added KOAc (7.1 g, 72 mmol), bis(pinacolato)diboron (9.2 g, 36 mmol), and Pd(dppf)Cl₂ (2 g, 2.47 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 80 °C and stirred for 2h, then the solid was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/0 to 50/1) to give the product 1-[o-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl]-1-butanone (5.2 g, yield 79%) as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ 7.72 (d, J = 7.7 Hz, 1H), 7.49-7.41 (m, 2H), 7.36-7.32 (m, 1H), 2.86 (t, J = 7.3 Hz, 2H), 1.70 (dd, J = 14.7, 7.4 Hz, 2H), 1.36 (s, 12H), 0.93 (t, J = 7.4 Hz, 3H) ppm. [00476] Step 4: To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]- 1-butanone (500 mg, 1.8 mmol) in DMSO (5 mL) was added 3-(methylthio)phenylhydrazine (277 mg, 1.8 mmol) at room temperature, and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 2-[m- (methylthio)phenyl]-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (48 mg, yield 8.6%) as an oil. ¹H NMR (400 MHz, DMSO-d₆): δ 8.42 (d, J = 7.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.3 Hz, 1H), 7.53 (s, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 2.93 (t, J = 7.5 Hz, 2H), 1.75 (dd, J = 14.7, 7.4 Hz, 2H), 1.01 (t, J = 7.3 Hz, 3H) ppm. MS: (M+H)⁺: m/z = 311.1. HPLC purity: 97.20% at 210 nm and 98.11% at 254 nm. [00477] EXAMPLE 64 [00478] 2-(p-Chlorophenyl)-4-cyclopropyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00479] The title compound was prepared by using the scheme and procedures shown below:

[00480] To a solution of cyclopropyl[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]methanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added 4- chlorophenylhydrazine hydrogen chloride (330 mg, 1.83 mmol) at room temperature, and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre- HPLC to give the desired product 2-(p-chlorophenyl)-4-cyclopropyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (96 mg, yield 17.8%) as a grey solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.03 (s, 1H), 8.42 (d, J = 7.5 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H), 7.67 (dd, J = 18.8, 8.1 Hz, 3H), 7.44 (d, J = 8.4 Hz, 2H), 2.41 (d, J = 4.8 Hz, 1H), 0.96 – 0.79 (m, 4H) ppm. MS: (M+H)⁺: m/z = 297.0. HPLC purity: 95.49% at 210 nm and 94.32% at 254 nm. [00481] EXAMPLE 65 [00482] 4-Cyclopropyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00483] The title compound was prepared by using the scheme and procedures shown below:

[00484] Step 1: To a solution of a 2-bromobenzaldehyde (10 g, 54 mmol) in THF (80 mL) was added ethylmagnesium bromide (22 mL, 65 mmol) at 0 °C under an inert nitrogen atmosphere. After addition, the reaction was allowed to warm to room temperature and stirred for 1h, then quenched by sat. NH₄Cl and extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product (o- bromophenyl)cyclopropylmethanol (7.5 g, yield 65%) as a light oil. ¹H NMR (400 MHz, DMSO- d₆): δ 7.64-7.47 (m, 2H), 7.38 (t, J = 7.4 Hz, 1H), 7.26-7.08 (m, 1H), 5.32 (d, J = 4.5 Hz, 1H), 4.63 (t, J = 5.1 Hz, 1H), 1.17-1.03 (m, 1H), 0.50-0.23 (m, 4H) ppm. [00485] Step 2: To a solution of (o-bromophenyl)cyclopropylmethanol (7.5 g, 34.9 mmol) in DCM (30 mL) was added Dess-Martin reagent (14.7 g, 34.9 mmol) in small portions at 0 °C. The reaction was stirred at room temperature for 1h, then the solid was filtered and washed with DCM. The organic layer was concentrated under reduced pressure, and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 50/1) to give the product (o- bromophenyl)cyclopropylmethanone (5.2 g, yield 70.7%) as a colorless oil. ¹H NMR (400 MHz, DMSO-d₆): δ 7.66 (d, J = 7.9 Hz, 1H), 7.49 (dd, J = 7.5, 1.6 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.40-7.33 (m, 1H), 2.42-2.33 (m, 1H), 1.10-0.99 (m, 4H) ppm. [00486] Step 3: To a solution of (o-bromophenyl)cyclopropylmethanone (5.26 g, 24.7 mmol) in dioxane (80 mL) was added KOAc (7.27 g, 74.1 mmol), bis(pinacolato)diboron (9.4 g, 37.05 mmol), and (dppf)PdCl₂ (2 g, 2.47 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 80 °C and stirred for 2h, then the solid was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/0 to 50/1) to give the product cyclopropyl[o- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone (4.8 g, yield 75%) as a yellow oil. The crude product was used in the next step without further purification. [00487] Step 4: To a solution of cyclopropyl[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]methanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added [m- (methylthio)phenyl]hydrazine (282 mg, 1.82 mmol) at room temperature and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 4-cyclopropyl-2-[m-(methylthio)phenyl]-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (63 mg, yield 18%) as a yellow oil. ¹H NMR (400 MHz, DMSO-d₆): δ 8.88-8.58 (m, 1H) 8.42 (d, J = 7.5 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.4 Hz, 1H), 7.52 (s, 1H), 7.45-7.27 (m, 2H), 7.09 (d, J = 7.5 Hz, 1H), 2.50 (s, 3H), 2.45-2.34 (m, 1H), 0.99-0.79 (m, 4H). MS: (M+H)⁺: m/z = 309.1. HPLC: Purity HPLC purity: 91.18% at 210 nm and 92.95% at 254 nm. [00488] EXAMPLE 66 [00489] 4-Isopropyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol

[00490] The title compound was prepared by using the scheme and procedures shown below:

[00491] Step 1: To a solution of a 2-bromobenzaldehyde (18.5 g, 0.10 mol) in THF (100 mL) was added isopropylmagnesium bromide (120 mL, 0.12 mol) at 0 °C under an inert nitrogen atmosphere. After addition, the reaction was allowed to warm to room temperature and stirred for 1h, then quenched with sat. NH₄Cl and extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product o-bromo(1,2- dimethylpropyl)benzene (5.4 g, yield 23.7%) as a light oil. MS: (M-OH)⁺: m/z = 211.0. [00492] Step 2: To a solution of o-bromo(1,2-dimethylpropyl)benzene (5.4 g, 24.7 mmol) in DCM (80 mL) was added Dess-Martin reagent (10.0 g, 24.7 mmol) in small portions at 0 °C. The reaction was stirred at room temperature for 1h, then the solid was filtered and washed with DCM. The organic layer was concentrated under reduced pressure, and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product 1-(o- bromophenyl)-2-methyl-1-propanone (4.5 g, yield 80.6%) as a light oil. ¹H NMR (300 MHz, DMSO-d₆): δ 7.70 (d, J = 7.8 Hz, 1H), 7.55-7.36 (m, 3H), 3.28-3.12 (m, 1H), 1.09 (d, J = 6.9 Hz, 6H) ppm. [00493] Step 3: To a solution of 1-(o-bromophenyl)-2-methyl-1-propanone (5.40 g, 22.5 mmol) in dioxane (80 mL) was added KOAc (6.61 g, 67.5 mmol), bis(pinacolato)diboron (8.59 g, 33.8 mmol), and (dppf)PdCl₂ (3.67 g, 4.5 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 80 °C and stirred for 5h, then the solid was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product 2-methyl-1-[o- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-propanone (4.5 g, yield 69.4%) as a yellow solid. MS: (M-OH)⁺: m/z = 275.2. [00494] Step 4: To a solution of 2-methyl-1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-propanone (500 mg, 1.8 mmol) in DMSO (10 mL) was added 3- (methylthio)phenylhydrazine (277 mg, 1.8 mmol) at room temperature, and the mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-isopropyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1- ol (144 mg, yield 25.9%) as a yellow oil. ¹H NMR (400 MHz, DMSO-d₆): δ 8.94 (s, 1H), 8.43 (d, J = 6.9 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.85-7.74 (m, 1H), 7.66 (t, J = 7.1 Hz, 1H), 7.61 (t, J = 1.9 Hz, 1H), 7.53-7.44 (m, 1H), 7.35 (t, J = 7.9 Hz, 1H), 7.12-7.06 (d, J = 7.8, 1H), 3.68-3.56 (m, 1H), 1.31 (d, J = 6.7 Hz, 6H) ppm. HPLC purity: 96.68% at 210 nm and 95.17% at 254 nm. MS: (M+H)⁺: m/z = 311.2. [00495] EXAMPLE 67 [00496] 2-[m-(Cyclopropylthio)phenyl]-6-fluoro-4-methyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00497] The title compound was prepared by using the scheme and procedures shown below:

[00498] To a solution of 1-[5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-ethanone (500 mg, 1.9 mmol) in DMSO (10 mL) was added 3- (isopropylthio)phenylhydrazine (346 mg, 1.9 mmol) at room temperature, and the mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 2-[m-(cyclopropylthio)phenyl]-6-fluoro-4-methyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (46 mg, yield 7.5%) as a light yellow solid. ¹H NMR (400 MHz, DMSO- d₆): δ 8.97 (s, 1H), 8.47 (dd, J = 8.4, 6.4 Hz, 1H), 7.66 (dd, J = 10.7, 2.3 Hz, 1H), 7.61-7.51 (m, 2H), 7.42-7.30 (m, 2H), 7.21 (dd, J = 5.3, 3.3 Hz, 1H), 2.54 (s, 3H), 2.35-2.25 (m, 1H), 1.14-1.06 (m, 2H), 0.67-0.54 (m, 2H) ppm. HPLC purity: 99.70% at 210 nm and 99.71% at 254 nm. MS: (M+H)⁺: m/z = 327.1. [00499] EXAMPLE 68 [00500] 4-Cyclopropyl-2-[p-(cyclopropylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00501] The title compound was prepared by using the scheme and procedures shown below:

[00502] To a solution of cyclopropyl[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]methanone (540 mg, 2 mmol) in DMSO (5 mL) was added [m- (cyclopropylthio)phenyl]hydrazine (360 mg, 2 mmol) at room temperature, and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 4-cyclopropyl-2-[p-(cyclopropylthio)phenyl]- 1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (72 mg, yield 11%) as a brown solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.91 (s, 1H), 8.39-8.19 (m, 2H), 7.81-7.61 (m, 3H), 7.39-7.10 (m, 3H), 2.39- 2.24 (m, 2H), 1.10-1.02 (m, 2H), 0.89-0.86 (m, 4H), 0.60-0.59 (m, 2H) ppm. MS: (M-H)-: m/z = 333.0. HPLC: 96.81 % at 210 nm and 97.01 % at 254 nm. [00503] EXAMPLE 69 [00504] 4-Ethyl-2-[m-(isopropylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1- ol

[00505] The title compound was prepared by using the scheme and procedures shown below:

[00506] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- propanone (500 mg, 1.92 mmol) in DMSO (5 mL) was added (3- (cyclopropylthio)phenyl)hydrazine (345 mg, 1.92 mmol) at room temperature, and the mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 4-ethyl-2-[m-(isopropylthio)phenyl]-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (100 mg, yield 15%) as an off-white solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.91 (s, 1H), 8.37 (d, J = 6.9 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.76–7.71(m, 1H), 7.63–7.59 (m, 2H), 7.51–7.48 (m, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.15–7.12 (m, 1H), 3.48- 3.40 (m, 1H), 2.94 (q, J = 7.4 Hz, 2H), 1.25-1.23 (m, 9H) ppm. MS: (M+H)⁺: m/z = 325.1. HPLC purity: 99.29% at 210 nm and 96.54% at 254 nm. [00507] EXAMPLE 70 [00508] 1-Hydroxy-2-phenyl-thieno[3,2-d]diazaborinine

[00509] The title compound was prepared by using the scheme and procedures shown below:

[00510] Step 1: To a solution of 3-bromothiophene (19.00 g, 116.54 mmol, 10.92 mL, 1 eq) in THF (200 mL) was added LDA (2 M, 87.40 mL, 1.5 eq) dropwise at -60 °C under N₂. The mixture was stirred at -60 °C for 1 h under N₂. Then to the reaction mixture was added DMF (43.00 g, 582.70 mmol, 45 mL, 5 eq) in one portion at -60 °C. The reaction mixture was stirred at -60 °C for 5 min and then warmed to 25 °C. The reaction mixture was quenched with sat. NH₄Cl (200 mL) and extracted with EtOAc (100 mL x 3). The combined organics were washed with brine (100 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash silica gel chromatography (ISCO®; 220 g SepaFlash® Silica Flash Column, Eluent of 0~5% Ethyl acetate/Petroleum ethergradient @ 150 mL/min) to give 3- bromothiophene-2-carbaldehyde (22.00 g, 115.16 mmol, 98.81% yield) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz) δ 9.98 (s, 1H), 7.72 (d, J = 5.2 Hz, 1H), 7.15 (d, J = 5.2 Hz, 1H). [00511] Step 2: To a solution of 3-bromothiophene-2-carbaldehyde (22.00 g, 115.16 mmol, 1 eq) in dioxane (200 mL) was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2 -dioxaborolane (146.00 g, 575.78 mmol, 5 eq), KOAc (33.90 g, 345.47 mmol, 3 eq) and Pd(dppf)Cl₂ (4.21 g, 5.76 mmol, 0.05 eq) in turns. The mixture was stirred at 80 °C for 16 h. The reaction mixture was filtered through a pad of CELITE and the filtrate was concentrated in vacuo. The residue was purified by flash silica gel chromatography (ISCO®; 220 g SepaFlash® Silica Flash Column, Eluent of 0~20% Ethyl acetate/Petroleum ethergradient @ 150 mL/min) to give 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carbaldehyde (25.00 g, crude) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 10.28 (s, 1H), 8.11 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 1.33 (s, 12H). [00512] Step 3: To a solution of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene- 2-carbaldehyde (600 mg, 2.52 mmol, 1 eq) and phenylhydrazine (327 mg, 3.02 mmol, 297 uL, 1.2 eq) in EtOH (5 mL) was added NH₃ ^.H₂O (1.77 g, 12.60 mmol, 1.94 mL, 25% purity, 5 eq) in one portion at 25 °C. The mixture was stirred at 60 °C for 2 h. The reaction mixture was concentrated in vacuo. The residue was purified by Prep-HPLC (column: Xtimate C18 150*25mm*5um; mobile phase: [water (0.04% NH₃H₂O+10mM NH₄HCO₃)-ACN]; B%: 38%-68%, 10.5min) to give 1-hydroxy-2-phenyl-thieno[3,2-d]diazaborinine (25 mg, 108.73 umol, 4.32% yield, 99.2% purity) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 8.90 (s, 1H), 8.38 (s, 1H), 7.88 (d, J = 4.8 Hz, 1H), 7.80 (d, J = 5.2 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H). MS (ESI): mass calcd. For C₁₁H₉BN₂OS 228.05, m/z found 227.1 [M-H]-. HPLC: 99.2% (220 nm), 97.9% (254 nm). [00513] EXAMPLE 71 [00514] 1-Hydroxy-7- (trifluoromethyl)-2-[3-(trifluoromethylsulfanyl)phenyl]-2,3,1- benzodiazaborinine

[00515] The title compound was prepared by using the scheme and procedures shown below:

[00516] Step 1: To a mixture of 2-bromo-4-(trifluoromethyl)benzaldehyde (1.00 g, 3.95 mmol, 1 eq) in dioxane (15 mL) was added B₂Pin₂ (1.51 g, 5.93 mmol, 1.5 eq), KOAc (969 mg, 9.88 mmol, 2.5 eq), and Pd(dppf)Cl₂ (289 mg, 395.23 umol, 0.1 eq) in one portion at 25 °C under N₂, then the mixture was heated to 80 °C and stirred for 16 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 3/1) to give 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzaldehyde (1.00 g, 3.33 mmol, 84.32% yield) as a yellow solid. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 10.65 (s, 1H), 8.15 (s, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 1.41 (s, 12H). [00517] Step 2: To a mixture of N-hydroperoxy-3-[(3-nitrophenyl)disulfanyl]aniline (4.50 g, 14.50 mmol, 1 eq) in THF (70 mL) was added NaBH₄ (1.92 g, 50.75 mmol, 3.5 eq) in portions at 0 °C. The reaction mixture was stirred at 20 °C for 2 h. The reaction mixture was poured into ice-water (w/w = 1/1) (150 mL) and adjusted pH to 3-4 with HCl (2 N). Then the aqueous layer was extracted with EtOAc (30 mL x 3). The combined organic phase was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuum. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=5/1 to 3/1) to give 3- nitrobenzenethiol (3.80 g, crude) as a yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 8.13 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 8.4 Hz, 1H), 3.72 (s, 1H). [00518] Step 3: To a solution of 3-nitrobenzenethiol (3.80 g, 24.49 mmol, 819.67 uL, 1 eq) in DMF (70 mL) was added NaH (1.47 g, 36.73 mmol, 60% purity, 1.5 eq) portionwise at 0 °C. The mixture was stirred at this temperature for 10 min. Then trifluoro(iodo)methane (28.79 g, 36.73 mmol, 1.5 eq) was added dropwise and the resulting reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was poured into ice-water (w/w = 1/1) (150 mL), the pH was adjusted to 3-4 with HCl (2 N), and the mixture was extracted with EtOAc (40 mL x 3). The combined organic phases was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 1-nitro-3-(trifluoromethylsulfanyl)benzene (5.00 g, 22.40 mmol, 91.49% yield) as a yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 8.54 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H). [00519] Step 4: To a mixture of 1-nitro-3-(trifluoromethylsulfanyl)benzene (4.7 g, 21.06 mmol, 1 eq) and NH₄Cl (4.51 g, 84.24 mmol, 4 eq) in EtOH (55 mL)/H₂O (15 mL) was added Fe (4.70 g, 84.24 mmol, 4 eq) in 4 portions at 25 °C under N2. The mixture was heated to 80 °C and stirred for 2 h. The reaction mixture was filtered through a pad of CELITE and the filtrate was concentrated under reduced pressure to remove the solvents. The residue was suspended in EtOAc (300 mL) and filtered. The filter cake was discarded to remove the inorganic salt. The filtrate was dried over Na₂SO₄, filtered, and concentrated in vacuo to give 3- (trifluoromethylsulfanyl)aniline (4.00 g, 20.71 mmol, 98.31% yield) as a yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 7.19 (t, J = 8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.97 (s, 1H), 6.78 (dd, J = 8.0, 2.4 Hz, 1H), 3.77 (s, 2H). [00520] Step 5: To an ice-cold solution of 3-(trifluoromethylsulfanyl)aniline (1.00 g, 5.18 mmol, 884.96 uL, 1 eq) in HCl (12 N, 10 mL) was added drop-wise a solution of NaNO₂ (357 mg, 5.18 mmol, 1 eq) in H₂O (1 mL). The reaction was stirred for 30 min at 0 °C. To the mixture above was added drop-wise a solution of SnCl₂.2H₂O (3.50 g, 15.53 mmol, 3 eq) in HCl (12 N, 10 mL). The reaction mixture was stirred for 4 h at 0 °C. The mixture was filtered and the filtrate was diluted with ice-water (w/w = 1/1) (20 mL). The aqueous phase adjusted pH to 6-7 with 1 N NaOH and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 3/1) to give [3-(trifluoromethylsulfanyl)phenyl]hydrazine (1.00 g, 4.80 mmol, 92.79% yield) as a brown solid. ¹H NMR (DMSO-d_6, 400 MHz) δ 10.12 (s, 2H), 8.54 (s, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.16 (d, J = 3.2 Hz, 1H). [00521] Step 6: To a mixture of [3-(trifluoromethylsulfanyl)phenyl]hydrazine (200 mg, 960.60 umol, 1.06 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4- (trifluoromethyl)benzaldehyde (300 mg, 999.73 umol, 1.1 eq) in EtOH (5 mL) was added NH₃.H₂O (273 mg, 1.95 mmol, 0.3 mL, 25% purity, 2.14 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18150*25mm*5um;mobile phase: [water(10mM NH4HCO3)-ACN];B%: 75%- 95%,10.5min) to give 1-hydroxy-7- (trifluoromethyl)-2-[3-(trifluoromethylsulfanyl)phenyl]-2,3,1- benzodiazaborinine (48 mg, 121.91 umol, 13.41% yield, 99.08% purity) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.61 (s, 1H), 8.86 (s, 1H), 8.40 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.90-7.88 (m, 1H), 7.60(d, J = 6.4 Hz, 2H). MS (ESI): mass calcd. For C₁₅H₉BF₆N₂OS 390.04, m/z found 391.0 [M+H]⁺. HPLC: 99.08% (220 nm), 98.64% (254 nm). [00522] EXAMPLE 72 [00523] 6-Chloro-1-hydroxy-2- (3-methylsulfanylphenyl)-7-(trifluoromethyl)-2,3,1- benzodiazaborinine

[00524] The title compound was prepared by using the scheme and procedures shown below:

[00525] Step 1: To a solution of 4-chloro-3-(trifluoromethyl)phenol (6.00 g, 30.53 mmol, 3.05 mL, 1 eq) in DMF (70 mL) was added NaH (1.83 g, 45.79 mmol, 60% purity, 1.5 eq) portionwise at 0 °C. The mixture was stirred at this temperature for 30 min. Then to the mixture above was added MeI (5.63 g, 39.68 mmol, 2.47 mL, 1.3 eq) dropwise at 0 °C. The reaction mixture was stirred at 20 °C for 1 h. The reaction mixture was poured into ice water (w/w = 1/1) (150 mL), pH was adjusted to 4-5 with HCl (2 N), and then the mixture was extracted with EtOAc (30 mL x 3). The combined organic phase was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 1-chloro-4-methoxy- 2- (trifluoromethyl)benzene (4.70 g, 22.32 mmol, 73.12% yield) as a yellow oil. ¹H NMR (CDCl₃- d_6, 400 MHz) δ 7.39 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 3.2 Hz, 1H), 6.99 (dd, J = 8.8, 2.8 Hz, 1H), 3.84 (s, 3H). [00526] Step 2: To a mixture of 1-chloro-4-methoxy-2-(trifluoromethyl)benzene (6.70 g, 31.82 mmol, 3.05 mL, 1 eq) and silver trifluoromethanesulfonate (10.00 g, 38.92 mmol, 1.22 eq) in DCM (60 mL) was added I2 (9.69 g, 38.18 mmol, 7.69 mL, 1.2 eq) portionwise at 20 °C under N2. The mixture was heated to 40 °C and stirred for 16 h. The mixture was poured into ice water (w/w = 1/1) (100 mL), pH was adjusted to 4-5 with HCl (2 N) and then the mixture was extracted with DCM (30 mL x 3). The combined organic phase was washed with brine (30 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 1-chloro-5- iodo-4-methoxy-2-(trifluoromethyl)benzene (7.00 g, crude) as a yellow solid. ¹H NMR (CDCl₃-d₆, 400 MHz) 7.91 (s, 1H), 7.04 (s, 1H), 3.93(s, 3H). [00527] Step 3: To a mixture of 1-chloro-5-iodo-4-methoxy-2-(trifluoromethyl)benzene (7.00 g, 20.80 mmol, 1 eq) in anhydrous THF (60 mL) was added n-BuLi (2.5 M, 9.0 mL, 1.08 eq) drop-wise at -78 °C under N2. The mixture was stirred at -78 °C for 30 min. DMF (2.28 g, 31.21 mmol, 2.40 mL, 1.5 eq) was added in one portion and the mixture was stirred at 0 °C for 1 h. The mixture was poured into sat. NH₄Cl (100 mL) and extracted with EtOAc (30 mL x 3). The combined organic phase was washed with brine (20 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 5-chloro-2-methoxy-4-(trifluoromethyl) benzaldehyde and 2-chloro-5-methoxy-3-(trifluoromethyl)benzaldehyde (2.30 g, crude, 4:4A =1:1.8 ) as a yellow solid. ¹H NMR (CDCl₃-d_6, 400 MHz) δ 10.44 (s, 1H), 7.91 (s, 1H), 7.32 (s, 1H), 4.01 (s, 3H). [00528] Step 4: To a mixture of 5-chloro-2-methoxy-4-(trifluoromethyl)benzaldehyde (3.00 g, 12.57 mmol, 1 eq) in DCM (25 mL) was added BBr₃ (9.45 g, 37.72 mmol, 3.60 mL, 3 eq) drop-wise at 20 °C under N₂. The mixture was heated to 50 °C and stirred for 2 h. The mixture was poured into ice water (w/w = 1/1) (40 mL) and extracted with DCM (20 mL x 3). The combined organic phase was washed with brine (10 mL x 2), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 5-chloro-2-hydroxy-4-(trifluoromethyl) benzaldehyde (1.00 g, 4.45 mmol, 35.42% yield) as a yellow solid. ¹H NMR (CDCl₃-d_6, 400 MHz) δ 10.91 (s, 1H), 9.94 (s, 1H), 7.72 (s, 1H), 7.38 (s, 1H). [00529] Step 5: To a mixture of 5-chloro-2-hydroxy-4-(trifluoromethyl)benzaldehyde (900 mg, 4.01 mmol, 1 eq) and pyridine (951 mg, 12.02 mmol, 970.45 uL, 3 eq) in DCM (10 mL) was added Tf₂O (1.36 g, 4.81 mmol, 793.51 uL, 1.2 eq) dropwise at 0 °C. The mixture was stirred at 20 °C for 1 h. The reaction mixture was quenched by sat. NH₄Cl (15 mL) and extracted with DCM (10 mL x 2). The combined organic phase was washed with brine (10 mL), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 0/1) to give [4-chloro-2-formyl-5- (trifluoromethyl)phenyl] trifluoromethanesulfonate (650 mg, crude) as a yellow oil. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 10.28 (s, 1H), 8.13 (s, 1H), 7.75 (s, 1H). [00530] Step 6: To a mixture of [4-chloro-2-formyl-5-(trifluoromethyl)phenyl] trifluoromethanesulfonate (550 mg, 1.54 mmol, 1 eq), B₂Pin₂ (783 mg, 3.08 mmol, 2 eq), and KOAc (302 mg, 3.08 mmol, 2 eq) in dioxane (8 mL) was added Pd(dppf)Cl₂ (90 mg, 123.38 umol, 0.08 eq) in one portion at 25 °C under N2. Then the mixture was heated to 80 °C and stirred for 16 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 0/1) to give 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-4-(trifluoromethyl) benzaldehyde (800 mg, crude) as a yellow solid. ¹H NMR (CDCl₃-d₆, 400 MHz) δ 10.67 (s, 1H), 8.24 (s, 1H), 8.07 (s, 1H), 1.40 (s, 1H). [00531] Step 7: To a mixture of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 4-(trifluoromethyl) benzaldehyde (300 mg, 448.40 umol, 1 eq) and (3- methylsulfanylphenyl)hydrazine (75 mg, 486.28 umol, 1.08 eq) in EtOH (5 mL) was added NH₃.H₂O (229 mg, 1.64 mmol, 252.46 uL, 25% purity, 3.65 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Nano- micro Kromasil C18100*30mm 5um;mobile phase: [water(0.1%TFA)-ACN];B%: 70%- 85%,10min) to give 6-chloro-1-hydroxy-2- (3-methylsulfanylphenyl)-7-(trifluoromethyl)-2,3,1- benzodiazaborinine (28 mg, 74.66 umol, 16.65% yield, 98.81% purity) as a yellow solid. ¹H NMR (DMSO-d_6, 400 MHz) δ 9.50 (s, 1H), 8.97 (s, 1H), 8.32 (s, 1H), 8.25 (s, 1H), 7.45 (s, 1H), 7.36(d, J = 7.2 Hz, 2H), 7.16 (d, J = 6.8 Hz, 1H), 2.50 (s, 3H). MS (ESI): mass calcd. For C₁₅H₁₁BClF₃N₂OS 370.03, m/z found 371.1 [M+H]⁺. HPLC: 98.81% (220 nm), 98.29% (254 nm). [00532] EXAMPLE 73 [00533] 2-(p-Butylphenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol [00534] The title compound was prepared by using the scheme and procedures shown below:

[00535] Step 1: 4-butylaniline (2 g, 13.4 mmol) was added to a round-bottomed flask containing 30 mL 6N HCl. The solution was vigorously stirred at 0 °C for 10 min. Sodium nitrite (0.9 g, 13.4 mmol) dissolved in 10 mL H₂O was added dropwise to the aniline solution, and the resulting mixture was stirred at 0 °C for an additional 1 h. To a beaker containing SnCl₂ (5 g, 26.8 mmol) was added 20 mL concentrated HCl, and the solution was sonicated and cooled to 0 °C. The SnCl₂ solution was added dropwise to the diazonium salt solution, and the mixture was stirred for an additional 1 h at room temperature. Then, 1N NaOH was added to quench the reaction. The resulting solution was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated in vacuo to give 4- butylphenylhydrazine (1.3 g, yield 61%). MS (M+H)⁺: 165.1. [00536] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (1 g, 3.2 mmol) and (4-butylphenyl)hydrazine (639 mg, 3.9 mmol) in DMSO (3 mL) and H₂O (8 mL) at room temperature was added HCl (2 mL, 6 N) dropwise. The acidic mixture was stirred for 2 h and extracted with EtOAc (2 × 25 mL). The combined organics were washed with H₂O, brine, dried over Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with PE/EtOAc (30:1 to 10:1) to give the title compound, which was further purified by Pre-HPLC (0.5% FA in MeCN) to afford 2-(p-butylphenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (221 mg, yield 20%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.55 (s, 1H), 8.66 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 8.37 (d, J = 4.9 Hz, 1H), 7.51 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.3 Hz, 2H), 2.68 (t, J = 7.6 Hz, 2H), 1.71 – 1.59 (m, 2H), 1.47 – 1.34 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H). HPLC purity: 96.37% at 210 nm and 95.30% at 254 nm. MS (M+H)⁺: 314.0. [00537] EXAMPLE 74 [00538] 2-(o-Butylphenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00539] The title compound was prepared by using the scheme and procedures shown below:

[00540] Step 1: o-Butylaniline (2 g, 13.4 mmol) was added to a round-bottomed flask containing 30 mL 6N HCl. The solution was vigorously stirred at 0 °C for 10 min. Sodium nitrite (0.9 g, 13.4 mmol) dissolved in 10 mL H₂O was added dropwise to the aniline solution, and the resulting mixture was stirred at 0 °C for an additional 1 h. To a beaker containing SnCl₂ (5 g, 26.8 mmol) was added 20 mL concentrated HCl, and the solution was sonicated and cooled to 0 °C. The SnCl₂ solution was added dropwise to the diazonium salt solution, and the mixture was stirred for an additional 1 h at room temperature. Then, 1N NaOH was added to quench the reaction. The resulting solution was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with brine, dried over MgSO₄, and concentrated in vacuo to give (o- butylphenyl)hydrazine (1.4 g, yield 63%). MS (M+H)⁺:165.1. [00541] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (1 g, 3.2 mmol) and (o-butylphenyl)hydrazine (639 mg, 3.9 mmol) in DMSO (3 mL) at room temperature was added sequentially HCl (2 mL, 6 N) and H₂O (8 mL). The acidic mixture was stirred for 2 h and extracted with EtOAc (2 × 25 mL). The combined organics were washed with H₂O, brine, dried over Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with PE/EtOAc (30:1 to 10:1) to give the title compound, which was further purified by Pre-HPLC (0.5% FA in MeCN) to afford 2-(o-Butylphenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1- bora-1-naphthol (15.5 mg, yield 2%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆):δ 9.22 (s, 1H), 8.61 (d, J = 4.8 Hz, 1H), 8.41 (s, 1H), 8.28 (d, J = 4.7 Hz, 1H), 7.38-7.24 (m, 3H), 7.20 (d, J = 7.4 Hz, 1H), 2.44 (t, J = 7.7 Hz, 2H), 1.47-1.33 (m, 2H), 1.20-1.07 (m, 2H), 0.69 (t, J = 7.3 Hz, 3H)ppm. HPLC purity: 95.16% at 210 nm and 99.06% at 254 nm. MS (M-H)-:312.0. [00542] EXAMPLE 75 [00543] 2-(m-Butylphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00544] The title compound was prepared by using the scheme and procedures shown below:

[00545] Step 1: n-BuLi (2.5M/hexanes, 7.7 mL, 19.46 mmol) was added drop wise to a - 78 °C cooled suspension of n-propyl triphenylphosphonium bromide (7.5 g, 19.46 mmol) in THF (50 mL) and the reaction was warmed to room temperature over 1 h. A solution of 3- nitrobenzaldehyde (2.94 g, 19.46 mmol) in THF (10.0 mL) was then added and the reaction mixture was warmed to 70 °C. After 12 h, saturated NH₄Cl solution was added and the mixture was diluted with water (25 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (25 mL). The combined organic layers were concentrated under reduced pressure. The residue was applied to silica chromatography eluting with PE / EtOAc (30:1 to 10:1) to give m-[(E)-1-butenyl]nitrobenzene (2.1 g, yield 58%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆):δ8.14-8.06 (m, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 6.52 (d, J = 11.7 Hz, 1H), 5.84 (dt, J = 11.7, 7.3 Hz, 1H), 2.38-2.27 (m, 1H), 1.05 (t, J = 7.5 Hz, 1H) ppm. [00546] Step 2: To the solution of m-[(E)-1-butenyl]nitrobenzene (800 mg, 4.4 mmol) in MeOH (10 mL) was added 10% Pd/C (200 mg). The reaction mixture was vacuumed and backfilled H₂ for 3 times, then stirred at room temperature for 4 h. After filtration and rotary evaporation, the residue was purified by column chromatography (PE / EtOAc = 10:1) to give m- butylaniline (620 mg, yield 95%) as a yellow solid. MS (M+H)⁺: 150.1 [00547] Step 3: m-Butylaniline (620 mg, 4.2 mmol) was added to a round-bottomed flask containing 10 mL 6N HCl. The solution was vigorously stirred at 0 °C for 10 min. Sodium nitrite (0.3 g, 4.4 mmol) dissolved in 3 mL H₂O was added dropwise to the aniline solution, and the resulting mixture was stirred at 0 °C for an additional 1 h. To a beaker containing SnCl₂ (1.7 g, 8.4 mmol) was added 5 mL concentrated HCl, and the solution was sonicated and cooled to 0 °C. The SnCl₂ solution was added dropwise to the diazonium salt solution, and the mixture was stirred for an additional 1 h at room temperature. Then, the 1N NaOH was added to quench the reaction. The resulting solution was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo to give (m-butylphenyl)hydrazine (660 mg, yield 97%). MS (M+H)⁺: 165.1 [00548] Step 4: To a solution of 2-[2-Chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (1 g, 3.2 mmol) and (m-butylphenyl)hydrazine (639 mg, 3.9 mmol) in DMSO (3 mL) at room temperature was added sequentially 6 N HCl (2 mL) and H₂O (8 mL). The acidic mixture was stirred for 2 h and extracted with EtOAc (2 × 25 mL). The combined organics were washed with H₂O, brine, dried over Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with PE / EtOAc (30:1 to 10:1) to give the title compound 2-(m-Butylphenyl)-1,2-dihydro- 2,3,1-benzodiazaborinin-1-ol (158 mg, yield 16%) as a yellow solid. ¹HNMR (400 MHz, DMSO- d₆): δ 9.55 (s, 1H), 8.61 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 8.30 (d, J = 4.6 Hz, 1H), 7.35 (dd, J = 17.1, 9.2 Hz, 3H), 7.12 (d, J = 6.6 Hz, 1H), 2.63 (t, J = 7.5 Hz, 2H), 1.58 (dd, J = 14.3, 6.9 Hz, 2H), 1.34 (dd, J = 14.5, 7.3 Hz, 3H), 0.91 (t, J = 7.3 Hz, 3H) ppm. HPLC purity: 97.04% at 210 nm and 97.61% at 254 nm. MS (M-H)-: 312.0 [00549] EXAMPLE 76 [00550] 2-(m-Chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00551] The title compound was prepared by using the scheme and procedures shown below:

[00552] Step 1: To a suspension of m-chloroaniline (2 g, 16 mmol) in water (20 mL) was added concentrated hydrochloric acid (5 mL). The mixture was cooled to -10 °C under nitrogen. A solution of sodium nitrite (1.2 g, 18 mmol) in water (5 mL) was added dropwise. After addition was complete the mixture was stirred for an additional 30 min at -10 °C. Tin(II) chloride dehydrate (9.8 g, 44 mmol) was dissolved in 6 M hydrochloric acid (10 mL), and the diazotization mixture was poured into this solution. The mixture was stirred for 3.5 h at -10 °C. The solids were then filtered off and dried overnight to give (m-chlorophenyl)hydrazine (1.8 g, crude) as a brown solid, which was not purified further but carried over into the next step. ¹HNMR (400 MHz, DMSO-d₆): δ 7.10-6.95 (m, 2H), 6.81 (s, 1H), 6.66 (d, J = 8.2 Hz, 1H), 6.60- 6.51 (m, 1H), 4.04 (s, 2H). [00553] Step 2: A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and (m- chlorophenyl)hydrazine (950 mg, 6.6 mmol) in DMSO / H₂O (10 mL, v/v = 1:4) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE: EtOAc = 30/1 to 5/1) to give the title compound 2-(m-chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (480 mg, yield 29%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.25 (s, 1H), 8.41 (d, J = 7.5 Hz, 1H), 8.23 (s, 1H), 7.86-7.75 (m, 2H), 7.73-7.66 (m, 2H), 7.63 (d, J = 8.2 Hz, 1H), 7.44 (t, J = 8.1 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H) ppm. HPLC purity: 98.75% at 210 nm and 99.66% at 254 nm. MS (M+H)⁺: m/z = 257.1. [00554] EXAMPLE 77 [00555] 2-(p-Nitrophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00556] The title compound was prepared by using the scheme and procedures shown below:

[00557] A mixture of 2-formylphenylboronic acid (1.0 g, 6.6 mmol) and (p- nitrophenyl)hydrazine (1.0 g, 6.6 mmol) in DMSO/H₂O (2 mL/8 mL) was stirred at room temperature for 2 h, the reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane to give a crude product, which was purified by silica gel chromatography (EtOAc: PE from 1:30 to 1:5) to give the title compound 2-(p-Nitrophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (102 mg, yield 6%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.64 (s, 1H), 8.45 (d, J = 7.4 Hz, 1H), 8.30 (d, J = 8.5 Hz, 3H), 8.01 (d, J = 8.9 Hz, 2H), 7.90-7.77 (m, 2H), 7.72 (t, J = 7.3 Hz, 1H) ppm. HPLC purity: 99.21% at 210 nm and 97.47% at 254 nm. MS (M+H)⁺: m/z = 268.1. [00558] EXAMPLE 78 [00559] 5-(1-Hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)-2- pyridinecarbonitrile

[00560] The title compound was prepared by using the scheme and procedures shown below:

[00561] A mixture of 2-formylphenylboronic acid (250 mg, 1.6 mmol) and 5-hydrazino-2- pyridinecarbonitrile (210 mg, 1.6 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2h, the reaction was monitored by TLC. After complete disappearance of 2- formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE/EtOAc = 30/1 to 5/1) to give the title compound 5-(1- hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)-2-pyridinecarbonitrile (47 mg, yield 12%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.81 (s, 1H), 9.14 (d, J = 2.4 Hz, 1H), 8.43 (d, J = 7.5 Hz, 1H), 8.35-8.31 (m, 1H), 8.30 (d, J = 2.5 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.84 (dt, J = 7.8, 4.3 Hz, 2H), 7.76-7.68 (m, 1H)ppm. HPLC purity: 95.09% at 210 nm. MS (M+H)⁺: m/z = 249.1. [00562] EXAMPLE 79 [00563] 2-(p-Trifluoromethoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00564] The title compound was prepared by using the scheme and procedures shown below:

[00565] Step 1: To a solution of 4-(trifluoromethoxy)aniline (1.77 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C, and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield ethyl 3-hydrazinobenzoate hydrogen chloride (1.3 g, yield 57%) as a white solid, which was used for the next reaction without further purification. ¹H NMR (400 MHz, DMSO-d6): δ 10.39 (s, 3H), 7.30 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.9 Hz, 2H) ppm. MS: (M+H)⁺: m/z = 193.1. [00566] Step 2: A solution of 2-formylphenylboronic acid (330 mg, 2.2 mmol) and (4- (trifluoromethoxy)phenyl)hydrazine hydrogen chloride (500 mg, 2.2 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-(p-trifluoromethoxyphenyl)-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (164 mg, yield 24%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.20 (s, 1H), 8.41 (d, J = 7.5 Hz, 1H), 8.23 (s, 2H), 7.90-7.70 (m, 1H), 7.87-7.76 (m, 5H), 7.41(d, J = 8.4 Hz, 1H) ppm. HPLC purity: 98.99% at 210 nm and 97.83% at 254 nm. MS: (M+H)⁺: m/z = 307.0. [00567] EXAMPLE 80 [00568] 2-(o-Trifluoromethoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00569] The title compound was prepared by using the scheme and procedures shown below:

[00570] Step 1: To a solution of 2-(trifluoromethoxy)aniline (1.77 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C, and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield (2-(trifluoromethoxy)phenyl)hydrazine hydrogen chloride (1.25 g, yield 55%) as a white solid, which was used for the next reaction without further purification. ¹HNMR (400 MHz, DMSO-d₆): δ 10.29 (s, 3H), 7.44-7.32 (m, 2H), 7.23 (d, J = 8.1 Hz, 1H), 7.04 (t, J = 7.8 Hz, 1H)) ppm. MS: (M+H)⁺: m/z = 193.1. [00571] Step 2: A solution of 2-formylphenylboronic acid (300 mg, 2.0 mmol) and (2- (trifluoromethoxy)phenyl)hydrazine hydrogen chloride (500 mg, 2.0 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-(o-trifluoromethoxyphenyl)-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (194 mg, yield 32%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.85 (s, 1H), 8.36 (d, J = 7.6 Hz, 1H), 8.16 (s, 1H), 7.81 (dt, J = 14.7, 7.5 Hz, 2H), 7.69 (dd, J = 10.5, 4.0 Hz, 1H), 7.55-7.45 (m, 4H) ppm. HPLC purity: 99.42% at 210 nm and 100% at 254 nm. MS: (M+H)⁺: m/z = 307.0. [00572] EXAMPLE 81 [00573] 2-(p-Methoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00574] The title compound was prepared by using the scheme and procedures shown below:

[00575] A solution of 2-formylphenylboronic acid (431 mg, 2.9 mmol) and (2- (methylthio)phenyl)hydrazine (400 mg, 2.9 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-(p-methoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (131 mg, yield 18%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.82 (s, 1H), 8.38 (d, J = 7.5 Hz, 1H), 8.16 (s, 1H), 7.83-7.73 (m, 2H), 7.65 (t, J = 6.8 Hz, 1H), 7.45 (d, J = 8.9 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 3.79 (s, 3H) ppm. HPLC purity: 99.56% at 210 nm and 99.69% at 254 nm. MS: (M+H)⁺: m/z = 253.1. [00576] EXAMPLE 82 [00577] 2-(o-Methoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00578] The title compound was prepared by using the scheme and procedures shown below:

[00579] Step 1: To a solution of 2-methoxyaniline (1.23 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C, and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield (2- methoxyphenyl) hydrazine hydrogen chloride (1.1 g, yield 63%) as a white solid, which was used for the next reaction without further purification. ¹HNMR (400 MHz, DMSO-d₆): δ 9.93 (s, 3H), 7.04-6.90 m, 4H), 3.84 (s, 3H). MS: (M+H)⁺: m/z = 139.1. [00580] Step 2: A solution of 2-formylphenylboronic acid (431 mg, 2.9 mmol) and (2- methoxyphenyl)hydrazine hydrogen chloride (500 mg, 2.9 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-(o-methoxyphenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (369 mg, yield 50%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.36 (s, 1H), 8.31 (d, J = 7.5 Hz, 1H), 8.08 (s, 1H), 7.76 (dt, J = 7.9, 4.7 Hz, 2H), 7.69-7.60 (m, 1H), 7.38-7.29 (m, 1H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 7.01 (td, J = 7.5, 1.0 Hz, 1H), 3.71 (s, 3H) ppm. HPLC purity: 98.58% at 210 nm and 99.65% at 254 nm. MS: (M+H)⁺: m/z = 253.1. [00581] EXAMPLE 83 [00582] 2-Ethyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00583] The title compound was prepared by using the scheme and procedures shown below:

[00584] A mixture of 2-formylphenylboronic acid (300 mg, 2.2 mmol) and ethylhydrazine (120 mg, 2.2 mmol) in EtOH (10 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and purified by silica gel chromatography (PE:EtOAc = 5:1) to give the title compound 2-ethyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (155 mg, yield 13%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.49 (s, 1H), 8.26 (d, J = 7.6 Hz, 1H), 8.02 (s, 1H), 7.75-7.67 (m, 2H), 7.61-7.55 (m, 1H), 3.86 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H) ppm. HPLC purity: 99.76% at 210 nm and 98.74% at 254 nm. MS (M+H)⁺: m/z = 175.1. [00585] EXAMPLE 84 [00586] 2-Propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00587] The title compound was prepared by using the scheme and procedures shown below:

[00588] A mixture of 1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (500 mg, 3.5 mmol), 1- Iodopropane (1 mL), and K₂CO₃ (690 mg, 5 mmol)in DMF (10 mL) was stirred at 80 °C for 6 h. The reaction was monitored by TLC. After complete disappearance of 1,2-dihydro-2,3,1- benzodiazaborinin-1-ol, the solvent was evaporated under reduced pressure. The resulting solid was purified through silica chromatography eluting with PE/EtOAc (30:1 to 10:1) and further purified by prep-HPLC (0.5% TFA in MeCN) to afford the title compound 2-propyl-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (152 mg, yield 23%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 8.47 (s, 1H), 8.26 (d, J = 7.4 Hz, 1H), 8.01 (s, 1H), 7.77-7.64 (m, 2H), 7.58 (t, J = 6.9 Hz, 1H), 3.77 (t, J = 7.0 Hz, 2H), 1.68 (dt, J = 14.3, 7.1 Hz, 2H), 0.85 (t, J = 7.3 Hz, 3H) ppm. HPLC purity: 95.86% at 210 nm and 95.35% at 254 nm. MS (M+H)⁺: m/z = 189.1. [00589] EXAMPLE 85 [00590] 2-(3,4-Dichlorophenyl)-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00591] The title compound was prepared by using the scheme and procedures shown below:

[00592] A solution of (2-acetylphenyl)boronic acid (300 mg, 1.8 mmol) and (3,4- dichlorophenyl)hydrazine (322 mg, 1.8 mmol) in DMSO/H₂O (10 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (25 mL), extracted with EtOAc (2 × 25 mL), washed with brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give the crude product. Further purification by crystallization with MeOH/H₂O (10 mL, v/v = 1/1) afforded the desired product 2-(3,4-dichlorophenyl)-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (390 mg, yield 71%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.25 (s, 1H), 8.42 (d, J = 7.4 Hz, 1H), 7.96-7.88 (m, 2H), 7.81 (t, J = 7.6 Hz, 1H), 7.75-7.61 (m, 3H), 2.56 (s, 3H) ppm. HPLC purity: 98.69% at 210 nm and 99.62% at 254 nm. MS: (M+H)⁺: m/z = 305.0. [00593] EXAMPLE 86 [00594] 1,2-Dihydro-2,3,1-benzodiazaborinin-1-ol

[00595] The title compound was prepared by using the scheme and procedures shown below:

[00596] A mixture of 2-formylphenylboronic acid (1 g, 6.6 mmol) and hydrazine hydrate (2 mL) in EtOH (10 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2-formylphenylboronic acid, the mixture was filtered. The filter cake was washed with hexane and dried in vacuo to give the title compound 1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (820 mg, yield 85%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.97 (s, 1H), 8.19 (d, J = 9.6 Hz, 2H), 7.99 (s, 1H), 7.70 (t, J = 6.3 Hz, 2H), 7.58 (dd, J = 8.8, 4.1 Hz, 1H) ppm. HPLC purity: 98.92% at 210 nm and 99.85% at 254 nm. MS (M+H)⁺: m/z = 147.1. [00597] EXAMPLE 87 [00598] 2-[p-(Methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00599] The title compound was prepared by using the scheme and procedures shown below:

[00600] Step 1: To a solution of 4-(methylthio)aniline (1.39 g, 10.0 mmol) in concentrated HCl (10 mL) was added an aqueous solution (2.5 mL) of NaNO₂ (690 mg, 10.0 mmol) at 0 °C, and the reaction mixture was stirred for 1 h. A solution of SnCl₂.2H₂O (4.52 g, 20 mmol) in concentrated HCl (1 mL) was then added at 0 °C. The reaction solution was stirred for 2 h at room temperature. The precipitate was filtered and washed with ethanol and ether to yield (4- (methylthio)phenyl) hydrazine hydrogen chloride (1.4 g, yield 74%) as a white solid, which was used for the next reaction without further purification. MS: (M+H)⁺: m/z = 155.1. [00601] Step 2: A solution of 2-formylphenylboronic acid (1.1 g, 7.4 mmol) and (4- (methylthio)phenyl)hydrazine hydrogen chloride (1.4 g, 7.4 mmol) in DMSO/H₂O (25 mL, v/v = 1/4) was stirred at room temperature for 2 h. LCMS analysis showed no starting materials left. The reaction mixture was diluted with water (50 mL), extracted with EtOAc (2 × 50 mL), washed with brine (2 × 50 mL), dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. Further purification by prep-HPLC (0.5% TFA in MeCN) afforded the desired product 2-[p-(methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (75 mg, yield 4%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.00 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.20 (s, 1H), 7.79 (dt, J = 14.7, 7.4 Hz, 2H), 7.67 (t, J = 7.3 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.6 Hz, 2H), 2.49 (s, 3H) ppm. HPLC purity: 96.17% at 210 nm and 95.89% at 254 nm. MS: (M+H)⁺: m/z = 269.1. [00602] EXAMPLE 88 [00603] 8-Chloro-2-ethyl-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00604] The title compound was prepared by using the scheme and procedures shown below:

[00605] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added ethylhydrazine hydrochloride (97 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, then poured into water and extracted with EtOAc (2 × 30 mL). The combined organic phases were dried and evaporated under reduced pressure. The crude was purified by pre-HPLC to give the desired product 8-chloro-2-ethyl-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (59 mg, yield 28.2%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ ppm. HPLC purity: 99.69% at 210 nm and 98.85% at 254 nm. MS: (M+H)⁺: m/z = 210.1. [00606] EXAMPLE 89 [00607] 8-Chloro-2-[o-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1- naphthol

[00608] The title compound was prepared by using the scheme and procedures shown below:

[00609] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4- (trifluoromethyl)phenylhydrazine (176 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 hours, the solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-[o-(trifluoromethyl)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora- 1-naphthol (124 mg, yield 38%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.40 (s, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.38 (s, 1H), 8.26 (d, J = 4.9 Hz, 1H), 7.90-7.71 (m, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H) ppm. HPLC purity: 95.08% at 210 nm and 94.22% at 254 nm. MS: (M+H)⁺: m/z = 326.0. [00610] EXAMPLE 90 [00611] 8-Chloro-2-methyl-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00612] The title compound was prepared by using the scheme and procedures shown below:

[00613] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in EtOH (6 mL) was added methylhydrazine (40% in water, 575 mg, 5.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solvent was removed under reduced pressure, and the residue was purified by pre-HPLC to give the desired product 8-chloro-2-methyl-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (33 mg, yield 16.9%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆): δ 9.19 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 8.28 (s, 1H), 8.18 (d, J = 5.0 Hz, 1H), 3.56 (s, 3H) ppm. HPLC purity: 97.67% at 210 nm and 95.53% at 254 nm. MS: (M+H)⁺: m/z = 196.0. [00614] EXAMPLE 91 [00615] 8-Chloro-2-(3-pyridyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00616] The title compound was prepared by using the scheme and procedures shown below:

[00617] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2-pyridinylhydrazine (109 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, then the solvent was removed under reduced pressure, and the residue was purified by pre-HPLC (0.1% MeCN and H₂O) to give the desired product 8-chloro-2-(3-pyridyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (10 mg, yield 3.9%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.81 (s, 1H), 8.83 (d, J = 2.3 Hz, 1H), 8.64 (d, J = 4.9 Hz, 1H), 8.51 (s, 1H), 8.48 (d, J = 4.7 Hz, 1H), 8.32 (d, J = 5.0 Hz, 1H), 7.99 (d, J = 8.2 Hz, 1H), 7.52-7.48 (m, 1H) ppm. HPLC purity: 94.86% at 210 nm and 88.12% at 254 nm. MS: (M+H)⁺: m/z = 259.0. [00618] EXAMPLE 92 [00619] 8-Chloro-2-(o-tolyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00620] The title compound was prepared by using the scheme and procedures shown below:

[00621] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2-methylphenylhydrazine (122 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and purified by pre-HPLC (0.1% MeCN and H₂O) to give the desired product 8-chloro-2-(o-tolyl)-1,2- dihydro-2,3,7-triaza-1-bora-1-naphthol (42 mg, yield 15.5%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.24 (s, 1H), 8.61 (d, J = 5.0 Hz, 1H), 8.41 (s, 1H), 8.29 (d, J = 5.0 Hz, 1H), 7.38-7.16 (m, 4H), 2.10 (s, 3H) ppm. HPLC purity: 99.09% at 210 nm and 99.15% at 254 nm. MS: (M+H)⁺: m/z = 272.1. [00622] EXAMPLE 93 [00623] 2-Butyl-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00624] The title compound was prepared by using the scheme and procedures shown below:

[00625] Step 1: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (1.0 g, 3.2 mmol) in EtOH (10 mL) was added hydrazine hydrate (80% in H₂O, 1 mL) at room temperature. The mixture was stirred for 20 min and 6N HCl (5 mL) was added. The reaction mixture was stirred for another 2 h, then solvent was removed under reduced pressure, and the residue was washed with EtOAc. The organic layer was evaporated under reduced pressure to give the product 8-chloro-1,2-dihydro-2,3,7-triaza-1- bora-1-naphthol (320 mg, yield 88.4%) as a light yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 10.65 (s, 1H), 8.90 (s, 1H), 8.52 (d, J = 4.9 Hz, 1H), 8.30 (s, 1H), 8.11 (d, J = 4.9 Hz, 1H) ppm. [00626] Step 2: To a solution of 8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (320 mg, 1.77 mmol) in DMF (10 mL) was added 1-iodobutane (1.63 g, 8.85 mmol) and K₂CO₃ (367 mg, 2.66 mmol). The mixture was stirred at 60 °C for 5 h then poured into water and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by column chromatography and further purified by pre-HPLC to give the product 2-butyl-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (23 mg, yield 5.5%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.12 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 8.19 (d, J = 5.0 Hz, 1H), 3.87 (t, J = 7.1 Hz, 2H), 1.79-1.53 (m, 2H), 1.28 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H) ppm. HPLC purity: 95.93% at 210 nm and 92.00% at 254 nm. MS: (M+H)⁺: m/z = 238.1. [00627] EXAMPLE 94 [00628] 8-Chloro-2-(m-methoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00629] The title compound was prepared by using the scheme and procedures shown below:

[00630] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of m-anisidine (2.46 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly, and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the product 3-methoxyphenylhydrazine (2.10 g, yield 76.1%) as a yellow oil. ¹HNMR (400 MHz, DMSO-d₆): δ 6.97 (t, J = 8.0 Hz, 1H), 6.66 (s, 1H), 6.39 (t, J = 2.2 Hz, 1H), 6.34 (dd, J = 8.1, 1.2 Hz, 1H), 6.15 (dd, J = 8.0, 1.8 Hz, 1H), 3.92 (s, 2H), 3.68 (s, 3H) ppm. [00631] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 3- methoxyphenylhydrazine (138 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-(m-methoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (116 mg, yield 40%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.59 (s, 1H), 8.61 (d, J = 5.0 Hz, 1H), 8.46 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.25-7.08 (m, 2H), 6.88 (dd, J = 7.3, 1.5 Hz, 1H), 3.80 (s, 3H) ppm. HPLC purity: 97.34% at 210 nm and 94.16% at 254 nm. MS: (M+H)⁺: m/z = 288.1. [00632] EXAMPLE 95 [00633] 8-Chloro-2-(2-pyridyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00634] The title compound was prepared by using the scheme and procedures shown below:

[00635] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2-hydrazinopyridine (109 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeOH, then filtered to give the desired product 8-chloro-2-(2-pyridyl)-1,2-dihydro-2,3,7-triaza-1- bora-1-naphthol (26 mg, yield 10.1%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.80 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 8.32 (d, J = 5.0 Hz, 1H), 7.68 (t, J = 2.0 Hz, 1H), 7.60 (d, J = 7.3 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 9.8 Hz, 1H) ppm. MS: (M+H)⁺: m/z = 259.0. [00636] EXAMPLE 96 [00637] 8-Chloro-2-[o-(methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00638] The title compound was prepared by using the scheme and procedures shown below:

[00639] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2-(mMethylthio)hydrazine (154 mg, 1.0 mmol) at room temperature. The mixture was stirred at room temperature for 20 min. 6N HCl (3 mL) was added to the mixture. The reaction mixture was stirred for another 2 h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-[o-(methylthio)phenyl]-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (12 mg, yield 3.9%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.26 (s, 1H), 8.62 (d, J = 4.9 Hz, 1H), 8.40 (s, 1H), 8.27 (d, J = 4.9 Hz, 1H), 7.41 (d, J = 3.5 Hz, 2H), 7.31-7.23 (m, 2H), 2.36 (s, 3H) ppm. HPLC purity: 96.17% at 210 nm and 97.04% at 254 nm. MS: (M+H)⁺: m/z = 304.0. [00640] EXAMPLE 97 [00641] 8-Chloro-2-(p-methoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00642] The title compound was prepared by using the scheme and procedures shown below:

[00643] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4- methoxyphenylhydrazine (138 mg, 1.0 mmol) at room temperature. The mixture was stirred at room temperature for 20 min. 6N HCl (3 mL) was added to the mixture. The reaction mixture was stirred for another 2 h, then it was poured into water and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the product 8-chloro-2-(p-methoxyphenyl)-1,2-dihydro- 2,3,7-triaza-1-bora-1-naphthol (70 mg, yield 24.3%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.44 (s, 1H), 8.60 (d, J = 5.0 Hz, 1H), 8.43 (s, 1H), 8.30 (d, J = 5.0 Hz, 1H), 7.45 (d, J = 8.9 Hz, 2H), 7.00 (d, J = 8.9 Hz, 2H), 3.80 (s, 3H) ppm. HPLC purity: 99.43% at 210 nm and 98.68% at 254 nm. MS: (M+H)⁺: m/z = 288.1. [00644] EXAMPLE 98 [00645] 5-(8-Chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2-naphthyl)-2- pyridinecarbonitrile

[00646] The title compound was prepared by using the scheme and procedures shown below:

[00647] Step 1: NaNO₂ (1.52 g, 22.0 mmol) in H₂O (10 mL) was added over 10 min to an ice-cooled and stirred suspension of 4-aminobenzonitrile (2.36 g, 20.0 mmol) in 6N HCl (30 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (9.0 g, 40.0 mmol) in 6N HCl (30 mL) was added slowly, and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure to give the product 4-cyanophenylhydrazine (1.9 g, yield 70.9%) as a yellow solid. ¹HNMR (400 MHz, DMSO-d₆): δ 7.99 (d, J = 2.6 Hz, 1H), 7.57 (d, J = 8.5 Hz, 1H), 6.94 (dd, J = 8.6, 2.7 Hz, 1H), 6.42 (s, 2H), 4.41 (s, 1H) ppm. [00648] Step 2: To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 4- cyanophenylhydrazine (133 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2h, the solid was filtered and triturated with MeCN and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 5-(8-chloro-1-hydroxy-1,2-dihydro-2,3,7-triaza-1-bora-2-naphthyl)-2- pyridinecarbonitrile (28 mg, yield 9.9%) as a brown solid. ¹H NMR (400 MHz, DMSO-d₆): δ 10.09 (s, 1H), 9.11 (d, J = 2.4 Hz, 1H), 8.65 (d, J = 4.9 Hz, 1H), 8.53 (s, 1H), 8.35-8.26 (m, 2H), 8.13 (d, J = 8.5 Hz, 1H) ppm. HPLC purity: 92.89% at 210 nm and 88.56% at 254 nm. MS: (M-H)-: m/z = 282.0. [00649] EXAMPLE 99 [00650] 2-(o-Bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00651] The title compound was prepared by using the scheme and procedures shown below:

[00652] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.6 mmol) in DMSO (10 mL) was added 2-bromophenylhydrazine (186 mg, 1.6 mmol) at room temperature. The mixture was stirred for 20 min and 6N HCl (6 mL) was added. The reaction mixture was stirred for another 2 h, then it was poured into water and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the product 2-(o-bromophenyl)-8-chloro-1,2-dihydro-2,3,7-triaza-1-bora- 1-naphthol (62.2 mg, yield 18.4%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.40 (s, 1H), 8.63 (d, J = 4.9 Hz, 1H), 8.43 (s, 1H), 8.28 (d, J = 4.9 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.53-7.47 (m, 2H), 7.40-7.31 (m, 1H) ppm. HPLC purity: 98.59% at 210 nm and 97.02% at 254 nm. MS: (M+H)⁺: m/z = 337.9. [00653] EXAMPLE 100 [00654] 8-Chloro-2-(o-methoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00655] The title compound was prepared by using the scheme and procedures shown below:

[00656] To a solution of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (311 mg, 1.0 mmol) in DMSO (6 mL) was added 2- methoxyphenylhydrazine (138 mg, 1.0 mmol) at room temperature. The mixture was stirred for 20 min, and 6N HCl (3 mL) was added. The reaction mixture was stirred for another 2 h, the solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 8-chloro-2-(o-methoxyphenyl)-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (80 mg, yield 27.9%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.04 (s, 1H), 8.59 (d, J = 4.9 Hz, 1H), 8.38 (s, 1H), 8.23 (d, J = 4.9 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.27 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 3.73 (s, 3H) ppm. HPLC purity: 96.21% at 210 nm and 95.53% at 254 nm. MS: (M+H)⁺: m/z = 288.0. [00657] EXAMPLE 101 [00658] 2-[m-(Cyclopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00659] The title compound was prepared by using the scheme and procedures shown below:

[00660] Step 1: To a solution of a 3-aminothiophenol (5.0 g, 40.0 mmol) in DMF (80 mL) was added NaH (1.92 g, 48.0 mmol) at 0 °C. The mixture was stirred for 30 min in a sealing tube. Cyclopropyl bromide (7.26 g, 60.0mmol) was added in one portion. The reaction was heated to 100 °C and stirred overnight, then poured into water and extracted with EtOAc (2 × 100 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product m-(cyclopropylthio)aniline (4.7 g, yield 71.2%) as a yellow oil. ¹H NMR (300 MHz, DMSO-d₆): δ 6.94 (t, J = 7.8 Hz, 1H), 6.57 (s, 1H), 6.48 (d, J = 7.6 Hz, 1H), 6.35 (d, J = 7.9 Hz, 1H), 5.09 (s, 2H), 2.23-2.08 (m, 1H), 1.03 (m, 2H), 0.63-0.40 (m, 2H) ppm. [00661] Step 2: NaNO₂ (2.17 g, 31.4 mmol) in H₂O (10 mL) was added over 20 min to an ice-cooled and stirred suspension of m-(cyclopropylthio)aniline (4.7 g, 28.5 mmol) in 6N HCl (50 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (12.8 g, 57.0 mmol) in 6N HCl (50 mL) was added slowly and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 200 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (20/1 to 3/1) to give the product [m-(cyclopropylthio)phenyl]hydrazine (3.0 g, yield 58.5%) as a yellow oil. [00662] Step 3: To a solution of a 2-acetylphenylboronic acid (164 mg, 2.0 mmol) in DMSO (10 mL) was added m-(cyclopropylthio)phenyl]hydrazine (360 mg, 2.0 mmol) at room temperature. The reaction was stirred for 30 min and poured into water. The solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 2- [m-(cyclopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (141 mg, yield 22.9%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.88 (s, 1H), 8.41 (d, J = 7.3 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.68 (t, J = 7.3 Hz, 1H), 7.62 (s, 1H), 7.45-7.31 (m, 2H), 7.20 (d, J = 7.6 Hz, 1H), 2.55 (s, 3H), 2.35-2.24 (m, 1H), 1.15-1.00 (m, 2H), 0.66-0.59 (m, 2H). HPLC purity: 96.39% at 210 nm and 95.52% at 254 nm. MS: (M+H)⁺: m/z = 309.1. [00663] EXAMPLE 102 [00664] 6-Fluoro-2-[m-(isopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00665] The title compound was prepared by using the scheme and procedures shown below:

[00666] To a solution of 1-[5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-ethanone (500 mg, 1.9 mmol) in DMSO (10 mL) was added 3- (isopropylthio)phenylhydrazine (346 mg, 1.9 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 6-fluoro-2-[m-(isopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (27 mg, yield 4.3%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.99 (s, 1H), 8.47 (dd, J = 8.5, 6.4 Hz, 1H), 7.66 (dd, J = 10.7, 2.4 Hz, 1H), 7.62-7.52 (m, 2H), 7.49-7.43 (m, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.25-7.18 (m, 1H), 3.49 (dt, J = 13.3, 6.6 Hz, 1H), 2.53 (s, 3H), 1.28 (d, J = 6.7 Hz, 6H) ppm. HPLC purity: 98.57% at 210 nm and 98.14% at 254 nm. MS: (M+H)⁺: m/z = 329.1. [00667] EXAMPLE 103 [00668] 4-Butyl-2-[m-(methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00669] The title compound was prepared by using the scheme and procedures shown below:

[00670] Step 1: To a solution of a 2-bromobenzaldehyde (10.0 g, 54.1 mmol) in THF (100 mL) was added buthylmagnesium bromide (64.9 mL, 64.9 mmol) at 0 °C under an inert nitrogen atmosphere. After addition, the reaction was allowed to warm to room temperature and stirred for 1h, then quenched by sat. NH₄Cl and extracted with EtOAc (2 × 300 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product 1-(o- bromophenyl)-1-pentanol (6.0 g, yield 45.8%) as a light oil. ¹H NMR (300 MHz, DMSO-d₆): δ 7.53 (t, J = 8.9 Hz, 2H), 7.37 (t, J = 7.4 Hz, 1H), 7.15 (t, J = 6.9 Hz, 1H), 5.32 (d, J = 4.5 Hz, 1H), 4.86-4.74 (m, 1H), 1.70-1.19 (m, 6H), 0.85 (t, J = 6.9 Hz, 3H). [00671] Step 2: To a solution of 1-(o-bromophenyl)-1-pentanol (6.0 g, 24.8 mmol) in DCM (80 mL) was added Dess-Martin reagent (10.5 g, 24.8 mmol) in small portions at 0 °C. The reaction was stirred at room temperature for 1h, then the solid was filtered and washed with DCM. The organic layer was concentrated under reduced pressure, and the residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product 1-(o- bromophenyl)-1-pentanone (5.4 g, yield 90.7%) as a light oil. ¹H NMR (300 MHz, DMSO-d₆): δ 7.69 (d, J = 7.6 Hz, 1H), 7.63-7.53 (m, 1H), 7.53-7.31 (m, 2H), 2.89 (t, J = 7.2 Hz, 2H), 1.66- 1.47 (m, 2H), 1.42-1.26 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H) ppm. [00672] Step 3: To a solution of 1-(o-bromophenyl)-1-pentanone (5.40 g, 22.5 mmol) in dioxane (80 mL) was added KOAc (6.61 g, 67.5 mmol), bis(pinacolato)diboron (8.59 g, 33.8 mmol), and (dppf)PdCl₂ (3.67 g, 4.5 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 80 °C and stirred for 5h. Then the solid was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product 1-[o-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl]-1-pentanone (4.5 g, yield 69.4%) as a yellow solid. ¹H NMR (300 MHz, CDCl₃): δ 7.81 (d, J = 7.7 Hz, 1H), 7.58-7.37 (m, 3H), 2.96 (t, J = 7.5 Hz, 2H), 1.82-1.67 (m, 2H), 1.42 (s, 12H), 0.96 (t, J = 7.3 Hz, 3H), 0.81 (t, J = 7.3 Hz, 2H) ppm. [00673] Step 4: To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]- 1-pentanone (500 mg, 1.7 mmol) in DMSO (10 mL) was added 3-(methylthio)phenylhydrazine (267 mg, 1.7 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-butyl-2-[m- (methylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (70 mg, yield 12.5%) as a yellow liquid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.89 (s, 1H), 8.41 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.1 Hz, 1H), 7.52 (s, 1H), 7.47-7.26 (m, 2H), 7.10 (d, J = 7.3 Hz, 1H), 3.03-2.88 (m, 2H), 2.47 (s, 3H), 1.80-1.62 (m, 2H), 1.55-1.34 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H) ppm. HPLC purity: 97.69% at 210 nm and 98.04% at 254 nm. MS: (M+H)⁺: m/z = 325.2. [00674] EXAMPLE 104 [00675] 4-Isopropyl-2-[m-(isopropylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00676] The title compound was prepared by using the scheme and procedures shown below:

[00677] To a solution of 2-methyl-1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-propanone (500 mg, 1.8 mmol) in DMSO (10 mL) was added 3- (isopropylthio)phenylhydrazine (328 mg, 1.8 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1 h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 4-isopropyl-2-[m-(isopropylthio)phenyl]-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (26 mg, yield 4.2%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.94 (s, 1H), 8.40 (d, J = 7.4 Hz, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.34 (t, J = 8.1 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 3.65-3.56 (m, 1H), 3.55-3.39 (m, 2H), 1.28 (d, J = 6.5 Hz, 12H) ppm. HPLC purity: 98.79% at 210 nm and 98.75% at 254 nm. MS: (M+H)⁺: m/z = 339.1. [00678] EXAMPLE 105 [00679] 2-[m-(Cyclopropylthio)phenyl]-4-ethyl-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol

[00680] The title compound was prepared by using the scheme and procedures shown below:

[00681] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- propanone (500 mg, 1.92 mmol) in DMSO (5 mL) was added (3- (cyclopropylthio)phenyl)hydrazine (345 mg, 1.92 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN) to give the desired product 2-[m-(cyclopropylthio)phenyl]-4-ethyl-1,2-dihydro- 2,3,1-benzodiazaborinin-1-ol (37 mg, yield 6.1%) as a brown solid. ¹H NMR (400 MHz, DMSO- d₆): δ 8.89 (s, 1H), 8.42 (d, J = 7.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.74-7.56 (m, 2H), 7.46 (d, J = 8.1 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 7.6 Hz, 1H), 2.99 (q, J = 7.3 Hz, 2H), 2.34 – 2.19 (m, 1H), 1.29 (t, J = 7.3 Hz, 3H), 1.11 (d, J = 5.3 Hz, 2H), 0.63 (d, J = 5.4 Hz, 2H) ppm. MS: (M+H)⁺: m/z = 323.1. HPLC: Purity at 210 nm = 98.10% and purity at 254 nm = 97.41%. [00682] EXAMPLE 106 [00683] 2-[m-(Isopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol

[00684] The title compound was prepared by using the scheme and procedures shown below:

[00685] Step 1: To a solution of a 3-aminothiophenol (5.0 g, 40.0 mmol) in DMF (80 mL) was added NaH (1.92 g, 48.0 mmol) at 0 °C. The mixture was stirred for 30 min in a sealed tube. Cyclopropyl bromide (7.26 g, 60.0mmol) was added in one portion. The reaction was heated to 100 °C, stirred overnight, then poured into water and extracted with EtOAc (2 × 100 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (100/1 to 20/1) to give the product m-(isopropylthio)aniline (5.1 g, yield 76.3%) as a yellow oil. ¹H NMR (300 MHz, CDCl₃): δ 7.10 (t, J = 7.8 Hz, 1H), 6.89-6.70 (m, 2H), 6.59 (d, J = 7.9 Hz, 1H), 3.42-3.32 (m, 1H), 1.31 (d, J = 6.7 Hz, 6H) ppm. [00686] Step 2: NaNO₂ (2.27 g, 32.9 mmol) in H₂O (10 mL) was added over 20 min to an ice-cooled and stirred suspension of m-(isopropylthio)aniline (5.0 g, 29.9 mmol) in 6N HCl (50 mL). After an additional 30 min, a suspension of SnCl₂·H₂O (13.4 g, 59.8 mmol) in 6N HCl (50 mL) was added slowly, and the resulting suspension was stirred at 0 °C for 2h. The pH was adjusted to 9-10 by 30% NaOH solution, and the mixture was extracted with EtOAc (2 × 200 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by silica chromatography eluting with PE/EtOAc (20/1 to 3/1) to give the product 3-(isopropylthio)phenylhydrazine (1.8 g, yield 33.1%) as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ 7.16 (t, J = 7.9 Hz, 1H), 6.95-6.81 (m, 2H), 6.70 (dd, J = 8.0, 1.5 Hz, 1H), 4.10 (s, 3H), 3.46-4.36 (m, 1H), 1.31 (d, J = 6.7 Hz, 6H) ppm. [00687] Step 3: To a solution of a 2-acetylphenylboronic acid (164 mg, 2.0 mmol) in DMSO (10 mL) was added 3-(isopropylthio)phenylhydrazine (364 mg, 2.0 mmol) at room temperature. The reaction was stirred for 30 min and poured into water. The solid was filtered and triturated with MeOH and H₂O (10 mL, v/v = 1:1), then filtered to give the desired product 2- [m-(isopropylthio)phenyl]-4-methyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (179 mg, yield 28.8%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.92 (s, 1H), 8.41 (d, J = 7.4 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 7.2 Hz, 1H), 7.68 (t, J = 7.2 Hz, 1H), 7.62 (s, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.20 (d, J = 7.7 Hz, 1H), 3.56-3.46 (m, 1H), 2.56 (s, 3H), 1.29 (d, J = 6.6 Hz, 6H) ppm. HPLC purity: 95.12% at 210 nm and 97.46% at 254 nm. MS: (M+H)⁺: m/z = 311.1. [00688] EXAMPLE 107 [00689] 2-[p-(Cyclopropylthio)phenyl]-4-propyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00690] The title compound was prepared by using the scheme and procedures shown below:

[00691] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- butanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added [p- (cyclopropylthio)phenyl]hydrazine (344 mg, 1.82 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN) to give the desired product 2-[p-(cyclopropylthio)phenyl]-4-propyl-1,2-dihydro- 2,3,1-benzodiazaborinin-1-ol (108 mg, yield 17.8%) as an orange solid. ¹H NMR (400 MHz, DMSO-d₆): δ 7.99-7.96 (d, J = 9.0 Hz 1H), 7.87-7.85 (d, J = 6.0 Hz, 1H), 7.80-7.75 (t, J = 15.0 Hz, 1H),7.58-7.53 (m, 2H) 7.22-7.08 (m, 2H), 7.2 (s, 2H), 2.94 (s, 2H), 1.85-1.69 (m, 3H), 1.00 – 0.95 (m, 3H), 0.83-0.81 (d, J = 5.7 Hz, 2H), 0.396 (s, 2H) ppm. MS: (M+H)⁺: m/z = 337.1. HPLC purity: 98.21% at 210 nm and 98.54% at 254 nm. [00692] EXAMPLE 108 [00693] 4-Butyl-2-[m-(isopropylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1- ol

[00694] The title compound was prepared by using the scheme and procedures shown below:

[00695] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- pentanone (500 mg, 1.7 mmol) in DMSO (10 mL) was added [m-(isopropylthio)phenyl]hydrazine (309 mg, 1.7 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-butyl-2-[m- (isopropylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (24 mg, yield 4.0%) as a white solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.93 (s, 1H), 8.42 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.79 (t, J = 7.1 Hz, 1H), 7.67 (d, J = 7.9 Hz, 2H), 7.52 (d, J = 8.3 Hz, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 3.59-3.45 (m, 1H), 2.96 (t, J = 7.3 Hz, 2H), 1.77-1.63 (m, 2H), 1.51-1.39 (m, 2H), 1.29 (d, J = 6.6 Hz, 6H), 0.94 (t, J = 7.2 Hz, 3H) ppm. HPLC purity: 99.65% at 210 nm and 99.90% at 254 nm. MS: (M+H)⁺: m/z = 353.2. [00696] EXAMPLE 109 [00697] 2-[m-(Cyclopropylthio)phenyl]-4-isopropyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00698] The title compound was prepared by using the scheme and procedures shown below:

[00699] To a solution of 2-methyl-1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]-1-propanone (500 mg, 1.8 mmol) in DMSO (10 mL) was added [m- (cyclopropylthio)phenyl]hydrazine (324 mg, 1.8 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 2-[m-(cyclopropylthio)phenyl]-4-isopropyl-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (17 mg, yield 2.8%) as a yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.92 (s, 1H), 8.42 (d, J = 6.7 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.82-7.76 (m, 1H), 7.75 (t, J = 1.9 Hz, 1H), 7.65 (t, J = 7.0 Hz, 1H), 7.55-7.47 (m, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.19-7.10 (m, 1H), 3.67-3.57 (m, 1H), 3.35-3.25 (m, 1H), 1.31 (d, J = 6.7 Hz, 6H), 1.17-1.05 (m, 2H), 0.70-0.56 (m, 2H) ppm. HPLC purity: 98.04% at 210 nm and 97.71% at 254 nm. MS: (M+H)⁺: m/z = 337.1. [00700] EXAMPLE 110 [00701] 4-Butyl-2-[m-(cyclopropylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol

[00702] The title compound was prepared by using the scheme and procedures shown below:

[00703] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- pentanone (500 mg, 1.7 mmol) in DMSO (10 mL) was added [m- (cyclopropylthio)phenyl]hydrazine (306 mg, 1.7 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-butyl-2-[m-(cyclopropylthio)phenyl]-1,2-dihydro-2,3,1-benzodiazaborinin- 1-ol (149 mg, yield 25.0%) as a light yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.89 (s, 1H), 8.41 (d, J = 6.9 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.82-7.74 (m, 1H), 7.70-7.62 (m, 2H), 7.46- 7.40 (m, 1H), 7.35 (t, J = 7.9 Hz, 1H), 7.21-7.14 (m, 1H), 3.01-2.91 (m, 2H), 2.34-2.24 (m, 1H), 1.77-1.65 (m, 2H), 1.50-1.37 (m, 2H), 1.14-1.04 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H), 0.66 – 0.9 (m, 2H) ppm. HPLC purity: 99.13% at 210 nm and 99.38% at 254 nm. MS: (M+H)⁺: m/z = 351.1. [00704] EXAMPLE 111 [00705] 2-[p-(Isopropylthio)phenyl]-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1- ol

[00706] The title compound was prepared by using the scheme and procedures shown below:

[00707] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- butanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added [p-(isopropylthio)phenyl]hydrazine (344 mg, 1.82 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC (0.1% TFA in MeCN and H₂O) to give the desired product 2-[p-(isopropylthio)phenyl]-4-propyl-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (42 mg, yield 7%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.93 (s, 1H), 8.42 (d, J = 7.1 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.72-7.60 (m, 2H), 7.56-7.47 (m, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 3.59-3.41 (m, 1H), 3.02-2.84 (m, 2H), 1.86-1.66 (m, 2H), 1.29 (d, J = 6.7 Hz, 6H), 1.01 (t, J = 7.3 Hz, 3H) ppm. MS: (M+H)⁺: m/z = 339.1. HPLC purity: 97.70% at 210 nm and 97.37% at 254 nm. [00708] EXAMPLE 112 [00709] 4-Cyclopropyl-2-[p-(isopropylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol

[00710] The title compound was prepared by using the scheme and procedures shown below:

[00711] To a solution of cyclopropyl[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]methanone (500 mg, 1.82 mmol) in DMSO (5 mL) was added [m- (isopropylthio)phenyl]hydrazine (330 mg, 1.83 mmol) at room temperature. The mixture was stirred for 30 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-cyclopropyl-2-[p-(isopropylthio)phenyl]-1,2-dihydro-2,3,1- benzodiazaborinin-1-ol (49 mg, yield 8%) as an orange solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.94 (s, 1H), 8.40-8.20 (m, 1H), 7.88-7.77 (m, 2H), 7.67-7.57(m, 1H), 7.15 (s, 1H), 7.12-7.02 (m, 3H), 3.09-3.02 (m, 1H), 1.26 (d, J=3.6 Hz, 1H), 1.00-0.87 (m, 10H) ppm. MS: (M+H)⁺: m/z = 337.1. HPLC: purity 96.84 % at 210 nm and 95.09 % at 254 nm. [00712] EXAMPLE 113 [00713] 4-Butyl-2-(p-chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00714] The title compound was prepared by using the scheme and procedures shown below:

[00715] To a solution of 1-[o-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1- pentanone (500 mg, 1.7 mmol) in DMSO (10 mL) was added 4-chlorophenylhydrazine (243 mg, 1.7 mmol) at room temperature. The mixture was stirred for 20 min. 6N HCl (5 mL) was added, and the mixture was stirred for another 1h, poured into water, and extracted with EtOAc (2 × 50 mL). The combined organic phases were dried and evaporated under reduced pressure. The residue was purified by pre-HPLC to give the desired product 4-butyl-2-(p-chlorophenyl)-1,2- dihydro-2,3,1-benzodiazaborinin-1-ol (106 mg, yield 20.0%) as a white solid. ¹H NMR (300 MHz, DMSO-d₆): δ 8.97 (s, 1H), 8.42 (d, J = 7.4 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.79 (t, J = 6.9 Hz, 1H), 7.66 (d, J = 8.7 Hz, 3H), 7.45 (d, J = 8.9 Hz, 2H), 3.04-2.87 (m, 2H), 1.84-1.59 (m, 2H), 1.55-1.32 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H) ppm. HPLC purity: 99.63% at 210 nm and 99.64% at 254 nm. MS: (M+H)⁺: m/z = 299.1. [00716] EXAMPLE 114 [00717] 6-Chloro-2-(p-chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol

[00718] The title compound was prepared by using the scheme and procedures shown below:

[00719] Step 1: To a solution of 2-bromo-5-chlorobenzaldehyde (2.2 g, 10 mmol) and (Bpin)2 (3.8 g 15 mmol) in dioxane (30 mL) was added AcOK (2.94 g, 30.0 mmol) and Pd(dppf)Cl₂ (816 mg, 1 mmol) at room temperature under N₂ atmosphere. The mixture was then heated to 80 °C for 2h. LCMS indicated the reaction was completed. The mixture was cooled to room temperature, diluted with EtOAc (20 mL), and filtered through a pad of CELITE. The filtrate was concentrated in vacuo and purified by silica chromatography eluting with PE/EtOAc (100:0 to 100:10) to give 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (2.1 g, yield 79%) as a white solid. ¹HNMR (400 MHz, CDCl₃): δ 10.59 (d, J = 1.0 Hz, 1H), 7.98-7.89 (m, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.60-7.50 (m, 1H), 1.39 (s, 12H) ppm. [00720] Step 2: To a suspension of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (532 mg, 2 mmol) in DMSO (5 mL) was added (4-chlorophenyl)hydrazine hydrochloride (356 mg, 2 mmol). The mixture was then stirred at room temperature for 30 min . 6N HCl (5mL) was added, and then the mixture was stirred at room temperature for another 30 min. The reaction was monitored by LCMS. The mixture was diluted with water (10 mL), extracted with EtOAc (15 mL×3)，washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The residue was purified by recrystallization with MeOH and water (v/v=4:1) to give the title compound 6-chloro-2-(p-chlorophenyl)-1,2-dihydro-2,3,1-benzodiazaborinin-1-ol (220 mg, 38%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.27 (s, 1H), 8.41 (d, J = 8.2 Hz, 1H), 8.22 (s, 1H), 7.96 (d, J = 1.8 Hz, 1H), 7.73 (dd, J = 8.2, 2.0 Hz, 1H), 7.66-7.57 (m, 2H), 7.51- 7.41 (m, 2H) ppm. MS: (M+H)⁺: m/z = 291.0. HPLC: 99.35 % at 210 nm and 99.45% at 254 nm. [00721] EXAMPLE 115 [00722] 8-Chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol

[00723] The title compound was prepared by using the scheme and procedures shown below:

[00724] A mixture of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (500 mg, 1.2 mmol) and hydrazine hydrate (1 mL) in THF (10 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC. After complete disappearance of 2-[2-chloro-4-(1,3-dioxolan-2-yl)-3-pyridyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, the mixture was filtered. The filter cake was washed with MeOH and dried to give the title compound 8-chloro-1,2-dihydro-2,3,7-triaza-1-bora-1-naphthol (150 mg, yield 48%) as a white solid. ¹H NMR (400 MHz, DMSO) δ 10.65 (s, 1H), 8.87 (s, 1H), 8.53 (d, J = 4.9 Hz, 1H), 8.30 (s, 1H), 8.11 (d, J = 4.9 Hz, 1H) ppm. HPLC purity: 98.96% at 210 nm and 99.39% at 254 nm. MS (M+H)⁺: m/z = 182.1. [00725] EXAMPLE 116 [00726] 6-chloro-1-hydroxy-2H-2,3,1-benzo diazaborinine

[00727] The title compound was prepared by using the scheme and procedures shown below:

[00728] Step 1: To a solution of 2-bromo-5-chloro-benzaldehyde (30.00 g, 136.70 mmol, 1 eq) in dioxane (400 mL) was added B2Pin2 (52.07 g, 205.05 mmol, 1.5 eq), KOAc (40.25 g, 410.09 mmol, 3 eq), and Pd(dppf)Cl₂-DCM (11.16 g, 13.67 mmol, 0.1 eq) in turns under N2. The mixture was stirred at 90 °C for 12 h under N2 protection. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (Petroleum ether/Ethyl acetate = 100/1 to 3/1) to afford 5-chloro-2-(4,4,5,5- tetramethyl -1,3,2-dioxaborolan -2-yl)benzaldehyde (30.00 g, 50% purity, crude) as a brown solid. [00729] Step 2: To a solution of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (20.00 g, 75.04 mmol, 1 eq) in THF (100 mL) and H₂O (100 mL) was added NaIO4 (48.15 g, 225.12 mmol, 12.47 mL, 3 eq) portion-wise. The resulting mixture was stirred at 30 °C for 3 h. The mixture was diluted with H₂O (200 mL) and then extracted with EtOAc (200 mL x 3). The combined organic phases was washed with brine (500 mL), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by Prep- HPLC (column: Phenomenex luna c18250mm*100mm*10um; mobile phase: [water (0.1%TFA)- ACN]; B%: 10%-40%, 15 min) to give (4-chloro-2-formyl-phenyl)boronic acid (2.90 g, 15.73 mmol, 20.96% yield) as a light yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 10.14 (s, 1H), 8.36 (br, s, 2H), 7.89 (s, 1H), 7.70 (d, J = 8.0Hz, 1H), 7.62 (d, J = 8.0Hz, 1H). [00730] Step 3: To a solution of (4-chloro-2-formyl-phenyl)boronic acid (69 mg, 372.94 umol, 1 eq) and 3-methyl-1,2,4-oxadiazole-5-carbohydrazide (53 mg, 372.94 umol, 1 eq) in EtOH (2 mL) was added NH₃.H₂O (261 mg, 1.86 mmol, 287.28 uL, 25% purity, 5 eq). The mixture was stirred at 60 °C for 2 h. The mixture was concentrated in vacuo and the residue was purified by Prep-HPLC (column: Waters Xbridge 150*255u; mobile phase: [water (10mM NH₄HCO3)-ACN]; B%: 10%-60%, 20 min) to give 6-chloro-1-hydroxy-2H-2,3,1-benzo diazaborinine (30 mg, 162.47 umol, 43.57% yield, 97.7% purity) as a white solid. (6-Chloro-1- hydroxy-1,2-dihydro-2,3,1-benzodiazaborinin-2-yl)(3-methyl-1,2,4-oxadiazol-5-yl)methanone was not obtained as a product. Since the hydrazino(3-methyl-1,2,4-oxadiazol-5-yl)methanone contains some NH₂NH₂.H₂O, the byproduct 6-chloro-1-hydroxy-2H-2,3,1-benzo diazaborinine was obtained after Prep-HPLC. ¹H NMR (DMSO-d₆, 400 MHz) δ 10.10 (s, 1H), 8.35 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.00 (s, 1H), 7.86 (d, J = 1.6 Hz, 1H), 7.63 (dd, J = 2.4, 8.4 Hz, 1H). MS (ESI): mass calcd. For C7H6BClN2O 180.03, m/z found 181.1 [M+H]⁺. HPLC: 97.70% (220 nm), 97.26% (254 nm). [00731] EXAMPLE 117 [00732] 1-Hydroxy-2H-thieno[3,2-d] diazaborinine

[00733] The title compound was prepared by using the scheme and procedures shown below:

[00734] To a solution of (2-formyl-3-thienyl)boronic acid (200 mg, 1.28 mmol, 1 eq) and NH₂NH₂ ^.H₂O (77 mg, 1.54 mmol, 75 uL, 1.2 eq) in EtOH (5 mL) was added NH₃ ^.H₂O (900 mg, 6.41 mmol, 1.0 mL, 25% purity, 5 eq) in one portion at 25 °C. The mixture was stirred at 60 °C for 2 h. The reaction mixture was concentrated in vacuo and the residue was triturated with MeCN (1 mL) to give 1-hydroxy-2H-thieno[3,2-d] diazaborinine (193 mg, 1.26 mmol, 98.02% yield, 98.98% purity) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 10.24 (s, 1H), 8.19 (s, 2H), 7.77 (d, J = 4.8 Hz, 1H), 7.63 (d, J = 4.8 Hz, 1H). MS (ESI): mass calcd. For C₅H₅BN₂OS 152.02, m/z found 151.1 [M-H]-. HPLC: 98.98% (220 nm), 99.3% (254 nm). [00735] EXAMPLE 118 [00736] 1-hydroxy-2-(3,4,5-trichlorophenyl) -7-(trifluoromethyl)-2,3,1- benzodiazaborinine

[00737] The title compound was prepared by using the scheme and procedures shown below:

[00738] Step 1: To an ice-cold aqueous solution of 12 N HCl (10 mL) and 3,4,5- trichloroaniline (2.00 g, 10.18 mmol, 885 uL, 1 eq) was added drop-wise an ice-cold solution of NaNO₂ (702 mg, 10.18 mmol, 1 eq) in H₂O (5 mL). The reaction mixture was stirred for 30 min at 0 °C. To the reaction mixture was added drop-wise an ice-cold solution of SnCl₂.2H₂O (6.89 g, 30.54 mmol, 3 eq) in 12 N HCl (20 mL). Then the reaction mixture was stirred at 0 w°C for 3 h. The reaction mixture was filtered and the filtrate was diluted with ice-water (w/w = 1/1) (100 mL). The pH of the aqueous phase was adjusted to 6-7 with solid NaOH and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=5/1 to 3/1) to give (3,4,5- trichlorophenyl)hydrazine (1.50 g, 7.09 mmol, 69.68% yield) as a brown solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 7.41 (s, 1H), 6.92 (s, 2H), 4.28 (s, 2H). [00739] Step 2: To a mixture of (3,4,5-trichlorophenyl)hydrazine (200 mg, 946 umol, 1.04 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzaldehyde (300 mg, 999 umol, 1.1 eq) in EtOH (5 mL) was added NH₃.H₂O (273 mg, 1.95 mmol, 0.3 mL, 25% purity, 2.14 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 2 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18100*25mm*3um;mobile phase: [water(0.1%TFA)-ACN];B%: 55%-85%,12min) to give 1-hydroxy-2-(3,4,5-trichlorophenyl) -7- (trifluoromethyl)-2,3,1-benzodiazaborinine (117 mg, 297 umol, 32.73% yield, 100% purity) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.84 (s, 1H), 8.83 (s, 1H), 8.39 (s, 1H), 8.10-8.07 (m, 1H), 8.05-8.03 (m, 1H), 7.96 (s, 2H). MS (ESI): mass calcd. For C₁₄H₇BCl₃F₃N₂O 391.97, m/z found 394.9 [M+H]⁺. HPLC: 100% (220 nm), 100% (254 nm). [00740] EXAMPLE 119 [00741] 1-Hydroxy-2-(3-methylsulfanylphenyl) -7-(trifluoromethoxy)-2,3,1- benzodiazaborinine

[00742] The title compound was prepared by using the scheme and procedures shown below:

[00743] Step 1: To a solution of 2-bromo-1-iodo-4-(trifluoromethoxy)benzene (5.00 g, 13.63 mmol, 1 eq) in dry THF (50 mL) was added a solution of iPrMgCl (1.3 M, 11.70 mL, 1.11 eq) drop-wise at -20 °C. The mixture was stirred at -20 °C for 10 min. The mixture was warmed slowly to 10 °C and stirred for 30 min. Then DMF (4.98 g, 68.15 mmol, 5.30 mL, 5 eq) was added in one portion and the resulting mixture was stirred at 10 °C for 1 h. The reaction mixture was quenched with sat. aq. NH₄Cl (100 mL) at 0 °C and extracted with EtOAc (30 mL x 3). The combined organic phases was washed with brine (50 mL ), dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=1/0 to 10/1) to give 2-bromo-4-(trifluoromethoxy) benzaldehyde (2.70 g, 10.04 mmol, 73.65% yield) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz) δ 10.32 (t, J = 2.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.52 (t, J = 5.2 Hz, 1H), 7.32-7.28 (m, 1H). [00744] Step 2: To a mixture of 2-bromo-4-(trifluoromethoxy)benzaldehyde (2.70 g, 10.04 mmol, 1 eq) in dioxane (40 mL) was added B2Pin2 (3.82 g, 15.05 mmol, 1.5 eq), KOAc (1.97 g, 20.07 mmol, 2 eq), and Pd(dppf)Cl₂ (587 mg, 803 umol, 0.08 eq) in turns at 25 °C under N2. Then the mixture was heated to 80 °C and stirred for 16 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO₂, Petroleum ether/Ethyl acetate=10/1 to 3/1) to give 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethoxy)benzaldehyde (2.50 g, 3.56 mmol, 35.46% yield, 45% purity) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 10.54 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.67 (s, 1H), 7.38 (d, J = 7.6 Hz, 1H), 1.40 (s, 12H). [00745] Step 3: To a mixture of (3-methylsulfanylphenyl)hydrazine (150 mg, 973 umol, 1 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethoxy)benzaldehyde (700 mg, 997 umol, 1.02 eq) in EtOH (5 mL) was added NH₃.H₂O (364 mg, 2.60 mmol, 0.4 mL, 25% purity, 2.67 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18100*25mm*3um;mobile phase: [water(0.1%TFA)-ACN];B%: 40%-80%,12min) to give 1-hydroxy-2-(3-methylsulfanylphenyl) -7- (trifluoromethoxy)-2,3,1-benzodiazaborinine (141 mg, 388 umol, 39.85% yield, 96.78% purity) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.23 (s, 1H), 8.39 (s, 1H), 8.28 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.46 (s, 1H), 7.36 (d, J = 2.0 Hz, 2H), 7.16-7.14 (m, 1H), 2.50 (s, 3H). MS (ESI): mass calcd. For C15H12BF3N2O₂S 352.07, m/z found 353.1 [M+H]⁺. HPLC: 96.78% (220 nm), 99.53% (254 nm). [00746] EXAMPLE 120 [00747] 1-Hydroxy-2- (3,4,5-trichlorophenyl)-7-(trifluoromethoxy)-2,3,1- benzodiazaborinine

[00748] The title compound was prepared by using the scheme and procedures shown below:

[00749] To a mixture of (3,4,5-trichlorophenyl)hydrazine (200 mg, 945.73 umol, 1 eq) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethoxy)benzaldehyde (598 mg, 853 umol, 0.9 eq) in EtOH (5 mL) was added NH₃.H₂O (364 mg, 2.60 mmol, 0.4 mL, 25% purity, 2.75 eq) in one portion at 25 °C. The mixture was heated to 50 °C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (column: Nano-micro Kromasil C18100*30mm 5um;mobile phase: [water(0.1%TFA)-ACN];B%: 70%-85%,10min) to give 1-hydroxy-2- (3,4,5-trichlorophenyl)-7- (trifluoromethoxy)-2,3,1-benzodiazaborinine (116 mg, 282.31 umol, 39.74% yield, 99.63% purity) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 9.74 (s, 1H), 8.39 (s, 1H), 8.33 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.96 (s, 2H), 7.79 (dd, J = 2.4, 9.2 Hz, 1H). MS (ESI): mass calcd. For C14H7BCl₃F3N2O₂407.96, m/z found 410.9 [M+H]⁺. HPLC: 99.63% (220 nm), 98.41% (254 nm). [00750] EXAMPLE 121 [00751] [4-chloro-2-[(Z)- [(6-chloropyridine-2 - carbonyl)hydrazono]methyl]phenyl]boronic acid

[00752] The title compound was prepared by using the scheme and procedures shown below:

[00753] Step 1: To a solution of methyl 6-chloropyridine-2-carboxylate (2.00 g, 11.66 mmol, 1 eq) in MeOH (20 mL) was added N2H4.H₂O (715 mg, 13.99 mmol, 694 uL, 98% purity, 1.2 eq) at 20 °C. The mixture was stirred at 20 °C for 4 h. The reaction mixture was concentrated under reduced pressure to remove MeOH. The residue was triturated with MTBE at 20 °C for 10 min. The result suspension was filtered, and the filter cake was washed with MTBE (5 mL x 3) to give 6-chloropyridine-2-carbohydrazide (1.00 g, 5.83 mmol, 50.00% yield) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 9.03 (br s, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 4.16 (d, J = 4.4 Hz, 2H). [00754] Step 2: A mixture of (4-chloro-2-formyl-phenyl)boronic acid (200 mg, 1.08 mmol, 1 eq) and 6-chloropyridine-2-carbohydrazide (205 mg, 1.19 mmol, 1.1 eq) in EtOH (10 mL) was stirred at 20 °C for 2 h under N2 atmosphere. The reaction mixture was filtered. The filter cake was washed with EtOH (5 mL x 3) and then dried in vacuo to give [4-chloro-2-[(Z)- [(6- chloropyridine-2 -carbonyl)hydrazono]methyl]phenyl]boronic acid (185 mg, 547.41 umol, 50.47% yield) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 12.24 (s, 1H), 8.96 (s, 1H), 8.52 (br s, 2H), 8.11-8.09 (m, 2H), 7.93 (d, J = 2.0 Hz, 1H), 7.80 (dd, J = 2.0 Hz, 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.46 (dd, J = 2.0 Hz, 8.0 Hz, 1H). MS (ESI): mass calcd. For C₁₃H₁₀BCl₂N₃O₃, 337.02, m/z found 336.0 [M-H]-. HPLC: N/A (220 nm), N/A (254 nm). [00755] EXAMPLE 122 [00756] [2-[(Z)-[(6-chloropyridine-2-carbonyl)hydrazono]methyl]phenyl]boronic acid

[00757] The title compound was prepared by using the scheme and procedures shown below:

[00758] To a solution of (2-formylphenyl)boronic acid (162 mg, 1.08 mmol, 1 eq) in EtOH (10 mL) was added 6-chloropyridine-2-carbohydrazide (204 mg, 1.19 mmol, 1.1 eq) in one portion. Then the mixture was stirred at 20 °C for 2 h under N2 atmosphere. The reaction mixture was filtered. The filter cake was washed with EtOH (5 mL x 3) and dried in vacuo to give [2-[(Z)-[(6-chloropyridine-2-carbonyl)hydrazono]methyl]phenyl]boronic acid (101 mg, 332.78 umol, 30.81% yield) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ 12.10 (s, 1H), 8.94 (s, 1H), 8.49 (br s, 2H), 8.12-8.09 (m, 2H), 7.92 (d, J = 7.2 Hz, 1H), 7.79 (dd, J = 1.6 Hz, 8.0 Hz, 1H), 7.63 (d, J = 7.2 Hz, 1H), 7.46 -7.39 (m, 2H). MS (ESI): mass calcd. For C₁₃H₁₁BClN₃O₃, 303.06, m/z found 302.0 [M-H]-. HPLC: N/A (220 nm), N/A (254 nm). [00759] Compounds may be made according to the general procedure, and are characterized as follows in Table A. Table A.

E

Section II: Biological Materials and Methods [00760] Throughout the examples, commercial active ingredients are used as positive controls for comparison purposes. These active ingredients are referred to by their common names (for example, fluopyram and fluazindolizine). Additionally, compounds of the present examples are referred to based on the designations within above Table A. Biological Example 1. Fungal Isolates [00761] The isolates of Botrytis cinerea B16, Botrytis cinerea B17, Candida albicans was obtained from the Plant Pathology and Environmental Microbiology Department at The Pennsylvania State University, University Park, PA. The Alternaria solani isolate was kindly gifted by Dr. Noah Rosenzweig at The Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, MI. The isolate Phytophthora capsici was obtained from the Texas A&M Agrilife Research, College Station, TX. The isolate of Zymoseptoria triticii CBS100329 was obtained from the Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands. The isolate of Phytophthora capcisi P1091 was obtained from American Type Culture Collection (ATCC), Manassas, VA. The isolate of Podosphaera xanthii was obtained from Dr. Lina Quesada-Ocampo at the Department of Entomology and Plant Pathology at North Carolina State University, Raleigh, NC. The isolate of Phakopsora pachyrhizi isolate was kindly gifted by Dr. Boyd Padgett at the Department of Plant Pathology and Crop Physiology, Louisiana State University, Baton Rouge, LA. Rhizoctonia solani (NRRL 66082) was obtained from USDA Agricultural Research Service. Pythium ultimum CBS588 was kindly gifted from Dr. Alejandro Rojas at the University of Arkansas . Fusarium oxysporum f.sp. glycines was obtained from ATCC (18774) and maintained on V8 agar. Fusarium virguliforme NRRL22292 was obtained from Travis Adkins at the USDA Agricultural Research Service and was also maintained on V8 agar. All cultures were grown at room temperature (~21C) with 12hr fluorescent light:12hr dark. [00762] Biological Example 2. Fungal and inoculum preparation [00763] Unless specified, most of the organisms were maintained on potato dextrose agar (PDA), and spores may be isolated from the cultures after 1-2 weeks of incubation at room temperature (20-22°C) with 12 hours fluorescent light (Philips, F40LW) and 12hours blacklight (Philips, F40T12) photoperiod. The final concentrations of all inocula were 1 x 10⁵ CFU/mL. [00764] Rhizoctonia solani: due to insufficient sporulation from these fungi, inoculum was prepared as mycelium visible fragments. In brief, fungal mycelium grown on agar media were cut into 1x1mm pieces and cultured in autoclaved broth medium (such as PDB and V8). After 3-7 days of incubation at 22-24°C, mycelia were harvested by filtering through one layer of Miracloth™ (Merck Millipore). The mycelia were homogenated in half strength of broth medium using household blender for 10 seconds and filtered through one layer of Miracloth™. The resultant visible fragments were diluted in half strength broth medium. [00765] Biological Example 3. In vitro antifungal efficacy of boron-based molecules [00766] A number of boron-based compounds were stocked in DMSO with the concentration of 5000 µg/mL (stored at -20°C). The stock solutions were further diluted into sterile half strength broth media in the in vitro assay, in which DMSO final concentration is not greater than 1% (v/v). [00767] The minimal inhibitory concentrations (MICs) for individual compounds were determined by following a modified broth microdilution protocol. The studies were performed in flat bottom, 96-well microtiter plates (Greiner Bio-One™, Greiner Bio-One North America, Inc., Monroe, NC). The individual MICs were determined in triplicate in a final volume of 0.2 mL/well with antifungal concentrations of 0.2 – 25 µg/mL (8 serial dilutions down from 25 µg/mL [25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 and 0.20 µg/mL]; control studies with 0 µg/mL of compounds were performed in parallel for each plate). [00768] Plates sealed with clear polyester film (VWR) were incubated at a temperature of about 22°C. The progress of fungal growth was monitored at 72 hours. The MICs were determined as the lowest antifungal concentrations that inhibited fungal growth by greater than 95% (determined as relative absorbance using the Bio-Tek® Synergy™ H1 microplate reader at 600 nm) relative to the corresponding antifungal-free control. When compounds were screened in vitro more than once, the average MIC of all trials is reported. [00769] Tables showing data against various fungi are provided as Figures. Biological Example 4. Agar-based antifungal efficacy of boron-based molecules [00770] A number of boron-based compounds were stocked in DMSO with the concentration of 5000 µg/mL (stored at -20°C). Stock solutions were further diluted in acetone to the final experimental concentrations. Grade AA 6mm antibiotic disks (Whatman) were soaked in these solutions for 1 hour prior to adding to 3 quadrants of ½-strength potato dextrose agar plates. One quadrant contained a disk with only acetone as a negative control. Agar medias for each fungal strain were the same as described in Biological Example 1. After compound-soaked disks were placed into quadrants of agar plates, a 6mm plug from the radial growth of a 2-week old agar culture was placed directly in the center of each plate. After 72 hour incubation (~21C; 12hr light:dark), fungal growth was measured from the inoculum plug to the edge of the petri dish across the treated disks. Percent inhibition was calculated by the following equation: (((Control growth – Treatment growth)/(Control growth))*100). [00771] Table 1: Agar-based Antifungal Disk Assay u^P % ^l _a ^R % o F %

Table 1. Percent inhibition values for compounds at 400ppm against soilborne fungal pathogens Pythium ultimum, Rhizoctonia solani, and Fusarium oxysporum. Biological Example 5: In vitro nematicidal efficacy of boron-based molecules [00772] Nematode inoculum: Soybean cyst nematode (SCN, Heterodera glycines) eggs were obtained from Cathy Johnson at the University of Minnesota Southern Research and Outreach Center in Watseca, MN. Root-knot nematode (RKN, Meloidogyne incognita) eggs were obtained from Dr. Gary Lawrence - Plant Diagnostics, LLC in Mt. Airy, NC. Roughly 1,000,000 eggs of each species were hatched by using a modified Baermann funnel described in Pettite et al., 2019. The eggs were placed on two layers of laboratory tissues supported by a wire screen sitting on a Petri dish filled with MilliQ (reverse osmosis, deionized water) water touching the bottom of the screen. This allowed hatched J2s to migrate through the laboratory tissue and fall into the petri dish. After 48-hour incubation at 30C, J2s of each species were collected into 50mL tubes and transported to the test facility. [00773] Compound preparation: Boron compounds were prepared as described previously.5mg/mL stocks in DMSO were supplied to in 96 well plates and 1 µL of this stock was dispensed into 100uL of sterile deionized water in column 2 of a new round bottom 96 well plate using a Biomek NX.1:2 dilutions in sterile deionized water were made from column 2 to column 11 as shown below. Negative control wells contained sterile, deionized water and positive control wells contained a mixture of 10ppm fluopyram and 10ppm abamectin. [00774] Assay: The hatched nematode J2 stocks were quantified via hemocytometer and diluted to 300 J2s/mL and 100uL was aliquoted into each well. Plates were incubated for 48 hours following addition of compounds. Activity was assessed using an LCD camera imaging system to determine nematode motility relative to the average motility of untreated nematodes in control wells containing DMSO with no compound. IDBS XLfit™ software was used to generate sigmoidal curves for EC50 determination in dose response plates. [00775] Post-processing: Due to time constraints, root-knot nematode data could not be generated using IDBS XLfit™ software, but a complete set of images was obtained. These images were evaluated in a similar fashion, using FIJI/ImageJ software to determine the number of motile nematodes in each well and the Schneider-Orelli formula was used to account for control mortality on each plate. Graphpad Prism 8 was used to convert the percent mortality data sets, using nonlinear regression analysis with a [Agonist/Inhibitor vs. normalized response] model, rendering EC50 values (Table 2). [00776] Table 2: Calculated Nematicidal Activity A

Table 2. EC50 values (in ppm) of compounds incubated with Meloidogyne incognita (RKN) or Heterodera glycines (SCN) in in vitro nematicide screens. Biological Example 6: In vitro nematicidal efficacy of boron-based molecules [00777] Nematode inoculum: RKN eggs were harvested from corn plants (Zea mays cv. Mycogen 2H723) in 500cm^3 pots in greenhouse. SCN eggs were harvested from soy plants (Glycine max) in 500cm^3 pots in greenhouse. Eggs were extracted by placing root systems in 0.625% NaOCl solution and agitating for 4min using rotary shaker at 120rpm. Eggs were rinsed with tap water, collected on 25um sieve, and separated by sucrose centrifugation- flotation at 240(x)g for 1min. Eggs were then placed in a Baermann funnel on a slide warmer and incubated at 31C for 5-7 days to obtain J2s. J2s were collected on a 25um sieve, and centrifuged at 5000(x)g for 1min, rinsed with sterile water, and diluted to 30-40 J2/10uL water. [00778] Assay: 10uL of J2 suspension were added to each well of a 96 well plate (30-40 J2/well).90uL of Boragen compounds (prepared as described above) diluted in sterile distilled water were added to wells at 5 rates (500, 100, 20, 5, 1ppm) with 3 replicates per treatment. Sterile distilled water was used as the negative control. Each plate was sealed with parafilm and incubated at room temp for 48hr. Numbers of live RKN and SCN were counted and recorded at experiment initiation and 48hr after exposure to compounds. Viability was determined by using a NaOH technique (Xiang & Lawrence 2016) to stimulate J2. Mortality percentage was calculated by using: [ (live J2 t0 - live J2 at 48h)/(live J2 t0)*100] (Table 3). [00779] Table 3:Calculated Nematicidal Activity B

Table 3. EC50 values (in ppm) of compounds incubated with Meloidogyne incognita (RKN) or Heterodera glycines (SCN) in in vitro nematicide screens. [00780] Biological Example 7: In vivo nematicidal and fungicidal efficacy of boron- based molecules Nematicidal efficacy [00781] Nematode inoculum: Nematodes were harvested from corn plants (Zea mays var. Mycogen 2H723) or soybean (Glycine max) in 500cm^3 pots in greenhouse. Eggs were extracted by placing root systems in 0.625% NaOCl solution and agitating for 4min using rotary shaker at 120rpm. Eggs were rinsed with tap water, collected on 25um sieve, and separated by sucrose centrifugation-flotation at 240g for 1min. Eggs were enumerated at 40x magnification and diluted to 2000 eggs/mL for greenhouse experiments. Work was conducted by Dr. Kathy Lawrence at Auburn University. Experiments were performed in 500cc Styrofoam pots with a sterilized 60:40 soil sand mix. Two squash (Curcurbita sp.) or corn (Zea mays) seeds were planted ~1cm deep in individual containers.1mL of 2000 RKN egg/mL was pipetted on seed at planting.15mL drench was applied to each pot. Example 1 was solubilized in acetone and diluted in water to make a 250ppm a.i. solution. Fluopyram was solubilized in acetone and diluted in water to make a 50ppm solution. Tap water was used as negative control. Experiments were arranged in randomized complete block design with 5 replicates per treatment. Plants were thinned to 1/pot after emergence. Plants were watered as needed and supplied with 1000- watt halide (110,000 lumen) light for 14hr/day. Experiments were terminated at 45 days after planting (squash was earlier). Plant height, shoot weight, root weight, and egg counts were recorded (Table 4). Treatment with boron-containing compounds significantly reduced RKN reproduction on maize and squash as compared to the negative control, with efficacy similar to the commercial a.i. fluopyram. Plant growth metrics were not significantly different between treatments in this study. Table 4:

Table 4. Mean number of root-knot nematode (Meloidogyne incognita) eggs per corn or squash plant one month after treatment. Fungicidal efficacy [00782] Inoculum: 2-week old agar cultures of Fusarium oxysporum, Fusarium virguliforme, Rhizoctonia solani, and Pythium ultimum (described in Biological Example 1) were diced and added to sterile beakers containing autoclaved sorghum grain and allowed to grow for an additional 2 weeks. [00783] Assay: Cone-tainers were filled halfway with 60% potting mix/40% play sand, followed by 2 grams of the infested grain, followed by another inch of soil/sand mix. Soybean (var. Envy) or cotton (Gossypium sp.var. PHY367WRF) were sown in cone-tainers and were drenched with 1mL of water (negative control), and Example 1 (1mg/mL) or fluopyram (1mg/mL) were applied, at planting. Plants were grown in a Conviron (23C, 16hr light:8hr dark) for 4 weeks. After 4 weeks, plants were removed from soil and dried at room temperature for 48 hours. Plant height, root length, and dry weights of the roots and shoots of each plant were recorded (Table 5). Treatment with boron-containing compounds resulted in increased biomass in cotton inoculated with Pythium ultimum and Rhizoctonia solani, and soybean inoculated with Fusarium virguliforme and Rhizoctonia solani. [00784] Table 5:

Table 5. Root and shoot weights of dried plants 4 weeks after treatment and inoculation (n=6). F. o: Fusarium oxysporum; F. v: Fusarium virguliforme; R. s: Rhizoctonia solani; P. u: Pythium ultimum. Biological Example 8: Nematicidal efficacy [00785] Inoculum: Root-knot nematode (RKN, Meloidogyne incognita) eggs were obtained from Dr. Gary Lawrence - Plant Diagnostics, LLC in Mt. Airy, NC. [00786] Assay: Cotton seeds (var. PHY367WRF) were sown in cone-tainers containing a 60% potting mix and 40% play sand. Seeds were drenched with 1mL of water, and Example 1 (1mg/mL) or fluopyram (1mg/mL) were applied at planting and subsequently inoculated with 15,000 root-knot nematode (RKN) eggs. Plants were grown in a Conviron (23C, 16hr light:8hr dark) for 4 weeks. After 4 weeks, plants were removed from soil and dried at room temperature for 48 hours. Plant height, root length, root gall rating (0=healthy roots, 5=severely galled roots), and dry weights of the roots and shoots of each plant were recorded (Table 6). [00787] Table 6: Treatment with boron-containing compounds significantly increased biomass and reduced RKN galling compared to the negative control.

Table 6. Mean root dry weight, shoot dry weight, root length, shoot length, and root gall ratings of cotton plants 4 weeks after treatment and inoculation with RKN. Levels not connected by the same letter are significantly different (t-test, a=0.05, n=10). Nematicidal and fungicidal efficacy [00788] Inoculum: Soybean cyst nematode (SCN, Heterodera glycines) eggs were obtained from Cathy Johnson at the University of Minnesota Southern Research and Outreach Center in Watseca, MN. A 2-week old V8 agar plate of Fusarium virguliforme was diced and placed in a sterile beaker containing autoclaved sorghum grain and allowed to grow for an additional 2 weeks. [00789] Assay: Cone-tainers were filled halfway with 60% potting mix/40% play sand, followed by 2 grams of the Fusarium-infested grain, followed by another inch of soil/sand mix. Soybean seeds (var. Envy) were sown in cone-tainers and were drenched with 1mL of water, and Example 1 (1mg/mL) or fluopyram (1mg/mL) were applied at planting and subsequently inoculated with 38,000 soybean-cyst nematode (SCN) eggs. Plants were grown in a Conviron (23C, 16hr light:8hr dark) for 4 weeks. After 4 weeks, plants were removed from soil and dried at room temperature for 48 hours. Plant height, root length, root cyst rating (0=healthy roots, 5=severely encysted roots), and dry weights of the roots and shoots of each plant were recorded (Table 7). [00790] Table 7: Treatment with boron-containing compounds significantly increased biomass and reduced SCN cyst development with similar efficacy as commercial a.i. fluopyram, compared to the negative control.

Table 7. Mean root dry weight, shoot dry weight, root length, shoot length, and root gall ratings of soy plants 4 weeks after treatment and inoculation with SCN and Fusarium virguliforme. Levels not connected by the same letter are significantly different (t-test, a=0.05, n=10). Biological Example 9: Okra Field Trial [00791] Cultural practices: Okra seeds, variety Clemson Spineless, were planted in 5’ x 23’ raised plastic mulched beds with double drip tape irrigation per bed at 10” spacing in a single row per plot. The trial was planted and maintained using methods that simulated commercial production of fresh market okra in Florida. [00792] Field prep. and maintenance: The trial area was broadcast fertilized before bedding with granular 6-7-10 at a rate of 1000 lbs/acre. Granular fertilizer contained 3.00% magnesium, 0.50% manganese, 0.08% iron, 0.29% zinc, and 0.05% boron as secondary and micronutrients. The fertilizer was incorporated into the soil with a tractor-mounted rototiller just prior to forming beds. Liquid 8-0-8 fertilizer was injected as needed through the drip system. Liquid 8-0-8 contained 1% magnesium and 0.04% chelated manganese as secondary and micronutrients. [00793] Application methods: A single drench application was conducted after planting, where all okra plants received 3 oz of treatment solution equivalent to 245 GPA. All treatments mixed well; no mixing issues were noticed. [00794] Evaluations: Plants were evaluated for phytotoxicity and none was observed. Soil samples were collected (one 5-core composite sample per replicate) to establish initial nematode population, where four (4) soil cores were collected from each plot were tested for nematode counts. One stand count and two plant height evaluations were conducted on this experiment. Plant vigor was evaluated using a Trimble GreenSeeker® to measure the vegetative index known as NDVI (normalized difference vegetative index). GreenSeeker® calculates NDVI using red and NIR (near-infrared) light. Red light is absorbed by plant chlorophyll as an energy source during photosynthesis. Healthy plants absorb more red light and reflect larger amounts of NIR than those that are less vigorous. An average reading was conducted per plot. At crop maturity, ten plants per plot were flagged and harvested four times over a 12-day period. Fruits over 3” long were collected, divided into small (3-5” long) and large (>5”), counted and weighed. A root knot evaluation was conducted where five plants from each plot were cut, dug, roots shaken, rinsed with water, and assessed for root galling based on a 0- 10 root gall index system (Bridge and Page).0 = no knots on roots, 1 = few small knots difficult to find, 2 = small knots only but clearly visible; main roots clean, 3 = some larger knots visible, but main roots clean, 4 = larger knots predominate but main roots clean, 5 = 50% of roots knotted; knotting on parts of main root system, 6 = knotting on some of main roots, 7 = majority of main roots knotted, 8 = all main roots knotted; few clean roots visible, 9 = all roots severely knotted; plant usually dying, 10 = all roots severely knotted; no root. Treatment with boron- containing compounds resulted in significantly reduced RKN galling as compared to the negative control. Also, no negative plant growth effects were observed after treatment with boron compound application. [00795] Table 8:

Table 8. Field trial results from GCC, July 2020. Levels not connected by the same letter are significantly different (ttest, a=0.05, n=30). [00796] Biological Example 10. In-field Meloidogyne incognita efficacy of boron- based molecules [00797] Cotton seeds were planted into four-row by 30-ft plots and replicated five times in a randomized complete block design. Four treatments (including an untreated control) were tested for efficacy in managing root-knot nematode (RKN) caused by Meloidogyne incognita. Prior to planting, soil samples were taken from each plot and RKN eggs were counted. An in- furrow application of treatments was applied at planting. Stand counts were taken in each plot 15 days after planting (DAP). A second soil sample was taken from each plot 59 DAP and RKN eggs were counted. Root gall count ratings were done at 59 and 149 DAP. At the completion of the growing season, each plot was harvested, and yield was calculated (156 DAP). Additionally, at harvest, a final soil sample was taken and RKN eggs were counted. [00798] Soil samples were taken from each plot, prior to planting. In each plot, 10 cores were taken throughout the plot and mixed together prior to analysis. Root-knot nematode eggs were then counted for each sample. This process was done again at 59 DAP and at harvest. At 59 DAP and 149 DAP, 10 plants were destructively sampled from each plot and given a 1-10 rating of root galling severity (1 being no galling, 10 being galled to the point of root girdling). Additionally, plant stand counts were taken from each plot 15 DAP by assessing the percentage of emerged plants in the middle two rows. Analysis of variance was used to examine nematode counts, stand counts, and yield data and means were separated using Fisher’s least significant difference at α=0.05. Results are as follows: [00799] Table 9: Root-knot nematode egg counts prior to planting and prior to treatment.

[00800] *Means followed by the same letter are not significantly different from each other (α=0.05). [00801] Table 10: Percent of cotton plants emerged in middle two rows in soil infested with root-knot nematode at 15 DAP.

[00802] *Means followed by the same letter are not significantly different from each other (α=0.05). [00803] Table 11: Root-knot nematode egg counts 59 DAP and treatment.

[00804] *Means followed by the same letter are not significantly different from each other (α=0.05). [00805] Table 12: Root-knot nematode egg counts 156 DAP and treatment.

[00806] *Means followed by the same letter are not significantly different from each other (α=0.05). [00807] Table 13: Root-knot nematode gall ratings (1-10) at 59 DAP and treatment.

[00808] *Means followed by the same letter are not significantly different from each other (α=0.05). [00809] Table 14: Root-knot nematode gall ratings (1-10) at 149 DAP and treatment.

[00810] *Means followed by the same letter are not significantly different from each other (α=0.05). [00811] Table 15: Cotton root-knot nematode trial yield data 156 DAP.

[00812] *Means followed by the same letter are not significantly different from each other (α=0.05). [00813] Biological Example 11. In-field Heterodera glycines efficacy of boron-based molecules [00814] Soybeans were planted into four-row by 30-ft plots and replicated five times in a randomized complete block design. Four treatments (including an untreated control) were tested for efficacy in managing soybean cyst nematode (SCN) caused by Heterodera glycines. Prior to planting, soil samples were taken from each plot and SCN eggs were counted. An in-furrow application of treatments was applied at planting. Stand counts were taken in each plot 13 days after planting (DAP). A second soil sample was taken from each plot 55 days after planting and SCN eggs were counted. At the completion of the growing season, each plot was harvested, and yield was calculated (146 DAP). Additionally, at harvest, a final soil sample was taken and SCN eggs were counted. [00815] Soil samples were taken from each plot, prior to planting. In each plot, 10 cores were taken throughout the plot and mixed prior to analysis. Soybean cyst nematode eggs were then counted for each sample. This process was done again at 55 DAP and at harvest. Additionally, plant stand counts were taken from each plot 13 DAP by assessing the number of emerged plants in 60 row-feet. Analysis of variance was used to examine nematode counts, stand counts, and yield data and means were separated using Fisher’s least significant difference at α=0.05. Results are as follows: [00816] Table 16: Soybean cyst nematode egg counts prior to planting and prior to treatment.

[00817] *Means followed by the same letter are not significantly different from each other (α=0.05). [00818] Table 17: Soybean stand counts per 60 row-feet in soil infested with soybean cyst nematode at 13 DAP.

[00819] *Means followed by the same letter are not significantly different from each other (α=0.05). [00820] Table 18: Soybean cyst nematode egg counts 55 DAP and treatment.

[00821] *Means followed by the same letter are not significantly different from each other (α=0.05). [00822] Table 19: Soybean cyst nematode egg counts 146 DAP and treatment.

[00823] *Means followed by the same letter are not significantly different from each other (α=0.05). [00824] Table 20: Soybean cyst nematode trial yield data 146 DAP.

[00825] *Means followed by the same letter are not significantly different from each other (α=0.05). [00826] Biological Example 12. Greenhouse Phakopsora pachyrhizi foliar efficacy of boron-based molecules [00827] Compounds were screened under greenhouse conditions against Asian soybean rust. Each compound was tested against 36 plants (3 doses, 4 plants per dose, 3 replication). Fourteen days after emergence of the soybean (V2-V3 growth stage), compound solutions were applied at three separate doses: 500, 250, and 125 ppm. Plants were allowed to dry for 24 hours. After 24 hours, plants were moved into a greenhouse room with optimal conditions for infection (28°C and 90% humidity). Inoculum was prepared by growing P. pachyrhizi on live, susceptible soybean plants at 28°C. Leaves were harvested and spores was washed off with sterile, distilled water. Spores were then place in a 0.1% Tween 20 (SigmaAldrich, St. Louis, MO) solution. Spore concentrations were adjusted to 1 x 10⁶ cfu/mL. Each plant was then soaked with the spore suspension. Ten to fourteen days after inoculation, when the untreated control plants reached 80-90% rust infection, disease ratings were taken and each plant was given a percent infection score. All data were reported and percent disease control compared to the untreated control plants. [00828] Table 21:

[00829] Biological Example 13. In vivo Post-Harvest Botrytis cinerea efficacy of boron-based molecules [00830] Compounds were screened under greenhouse conditions against grey mold of grape. Each compound was tested against 18 grapes (3 doses, 6 grapes per dose). Grapes were sanitized in 10% bleach solution and triple rinsed in ddH2o. Each grape was briefly submerged in compound solutions at three separate doses: 500, 250, and 125 ppm. Grapes were then allowed to dry for two hours. Inoculum was prepared by flooding a two week-old culture on PDA with ddH20 with 0.1% Tween20 and pouring off the supernatant Spore concentrations were adjusted to 1 x 10⁶ cfu/mL in ddH20 with 0.1% Tween20. Each plate of six grapes was then sprayed with 0.5mL of the spore suspension then allowed to dry. Seven to ten days after inoculation, when the untreated control grapes reached 80-90% grey mold infection, disease ratings were taken and each grape was given a percent colonization score. All data was reported and percent disease control was compared to the untreated controls. [00831] Table 22

[00832] Experimental details provided in the present disclosure are intended to be representative of activity of the compounds of the present disclosure. Additional and alternative activity may be demonstrated through one or more additional and alternative assays available to those skilled in the art. [00833] While this specification contains many specific implementation details, these should not be construed as limitations on the scope of any invention or on the scope of what may be claimed, but rather as descriptions of features that may be specific to particular implementations of particular inventions. Certain features that are described in this specification in the context of separate implementations may also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation may also be implemented in multiple implementations separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination may in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or variation of a sub-combinations. [00834] Particular implementations of the subject matter have been described. Other implementations, alterations, and permutations of the described implementations are within the scope of the following claims as will be apparent to those skilled in the art. For example, the actions recited in the claims may be performed in a different order and still achieve desirable results. [00835] Accordingly, the above description of example implementations does not define or constrain this disclosure. Other changes, substitutions, and alterations are also possible without departing from the spirit and scope of this disclosure. [00836] A number of embodiments of the present disclosure have been described. While this specification contains many specific implementation details, the specific implementation details should not be construed as limitations on the scope of any disclosures or of what may be claimed, but rather as descriptions of features specific to particular embodiments of the present disclosure. [00837] In certain implementations, multitasking and parallel processing may be advantageous. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the claimed disclosure.

Claims

WHAT IS CLAIMED IS: 1. A compound of formula (I):

wherein: A is an aryl or heteroaryl; each occurrence of X is independently selected from the group consisting of: fluorine, chlorine, bromine, and iodine; n is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when n is 0, X is absent; R¹ is selected from the group consisting of: hydrogen, C₁-C₄ hydrocarbyl, and C₃-C₄ cyclohydrocarbyl; and R² is selected from the group consisting of: aryl, heteroaryl, C₁-C₆ hydrocarbyl, and C₃-C₆ cyclohydrocarbyl, where each R² is substituted with (Y)_m; wherein: each occurrence of Y is independently selected from the group consisting of: fluorine, chlorine, bromine, iodine, C₁-C₆ hydrocarbyl, C₁-C₆ halohydrocarbyl, O(C₁-C₆ hydrocarbyl), S(C₁-C₆ hydrocarbyl), O(C₁-C₆ halohydrocarbyl), S(C₁-C₆ halohydrocarbyl), S(O)_w(C₁-C₆ hydrocarbyl), S(O)_w(C₁-C₆ halohydrocarbyl), O(C₃-C₆ cyclohydrocarbyl), S(C₃-C₆ cyclohydrocarbyl), O(C₃-C₆ heterocyclohydrocarbyl), S(C₃-C₆ heterocyclohydrocarbyl), NO₂, CN, C(O)O(C₁-C₆ hydrocarbyl),; and m is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when m is 0, Y is absent, w is number selected from the group consisting of 1 and 2; wherein when A is a heterorayl, the heteroaryl contains 1 ring or 2 fused rings and includes 1, 2, or 3 ring heteroatoms that are the same or different and wherein each is selected from one or more of nitrogen, oxygen, and sulfur, or a salt, stereoisomer, enantiomer, or tautomer thereof. 2. A compound of formula (I’):

wherein: A is an aryl or heteroaryl; each occurrence of X is independently selected from the group consisting of: fluorine, chlorine, bromine, and iodine; n is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when n is 0, X is absent; R¹ is selected from the group consisting of: hydrogen, C₁-C₄ hydrocarbyl, and C₃-C₄ cyclohydrocarbyl; and R² is selected from the group consisting of: aryl, C₁-C₆ hydrocarbyl, and C₃-C₆ cyclohydrocarbyl, where each R² is substituted with (Y)_m; wherein: each occurrence of Y is independently selected from the group consisting of: fluorine, chlorine, bromine, iodine, C₁-C₆ hydrocarbyl, C₁-C₆ partially of fully fluorinated hydrocarbyl, O(C₁-C₆ hydrocarbyl), and S(C₁-C₆ hydrocarbyl); and m is a number selected from the group consisting of: 0, 1, 2, 3, and 4, such that when m is 0, Y is absent, wherein when A is a heterorayl , the heteroaryl contains 1 ring or 2 fused rings and includes 1,

2, or 3 ring heteroatoms that are the same or different and wherein each is selected from one or more of nitrogen, oxygen, and sulfur, or a salt, stereoisomer, enantiomer, or tautomer thereof.

3. The compound of claim 1 or 2, wherein at least one of m or n is not 0.

4. The compound of any one of claims 1 to 3, wherein A is phenyl or pyridine.

5. The compound of any one of claims 1 to 4, wherein the compound is a compound of formula Ia:

6. The compound of any one of claims 1 to 5, wherein the compound is a compound of formula Ib:

7. The compound of any one of claims 1 to 6, wherein R¹ is hydrogen, methyl, or ethyl.

8. The compound of any one of claims 1 to 7, wherein R² is phenyl or substituted phenyl.

9. The compound of any one of claims 1 to 8, wherein the sum of m and n is 1, 2, or 3.

10. The compound of any one of claims 1 to 8, wherein m is 1 and n is 0.

11. The compound of any one of claims 1 to 8, wherein m is 1 and n is 1.

12. The compound of any one of claims 1 to 8, wherein m is 2 and n is 1.

13. The compound of any one of claims 1 to 12, wherein each X is independently selected from the group consisting of fluorine and chlorine.

14. The compound of any one of claims 1 to 13, wherein each Y is independently selected from the group consisting of: fluorine, chlorine, SCH₃, OCH₃, CH₃, and CF₃.

15. A compound selected from the group consisting of:

or a salt thereof.

16. A compound selected from the group consisting of:

or a salt thereof

17. A compound selected from

or a salt thereof.

18. A compound selected from:

or a salt thereof.

19. A compound selected from the group consisting of:

or a salt thereof.

20. A method for reducing, preventing, ameliorating, or inhibiting an infestation by a pathogen by applying a compound or a composition according to any one of claims 1 to 19.

21. The method of claim 20, wherein the pathogen is phytopathogenic.

22. The method of claim 20 or 21, wherein the pathogen is a soil-borne pathogen.

23. The method of any one of claims 20 to 22, wherein the pathogen is a fungus.

24. The method of any one of claims 20 to 22, wherein the pathogen is a nematode.

25. The method of any one of claims 20 to 22, wherein the pathogen includes both a fungus and a nematode.

26. The method of any one of claims 20 to 25, wherein the pathogen is selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, Phoma, Plasmodiophora, and Spongospora.

27. The method of any one of claims 20 to 26 wherein the pathogen is a nematode from the class Chromodorea, Rhabditida, or Enoplea.

28. The method of any one of claims 20 to 27, wherein the pathogen is a nematode from the genera Xiphinema, Roylenchulus, Tylenchulus, Helicotylenchus, Pratylenchus, Radopholus, Hirschmanniella, Heterodera, Globodera, Meloidogyne, Ditylenchus, Bursaphelencus, Anguina, Aphelenchoides. Longidorus, or Paratrichodorus

29. The method of claim 25, wherein the pathogen is a fungus selected from the group consisting of: Pythium, Phytophthora, Rhizoctonia, Cylindrocladium, Fusarium, Verticillium, Sclerotinia, Aphanomyces, Bremia, Monosporascus, Helminthosporium, Armilaria, Rhizopus, Mucor, Glomerella, Colletotrichum, Candida, Stagonosporum, Penicillium, Phomopsis, Diplodia, Sclerotium, and Phoma; and a nematode selected from the class consisting of: Chromodorea, Rhabditida, and Enoplea.

30. The method of claim 25, wherein: the fungus is Fusarium and the nematode is soybean cyst nematode, or the fungus is Verticillium and the nematode is Pratylenchus, or the fungus is Fusarium (oxy) and the nematode is root knot nematode.

31. The method of any one of claims 20 to 30, wherein the compound is applied to one or more of a plant, a plant part, plant propagation material, and soil.

32. The method of any one of claims 20 to 31, wherein the application of the compound or the composition is selected from the group consisting of: topical, to the soil, foliar, a foliar spray, a seed coating, a seed treatment, a soil drench, directly in-furrow dipping, drenching, soil drenching, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, overhead chemigation, watering (drenching), and drip irrigating, or any combinations thereof.

33. The method of any one of claims 20 to 32, wherein the application of the compound or the composition is a seed treatment.

34. A method or use for treating a fungal infection by applying a compound or a composition according to any one of claims 1 to 19.

35. The method or use of claim 34, wherein the fungal infection is a True Fungal infection.

36. The methof or use of claim 34, wherein the fungal infection is a fungal-like infection.

37. The method or use of any one of claims 34 to 36, wheren the fungal infection is caused by an organism characterized as Ascomycota, Basidiomycota, Cercozoa, Chytridiomycota, Deuteromycota (fungi imperfecti), Glomeromycota, Oomycota, or Zygomycota.

38. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Ascomycota.

39. The method or use of claim 38, wherein the fungal infection is further characterized as Pzizomycotina, Saccharomycotina, Taphrinomycotina, Arthoniomycetes, Coniocybomycetes, Dothideomycetes, Eurotiomycetes, Geoglossomycetes, Laboulbeniomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes, Omnivoromycetes, Orbiliomycetes, Pezizomycetes, Sordariomycetes, Xylonomycetes, Lahmiales, Itchiclahmadion, Triblidiales, Saccharomycetes, Archaeorhizomyces, Neolectomycetes, Pneumocystidomycetes, Schizosaccharomycetes, or Taphrinomycetes.

40. The method or use of any one of claims 34 to 36, wherein the fungal infection is characterized as Basidiomycota.

41. The method or use of claim 40, wherein the fungal infection is the Basidiomycota is further characterized as Pucciniomycotina, Ustilaginomycotina, or Agaricomycotina.

42. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Cercozoa.

43. The method or use of claim 42, wherein the Cercozoa is further chracterized as Endomyxa, Phytomyxea, Plasmodiophoromycota, or Phagomyxida.

44. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Chytridiomycota.

45. The method or use of claim 44 wherein the Chytridiomycota is further characterized as Synchytriales.

46. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Glomeromycota.

47. The method or use of claim 46, wherein the Glomerocycota is further characterized as Achaeosporales, Diversisporales, Glomerales, Paraglomerales, or Nematophytales.

48. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Oomycota.

49. The method or use of claim 48, wherein the Oomycota is further characteriezed as Lagenidiales, Leptomitales, Peronosporales, Phipidiales, or Saprolegniales.

50. The method or use of any one of claims 34 to 36, wherein the fungal infection is caused by a fungal organism characterized as Zygomycota.

51. The method or use of claim 50, wherein the Zygomycota is further characterized as Mucoromycotina, Kickxellomycotina, Entomophthoromycotina, Zoopagomycotina; Endogonales, Mucorales, Mortierellales, Asellariales, Kickxellales, Dimargaritales, Harpellales, Entomophthorales, and Zoopagales.

52. The method or use of any one of claims 34 to 36, wherein the fungal infection is selected from one or more of the group consisting of Alternaria, Aspergillus, Bipolaris, Blumeria, Botrytis, Candida, Cercospora, Cercosporidium, Claviceps, Cochliobolus, Colletotrichum, Corynespora, Dybotryon, Dilophospora, Erysiphe, Exserohilum, Fusarium, Leveillula, Magnaporthe, Melampsora, Microsphaera, Microsphaeropsis, Monilia, Monilinia, Mycosphaerella, Oidiopsis, Peronospora, Phaeosphaeria, Phakopsora, Phomopsis, Phymatotrichum, Phytophthora, Plasmopora, Podosphaera, Pseudoperonospora, Puccinia, Pyrenophora, Pyricularia, Pythium, Rhizoctonia, Sclerophthora, Sclerotinia, Septoria, Setosphaeria, Stangospora, Uncinula, Ustilago, Venturia, Verticillium, and Zymoseptoria.

53. The method or use of any one of claims 34 to 36, wherein the fungal infection is selected from one or more of the group consisting of Alternaria, Aspergillus, Bipolaris, Blumeria, Botrytis, Candida, Cercospora, Cercosporidium, Colletotrichum, Corynespora, Erysiphe, Fusarium, Magnaporthe, Mycosphaerella, Peronospora, Phaeosphaeria, Phakopsora, Phytophthora, Plasmopora, Podosphaera, Pseudoperonospora, Puccinia, Pyricularia, Pythium, Rhizoctonia, Sclerotinia, Septoria, Stangospora, Verticillium, and Zymoseptoria.

54. The method or use of any one of claims 34 to 53, wherein the plants or plant propagation material is agricultrual, horticultural, or ornamental.

55. The method or use of any one of claims 34 to 53, wherein the plant propagation materials is seed.

56. The method or use of any one of claims 34 to 53, wherein the plants or plant propagation materials are one or more of maize, soya bean, alfalfa, cotton, sunflower, Brassica oil seeds, Brassica napus, Brassica rapa, B. juncea, Brassica carinata, Arecaceae sp., Rosaceae sp., Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp., Rubiaceae sp., Theaceae sp., Sterculiceae sp., Rutaceae sp., Solanaceae sp., Liliaceae sp., Compositae sp., Umbelliferae sp., Cucurbitaceae sp., Alliaceae sp., Cruciferae sp., Leguminosae sp., Chenopodiaceae sp., Linaceae sp., Cannabeacea sp., Malvaceae sp., Papaveraceae, Asparagaceae, Stevia rebaudiana, and genetically modifed versions thereof.

57. The method or use of any one of claims 34 to 53, wherein the plants or plant propagation materials are one or more of a variety of soybean. In one aspect, the plants or plant propagation materials are one or more of the family Solanaceae sp. In one aspect, the plants or plant propagation materials are one or more of tomatoes, potatoes, peppers, tomatillo, aubergines, and tobacco.

58. The method or use of any one of claims 34 to 53, wherein the plants or plant propagation materials are one or more of: (a) Fabaceae: soybean, dry beans, peanuts; (b) Poaceae: grasses including maize, wheat, rice, barley, and millet; (c) Solanaceae: tomato, potato, eggplant, peppers; (d) Cucurbitaceae: squash, pumpkin, zucchini, gourds, watermelon, melons, cucumber; (e) Rosaceae: apple, pear, quinces, apricots, plums, cherries, peaches, raspberries, strawberries, almonds; (f) Brassicaceae: broccoli, cabbage, cauliflower, kale, collards, turnips, rapeseed, radish; (g) Asteraceae or Compositae: lettuces, sunflower, artichoke; (h) Amaranthaceae: spinach, beets, chard, quinoa; (i) Convolvulaceae: sweet potato; (j) Amaryllidaceae: onion, chive, leek, garlic; (k) Ubelliferae: carrots, celery, cilantro, parsley, dill, fennel; (l) Rutaceae: citrus fruit; (m) Juglandaceae: walnut, pecan; (n) Fagaceae: oak, beeches, chesnut; (o) Pinaceae: cedar, fir, hemlock, spruce, pine; and (p) Anacardiacea: cashew, mango, pistachio.

59. The method or use of any one of claims 34 to 53, wherein the compound or composition is applied to one or more of a plant, a plant part, plant propagation material, and soil.

60. The method or use of any one of claims 34 to 53, wherein the application of the compound or the composition is selected from the group consisting of: topical, to the soil, foliar, a foliar spray, a seed coating, a seed treatment, a soil drench, directly in-furrow dipping, drenching, soil drenching, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, overhead chemigation, watering (drenching), and drip irrigating, or any combinations thereof.

61. The method or use of any one of claims 34 to 53, wherein the application of the compound or the composition is a seed treatment.

62. A composition comprising a compound of any one of claims 1 – 19 and one or more carrier.

63. The composition of claim 62, in the form of a powder.

64. The composition of claim 62, in the form of a liquid.

65. The composition of claim 64, wherein the liquid is at least 50 percent water.

66. The composition of claim 64 or 65, having a pH value of about 5 to about 10.

67. A composition comprising a compound of any one of claims 1 – 19 and one or more additional active agent.

68. The compositon of claim 67 and one or more additional active agent is selected from the group consisting of: a fungicide, a nematicide, an insecticide, and a bactericide, or any combination thereof.

69. The compositon of claim 68, wherein the one or more additional active agent is a fungicide.

70. The compositon of claim 69, wherein the fungicide has a mode as action as described by a FRAC target site code.

71. The compositon of claim 70, wherein the FRAC target site code is selected from the group consisting of: B1, B3, C2, C3, C4, C6, D1, E1, E2, E3, G1, H5, M4, and M5.

72. The compositon of any one of claims 67 to 71, wherein the additional active agent is a fungicide selected from the group consisting of: carbendazim, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, zoxamide, ethaboxam, pencycuron, fluopicolide, metrafenone, pyriofenone, flutolanil, fluopyram, fluxapyroxad, penthiopyrad, benodanil, mepronil, isofetamid, fenfuram, carboxin, oxycarboxin, thifluzamide, benzovindiflupyr, bixafen, furametpyr, inpyrfluxam, isopyrazam, penflufen, sedaxane, isoflucypram, pydiflumetofen, pyraziflumid, boscalid, benomyl, fuberidazole, diflumetorim, tolfenpyrad, fenazaquin, azoxystrobin, coumaxystrobin, enoxastrobin, flufenoxystrobin, picoxystrobin, pyraoxystrobin, mandestrobin, pyraclostrobin, pyrametostrobin, triclopyricarb, kresoxim-methyl, trifloxystrobin, dimoxystrobin, fenamistrobin, methominostrobin, orysastrobin, famoxadone, fluoxastrobin, fenamidone, pyribencarb, cyazofamid, amisulbrom, fenpicoxamid, binapacryl, meptyldinocap, dinocap, fluazinam, ferimzone, fentin chloride, fentin acetate, fentin hydroxide, silthiofam, ametoctradin, cyprodinil, mepanipyrim, pyrimethanil, kasugamycin, blasticidin-s, quinoxyfen, proquinazid, fenpiclonil, fludioxonil, nuarimol, imazalil, oxpoconazole, pefurazoate, prochloraz, triflumizole, azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, prothioconazole, aldimorph, dodemorph, fenpropimorph, tridemorph, fenpropidin, spiroxamine, fenhexamid, fenpyrazamine, piperalin, pyributicarb, naftifine, terbinafine, validamycin, polyoxin, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, valifenalate, mandipropamid, copper, sulphur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, zinc thiazole, ziram, captan, captafol, folpet, dichlofluanid, tolylfluanid, chlorothalonil, chlozolinate, dimethachlone, anilazine, iprodione, procymidone, vinclozolin, triforine, pyrifenox, pyrisoxazole, fenarimol, guazatine, iminoctadine, dithianon, chinomethionat, quinomethionate, fluoroimide, methasulfocarb, and phenamacril.