Compositions comprising nitrification inhibitors

Abstract

Disclosed herein are compositions comprising certain heterocyclic nitrification inhibitors showing beneficial effects on plant growth and / or vigor. In some aspects, the agrochemical compositions disclosed herein comprise an additional active, wherein the active is selected from the group consisting of an insecticide, nematicide, fungicide, inoculant and a biological agent.

Description

COMPOSITIONS COMPRISING NITRIFICATION INHIBITORS

[0001] This disclosure relates to agrochemical compositions comprising nitrification inhibitors.

[0002] Nitrogen is an essential element for plant health. In growing media (e.g., soil), bound nitrogen can be present in the form of ammonium compounds or nitrates. The ammonium form of nitrogen is preferred because it is readily incorporated into plants. In contrast, nitrate nitrogen must be reduced to ammonium by the plant before it can be used, an energetically costly process. Accordingly, it is beneficial to keep the media-bound nitrogen in the form of ammonium compounds; otherwise, it will be converted to the nitrates that cannot be directly used by the crops. Certain ammonia-oxidizing bacteria of the genera Nitrosomoncis and Nitrobacter convert the ammonium nitrogen to nitrates process known as nitrification. This process leads to the loss of ammonium nitrogen. Therefore, it is important to prevent or inhibit the nitrification process. In this regard, certain chemical compounds selectively inhibit the growth of bacterial strains that facilitate the nitrification process. These compounds are called nitrification inhibitors.

[0003] Disclosed herein are agrochemical compositions comprising particular nitrification inhibitors possessing desirable agrochemical properties.SUMMARY

[0004] The agrochemical compositions disclosed herein comprise at least one nitrification inhibitor illustrated in Table 1. In some aspects, the compositions disclosed herein comprise A) at least one nitrification inhibitor selected from the group consisting of F1-F403 and B) another active selected from the group consisting of an insecticide, nematicide, fungicide, biological agent and / or an inoculant. Disclosed herein are also methods of using such agrochemical compositions to promote plant growth or vigor.DESCRIPTION OF THE DRAWINGS

[0005] Figure 1-1. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 3 days after emergence (DAE) for nitrogen inhibitor compound F402 comparing 100 ug ai / seed and 250 ug ai / seed rates.

[0006] Figure 1-2. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 3 days after emergence (DAE) for nitrogen inhibitor compound F402 + fungicide seed treatment (FST) + insecticide seed treatment (1ST) comparing 100 ug ai / seed and 250 ug ai / seed rates.

[0007] Figure 2-1. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 3 days after emergence (DAE) for nitrogen inhibitor compound F403 comparing 100 ug ai / seed and 250 ug ai / seed rates.

[0008] Figure 2-2. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 5 days after emergence (DAE) for nitrogen inhibitor compound F403 + fungicide seed treatment (FST) + insecticide seed treatment (1ST) comparing 100 ug ai / seed and 250 ug ai / seed rates.

[0009] Figure 3-1. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 5 days after emergence (DAE) for nitrogen inhibitor compound F401 comparing 100 ug ai / seed and 250 ug ai / seed rates.

[0010] Figure 3-2. Average standard deviation in hyperspectral wavelength (400 - 1000 nm) at 6 days after emergence (DAE) for nitrogen inhibitor compound F403 + fungicide seed treatment (FST) + insecticide seed treatment (1ST) comparing 100 ug ai / seed and 250 ug ai / seed rates.DETAILED DESCRIPTION

[0011] A number of nitrification inhibitors are known including linoleic acid, a-linoleic acid, m ethyl - / i-coumarate, methyl ferulate, MHPP, Karanjin, brachialacton, 2-chloro-6- trichlorom ethylpyridine (nitrapyrin), dicyandiamide, 3,4-dimethylpyrazole phosphate, 4-amino-1.2.4-triazole hydrochloride, l-amido-2-thiourea, 2-amino-4-chloro-6-methylpyrimidine, 5- ethoxy-3-trichloromethyl-l,2,4-thiodiazole, 2-sulfanilamidethiazole, 3, 5 -dimethyltetrahydro-1.3.5-thiadiazine-2-thione (dazomet).

[0012] These nitrification inhibitors are expected to show beneficial effects on crops related to inhibition of the nitrification process. That is, they increase the availability of absorbable nitrogen. However, it is known that the nitrogen uptake and / or demand is minimal in the early stages of the plant growth and development. Thus, the beneficial effects of nitrogen inhibition are not visible or measurable until plants enter accelerated and peak uptake stages. Generally, the nitrogen uptake drastically increases around 30 days after the emergence (Bender, R.R, J.W. Haegele, M.L. Ruffo, and F.E. Below. 2013. Nutrient uptake, partitioning, and remobilization in modern, transgenic insect-protected maize hybrids. Agron. J. 105:161-170.

[0013] Certain substituted heterocyclic compounds have shown a potent nitrification inhibition activity (See Table 1). Surprisingly and unexpectedly, it has been found that these compounds also show other important beneficial effects on plants when applied at certain stages.In particular, when the nitrification inhibitor compounds were applied at pre-emergence stages, they exhibited surprising beneficial effects on plant growth and vigor. In particular aspects, these beneficial effects are manifested at VE-V3 growth stages (emergence to plants with three visible collared leaves (com) or leaflets on the first unifoliate through the 4thnode leaf (soybean)).

[0014] In this regard, seed treatment, that is treating a seed or any other plant propagule with the nitrification inhibitor compounds disclosed herein, enables achieving the beneficial effects on the plant growth on the plants grown from such treated seeds. For example, a plant grown from a treated seed, that is a seed coated, applied, or mixed with compositions disclosed herein, shows beneficial effects on plant growth and vigor at VE-V3 growth stages. Generally, in field conditions, new vegetative (V) growth stages appear about every 4 days for com and every five days for soybean. In a greenhouse with ideal temperature and growth conditions the growth stages from VE to V3 can occur in approximately 10 total days after planting.

[0015] In one aspect of the compositions disclosed herein, a plant propagule is treated with a composition comprising nitrification inhibitors. In a particular aspect, the plant propagule is a seed. As used herein “treating” means coating, dipping, spraying, dusting, or mixing a seed with a composition disclosed herein. Various agrochemically-useful formulations known in the art can be used for this purpose.

[0016] The effects on plant growth or vigor can be measured using any of the state-of-the-art indications that visually or otherwise reflect the effects of these compositions on a plant. For example, pixel area, average green index, leaf size, leaf length, shoot length, root density, root thickness, root length, oil content of the plants, number of flowers, and size and number of fruits are indications that can be used to measure the plant growth or vigor in comparison to a control specimen. These parameters can be measured visually. However, there are more sensitive and precise measurement techniques such as spectral-based methods that have been developed. In this regard, using a hyperspectral imaging spectroscopic method offers unique aspects of precision, efficiency, and accuracy.

[0017] Hyperspectral image analysis techniques utilizing spectral reflectance to identify subtle differences in plant growth as a non-destructive assay have been developed (Lowe, A., N. Harrison, and A.P. French. 2017. Hyperspectral image analysis techniques for the detection and classification of early onset of plant disease and stress. Plant Methods 13:80. doi 10.1186 / sl3007-017-0233-z). Hyperspectral cameras can capture the spectrum from 250nanometers (nm) to 2500 nm, which is a much wider range than the 400 nm to 700 nm visible to the human eye (Lowe et al., 2017). For measuring plant growth, the most commonly used wavelengths combine the visible range with the near-infrared range (400 nm-1000 nm), which can capture changes in leaf coloration and cell structure (Lowe et al., 2017). Developing an assay with hyperspectral precision enables objective quantification, whereas traditional methods of different individuals visually scoring field plots across different locations introduces variability inherent with subjectivity of observer bias and inconsistencies between observers.

[0018] The Mahalanobis distance is a measure of the distance between a datapoint and the distribution of data, quantifying the number of standard deviations the datapoint is away from the mean of the distribution. The larger the value, the further away the seed treatment is from the control. Within each plant age, the different nitrogen inhibitor compounds were significantly different compared to the not treated control and significantly different compared to each other, with almost all values greater than 3.0000 (See experimental section).

[0019] The heterocyclic nitrification inhibitors are selected from the compounds illustrated in Table 1.

[0020] Described herein is a composition comprising a) a seed, b) a compound selected from the group consisting of F1-F403. The seed is treated sequentially, simultaneously or with a composition comprising a compound selected from the group consisting of F1-F403. A plant is allowed to grow from such a treated seed, and features that reflect the growth and vigor have been measured and compared with a plant that is grown from a not treated seed. The plant arising from a seed that is treated with compositions disclosed herein shows a Mahalanobis distance of equal to or greater than 2.0000 in comparison with a plant grown from a not treated seed. In some specific aspects, the plant arising from a seed that is treated with compositions disclosed herein shows a Mahalanobis distance of equal to or greater than 2.5000 in comparison with a plant grown from an not treated seed. In some other aspects, the plant arising from a seed that is treated with compositions disclosed herein shows a Mahalanobis distance of equal to or greater than 3.0000 in comparison with a plant grown from an not treated seed. In yet another aspect, the plant arising from a seed that is treated with compositions disclosed herein shows a Mahalanobis distance of equal to or greater than 3.5000 in comparison with a plant grown from not treated seed.

[0021] The compositions disclosed herein have beneficial effects on plant growth and vigor on a plant that is grown from a treated seed. The Mahalanobis distance is measured on any ofthe features that reflects or indicates plant growth and vigor. For example, the Mahalanobis distance is measured in relation to any of the features selected from the group consisting of pixel area, average green index, average percent green, average yellow index, average percent yellow, average brown index, average percent brown, leaf size, leaf length, shoot length, root density, oil content of the plant parts, number of flowers, size and number of fruits, and root length.

[0022] The beneficial effects on plant growth and vigor can be seen at VE-V3 growth stages.

[0023] The seed is selected from any of the agronomically-important crops. For example, the crops can be selected from the group consisting of alfalfa, canola, com, cereals, cotton, pulse crops (field beans, field peas, lentils, kidney beans), millet, oilseed rape, rice, sorghum, soybean, sugarbeet, sunflower, vegetable crops, and wheat.

[0024] In some aspects, the compositions disclosed herein further comprise another active in addition to the nitrification inhibitor compound. The terms “active” and “active ingredient” are used interchangeably throughout this disclosure. The active is selected from the group consisting of an insecticide, nematicide, fungicide, inoculant and / or a biological agent. In some instances, the active is an insecticide. In some other instances, the active is a nematicide. In yet another instances, the active is a fungicide. In some other instances, the active is an inoculant. In some instances, the active is a biological agent. In other instances, the actives are mixture combinations of fungicide, insecticide, nematicide and / or biological agents. An inoculant is a beneficial bacteria or beneficial microorganism such as Rhizobium that forms an endosymbiotic association with the plant roots, assisting with nitrogen fixation in legume plants.

[0025] In some aspects, the active is selected from the group consisting of 1,3- dichloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole , afidopyropen , avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenvalerate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen,spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox.

[0026] In some specific instances, the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0027] In some aspects, the nitrification inhibitor compound is selected from the group consisting of Fl -F403. In some specific instances, the nitrification inhibitor compound is selected from the group consisting of F400-F403. In some instances, the nitrification inhibitor compound is F400. In some other instances, the nitrification inhibitor compound is F401. In some instances, the nitrification inhibitor compound is F402. In some other instances, the nitrification inhibitor compound is F403.

[0028] In some aspects, the compositions disclosed herein comprise a nitrification inhibitor compound selected from the group consisting of F1-F403 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0029] In some aspects, the compositions disclosed herein comprise a nitrification inhibitor compound selected from the group consisting of F400 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0030] In some aspects, the compositions disclosed herein comprise a nitrification inhibitor compound selected from the group consisting of F401 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0031] In some aspects, the compositions disclosed herein comprise a nitrification inhibitor compound selected from the group consisting of F402 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0032] In some aspects, the compositions disclosed herein comprise a nitrification inhibitor compound selected from the group consisting of F403 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0033] In any of the compositions disclosed herein, the ratio of the nitrification inhibitor Fl- F403 to the other active is selected from 1 : 160,000 to 160,000: 1 , 1 :80,000 to 80,000: 1, 1 :40,000 to 40,000: 1, 1 :20,000 to 20,000: 1, 1 : 10,000 to 10,000: 1, 1 :8000 to 8000: 1, 1 :5000 to 5000:1, 1 :2000 to 2000: 1, 1 : 1000 to 1000: 1, 1 :500 to 500: 1, 1 :250 to 250: 1, 1: 100 to 100: 1; 1 :50 to 50: 1, 1 :25 to 25: 1, 1:10 to 10:1, l :5 to 5: l, and 1 : 1.

[0034] Disclosed herein also is a method of improving growth and / or vigor of a plant. The method comprises treating a plant propagule, for example, a seed, with a composition comprising a nitrification inhibitor selected from the group consisting of F1-F403. In some instances, the composition comprises another active selected from the group consisting of 1,3 -di chloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos- methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenvalerate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma-cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine,tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox. In some specific instances, the another active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0035] Treating the seed in this context means contacting the seed with a composition comprising nitrification inhibitor, in some instances further comprising another active using any of techniques known in the state of the art, for example, coating, dipping, mixing, and dusting the seed with a composition disclosed herein. The seed is then placed in a suitable medium for it to germinate and emerge. The growth and / vigor of the plant is measured with respect to a control plant (a plant grown from a not treated seed). Any known features that reflect the plant growth or vigor is measured. For example, pixel area, average green index, average percent green, average yellow index, average percent yellow, average brown index, average percent brown, leaf size, leaf length, shoot length, root density, oil content of the plant parts, number of flowers, size and number of fruits can be used to measure plant growth or vigor. The measurement can be done visually, or using more precise, advanced measurement techniques such as spectral-based methods. A plant grown from a seed treated with a composition disclosed herein shows a Mahalanobis distance with respect to any of the plant growth or vigor indications of equal to or more than 2.0000 in comparison to a control plant. In some instances, the Mahalanobis distance is equal to or more than 2.5000 in comparison to a control plant. In some instances, the Mahalanobis distance is equal to or more than 3.0000 in comparison to a control plant.

[0036] Disclosed herein is a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising a nitrification inhibitor compound selected from the group consisting of F400-F403.

[0037] Disclosed herein is also a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F400.

[0038] Disclosed herein is also a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F401.

[0039] Disclosed herein is also a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F402.

[0040] Disclosed herein is also a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F403.

[0041] Also disclosed herein is a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F400 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0042] Also disclosed herein is a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F401 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0043] Also disclosed herein is a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F402 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0044] Also disclosed herein is a method of improving plant growth or vigor in comparison to a control plant comprising the step of treating a seed with a composition comprising F403 and another active selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

[0045] The following details are additionally provided: dl. A composition comprising a) a seed, b) a compound selected from the group consisting of F1-F403, wherein a plant grows from the seed showing a Mahalanobis distance of equal to or more than 3.0000 in comparison to a seed that is not treated with a compound selected from the group consisting of F1-F403.d2. The composition according to dl, wherein the Mahalanobis distance is measured in relation to at least one of the parameters selected from the group consisting of pixel area, average green index, average percent green, average yellow index, average percent yellow, average brown index, average percent brown, leaf size, leaf length, shoot length, root density, oil content of the plant parts, number of flowers, size and number of fruits and root length. d3. The composition according to dl-d2, wherein the Mahalanobis distance is measured and compared with a seed that is not treated with a compound selected from the group consisting of F1-F403 at VE-V3 growth stages. d4. The composition according to dl-d3, further comprising an active selected from the group consisting of insecticide, nematicide, fungicide, inoculant and biological agent. d5. The composition according to d4, wherein the active is selected from the group consisting of 1,3 -di chloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenvalerate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox. d6. The composition according to d4-d5, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole,cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam. d7. The composition according to dl-d6, wherein the compound is selected from the group consisting of F400-F403. d8. A method of improving growth and / or vigor of a plant grown from a seed comprising the step of treating the seed with a composition comprising a compound selected from the group consisting of F1-F403. d9. The method according to d8, wherein the composition further comprises an active selected from the group consisting of insecticide, nematicide, fungicide and biological agent. dlO. The method according to d9, wherein the active is selected from the group consisting of 1,3 -di chloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenval erate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox. dl l. The method according to d8-dlO, wherein the composition comprises a compound selected from the group consisting of F400-F403.dl 2. The method according to d9-d 11, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam. dl3. A composition comprising: a) a seed, b) a compound selected from the group consisting of F400-F403, wherein a plant grows from the seed showing a Mahalanobis distance of equal to or more than 3.0000 in comparison to a seed that is not treated with a compound selected from the group consisting of F400-F403. dl4. The composition according to dl 3 , wherein the Mahalanobis distance is measured in relation to at least one of the parameters selected from group consisting of pixel area, average green index, average percent green, average yellow index, average percent yellow, average brown index, average percent brown, leaf size, leaf length, shoot length, root density, oil content of the plant parts, number of flowers, size and number of fruits and root length. dl 5. The composition according to d 13, further comprising an active selected from the group consisting of insecticide, nematicide, fungicide and biological agent. dl6. The composition according to d 13 , wherein the active is selected from the group consisting of 1,3-dichloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenval erate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram,fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox. dl 7. The composition according dl6, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam. dl 8. A method of improving growth and / or vigor of a plant grown from a seed comprising the step of treating the seed with a composition comprising a compound selected from the group consisting of F400-F403. dl9. The method according to dl 8, wherein the composition further comprises an active selected from the group consisting of insecticide, nematicide, fungicide and / or biological agent. d20. The method according d 19, wherein the active is selected from the group consisting of 1,3- dichloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenval erate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen,fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox. d21. The method according to dl9-d20, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-lGeneral Synthesis ProceduresGeneral Procedure 1

[0046] To a stirred solution of the heterocycle (1 equiv, 0.7 g, 3.95 mmol) in EtOAc (0.2 mM) were added TEA (4 equiv) and Cui (5 mol %) at RT (room temperature), and the reaction mixture was degassed with argon for 5 min, followed by addition of TMS-acetylene (4.5 equiv) and bis(triphenylphosphine)palladium chloride (15 mol%). The reaction mixture was stirred at 50 °C for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was filtered through a Celite® pad, and the filtrate was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using 10 - 20% EtOAc in petroleum ether to afford the desired products.General Procedure 2

[0047] To a stirred solution of the ethynyl TMS heterocycle (1.0 equiv) in methanol (0.2 mM) was added 1 equiv potassium carbonate. The reaction mixture was stirred at room temperature until completion of the reaction (monitor by TLC). The reaction mixture was filtered through a Celite® pad, and the filtrate was dried over Na2SC>4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using 10 - 20% EtOAc in petroleum ether to afford the desired products.General Procedure 3

[0048] Aldehyde (1.0 equiv) was a dissolved in anhydrous methanol (0.2-0.5 mM), cesium carbonate (1.0 equiv) was added, and the reaction mixture was cooled to 0-5 degrees C. Dimethyl (l-diazo-2-oxopropyl) phosphonate (1.0 equiv) was added dropwise after which the211823-US-PRV-l reaction mixture was allowed to stir for 1-18 h. The crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne.Synthesis ProceduresF3

[0049] Trimethylsilylacetylene, (1.5 mL, 10.81 mmol), bis(triphenylphosphine)palladium(II) chloride (79 mg, 0.113 mmol) and copper(I) iodide (4.29 mg, 0.023 mmol) was added to a degassed solution of methyl 2-bromo-l,3-thiazole-5-carboxylate (500 mg, 2.252 mmol) and EtiN (1.4 mL, 9.68 mmol) in EtOAc (2.0 mL). The mixture was heated to 50 °C for 7 h before cooling to 25 °C and filtering the reaction mixture through Celite®. The solvent was evaporated under reduced pressure to obtain the desired product.F6

[0050] To a solution of l-(4-(trifluoromethyl)-2-((trimethylsilyl)ethynyl)thiazol-5-yl)ethan- 1-one (0.4 g, 1.37 mmol) in MeOH (5 mL) was added NaBEL (0.025 g, 0.68 mmol) at 0 °C, and the mixture was stirred for 1 h at the same temperature. Water (10 mL) was added, and the reaction mixture was extracted with DCM. The extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.2 g (65%) of target as an off-white solid.F7

[0051] To a solution of 4-(trifluoromethyl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide 0.2 g, 0.68 mmol) in a THF-H2O mixture (3: 1, 5 mL) was added LiOH’FEO (0.03 g, 0.68 mmol), and the reaction mixture was stirred for 2 h at RT. The reaction mixture was acidified with 1 N HC1 and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 60 - 70% EtOAc in petroleum ether to afford 0.035 g (23%) of the target as a pale brown solid.F8

[0052] To a solution of ethyl 2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (0.1 g, 0.44 mmol) in a THF-H2O mixture (3:1, 5 mL) was added LiOH’FEO (0.02 g, 0.44 mmol), and the reaction mixture was stirred for 2 h at RT. The reaction mixture was acidified with 1 N HC1 and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous211823-US-PRV-lNa2SO4, filtered, and concentrated under reduced pressure to afford 0.03 g (44%) of the target as a pale brown solid.F9

[0053] To a solution of l-(2-ethynylthiazol-5-yl)ethan-l-one (0.1 g, 0.66 mmol) in MeOH (3 mL) was added NaBF (0.013 g, 0.33 mmol) at 0 °C, and the reaction mixture was stirred for 1 h at the same temperature. Water (10 mL) added. The reaction mixture was extracted with DCM, and the extracts were washed with brine (20 mL), dried over anhydrous Na2SC>4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.09 g (89%) of the target as a brown solid.Fl l

[0054] To a solution ethyl 2-ethynylthiazole-5-carboxylate (1 .4 g, 5.53 mmol) in a TFHFFLO mixture (3:1, 15 mL) was added LiOFFFEO (0.28 g, 6.64 mmol), and the reaction mixture was stirred at RT for 16 h. The reaction mixture was acidified with 1 N HC1 (pH ~ 2) and was extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 0.8 g (72%) of the target as a black solid.F12

[0055] To a solution of 2-ethynylthiazole-5-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) were added HATU (0.745 g, 1.96 mmol), DIPEA (0.315 g, 2.45 mmol), NH4C1 (0.1 g, 1.96 mmol), and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 50 - 60% EtOAc in petroleum ether to afford 0. 17 g (66%) of the target as an off-white solid.F13

[0056] To a solution of 2-ethynylthiazole-4-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) were added HATU (0.93 g, 2.45 mmol), DIPEA (0.42 g, 3.26 mmol), 2-methylbut-3-yn-2- amine (0.16 g, 1.96 mmol), and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 -211823-US-PRV-l200 mesh) eluting with 30 - 40% EtOAc in petroleum ether to afford 0.16 g (45%) of the target as an off-white solid.F14

[0057] To a solution of 2-ethynylthiazole-4-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) were added HATU (0.93 g, 2.45 mmol), DIPEA (0.42 g, 3.26 mmol), 2-methylbut-3-yn-2- amine (0.16 g, 1.96 mmol), and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 30 - 40% EtOAc in petroleum ether to afford the product as an off-white solid (0.17 g, 54%).F16

[0058] To a solution of 2-bromo-A'-(2-methylbut-3-yn-2-yl)thiazolc-4-carboxamide (0.4 g, 1.46 mmol) in toluene (5 mL) were added Cui (0.03 g, 0.14 mmol), followed by DIPEA (0.37 g, 2.93 mmol), PdCh(PPh3)2 (0.05 g, 0.07 mmol), and TMS acetylene (0.18 g, 1.75 mmol) under argon atmosphere, and the reaction mixture was stirred at 70 °C for 16 h. The reaction mixture was cooled to RT, EtOAc (30 mL) was added, and the mixture was filtered through a pad of Celite®. The filtrate was washed with brine (20 mL), dried over anhydrous Na SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.12 g (28%) of the target as a brown liquid.F17

[0059] To a solution of 2-bromo-A-(prop-2-yn-l-yl)thiazole-4-carboxamide (0.4 g, 1.46 mmol) in toluene (5 mL) were added Cui (0.03 g, 0.14 mmol), followed by DIPEA (0.37 g, 2.93 mmol), PdCh(PPh3)2 (0.05 g, 0.07 mmol), and TMS acetylene (0.18 g, 1.75 mmol) under argon atmosphere, and the reaction mixture was stirred at 70 °C for 16 h. The reaction mixture was cooled to RT, EtOAc (30 mL) was added, and the mixture was filtered through a pad of Celite®. The filtrate was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.12 g (28%) of the target as a pale brown solid (0.11 g, 25%).F28211823-US-PRV-l

[0060] To a stirred solution of l-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)prop-2-yn-l-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured into ice water (5 mL), acidified with 1 N HC1 (2 mL, pH ~4) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% EtOAc in petroleum ether eluent to afford the product as a pale brown solid (0.032 g 27%).F30

[0061] To a stirred solution of (£)-l-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)but-2-en-l-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured into ice water (5 mL), acidified with 1 N HC1 (2 mL, pH ~4) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% EtOAc in petroleum ether eluent to afford a pale brown solid (0.025 g, 17%).F31

[0062] To a stirred solution of l-(2-((trimethylsilyl)ethynyl)thiazol-5-yl)prop-2-yn-l-one (1.2 g, 5.76 mmol) in DCM (15 mL) was added DMP (3.17 g, 7.49 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10 - 20% EtOAc in petroleum ether eluent to afford the product as a brown solid (0.2 g, 50%).F32

[0063] To a stirred solution of (£)-l-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)but-2-en-l-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured into ice water (5 mL), acidified with 1 N HC1 (2 mL, pH ~4) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% EtOAc in petroleum ether eluent to afford the target (0.025 g, 21%) as a pale brown solid (0.025 g, 17%).211823-US-PRV-lF41

[0064] 1 mL MeOH was added to A-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to get product (40 mg, 86%) as a yellow solid.F42

[0065] 1 mL MeOH was added to A-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to get product (40 mg, 83%), a brown solid.F43

[0066] Under N2, 2-bromo-A-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh.)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), NEt3 (1.5 mL) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product, a yellow solid.F44

[0067] Under N2, 2-bromo-A-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPhs)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product as a yellow solid.F45

[0068] Under N2, 2-bromo-A-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction211823-US-PRV-l mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product as a yellow solid.F46

[0069] Under N2, 2-bromo- / V-methylthiazole-5-carboxamide (0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mb of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product / V-methyl- 2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide as a brown solid (63%).F51

[0070] 1 mL MeOH was added to A-methyl-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the desired product as a brown solid (55 mg, 98%).F47

[0071] 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the product (40 mg, 86%) as a brown solid.F48

[0072] 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the product (40 mg, 86%) as a brown solid.F49211823-US-PRV-l

[0073] 1 mL MeOH was added to / V-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the product (40 mg, 86%) as a brown solid.F50

[0074] Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPha)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product 1 (161mg, 64%) as a brown solid.F51

[0075] Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product (114 mg, 72%) as a brown solid.F52

[0076] Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product 1 (150 mg, 49%) as a white solid.F54

[0077] To a solution of ethyl 2-bromooxazole-4-carboxylate (1.5 g, 6.81 mmol) in toluene (10 mL) were added Cui (0.13 g, 0.0.68 mmol), DIPEA (1.75 g, 13.62 mmol), PdCh(PPh3)2211823-US-PRV-l(0.24 g, 0.34 mmol) and trimethylsilylacetylene (1 g, 10.21 mmol) under argon atmosphere, and the reaction mixture was stirred at 50 °C for 16 h. The reaction mixture was cooled to RT, EtOAc (150 mL) was added, and the mixture was filtered through a pad of Celite®. The filtrate was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.8 g (50%) of the target as a brown liquid.F55

[0078] To a solution of 2-ethynyloxazole-4-carboxylic acid (0.8 g, 3.37 mmol) in a THF- H2O mixture (3: 1, 10 mL) was added LiOH’FLO (0.14 g, 3.37 mmol), and the reaction mixture was stirred for 2 h at RT. The reaction mixture was acidified with 1 N HC1 and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 0.6 g (86%) of the target as a brown solid. F56

[0079] To a solution of 2-ethynyloxazole-4-carboxylic acid (0.1 g, 0.72 mmol) and amine input (0.073 g, 0.87 mmol) in DMF (3 mL) were added HATU (0.42 g, 1.09 mmol) and DIPEA (0.19 g, 1.44 mmol) at 0 °C, and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with ice water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 30 - 35% EtOAc in petroleum ether to afford 0.08 g (54%) of the target as a brown solid.F57

[0080] To a solution of 2-ethynyloxazole-5-carboxylic acid (0.35 g, 2.55 mmol) and amine input (0.318 g, 3.83 mmol) in DMF (5 mL) were added HATU (1.45 g, 3.82 mmol) and DIPEA (0.98 g, 7.66 mmol) at 0 °C, and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (30 mL) and was extracted with EtOAc. The organic layer was washed with ice water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.240 g (46%) of the product as an off-white solid.F58211823-US-PRV-l

[0081] To a solution of ethyl 2-iodooxazole-5-carboxylate (2.5 g, 9.36 mmol) in toluene (25 mL) were added Cui (0.178 g, 0.93 mmol), DIPEA (2.4 g, 18.72 mmol), PdCh(PPh3)2 (0.33 g, 0.468 mmol) and trimethylsilylacetylene (1.8 g, 18.72 mmol) under argon atmosphere, and the reaction mixture was stirred at 50 °C for 16 h. The reaction mixture was cooled to RT. EtOAc (100 mL) was added, and the mixture was filtered through a pad of Celite®. The filtrate was washed with brine (30 mL), dried over anhydrous Na2SC>4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 1 g (45%) of the product as a brown liquid.F59

[0082] To a solution of 2-ethynyloxazole-4-carboxamide (0.3 g, 2.18 mmol) and Aq. NH3 (2 mL) in THF (5 mL) were added HATU (1 g, 2.62 mmol) and DIPEA (0.42 g, 3.28 mmol) at 0 °C, and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with ice water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 40 - 45% EtOAc in petroleum ether to afford 0.05 g (42%) of the product as a pale brown solid. F60

[0083] To a stirred solution of 2-((trimethylsilyl)ethynyl)oxazole-4-carbaldehyde (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured into ice water (5 mL), acidified with 1 N HC1 (2 mL, pH ~4) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% EtOAc in petroleum ether eluent to afford the product as an off-white solid (0.078 g, 43%); M P 110 - 114 °C; 'H NMR (400 MHz, CDCI3) 8 9.93 (s, 1H), 8.24 (s, 1H), 3.33 (s, 1H); ESIMS m / z 122.12 ([M+H]+).F65

[0084] To a stirred solution of l-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)prop-2-yn-l-ol (0.27 g, 1.14 mmol) in dichloromethane (6 mL) was added DMP (0.63 g, 1.49 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash column211823-US-PRV-l chromatography (Column size: 24 g) using 10% EtOAc in petroleum ether eluent to afford the product as a pale brown solid (0.12 g, 42%).F66

[0085] To a stirred solution of l-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)prop-2-yn-l-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured into ice water (5 mL), acidified with 1 N HC1 (2 mL, pH ~4) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% EtOAc in petroleum ether eluent to afford a pale brown solid (0.024 g, 45%).F68

[0086] 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the product (25 mg, 86%) as a yellow solid.F69

[0087] 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5- carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C, and the reaction mixture was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under low temperature to provide the product as a brown solid (85%).F70

[0088] Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidePhenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product a yellow oil.F71211823-US-PRV-l

[0089] Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidePhenyl)benzamide (150 mg, 0.54 mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPha)4 (62 mg, 0.05 mmol), Cui (21 mg, 0.11 mmol), and NEt3 (1.5 mL) in 4.5 mL of THF. The reaction mixture was stirred at 50 °C for 2 h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 5: 1) to give the product as a white solid (25%).F73

[0090] To a solution of A-(2-methylbut-3-yn-2-yl)-2-(trichloromethyl)-4- (trifluoromethyl)thiazole-5-carboxamide (273 mg, 0.719 mmol) in THF-H20 (5: 1, 6 mL) was added Fe(s) in a single portion. The resulting reaction mixture was allowed to warm to 60 °C and maintained at that temperature for 16 h. The reaction was monitored by TLC (n-hexane-ethyl acetate 8:2) and LC-MS. No SM was visible by TLC after 16 h. The reaction mixture was concentrated (nitrogen) and adsorbed onto a Celite® pre-column and chromatographed over silica gel.F90

[0091] To a solution of 5-ethynylthiazole-2-carbaldehyde (40 mg, 0.292 mmol) in anhydrous THF at -78 °C was slowly added methylmagnesium bromide (86 pL, 0.292 mmol) as a 3.4 molar solution in THF. After the addition was complete, the reaction mixture was allowed to slowly warm to 25 °C over 30 minutes and then quenched with sat aq NH4CI and diluted with 50 mL ether. The layers were partitioned, and the ether layer was dried over magnesium sulfate and concentrated over a stream of nitrogen to afford a brown residue (42 mg, 85%).F94

[0092] To a stirred solution of (5-ethynylfuran-2-yl)methanol (0.1 g, 0.82 mmol) in THF (5 mL) were added NaH (60%, 0.078 g, 1.63 mmol) and CH3I (0.12 mL, 2.04 mmol) at 0 °C. The reaction mixture was stirred at RT for 2 h. After completion of the reaction (monitored by TLC), the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 5 - 10% EtOAc in petroleum ether to afford the product (0.026 g, 23%) as a pale brown liquid.F97211823-US-PRV-l

[0093] To a stirred solution of l-(5-ethynylfuran-2-yl)ethan-l-ol (0.1 g, 0.60 mmol) in DMF (5 mL) was added K2CO3 (0.1 g, 0.73 mmol) and methyl iodide (0.1 mL, 1.20 mmol) at RT. The reaction mixture was stirred at RT for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 - 20% EtOAc in petroleum ether to afford the product as a brown liquid (0.026 g, 26%). F106

[0094] To a stirred solution of l-(2-ethynyloxazol-4-yl)ethan-l-ol (0.1 g, 0.72 mmol) in THF (5 mL) was added NaH (48 mg, 0.72 mmol) at 0 °C. The mixture was stirred for 15 minutes at 0 °C, followed by the addition of CH3I (0.091 mL, 1.45 mmol). The reaction mixture was slowly warmed to RT and stirred for 2 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with cold water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10-20% EtOAc in petroleum ether eluent to afford the product (0.036 g, 33%) a pale yellow liquid.Fl 07

[0095] To a stirred solution of l-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)ethan-l-one (0.3 g, 1.55 mmol) in THF (10 mL) was added CHsMgl [3M in Diethyl ether (0.6 mL, 1.86 mmol)] at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with saturated NH4CI (20 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10-20% EtOAc in petroleum ether eluent to afford the product (0.2 g, 59%) a pale yellow liquid.F123

[0096] To a stirred solution of thiazole-2-thiol (0.3 g, 2.56 mmol) in acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and propargyl bromide (0.2 mL, 2.56 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion (monitored by TLC) of the reaction, the reaction mixture was poured in water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to211823-US-PRV-l afford the product (0.15 g, 38%) as a brown liquid; FT IR 2117.84 cm'1(C=C stretching present).F124

[0097] To a stirred solution of 2-bromothiazole (0.3 g, 1.82 mmol) in 1,4-dioxane (10 mL) were added LiCl (0.23 g, 5.48 mmol) and Cui (0.1 g, 0.55 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added input- 1 (0.66 g, 2.01 mmol) and Pd(PPh3)4 (0.1 g, 0.09 mmol) at RT. The reaction mixture was stirred at 100 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 5% - 10% EtOAc in petroleum ether to afford the product (0.05 g, 22%) as a brown liquid.F125

[0098] To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added Et:iN (3.6 mL, 26.21 mmol) and Cui (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then prop-2-yn-l-ol (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) were added at RT. The reaction mixture was stirred at 50-55 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the product (0.25 g, 29%) as a brown liquid.F126

[0099] To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added EtsN (3.6 mL, 26.21 mmol) and Cui (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then the alkyne (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) were added at RT. The reaction mixture was stirred at 50-55 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product as a brown liquid (0.4 g, 43%).F127211823-US-PRV-l

[0100] To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added EtsN (3.6 mL, 26.21 mmol) and Cui (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then prop-2-yn-l-ol (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) were addedat RT. The reaction mixture was stirred at 50-55 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the product as a brown liquid (0.1 g, 21%).F134

[0101] To a stirred solution of 2 bromothiazole (0.3 g, 2.56 mmol) in acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and propargyl alcohol (0.2 mL, 2.56 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion (monitored by TLC) of the reaction, the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a colorless liquid (0.03 g, 17%).F135

[0102] To a stirred solution of 2,4-dibromothiazole (0.5 g, 2.07 mmol) in 1,4-dioxane (10 mL) was added CsF (0.47 g, 3.11 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then input-1 (0.82 g, 2.48 mmol) and Pd(tBu3P)2 (53 mg, 0.11 mmol) were added at RT. The reaction mixture was stirred at 100 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 5% - 10% EtOAc in petroleum ether to afford product (0.2 g, 41%), a yellow semi solid (0.15 g, 45%).F140

[0103] 3-Ethynyl-5-methylisothiazole (1.0 equiv) was dissolved in anhydrous methanol (0.2- 0.5 mM), charged with cesium carbonate (1.0 equiv) and cooled to 0-5 degrees C. Dimethyl (1- diazo-2-oxopropyl)phosphonate (1.0 equiv) was added dropwise after which the reaction mixture was allowed to stir for 1-18 h. The crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne.F174211823-US-PRV-l

[0104] To a stirred solution of TMS acetylene (0.9 mL, 8.01 mmol) in THF (15 mL) was added n-Bug ai / seedi (2.5 M, 3.2 mL, 7.69 mmol) at -78 °C. The reaction mixture was stirred at - 78 °C for 30 minutes. Furan-2-carbaldehyde (0.5 g, 6.41 mmol) was then added into the reaction mixture at -78 °C and stirred for 5 h at RT. After completion of the reaction, the reaction mixture was quenched with aq. NH4CI (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 40 g) using 15% - 20% EtOAc in petroleum ether eluent to afford the intermediate (0.2 g, 16%) as a yellow solid; FT IR 2177.63 cm’1(C=C stretching present); ‘H NMR (400 MHz, CDCI3) 5 7.41 (m, 1H), 6.45 (m, 1H), 6.35 (m, 1H), 5.45 (d, J = 6.8 Hz, 1H), 2.22 (d, J= 7.2 Hz, 1H), 0.21 (s, 9H); ESIMS m z 194.94 ([M+H]Synthesis of l-(furan-2-yl)-3-(trimethylsilyl)prop-2-yn-l-one:

[0105] To a stirred solution of l-(furan-2-yl)-3 -(trimethyl silyl)prop-2-yn-l-ol (0.1 g, 0.51 mmol) in DCM (5 mL) was added pyridinium chlorochromate (0.16 g, 0.77 mmol) at RT. The reaction mixture was stirred at RT for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 2% - 5% EtOAc in petroleum ether to afford product (0.03 g, 30%), a brown liquid.General Procedure A

[0106] Under air, to a 20 mL vial, aryl halide (1 equiv), triethylamine (3 equiv) and copper(I) iodide (0.1 equiv) were charged and diluted with dioxane (0.3 M concentration of substrate). The reaction was degassed for 5 min, then ethynyltrimethyl silane (4.0 equiv) and bis(triphenylphosphine)palladium (II) chloride (0.1 equiv) were added under an inert atmosphere. The vial was placed in a heating block that was warmed to 80 °C and the solution was stirred for 20 h. The reaction was cooled and passed through a pad of Celite®. The filtrate was concentrated, and the resulting residue was purified by flash chromatography on silica gel. General Procedure B

[0107] To a 50 mL RBF charged with TMS-Alkyne (1.0 equiv), MeOH (0.25 M concentration of substrate) and potassium carbonate (0.2 equiv.) were added. The reaction mixture was stirred at ambient temperature for 30 min. After reaction completion, the reaction was diluted with H2O and extracted with DCM. The combined organics were passed through a211823-US-PRV-l phase separator and concentrated. The resulting residue was purified by flash chromatography on silica gel.General Procedure C

[0108] Aldehyde (1.0 equiv) was a dissolved in anhydrous methanol (0.2-0.5 mM) and charged with cesium carbonate (1.0 equiv), and the mixture was cooled to 0-5 degrees C. Dimethyl (l-diazo-2-oxopropyl) phosphonate (1.0 equiv) was added dropwise after which the reaction mixture was allowed to stir for 1-18 h. The crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne. General Procedure D

[0109] To a 20 mL vial, sodium hydride (60% Wt., 1.0 equiv) was charged and diluted with THF (1.0 M concentration of substrate) under an inert atmosphere. The alcohol (1.0 equiv) was added at ambient temperature, and the reaction mixture was allowed to stir for 30 min. The aryl halide (1.0 equiv) in THF (0.5 M concentration of substrate) was added. The vial was placed in a heating block that was warmed to 50 °C, and the solution was stirred for 20 h. The reaction was quenched with satd NH4CI and extracted with Et2O. The combined organics were dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash chromatography on silica gelGeneral Procedure E

[0110] Under air, a 20 mL vial equipped with a magnetic stirring bar was charged with P(tBu)3 Pd G2 (0.03 equiv) and the aryl halide (1 equiv if solid). The vial was capped, and the air was purged by evacuating the vial and backfilling with nitrogen three times. Dry DMF was added (0.4 M concentration of substrate) to the vial followed by the aryl halide (1 equiv if liquid), the TMS-protected alkyne (1.5 equiv) and TBAF (1.5 equiv, 1 M in THF). The vial was placed in a heating block that was warmed to 80 °C, and the solution was stirred for 20 h. After the reaction time, the vial was opened to air and aqueous Na2COs was added (4 mL). The crude product was extracted with CH2CI2 and purified by flash chromatography on silica gel.General Procedure F

[0111] To a 20 mL vial, sodium alkoxide (1.0 equiv) was charged. Then a solution of aryl halide (1.0 equiv) in THF (0.2 M concentration of substrate) was added. The vial was placed in a heating block that was warmed to 50 °C, and the solution was stirred for 20 h. The reaction was quenched with saturated NH4CI and extracted with Et2O. The combined organics were dried over211823-US-PRV-lMgS04, filtered, and concentrated. The resulting residue was purified by flash chromatography on silica gel.General Procedure G

[0112] A stock solution of [l,r-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.1 equiv) in dioxane (2 mb) and copper(I) iodide (0.1 equiv) in dioxane (1 mL) and triethylamine (3 equiv) were added to a vial containing a solution of Br / Cl-heterocycle (1 equiv) in dioxane (2 mL). The contents were sealed and degassed with nitrogen and the overall reaction concentration was 0.2 M. With stirring, ethynyltrimethylsilane (2 equiv) was added neat and the contents were heated to 60 C overnight for 18 hours. The reaction was quenched with AcOH (10 equiv). The product mass was observed by LCMS. The contents were diluted with EtOAc and partitioned between 2.5 M KHCO3 (2 x) and brine then dried over MgSCL. The contents were condensed by rotoary evaporation and the residue was purified by silica-gel chromatography eluting with hexanes / EtOAc 10-100% over 10 minutes to yield the product.General Procedure H

[0113] To a flask containing ((trimethylsilyl)ethynyl)-heterocycle was dissolved in a solution of potassium fluoride (0.1 M, 2 equiv) in methanol and stirred at ambient temperature for 18 hours. The contents were condensed by rotary evaporation and purified over silica-gel eluting with DCM / MeOH 0-10% to obtain the product.General Procedure I

[0114] To a stirring solution of aldehyde (1 M, 1 equiv), potassium carbonate (2 equiv) in methanol was added dimethyl (l-diazo-2-oxopropyl)phosphonate (1.1 equiv) neat. Gas evolution was observed. The contents were stirred at ambient temperature for 2 - 5 hours. The contents were diluted with water and extracted with dichloromethane. The pooled organics were dried over MgSO4 and condensed by fractional distillation. The residue was purified over a silica-gel column eluting with DCM / MeOH 0-10% over 10 minutes. The fractions containing the product were pooled and evaporated to give the product.Procedure J

[0115] A nitrogen containing heterocycle posing an alkyne was dissolved in diethyl ether (1 M) and treated with an equal volume of 1 M acid (HC1 or anhydrous H3PO4) in diethyl ether. The volatile components were removed by evaporation using a stream of nitrogen gas to give the desired salt form of the heterocycle.General Procedure K211823-US-PRV-l

[0116] To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added EtsN (3.6 mL, 26.21 mmol) and Cui (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then prop-2-yn-l-ol (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) were added at RT. The reaction mixture was stirred at 50-55 °C for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was filtered through Celite® pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product.General Procedure L

[0117] To a stirred solution of alkynyl alcohol (0.15 g, 1.07 mmol) in di chloromethane (10 mL) were added E iN (0.2 mL, 1.60 mmol) and acetyl chloride (0.1 mL, 1.28 mmol) at 0 °C. The reaction mixture was stirred at RT for 16 h. After completion (monitored by TLC) of the reaction, the reaction mixture was concentrated under reduced pressure, poured into water and extracted with DCM. The organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product. Procedure M

[0118] To a stirred solution of thiazole-2-thiol (0.3 g, 2.56 mmol) in acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and methyl propargyl bromide (0.2 mL, 2.56 mmol) at 0 °C. The reaction mixture was stirred at RT for 3 h. After completion (monitored by TLC) of the reaction, the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the desired product.Procedure N

[0119] To a stirred solution of 3-bromopyrazole (0.5 g) in TEA (5 mL) was added Cui (0.049 g). The reaction mixture was degassed with argon gas for 10 mins followed by addition of Pd(PPha)4 (0.148 g) and the acetylated alkyne input (5.14 mmol) at RT. The resultant reaction mixture was stirred at 80 °C for 2 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure at 38 °C to get the crude compound, which was purified by prep-HPLC to give the desired product.Procedure O211823-US-PRV-l

[0120] To a stirred solution of pyrazole (0.5 g) in dry THF (5V) wer added NaH (2 equiv) followed by propargyl bromide (1.2 equiv) at 0 °C. The resultant reaction mixture was stirred at 0 °C to RT for 3 h. After completion of the reaction, the reaction mixture was quenched with ice- cold water, extracted with ethyl acetate. The extracts were washed with aqueous NaCl solution and dried over with anhydrous Na2SO4. The resultant solution was concentrated under reduced pressure at 38 °C to get the crude compound, which was purified by combi flash chromatography to afford the desired product.Analytical Data211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-l211823-US-PRV-lEXPERIMENTAL SECTIONExample 1 Corn nitrogen inhibitor seed treatmentsMaterials and Methods

[0121] Corn commercial hybrid P9998CYFR seed were treated with different nitrogen inhibitor compounds at 100 ug ai / seed or 250 ug ai / seed as a seed treatment (Table 1-1). Nitrification Inhibitor (NIN) compounds were treated alone and in combination with commercial fungicide and insecticide seed treatments (Table 1-1). Corn hybrid seed were treated as waterbased slurries using a Hege 11 laboratory seed treater (Wintersteiger AG, Ried im Innkreis, Austria). Slurries were created by mixing the treatment components in a sufficient volume of tap water to ensure uniform seed coverage. Prepared slurries were pipetted onto the spinning disk of a Hege 11 seed treater in application volumes of 90-130 mL slurry per 80,000 seed. Seeds were circulated in treater bowl for 15-25 seconds to uniformly coat the seed. Treated seed were air dried prior to planting.

[0122] Corn seed treatment experiments were planted on October 9, 2023, in the Corteva Agriscience (Johnston, IA) greenhouse facilities. Experiments consisted of 16 replicates per seed treatment entry. Seed was planted at a standard planting depth of 20 to 25 mm in a standard germination mix comprising of 76.49% peat, 16.10% peat, 7.38% vermiculite, 5 lbs / yd3lime, 3 lbs / yd3starter fertilizer, and 0.5 lbs / yd3wetting agent. The individual seeds were placed in flats of 32 plants each in an 8x4 configuration resulting in a 212 plants / m2density.

[0123] The plants were grown in a glass greenhouse with day length of 16 hours and growth conditions of daytime temperature at 22.22C, and nighttime temperature at 19.44C. Plants were imaged at first visual sight of the plumule using a Hyperspectral Visible and Near InfraRed camera and a short-wave infrared camera. The cameras capture reflectance between 400 nm and 2500 nm. Plants grown under normal conditions were imaged daily from 5 days after planting until approximately 9 days after planting (VE to V3 growth stage). Data were processed using proprietary software into average reflectance spectra of individual plants and physiologically relevant features. These data were standardized and processed using R. Custom algorithms were developed to adjust data and remove variability. Data were processed using a modified version of Mahalanobis distance to determine differences between treatments. Resulting distance matrices were log-transformed, with values over 3 considered significantly different.211823-US-PRV-lResults and discussion

[0124] The Mahalanobis distance is a measure of the distance between a datapoint and the distribution of data; quantifying the number of standard deviations the datapoint is away from the mean of the distribution. The larger the value, the further away the seed treatment is from the control. Within each plant age, the different nitrogen inhibitor compounds were significantly different compared to the not treated control and significantly different compared to each other, with almost all values greater than 3.0 (Table 1-2). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a compound at each individual day and across all days, the 250 ug ai / seed generally had a higher difference value compared to not treated control for F402, while the 100 ug ai / seed rate had a higher difference value compared to not treated control for F401 and F403 (Table 1-2).

[0125] When the visible spectrum data are averaged across all timepoints measured, all NIN compounds at each rate had positive average pixel area values, indicating these compounds increased plant size compared to not treated control (Table 1-3). In addition, all NIN compounds and rates except F403 250 ug ai / seed had positive average green index and average percent green, indicating an improvement in plant health compared to not treated control (Table 1-3). In contrasting rates within a specific NIN compound, F402 250 ug ai / seed had higher values for all traits compared to F402 100 ug ai / seed (Table 1-3). F403 100 ug ai / seed and F401 100 ug ai / seed had higher average pixel area and average green index values compared to the 250 ug ai / seed rates of the same NIN compound (Table 1-3). Across all visual spectrum data, F402 250 ug ai / seed had the highest average pixel area and second highest average green index values (Table 1-3). The hyperspectral data from 400 nm to 1000 nm show F402 250 ug ai / seed rate had higher positive values compared to the F402 100 ug ai / seed rate and the not treated control (Figure 1-1). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to select nitrogen inhibitor compounds as a corn seed treatment and identify the optimal rate needed for early growth improvement.

[0126] When the NIN compounds were added to seed treated with FST + 1ST, within each plant age, the different NIN compounds were significantly different compared to the FST + 1ST control and significantly different compared to each other, with almost all Mahalanobis distance values greater than 3.0 (Table 1-4). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a NIN compound (+FST +IST) at each individual day and across all days, the 250 ug ai / seed rate generally had a higher difference value compared to FST + 1ST control for211823-US-PRV-lF402 and F401, while the 100 ug ai / seed rate had a higher difference value compared to FST + 1ST control for F403 (Table 1-4).

[0127] When the visible spectrum data are averaged across time for NIN compounds with FST + 1ST, F402 100 ug ai / seed rate had higher average pixel area, average green index, and average percent green compared to the F402 250 ug ai / seed (Table 1-5). Conversely, the 250 ug ai / seed rate of F403 + FST + 1ST and F401 + FST + 1ST rates had higher average pixel area, average green index, and average percent green compared to the 100 ug ai / seed rate of the same NIN compound (Table 1-5). The values for F402 100 ug ai / seed + FST + 1ST, F403 250 ug ai / seed + FST + 1ST and F401 250 ug ai / seed + FST + 1ST were positive for all the visible spectrum data, indicating these compounds increased plant size and plant health compared to the FST + 1ST control (Table 1-5). Over all data, F402 100 ug ai / seed + FST + 1ST had the highest average pixel area, average percent green, and average green index values (Table 1-5). The hyperspectral data from 400 nm to 1000 nm show the F402 100 ug ai / seed rate + FST + 1ST had higher values compared to the F402 250 ug ai / seed rate + FST + 1ST (Figure 1-2). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to select nitrogen inhibitor compounds as a com seed treatment and identify the optimal rate needed in combination with FST + 1ST to improve early com growth.

[0128] Improvement in early plant growth and plant health was observed for several different NIN compounds as a corn seed treatment. Combining the visible spectrum data with hyperspectral data analyses enabled the selection of the NIN compound (alone and in combination with FST + 1ST) with the best performance. Utilizing these analytic techniques was a rapid method to screen and select the optimal NIN compound and ideal rate as a seed treatment in com.211823-US-PRV-l

[0129] Table 1-1. Nitrogen inhibitor seed treatment components for corn hyperspectral experiments

[0131] Table 1-2. Mahalanobis distance (log transformation) of com treated with nitrogen inhibitor compounds compared to wild type (not treated control).Not treated F402 F400 F401 F403100 ug , , , , 100 ug 250 ug , , 100 ug 250 ug ,e250 ugPlant age1Seed treatment control . . , . . , lOO ug ai / seed . . , . . , ai / see . . ai / seed ai / seed ai / seed ai / seed ai / seed5 DAP Not treated control 0.00005 DAP F402_100 ug ai / seed 3.8183 0.00005 DAP F402 250 ug ai / seed 4.0819 3.5735 0.00005 DAP F400_100 ug ai / seed 4.1977 3.3405 2.6659 0.00005 DAP F401_100 ug ai / seed 4.4928 4.4262 3.2607 2.9643 0.00005 DAP F401_250 ug ai / seed 3.2452 3.4532 3.4775 3.8334 4.5419 0.00005 DAP F403_100 ug ai / seed 4.3737 4.2264 3.7217 3.7902 4.2242 2.8210 0.00005 DAP F403 250 ug ai / seed 2.9709 3.7250 3.8481 4.3134 4.1087 3.3022 3.2717 0.00006 DAP Not treated control 0.00006 DAP F402_100 ug ai / seed 3.5109 0.00006 DAP F402 250 ug ai / seed 3.6230 4.1673 0.00006 DAP F400 100 ug ai / seed 2.9333 3.3474 3.1257 0.00006 DAP F401_100 ug ai / seed 3.8649 4.5455 3.6921 3.5631 0.00006 DAP F401_250 ug ai / seed 3.1610 4.6898 3.8584 3.7322 3.7130 0.00006 DAP F403_100 ug ai / seed 2.9865 3.5594 3.7043 3.7615 3.2523 3.0869 0.00006 DAP F403 250 ug ai / seed 3.8223 4.6869 3.6120 3.6469 3.7849 3.9898 3.5343 0.00008 DAP Not treated control 0.00008 DAP F402_100 ug ai / seed 2.4514 0.00008 DAP F402 250 ug ai / seed 3.9309 3.7784 0.00008 DAP F400_100 ug ai / seed 3.9608 4.0963 2.6076 0.00008 DAP F401_100 ug ai / seed 3.5087 3.4139 3.4385 3.7701 0.00008 DAP F401_250 ug ai / seed 3.1003 4.2247 3.9242 4.0188 4.2023 0.00008 DAP F403_100 ug ai / seed 2.6281 3.6918 3.6691 3.9340 4.1129 2.0051 0.00008 DAP F403 250 ug ai / seed 2.9637 3.5995 3.2620 3.2683 3.1563 4.1056 4.3286 0.00009 DAP Not treated control 0.00009 DAP F402 100 ug ai / seed 2.6085 0.00009 DAP F402 250 ug ai / seed 4.0119 4.1018 0.00009 DAP F400_100 ug ai / seed 3.3100 4.0857 2.7679 0.00009 DAP F401 100 ug ai / seed 3.8599 3.8928 4.1453 4.0885 0.00009 DAP F401_250 ug ai / seed 3.8310 4.2844 4.3899 3.8526 3.7837 0.00009 DAP F403_100 ug ai / seed 3.6036 3.7977 4.4280 4.0748 3.3690 3.5582 0.00009 DAP F403 250 ug ai / seed 3.5213 3.9405 4.0027 4.0818 3.5044 3.4212 3.0631 0.0000 all Not treated control 0.0000 all F402_100 ug ai / seed 0.8441 0.0000 all F402_250 ug ai / seed 2.2950 2.0197 0.0000 all F400_100 ug ai / seed 2.8011 2.7699 0.4550 0.0000 all F401_100 ug ai / seed 2.1041 2.4421 0.8192 0.7385 0.0000 all F401 250 ug ai / seed 1.8731 2.3322 1.8030 2.2583 1.7789 0.0000 all F403_100 ug ai / seed 2.2061 2.4866 1.3544 1.6770 1.4110 0.7101 0.0000 all F403_250 ug ai / seed 1.8543 2.1247 1.7376 2.0317 1.5051 1.4691 1.3531 0.00001. Plant age average across 5 to 9 days after planting (DAP)

[0132] Table 1-3. Hyperspectral differences1of corn treated with nitrogen inhibition compounds compared to wild type (not treated control).Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Green5-9 DAP F402 100 ug ai / seed Not Treated control 0.24 0.04 0.065-9 DAP F402 250 ug ai / seed Not Treated control 1.53 1.76 0.375-9 DAP F403_100 ug ai / seed Not Treated control 0.22 0.10 2.095-9 DAP F403 250 ug ai / seed Not Treated control 0.03 -0.16 -0.045-9 DAP F401 100 ug ai / seed Not Treated control 0.36 2.20 0.505-9 DAP F401 250 ug ai / seed Not Treated control 0.01 0.04 1.815-9 DAP F400 100 ug ai / seed Not Treated control 0.67 1.73 1.111. Positive values indicate better performance compared to not treated control and negative values indicate worse performance compared to not treated control2. Plant age average across 5 to 9 days after planting (DAP)

[0133] Table 1-4. Mahalanobis distance (log transformation) of corn treated with nitrogen inhibitor compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to FST + 1ST control.F402 F401 F403F400 +FST + STPlant FST + 1ST + FST + 1ST +FST + IST + FST + 1ST100 us 1 . . , 100 ug 250 ug _ 100 ug 250 uge250 ugAge1Seed treatment control . . , . . , lOO ug ai / seed . . , . . , ai / see . . ai / seed ai / seed ai / seed ai / seed ai / seed5 DAP FST + 1ST Control 0.00005 DAP F402 100 ug ai / seedFSTIST 3.0071 0.00005 DAP F402 250 ug ai / seedFSTIST 4.1771 3.9480 0.00005 DAP F400 100 ug ai / seedFSTIST 3.7332 3.5207 3.4145 0.00005 DAP F401_100 ug ai / seedFSTIST 3.2016 3.2679 3.3720 2.9438 0.00005 DAP F401_250 ug ai / seedFSTIST 3.5552 3.9288 4.3390 4.3389 3.5961 0.00005 DAP F403_100 ug ai / seedFSTIST 3.5247 3.6661 4.5262 3.9263 3.6322 3.1688 0.00005 DAP F403 250 ug ai / seedFSTIST 2.8745 3.4263 4.3956 4.7370 3.8487 4.2556 4.3083 0.00006 DAP FST + 1ST Control 0.00006 DAP F402 100 ug ai / seedFSTIST 2.8588 0.00006 DAP F402 250 ug ai / seedFSTIST 3.3548 2.0739 0.00006 DAP F400 100 ug ai / seedFSTIST 3.2117 2.8518 3.4866 0.00006 DAP F401_100 ug ai / seedFSTIST 3.0447 3.6166 3.0678 3.7942 0.00006 DAP F401_250 ug ai / seedFSTIST 3.8256 3.6169 4.4678 4.6994 3.3107 0.00006 DAP F403_100 ug ai / seedFSTIST 3.8507 3.0325 4.2978 4.4206 3.2983 3.2577 0.00006 DAP F403 250 ug ai / seedFSTIST 3.7127 4.0793 3.6496 3.7812 4.4978 3.6861 3.9383 0.00008 DAP FST + 1ST Control 0.00008 DAP F402 100 ug ai / seedFSTIST 3.0234 0.00008 DAP F402 250 ug ai / seedFSTIST 3.9711 3.7661 0.00008 DAP F400_100 ug ai / seedFSTIST 4.5127 3.6617 3.0191 0.00008 DAP F401_100 ug ai / seedFSTIST 4.3752 3.9095 3.7305 3.9727 0.00008 DAP F401 250 ug ai / seedFSTIST 4.1976 3.6134 4.1121 3.6832 4.3458 0.00008 DAP F403_100 ug ai / seedFSTIST 4.2786 3.4774 4.3107 4.0769 3.8758 2.7957 0.00008 DAP F403 250 ug ai / seedFSTIST 4.5350 4.2571 4.0856 3.7632 3.1553 4.4549 4.2400 0.00009 DAP FST + 1ST Control 0.00009 DAP F402 100 ug ai / seedFSTIST 3.0165 0.00009 DAP F402 250 ug ai / seedFSTIST 3.3752 3.6690 0.00009 DAP F400 100 ug ai / seedFSTIST 3.6869 3.6410 3.3786 0.00009 DAP F401 100 ug ai / seedFSTIST 4.2497 4.1066 4.2767 4.1438 0.00009 DAP F401_250 ug ai / seedFSTIST 4.0135 3.5177 2.8715 2.7875 4.2159 0.00009 DAP F403_100 ug ai / seedFSTIST 4.0685 4.1319 3.5490 3.6750 3.7358 2.2247 0.00009 DAP F403 250 ug ai / seedFSTIST 3.8735 4.1017 2.6082 2.8768 3.1225 3.9561 3.1466 0.0000Avg all FST + 1ST Control 0.0000Avg all F402 100 ug ai / seedFSTIST 0.5453 0.0000Avg all F402 250 ug ai / seedFSTIST 1.7138 1.8161 0.0000Avg all F400 100 ug ai / seedFSTIST 1.4421 1.4532 1.2168 0.0000Avg all F401_100 ug ai / seedFSTIST 1.5871 1.3872 2.4621 2.3222 0.0000Avg all F401 250 ug ai / seedFSTIST 1.6466 1.7327 2.3679 2.2654 0.9533 0.0000Avg all F403_100 ug ai / seedFSTIST 1.3939 1.3476 2.6943 2.3448 0.6081 1.0607 0.0000Avg all F403 250 ug ai / seedFSTIST 1.5498 1.6200 2.0145 1.8682 1.3505 0.4661 0.8593 0.00001. Plant age average across 5 to 9 days after planting (DAP)

[0134] Table 1-5. Hyperspectral differences1of com treated with nitrogen inhibition compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to FST + 1ST control.Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Green5-9 DAP F402 _100 ug ai / seed FSTIST FST + 1ST Control 0.34 9.87 2.345-9 DAP F402_250 u ai / seedFSTIST FST + 1ST Control 0.32 0.34 1.515-9 DAP F403_100 Ug ai / seedFSTIST FST + 1ST Control -0.01 2.17 0.525-9 DAP F403 250 u ai / seedFSTIST FST + 1ST Control 0.09 1.40 1.065-9 DAP F401_100 ug ai / seedFSTIST FST + 1ST Control -0.05 0.13 0.845-9 DAP F401_250 ug ai / seedFSTIST FST + 1ST Control 0.06 3.20 0.605-9 DAP F400_100 ug ai / seedFSTIST FST + 1ST Control -0.03 -0.30 1.25. Positive values indicate better performance compared to FST + 1ST control and negative values indicate worse performance compared to FST + 1ST control2. Plant age average across 5 to 9 days after planting (DAP)Example 2. Soybean nitrogen inhibitor seed treatmentsMaterials and Methods

[0135] Soybean commercial variety P28A65E seed were treated with different nitrogen inhibitor compounds as a seed treatment at 100 ug ai / seed or 250 ug ai / seed (Table 2-1). NIN compounds were treated alone and in combination with commercial fungicide and insecticide seed treatments (Table 2-1). Soybean seed were treated as water-based slurries using a Hege 11 laboratory seed treater (Wintersteiger AG, Ried im Innkreis, Austria). Slurries were created by mixing the treatment components in a sufficient volume of tap water to ensure uniform seed coverage. Prepared slurries were pipetted onto the spinning disk of a Hege 1 1 seed treater in application volumes of 90-130 rnL slurry per 80,000 seed. Seeds were circulated in treater bowl for 15-25 seconds to uniformly coat the seed. Treated seed were air dried prior to planting.

[0136] Soybean seed treatment experiments were planted on October 9, 2023, in the Corteva Agriscience (Johnston, IA) greenhouse facilities. Experiments consisted of 16 replicates per seed treatment entry. Seed was planted at a standard planting depth of 20 to 25 mm in a standard germination mix comprising of 76.49% peat, 16.10% peat, 7.38% vermiculite, 5 lbs / yd3lime, 3 lbs / yd3starter fertilizer, and 0.5 lbs / yd3wetting agent. The individual seeds were placed in flats of 32 plants each in an 8x4 configuration resulting in a 212 plants / m2density.

[0137] The plants were grown in a glass greenhouse with day length of 16 hours and growth conditions of daytime temperature at 22.22C, and nighttime temperature at 19.44C. Plants were imaged at first visual sight of the plumule using a Hyperspectral Visible and Near InfraRed camera and a short-wave infrared camera. The cameras capture reflectance between 400 nm and2500 nm. Plants grown under normal conditions were imaged daily from 4 days after planting until 10 days after planting (VE to V3 growth stage). Data were processed using proprietary software into average reflectance spectra of individual plants and physiologically relevant features. These data were standardized and processed using R. Custom algorithms were developed to adjust data and remove variability. Data were processed using a modified version of Mahalanobis distance to determine differences between treatments. Resulting distance matrices were log-transformed, with values over 3 considered significantly different.Example 2. Results and discussion

[0138] The Mahalanobis distance is a measure of the distance between a datapoint and the distribution of data; quantifying the number of standard deviations the datapoint is away from the mean of the distribution. The larger the value, the further away the seed treatment is from the control. Within each plant age, the different nitrogen inhibitor compounds were significantly different compared to the not treated control and significantly different compared to each other, with almost all values greater than 3.0 (Table 2-2). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a compound across all days, the 100 ug ai / seed had a higher difference value compared to not treated control for F402, while the 250 ug ai / seed rate had a higher difference value compared to control for F401 and F403 (Table 2-2).

[0139] When the visible spectrum data are averaged across time, all NIN compounds at each rate except F402 250 ug ai / seed had positive average pixel area values, indicating these compounds increased plant size compared to control (Table 2-3). In addition, NIN compounds F403 100 ug ai / seed, F403 250 ug ai / seed and F401 250 ug ai / seed had positive average green index and average percent green across all plant dates, indicating an improvement in plant health compared to control (Table 2-3). In contrasting rates within a specific NIN compound, F402 100 ug ai / seed had higher values for all traits compared to F402 250 ug ai / seed (Table 2-3). F403 250 ug ai / seed and F401 250 ug ai / seed had higher average pixel area and average green index values compared to the 100 ug ai / seed rates of the same NIN compound (Table 2-3). Over all data, F403 250 ug ai / seed had the highest average pixel area, average green index, and average percent green values (Table 2-3). The hyperspectral data from 400 nm to 1000 nm show the 250 ug ai / seed rate of F403 as having higher values compared to the 100 ug ai / seed rate and the not treated control (Figure 2-1). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to differentiate rates and select the ideal nitrogen inhibitor compound as a seed treatment for soybean.

[0140] When the NIN compounds were added to soybean seed treated with FST + 1ST, within each plant age, the different NIN compounds were significantly different compared to the FST + 1ST control and significantly different compared to each other, with almost all Mahalanobis distance values greater than 3.0 (Table 2-4). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a NIN compound (+ FST + 1ST) at each individual day and across all days, the 250 ug ai / seed rate generally had a higher difference value compared to FST+ 1ST control for F402 and F401. For F403 the 100 ug ai / seed rate had a higher difference value compared to FST + 1ST control compared to the 250 ug ai / seed rate (Table 2-4).

[0141] When the visible spectrum data are averaged across time for NIN compounds with FST + 1ST, F401 100 ug ai / seed rate + FST + 1ST had higher average pixel area, average green index, and average percent green compared to the F401 250 ug ai / seed rate + FST + 1ST (Table 2-5). Conversely, F403 250 ug ai / seed + FST + 1ST and F401 250 ug ai / seed + FST + 1ST rates had higher average pixel area, average green index, and average percent green compared to the 100 ug ai / seed rate of the same NIN compound (Table 2-5). Over all data, F403 250 ug ai / seed + FST + 1ST had the highest average pixel area and positive average green index values (Table 2-5). The hyperspectral data from 400 nm to 1000 nm show the 250 ug ai / seed rate of F403 as having higher values compared to the 100 ug ai / seed rate and the FST + 1ST control (Figure 2-2). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to differentiate rates and select nitrogen inhibitor compounds as a soybean seed treatment when combined with a FST + 1ST.

[0142] Improvement in early plant growth and plant health was observed for several different NIN compounds as a seed treatment on soybean. Combining the visible spectrum data with hyperspectral data analyses enabled the selection of the NIN compound (alone and in combination with FST + 1ST) with the best performance. Utilizing these analytic techniques was a rapid method to screen and select the optimal NIN compound and ideal rate as a seed treatment in soybean.

[0143] Table 2-1. Nitrogen inhibitor seed treatment components for soybean hyperspectral experiments

[0145] Table 2-1 . Mahalanobis distance (log transformation) of soybean treated with nitrogen inhibitor compounds compared to wild type(not treated control).Not Treated F402 F400 F401 F403100 ug , , , , 100 ug 250 ug , , 100 ug 250 ug ,e250 ugPlant Age1Seed Treatment Control . . . . . . lOO ug ai / seed . . . . . . ai / see . . ai / seed ai / seed ai / seed ai / seed ai / seed4 DAP Not treated 0.00004 DAP F402_100 ug ai / seed 3.2578 0.00004 DAP F402 250 ug ai / seed 2.7031 3.3071 0.00004 DAP F400_100 ug ai / seed 2.7859 3.2952 3.3383 0.00004 DAP F401_100 ug ai / seed 4.6827 4.3181 2.8117 2.9662 0.00004 DAP F401_250 ug ai / seed 4.2303 4.6230 3.3463 2.9022 4.1736 0.00004 DAP F403_100 ug ai / seed 4.1090 4.3431 3.2946 3.0283 4.0914 3.1577 0.00004 DAP F403 250 ug ai / seed 3.6239 3.4417 3.5280 3.5090 3.7196 3.3871 3.3897 0.00005 DAP Not treated 0.00005 DAP F402_100 ug ai / seed 2.7319 0.00005 DAP F402 250 ug ai / seed 4.2123 3.6784 0.00005 DAP F400 100 ug ai / seed 3.7246 2.9526 3.4669 0.00005 DAP F401_100 ug ai / seed 4.1940 4.2862 4.1398 4.5072 0.00005 DAP F401_250 ug ai / seed 3.8853 4.7173 3.0479 3.4604 3.3247 0.00005 DAP F403_100 ug ai / seed 3.7063 4.3593 3.3071 2.9932 3.6292 2.1850 0.00005 DAP F403 250 ug ai / seed 4.4836 3.5047 3.4177 3.3520 5.5181 4.0037 3.5811 0.00006 DAP Not treated 0.00006 DAP F402_100 ug ai / seed 2.5981 0.00006 DAP F402 250 ug ai / seed 4.2832 4.6134 0.00006 DAP F400_100 ug ai / seed 3.7919 3.7030 3.1482 0.00006 DAP F401_100 ug ai / seed 3.0544 2.9100 2.8120 3.0385 0.00006 DAP F401_250 ug ai / seed 3.7599 3.3151 3.5739 3.9067 3.5842 0.00006 DAP F403_100 ug ai / seed 2.5708 3.2059 3.0293 2.9030 3.6825 3.4873 0.00006 DAP F403 250 ug ai / seed 3.4034 3.4155 2.7903 2.9119 4.0512 2.7074 2.8796 0.00008 DAP Not treated 0.00008 DAP F402_100 ug ai / seed 3.3175 0.00008 DAP F402 250 ug ai / seed 3.2890 3.1617 0.00008 DAP F400 100 ug ai / seed 3.8276 2.6425 2.8597 0.00008 DAP F401 100 ug ai / seed 3.5088 3.3593 4.2017 4.3867 0.00008 DAP F401_250 ug ai / seed 3.4296 3.1124 3.9498 4.0380 3.2705 0.00008 DAP F403_100 ug ai / seed 3.9371 3.5906 3.7789 4.0644 2.9725 2.4960 0.00008 DAP F403 250 ug ai / seed 4.3147 3.3358 4.6242 4.0441 4.4456 3.9239 4.3053 0.00009 DAP Not treated 0.00009 DAP F402_100 ug ai / seed 3.0823 0.00009 DAP F402 250 ug ai / seed 4.1592 4.5225 0.00009 DAP F400 100 ug ai / seed 4.2923 4.2535 3.0653 0.00009 DAP F401_100 ug ai / seed 2.7673 3.1897 3.9605 3.8945 0.00009 DAP F401 250 ug ai / seed 3.3998 3.3354 4.1225 4.1002 3.9383 0.00009 DAP F403_100 ug ai / seed 3.4009 3.6505 4.1041 4.0296 3.6196 2.4431 0.00009 DAP F403 250 ug ai / seed 3.8558 3.5786 3.8805 3.4968 4.1761 4.1571 4.0778 0.000010 DAP Not treated 0.000010 DAP F402 100 ug ai / seed 3.5404 0.000010 DAP F402 250 ug ai / seed 4.1586 4.1967 0.000010 DAP F400_100 ug ai / seed 4.0050 3.9323 3.4362 0.000010 DAP F401_100 ug ai / seed 3.7392 3.8796 3.7196 3.5689 0.000010 DAP F401 250 ug ai / seed 3.9793 4.2081 4.5713 4.2307 4.0480 0.000010 DAP F403_100 ug ai / seed 4.1818 4.7223 3.9505 3.6723 4.1229 3.0186 0.000010 DAP F403 250 ug ai / seed 4.0707 3.7919 4.2533 3.8110 4.1589 3.4209 4.2783 0.0000 all Not treated 0.0000 all F402_100 ug ai / seed 1.4575 0.0000 all F402 250 ug ai / seed 1.4032 1.6146 0.0000 all F400 100 ug ai / seed 2.0403 1.4956 1.0472 0.0000 all F401 100 ug ai / seed 1.7534 1.6993 1.2546 1.4493 0.0000 all F401_250 ug ai / seed 2.1913 2.2826 1.9830 2.3573 2.3024 0.0000all F403_100 ug ai / seed 1.9589 2.1987 1.7506 1.9065 2.0570 0.7868 0.0000 all F403 250 ug ai / seed 2.8407 2.7255 2.6221 2.8066 2.0202 2.3386 2.5966 0.00001. Plant age average across 4 to 10 days after planting (DAP)

[0146] Table 2-3. Hyperspectral differences1of soybean treated with nitrogen inhibition compounds compared to wild type (not treated control).Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Green4-10 DAP F402 100 ug ai / seed Not treated control 0.19 -0.05 0.054-10 DAP F402 250 ug ai / seed Not treated control -0.03 -0.35 -0.084-10 DAP F403_100 ug ai / seed Not treated control 0.22 2.58 0.394-10 DAP F403_250 ug ai / seed Not treated control 0.62 4.42 1.674-10 DAP F401_100 ug ai / seed Not treated control 0.10 0.07 -0.034-10 DAP F401_250 ug ai / seed Not treated control 0.38 2.47 0.404-10 DAP F400 100 ug ai / seed Not treated control 0.33 -0.50 -0.091. Positive values indicate better performance compared to not treated control and negative values indicate worse performance compared to not treated control2. Plant age average across 4 to 10 days after planting (DAP)

[0147] Table 2-4. Mahalanobis distance (log transformation) of soybean treated with nitrogen inhibitor compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to FST + 1ST control.F402 F400 F401 F403Plant FST + 1ST + FST + 1ST + FST + 1ST +FST+IST + FST + 1ST100 ug 250 ug 100 ug 250 ug 100 ug 250 ugAge1Seed Treatment Control ai / seed ai / seed lOO ug ai / seed ai / seed ai / seed ai / seed ai / seed5 DAP FST + 1ST Control 0.00005 DAP F402_100 ug ai / seedFSTIST 3.9104 0.00005 DAP F402 250 ug ai / seedFSTIST 4.3435 3.9839 0.00005 DAP F400 100 ug ai / seedFSTIST 4.2628 3.6111 3.0037 0.00005 DAP F401_100 ug ai / seedFSTIST 4.1851 4.1252 3.5457 3.1048 0.00005 DAP F401_250 ug ai / seedFSTIST 4.3187 4.3551 4.9198 4.3970 3.0740 0.00005 DAP F403 100 ug ai / seedFSTIST 4.3905 3.8509 4.8403 4.2198 3.3433 2.9369 0.00005 DAP F403 250 ug ai / seedFSTIST 4.9510 4.5416 3.5680 2.6564 3.0135 3.8392 3.3724 0.00006 DAP FST + 1ST Control 0.00006 DAP F402 100 ug ai / seedFSTIST 3.5652 0.00006 DAP F402 250 ug ai / seedFSTIST 3.3285 3.6289 0.00006 DAP F400 100 ug ai / seedFSTIST 3.3903 3.2025 3.4162 0.00006 DAP F401_100 ug ai / seedFSTIST 3.0731 2.5058 3.6343 3.9010 0.00006 DAP F401_250 ug ai / seedFSTIST 3.4458 3.4058 3.5919 4.1975 3.9365 0.00006 DAP F403_100 ug ai / seedFSTIST 3.6281 3.4951 3.6526 3.4527 3.7719 3.3184 0.00006 DAP F403 250 ug ai / seedFSTIST 3.2120 3.0654 3.9744 4.4526 3.7851 3.6514 3.2601 0.00008 DAP FST + 1ST Control 0.00008 DAP F402 100 ug ai / seedFSTIST 4.0858 0.00008 DAP F402 250 ug ai / seedFSTIST 3.9868 4.1570 0.00008 DAP F400 100 ug ai / seedFSTIST 4.4107 3.6252 3.1164 0.00008 DAP F401 100 ug ai / seedFSTIST 5.4812 4.4509 4.3661 4.2682 0.00008 DAP F401_250 ug ai / seedFSTIST 5.5771 4.5569 4.2370 4.3149 3.0534 0.00008 DAP F403_100 ug ai / seedFSTIST 5.5350 3.9395 4.2636 3.9164 3.1396 3.2156 0.00008 DAP F403 250 ug ai / seedFSTIST 4.9519 4.8520 3.0364 3.4430 3.7397 3.6993 3.3680 0.00009 DAP FST + 1ST Control 0.00009 DAP F402 100 ug ai / seedFSTIST 2.7923 0.00009 DAP F402 250 ug ai / seedFSTIST 3.6018 3.4478 0.00009 DAP F400 100 ug ai / seedFSTIST 3.0136 3.1337 2.1987 0.00009 DAP F401_100 ug ai / seedFSTIST 2.9166 2.7752 4.0183 4.1902 0.00009 DAP F401_250 ug ai / seedFSTIST 3.5285 3.2523 3.7642 3.2297 3.6839 0.00009 DAP F403_100 ug ai / seedFSTIST 3.2993 2.9540 3.7951 3.1462 3.7989 2.3724 0.00009 DAP F403 250 ug ai / seedFSTIST 3.8214 3.3065 3.7328 4.1155 3.5770 4.1002 4.3309 0.000010 DAP FST + 1ST Control 0.000010 DAP F402 100 ug ai / seedFSTIST 3.0210 0.000010 DAP F402 250 ug ai / seedFSTIST 3.7854 4.5305 0.000010 DAP F400 100 ug ai / seedFSTIST 3.9940 4.4480 2.0425 0.000010 DAP F401_100 ug ai / seedFSTIST 3.7136 4.0065 4.1412 4.0344 0.000010 DAP F401_250 ug ai / seedFSTIST 2.9975 3.0845 4.5344 4.1009 4.4373 0.000010 DAP F403_100 ug ai / seedFSTIST 2.9970 3.2463 4.7061 4.0529 4.4626 2.4588 0.000010 DAP F403 250 ug ai / seedFSTIST 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 all FST + 1ST Control 0.0000 all F402 100 ug ai / seedFSTIST 1.2574 0.0000 all F402 250 ug ai / seedFSTIST 1.5161 1.4869 0.0000 all F400 100 ug ai / seedFSTIST 2.1697 1.2819 1.1114 0.0000 all F401_100 ug ai / seedFSTIST 1.7387 2.0581 1.1565 2.1420 0.0000 all F401 250 ug ai / seedFSTIST 2.0536 1.4361 1.2340 1.2879 1.3437 0.0000 all F403 100 ug ai / seedFSTIST 1.9331 1.5480 1.5167 1.5674 1.4599 0.9154 0.0000 all F403 250 ug ai / seedFSTIST 1.8101 1.4303 0.9786 0.6649 1.2727 0.4595 0.8084 0.00001. Plant age average across 4 to 10 days after planting (DAP)

[0148] Table 2-5. Hyperspectral differences1of soybean treated with nitrogen inhibition compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to FST + 1ST control.Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Green4-10 DAP F402 100 ug ai / seedFSTIST FST + IST control -0.09 0.06 0.004-10 DAP F402_250 ug ai / seedFSTIST FST + 1ST control 0.17 0.74 0.004-10 DAP F403_100 ug ai / seedFSTIST FST + 1ST control -0.33 1.48 -0.044-10 DAP F403_250 ug ai / seedFSTIST FST + IST control 0.21 0.80 0.004-10 DAP F401_100 ug ai / seedFSTIST FST + IST control 0.08 1.69 -0.174-10 DAP F401_250 ug ai / seedFSTIST FST + 1ST control -0.12 1.30 0.044-10 DAP F400_100 ug ai / seedFSTIST FST + 1ST control 0.04 0.60 -0.061. Positive values indicate better performance compared to FST + 1ST control and negative values indicate worse performance compared to FST + 1ST control.2. Plant age average across 4 to 10 days after planting (DAP)Example 3. Wheat nitrogen inhibitor seed treatmentsMaterials and Methods

[0150] Wheat commercial variety ND Frohberg seed were treated with different nitrogen inhibitor compounds as a seed treatment at 100 ug ai / seed or 250 ug ai / seed (Table 3-1). NIN compounds were treated alone and in combination with commercial fungicide and insecticide seed treatments (Table 3-1). Wheat seed were treated as water-based slurries using a Hege 11 laboratory seed treater (Wintersteiger AG, Ried im Innkreis, Austria). Slurries were created by mixing the treatment components in a sufficient volume of tap water to ensure uniform seed coverage. Prepared slurries were pipetted onto the spinning disk of a Hege 11 seed treater in application volumes of 90-130 m slurry per 80,000 seed. Seeds were circulated in treater bowl for 15-25 seconds to uniformly coat the seed. Treated seed were air dried prior to planting.

[0151] Wheat seed treatment experiments were planted on October 9, 2023, in the Corteva Agriscience (Johnston, IA) greenhouse facilities. Experiments consisted of 16 replicates per seed treatment entry. Seed was planted at a standard planting depth of 20 to 25 mm in a standard germination mix comprising of 76.49% peat, 16.10% peat, 7.38% vermiculite, 5 lbs / yd3lime, 3 lbs / yd3starter fertilizer, and 0.5 lbs / yd3wetting agent. The individual seeds were placed in flats of 32 plants each in an 8x4 configuration resulting in a 212 plants / m2density.

[0152] The plants were grown in a glass greenhouse with day length of 16 hours and growth conditions of daytime temperature at 22.22C, and nighttime temperature at 19.44C. Plants were imaged at first visual sight of the plumule using a Hyperspectral Visible and Near InfraRed camera and a short-wave infrared camera. The cameras capture reflectance between 400 nm and 2500 nm. Plants grown under normal conditions were imaged daily from 8 days after planting until 10 days after planting (VE to V3 growth stage). Data were processed using proprietary software into average reflectance spectra of individual plants and physiologically relevant features. These data were standardized and processed using R. Custom algorithms were developed to adjust data and remove variability. Data were processed using a modified version of Mahalanobis distance to determine differences between treatments. Resulting distance matrices were log-transformed, with values over 3 considered significantly different.Example 3. Results and discussion

[0153] The Mahalanobis distance is a measure of the distance between a datapoint and the distribution of data; quantifying the number of standard deviations the datapoint is away from the mean of the distribution. The larger the value, the further away the seed treatment is from the control. Within each plant age, the different nitrogen inhibitor compounds were significantly different compared to the not treated control and significantly different compared to each other, with almost all values greater than 3.0 (Table 3-2). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a compound across all days, the 100 ug ai / seed had a higher difference value compared to not treated control for F401 (Table 3-2). Across all days the 250 ug ai / seed rate had a higher difference value compared to control for F402 and F403 (Table 3-2).

[0154] When the visible spectrum data are averaged across time, all NIN compounds at each rate except F402 100 ug ai / seed and F403 250 ug ai / seed had positive average pixel area values, indicating these compounds increased plant size compared to control (Table 3-3). In addition, all NIN compounds and all rates had positive average green index and average percent green across all plant dates, indicating an improvement in plant health compared to not treated control (Table 3-3). In contrasting rates within a specific NIN compound, F402 250 ug ai / seed had higher values for all traits compared to F402 100 ug ai / seed (Table 3-3). F403 100 ug ai / seed and F401 100 ug ai / seed had higher average pixel area and average green index values compared to the 250 ug ai / seed rates of the same NIN compound (Table 3-3). Over all data, F401 100 ug ai / seed had the highest average pixel area and average green index values (Table 3-3). The hyperspectral data from 400 nm to 1000 nm show the 100 ug ai / seed rate of F401 as generally having higher values compared to the 250 ug ai / seed rate and the not treated control (Figure 3-1). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to differentiate rates and select the ideal nitrogen inhibitor compound as a seed treatment for wheat.

[0155] When the NIN compounds were added to seed treated with FST + 1ST, within each plant age, the different NIN compounds were significantly different compared to the FST + 1ST control and significantly different compared to each other, with almost all Mahalanobis distance values greater than 3.0 (Table 3-4). When comparing the 100 ug ai / seed rate to the 250 ug ai / seed rate within a NIN compound (+ FST + 1ST) at each individual day and across all days, the 250 ug ai / seed rate generally had a higher difference value compared to FST + 1ST control for F403, F402 and F401 (Table 3-4).

[0156] When the visible spectrum data are averaged across time for NIN compounds with FST + 1ST, F403 100 ug ai / seed + FST + 1ST, F403 250 ug ai / seed + FST + 1ST and F401 250 ug ai / seed + FST + 1ST had positive pixel area, average green index, and average percent green, indicating an improvement in early growth and plant health (Table 3-5). In contrast, F402 100 ug ai / seed + FST + 1ST and 250 ug ai / seed rates and F400 100 ug ai / seed + FST + 1ST had negative pixel area across all dates evaluated (Table 3-5). Over all data, F403 250 ug ai / seed + FST + 1ST had the highest average pixel area, average green index, and average percent green values (Table 3-5). The hyperspectral data from 400 nm to 1000 nm show the 250 ug ai / seed rate of F403 as having higher values compared to the 100 ug ai / seed rate and the not treated control (Figure 3-2). These data indicate that the visual spectrum data in combination with the hyperspectral data can be utilized to differentiate rates and select the ideal nitrogen inhibitor compound as a seed treatment for wheat treated with FST + 1ST.

[0157] Improvement in early plant growth and plant health was observed for several different NIN compounds as a seed treatment on wheat. Combining the visible spectrum data with hyperspectral data analyses enabled the selection of the NIN compound (alone and in combination with FST + 1ST) with the best performance. Utilizing these analytic techniques was a rapid method to screen and select the optimal NIN compound and ideal rate as a seed treatment in wheat.

[0158] Table 3-1. Nitrogen inhibitor seed treatment components for wheat hyperspectral experiments

[0160] Table 3-2. Mahalanobis distance (log transformation) of wheat treated with nitrogen inhibitor compounds compared to wild type (not treated control).Not Treated F402 F400 F401 F403. , _ . , 100 ug 250 ug „„„ . . . 100 ug 250 ug 100 ug 250 ugPlant Age1Seed Treatment Control , , , , lOO ug ai / seed . , . , , , . , ai / seed ai / seed ai / seed ai / seed ai / seed ai / seed8 DAP Not treated control 0.00008 DAP F402 100 ug ai / seed 3.8129 0.00008 DAP F402 250 ug ai / seed 2.9469 4.2488 0.00008 DAP F400_100 ug ai / seed 4.4284 4.6852 4.4367 0.00008 DAP F401_100 ug ai / seed 3.9469 5.1147 3.8297 3.8035 0.00008 DAP F401_250 ug ai / seed 4.3746 5.3297 4.2111 4.2405 3.5646 0.00008 DAP F403_100 ug ai / seed 4.2025 4.2993 4.0126 4.6254 4.5838 3.6763 0.00008 DAP F403 250 ug ai / seed 3.4663 4.2896 4.4405 4.2289 3.5290 4.5052 4.4285 0.00009 DAP Not treated control 0.00009 DAP F402_100 ug ai / seed 3.2361 0.00009 DAP F402 250 ug ai / seed 3.0506 3.4094 0.00009 DAP F400_100 ug ai / seed 4.2537 5.2077 3.3517 0.00009 DAP F401_100 ug ai / seed 3.4237 3.9420 3.9946 4.5530 0.00009 DAP F401_250 ug ai / seed 4.4779 5.0973 3.7866 3.4829 4.3437 0.00009 DAP F403_100 ug ai / seed 3.1097 3.5308 3.8319 3.8221 3.6600 3.9585 0.00009 DAP F403 250 ug ai / seed 5.1212 5.7855 4.9639 5.6183 4.8139 3.5539 5.1957 0.000010 DAP Not treated control 0.000010 DAP F402_100 ug ai / seed 2.5050 0.000010 DAP F402 250 ug ai / seed 3.5236 3.8962 0.000010 DAP F400_100 ug ai / seed 4.4806 5.4584 3.5465 0.000010 DAP F401_100 ug ai / seed 4.0288 4.3986 4.3663 4.8794 0.000010 DAP F401_250 ug ai / seed 3.6917 4.1118 4.0580 3.6272 4.3729 0.000010 DAP F403_100 ug ai / seed 3.2609 3.5536 3.7896 4.0983 3.4768 3.9111 0.000010 DAP F403 250 ug ai / seed 4.4187 5.1420 4.1581 3.7058 3.2678 3.0665 4.0612 0.0000 all Not treated control 0.0000all F402_100 ug ai / seed 2.0257 0.0000 all F402 250 ug ai / seed 3.4241 5.0994 0.0000 all F400 100 ug ai / seed 3.9839 5.5361 2.3664 0.0000 all F401 100 ug ai / seed 3.6523 3.9609 3.1086 4.4930 0.0000 all F401 250 ug ai / seed 3.4605 4.5868 2.8031 2.4273 3.7537 0.0000 all F403 100 ug ai / seed 3.3479 4.0475 3.0366 2.9189 3.3901 2.5237 0.0000 all F403 250 ug ai / seed 3.6712 3.7978 2.8364 3.0615 4.5576 2.5090 3.5863 0.00001. Plant age average across 8 to 10 days after planting (DAP)

[0161] Table 3-3. Hyperspectral differences1of wheat treated with nitrogen inhibition compounds compared to wild type (not treated control).Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Green8-10 DAP F402 100 ug ai / seed Not treated control -0.01 0.98 1.638-10 DAP F402 250 ug ai / seed Not treated control 0.04 4.34 5.688-10 DAP F403_100 ug ai / seed Not treated control 0.63 4.19 4.038-10 DAP F403 250 ug ai / seed Not treated control -0.58 2.45 4.428-10 DAP F401_100 ug ai / seed Not treated control 1.44 12.37 5.568-10 DAP F401 250 ug ai / seed Not treated control 0.36 1.22 4.388-10 DAP F400 100 ug ai / seed Not treated control 1.35 5.79 6.261. Positive values indicate better performance compared to not treated control, negative values indicate worse performance compared to not treated control.2. Plant age average across 8 to 10 days after planting (DAP)

[0162] Table 3-4. Mahalanobis distance (log transformation) of wheat treated with nitrogen inhibitor compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to not treated control.Not F402 F401 F403Plant Treated +FST+IST F400 +FST+IST +FST+IST +FST+IST100 ug . .1 T, 100 ug 250 ug „„„ , 100 ug 250 uge250 ugAge Seed Treatment Control . . . . . . lOO ug ai / seed . . . . . . ai / see . . ai / seed ai / seed ai / seed ai / seed ai / seed8 DAP Not treated control 0.00008 DAP F402 100 ug ai / seedFSTIST 4.9242 0.00008 DAP F402 250 ug ai / seedFSTIST 3.7626 5.5368 0.00008 DAP F400 100 ug ai / seedFSTIST 4.7114 4.5524 3.5837 0.00008 DAP F401_100 ug ai / seedFSTIST 4.4839 5.6617 5.3100 4.8087 0.00008 DAP F401_250 ug ai / seedFSTIST 3.5354 5.5823 3.4534 4.4395 3.8117 0.00008 DAP F403_100 ug ai / seedFSTIST 4.5818 5.4173 4.2358 4.1569 4.8162 4.0727 0.00008 DAP F403 250 ug ai / seedFSTIST 3.8205 5.5310 4.7503 4.7116 5.2028 3.6074 5.0274 0.00009 DAP Not treated control 0.00009 DAP F402 100 ug ai / seedFSTIST 3.7199 0.00009 DAP F402 250 ug ai / seedFSTIST 4.4173 4.7237 0.00009 DAP F400 100 ug ai / seedFSTIST 2.7764 3.7378 4.0924 0.00009 DAP F401_100 ug ai / seedFSTIST 3.3320 4.5132 5.4794 4.6817 0.00009 DAP F401_250 ug ai / seedFSTIST 3.5411 4.1449 3.6325 3.1756 4.3975 0.00009 DAP F403_100 ug ai / seedFSTIST 3.7425 3.9280 3.8019 2.8073 4.3697 3.8036 0.00009 DAP F403 250 ug ai / seedFSTIST 6.4302 6.1091 6.2397 6.8889 6.4899 7.2897 7.0751 0.000010 DAP Not treated control 0.000010 DAP F402 100 ug ai / seedFSTIST 3.6034 0.000010 DAP F402 250 ug ai / seedFSTIST 4.0763 3.7384 0.000010 DAP F400_100 ug ai / seedFSTIST 3.9470 3.5927 3.2995 0.000010 DAP F401_100 ug ai / seedFSTIST 3.5822 4.8239 3.7024 3.2574 0.000010 DAP F401 250 ug ai / seedFSTIST 3.2367 3.6963 3.5181 2.9988 4.3858 0.000010 DAP F403_100 ug ai / seedFSTIST 3.4007 4.1632 3.9958 3.5616 4.2569 2.8873 0.000010 DAP F403 250 ug ai / seedFSTIST 6.2031 6.6036 6.7543 6.0945 6.0049 7.3978 5.3757 0.0000all Not treated control 0.0000 all F402 100 ug ai / seedFSTIST 3.4937 0.0000 all F402 250 ug ai / seedFSTIST 3.4203 2.8159 0.0000 all F400 100 ug ai / seedFSTIST 3.4183 2.3421 2.2783 0.0000 all F401 100 ug ai / seedFSTIST 3.0840 4.2572 3.2580 4.0871 0.0000 all F401 250 ug ai / seedFSTIST 2.8286 2.7119 2.5187 2.9766 3.0248 0.0000 all F403 100 ug ai / seedFSTIST 2.8942 2.8651 2.8651 3.0051 3.1831 1.9174 0.0000 all F403 250 ug ai / seedFSTIST 4.9190 4.7025 4.7649 5.0816 4.5500 3.6070 3.5625 0.00001. Plant age average across 8 to 10 days after planting (DAP)

[0163] Table 3-5. Hyperspectral differences1of wheat treated with nitrogen inhibition compounds + fungicide (FST) + insecticide (1ST) seed treatments compared to not treated control.Plant Age2Seed Treatment Comparison Avg Pixel Area Avg Green Index Avg Percent Grei8-10 DAP F402_100 ug ai / seedFSTIST Not treated control -1.08 10.24 0.708-10 DAP F402_250 ug ai / seedFSTIST Not treated control -0.08 4.78 4.098-10 DAP F403_100 ug ai / seedFSTIST Not treated control 1.58 0.30 2.838-10 DAP F403_250 ug ai / seedFSTIST Not treated control 1.64 6.17 37.338-10 DAP F401_100 ug ai / seedFSTIST Not treated control -0.23 5.74 2.478-10 DAP F401_250 ug ai / seedFSTIST Not treated control 0.81 0.18 2.138-10 DAP F400_100 ug ai / seedFSTIST Not treated control -1.31 5.25 3.80 . Positive values indicate better performance compared to FST + 1ST control and negative values indicate worse performance compared to FST + 1ST control.2. Plant age average across 8 to 10 days after emergence (DAP)

Claims

Claims1. A composition comprising a) a seed, b) a compound selected from the group consisting of F1-F403, wherein a plant grows from the seed showing a Mahalanobis distance of equal to or more than 3.0000 in comparison to a seed that is not treated with a compound selected from the group consisting of F1-F403.

2. The composition according to claim 1, wherein the Mahalanobis distance is measured in relation to at least one of the parameters related to plant growth and / or vigor selected from group consisting of pixel area, average green index, average percent green, average yellow index, average percent yellow, average brown index, average percent brown, leaf size, leaf length, shoot length, root density, oil content of the plant parts, number of flowers, size and number of fruits and root length.

3. The composition according to claims 1-2, wherein the Mahalanobis distance is measured and compared with a seed that is not treated with a compound selected from the group consisting of F1-F403 at VE-V3 growth stages.

4. The composition according to claims 1-3, further comprising an active selected from the group consisting of insecticide, nematicide, fungicide, inoculant and biological agent.

5. The composition according to claims 4, wherein the active is selected from the group consisting of 1,3 -dichloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenval erate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma- cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide,novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox.

6. The composition according to claims 4-5, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

7. The composition according to claims 1-6, wherein the compound is selected from the group consisting of F400-F403.

8. A method of improving growth and / or vigor of a plant grown from a seed comprising the step of treating the seed with a composition comprising a compound selected from the group consisting of F1-F403.

9. The method according to claim 8, wherein the composition further comprises an active selected from the group consisting of insecticide, nematicide, fungicide, inoculant and biological agent.

10. The method according to claim 9, wherein the active is selected from the group consisting of 1,3-dichloropropene, abamectin, acephate, acequinocyl, acetamiprid, acetoprole, afidopyropen, avermectin, azinphos-methyl, benzpyrimoxan, bifenazate, bifenthrin, broflanilide, buprofezin, carbaryl, carbofuran, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chromafenozide, clothianidin, cyantraniliprole, cyclaniliprole, cycloxaprid, cyfluthrin, cypermethrin, cyproflanilide, deltamethrin, diafenthiuron, dimpropyridaz, dinotefuran, emamectin benzoate, endosulfan, esfenvalerate, ethiprole, etoxazole, fenmezoditiaz, fipronil, flonicamid, fluacrypyrim, flubendiamide, flupyradifurone, flupyrimin, fluxametamide, gamma-cyhalothrin, halofenozide, hexaflumuron, imidacloprid, indazapyroxamet, indoxacarb, isocycloseram, lambda-cyhalothrin, lufenuron, malathion, methomyl, methoxyfenozide, novaluron, noviflumuron, oxamyl, oxazosulfyl, permethrin, pymetrozine, pyridalyl, pyrifluquinazon, pyrimidifen, pyriproxyfen, spidoxamat, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropidion, spirotetramat, sulfoxaflor, tebufenozide, tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, triflumezopyrim, zeta-cypermethrin, cyclobutrifluram, fluensulfone, fluopyram, fluazaindolizine, tioxazafen, metalaxyl, mefenoxam, ipconazole, fludioxonil, azoxystrobin, inpyrfluxam, ethaboxam, oxathiapiprolin, sedaxane, difenoconazole, picoxystrobin, prothioconazole, penflufen, thiabendazole, tebuconazole, pydiflumetofen, fluoxastrobin, fluxapyroxad, copper hydroxide, trifloxystrobin, thiram, fluoxapiprolin, isoflucypram, metconazole, and picarbutrazox.

11. The method according to claims 8-10, wherein the composition comprises a compound selected from the group consisting of F400-F403.

12. The method according to claims 9-11, wherein the active is selected from the group consisting of ethaboxam, inpyrfluxam, metalaxyl, ipconazole, clothianidin, chlorantraniliprole, cyantraniliprole, oxathiapiprolin, prothioconazole, penflufen, imidacloprid, difenoconazole, fludioxonil, mefenoxam, sedaxane, and thiamethoxam.

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