Pyrazine-4-carbamate or -urea derivatives as herbicides
11678665 · 2023-06-20
Assignee
Inventors
- Jeffrey Steven Wailes (Bracknell, GB)
- Neil Brian Carter (Bracknell, GB)
- John Martin Clough (Bracknell, GB)
- John Williams (Bracknell, GB)
Cpc classification
International classification
Abstract
The present invention relates to herbicidal) active pyridyl-/pyrimidyl-pyrazine derivatives, as well as to processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions in controlling undesirable plant growth: in particular the use in controlling weeds, in crops of useful plants.
Claims
1. A compound of formula (I) ##STR00045## or a salt thereof, wherein: X.sup.1 is N or CR.sup.1; R.sup.1 is selected from the group consisting of halogen and cyano; R.sup.2 is selected from the group consisting of halogen, cyano, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl; R.sup.3 is —C(O)C.sub.1-C.sub.6alkyl, or —C(O)C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl; R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl and —C(O)R.sup.9; each R.sup.9 is independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, butenyl, —C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl, and —(CH.sub.2).sub.2C(O)OR.sup.c; and R.sup.c is hydrogen or C.sub.1-C.sub.4alkyl.
2. The compound of formula (I) according to claim 1, wherein X.sup.1 is N.
3. The compound of Formula (I) according to claim 1, wherein X.sup.1 is CR.sup.1 and R.sup.1 is selected from the group consisting of fluoro, chloro, and cyano.
4. The compound of Formula (I) according to claim 1, wherein R.sup.2 is cyano, methyl or trifluoromethyl.
5. The compound of Formula (I) according to claim 1, wherein R.sup.4 is —C(C)R.sup.9.
6. The compound of Formula (I) according to claim 1, wherein R.sup.4 is hydrogen or methyl.
7. A herbicidal composition comprising a compound of Formula (I) as defined in claim 1 and an agriculturally acceptable formulation adjuvant.
8. The herbicidal composition according to claim 7, further comprising at least one additional pesticide.
9. A method of controlling grassy weeds at a locus comprising application to the locus of a grassy weed controlling amount of a compound of formula (I) as defined in claim 1.
10. A compound selected from the group consisting of: ##STR00046## ##STR00047##
Description
PREPARATION EXAMPLES
(1) Xantphos palladacycle 4th generation refers to methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2′-methylamino-1,1′-biphenyl-2-yl)palladium(II) [1621274-19-8] see Org. Lett. 2014, 16, 4296 and WO13184198.
Example P1: Preparation of 2-(diacetylamino)-3-methyl-5-(5-fluoropyrid-3-yl)pyrazine (Compound I5)
(2) ##STR00018##
Step 1: Preparation of 2-(diacetylamino)-3-methyl-5-(5-fluoropyrid-3-yl)pyrazine (Compound I5)
(3) ##STR00019##
(4) A mixture of 2-amino-3-methyl-5-(5-fluoropyrid-3-yl)pyrazine (190 mg, 0.93 mmol) and acetic anhydride (4 ml, 42 mmol) was heated for 30 minutes in the microwave at 100° C. After cooling, the mixture was diluted with toluene and excess acetic anhydride was removed by azeotropic distillation. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate in isohexane as eluent to give 2-(diacetylamino)-3-methyl-5-(5-fluoropyrid-3-yl)pyrazine (200 mg, 75%) as a yellow solid.
(5) .sup.1H NMR (400 MHz, CDCl.sub.3) δ9.10 (s, 1H), 8.90 (s, 1H), 8.60 (s, 1H), 8.15 (dd, 1H), 2.60 (s, 3H), 2.30 (s, 6H).
Example P2: Preparation of 2-(acetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (I3) and 2-(diacetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (I4)
(6) ##STR00020##
(7) Step 1: Preparation of 2-(acetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (I3) and 2-(diacetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (I4)
(8) ##STR00021##
(9) A mixture of 2-amino-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (100 mg, 0.39 mmol) and acetic anhydride (2.0 ml, 21 mmol) was heated for 30 minutes in the microwave at 100° C., and then for a further 4 hours at 150° C. After cooling, the mixture was purified by mass directed reverse phase HPLC to give 2-(acetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (22 mg, 19%) and 2-(diacetylamino)-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (40 mg, 30%) both as white solids.
(10) I3: .sup.1H NMR (400 MHz, CDCl.sub.3) δ9.10 (s, 2H), 8.60 (s, 1H), 8.15 (dd, 1H), 7.85 (br s, 1H), 2.45 (s, 3H)
(11) I4: .sup.1H NMR (400 MHz, CDCl.sub.3) δ9.30 (s, 1H), 9.15 (s, 1H), 8.70 (s, 1H), 8.25 (dd, 1H), 2.35 (s, 6H)
Example P3: Preparation of 2-amino-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine
(12) ##STR00022##
Step 1: Preparation of 2-amino-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine
(13) ##STR00023##
(14) 2-Amino-3-trifluoromethyl-5-bromopyrazine (3.2 g, 13 mmol), (5-fluoro-3-pyridyl)boronic acid (2.6 g, 19 mmol) and Xantphos Palladacycle G4 (570 mg, 0.60 mmol) were dissolved in a mixture of toluene (64 ml), ethanol (16 ml) and aqueous potassium carbonate (2M, 13 ml) and the resulting mixture was heated under reflux for 2 hours and then allowed to cool. Volatiles were removed under reduced pressure and the resulting brown solid was dissolved in ethyl acetate then washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate in isohexane as eluent to give 2-amino-3-trifluoromethyl-5-(5-fluoropyrid-3-yl)pyrazine (430 mg, 13%) as a yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.95 (s, 1H), 8.75 (s, 1H), 8.50 (s, 1H), 8.00 (d, 1H), 5.35 (br s, 2H).
Example P4: Preparation of tert-butyl N-(5-bromo-3-methyl-pyrazin-2-yl)-carbamate
(15) ##STR00024##
Step 1: Preparation of tert-butyl N-(3-methyl-pyrazin-2-yl)-carbamate
(16) ##STR00025##
(17) Diphenylphosphoryl azide (22.2 g, 80.5 mmol) was added to a stirred solution of 3-methylpyrazine-2-carboxylic acid (9.0 g, 61.9 mmol) in toluene (90 ml), tert-butanol (45 ml) and triethylamine (8.18 g, 80.5 mmol). The resulting mixture was heated at 90° C. for 4 hours (reaction was observed to begin during heating, at about 65° C. internal temperature) and then allowed to cool. The solvent was removed under reduced pressure and the residue was re-dissolved in ethyl acetate (150 ml). The resulting solution was washed with 2M aqueous sodium bicarbonate then dried using a phase separation membrane, concentrated under reduced pressure and purified by chromatography on silica gel using a gradient of ethyl acetate in hexane as eluent to give tert-butyl N-(3-methyl-pyrazin-2-yl)-carbamate (8.0 g, 59%) as a colourless oil which slowly crystallised.
(18) .sup.1H NMR (400 MHz CDCl.sub.3) δ8.27 (d, 1H), 8.23 (d, 1H), 6.85 (br s, 1H), 1.53 (s, 9H).
(19) Step 2: Preparation of N-(5-bromo-3-methyl-pyrazin-2-yl)-carbamate
(20) ##STR00026##
(21) Bromine (127 mg, 0.79 mmol) was added dropwise at room temperature to a stirred solution of tert-butyl N-(3-methyl-pyrazin-2-yl)-carbamate (150 mg, 0.72 mmol) and pyridine (69 mg, 0.86 mmol) in chloroform (4.5 ml). The resulting mixture was stirred at room temperature for 24 hours and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 ml), washed with water, dried using a phase-separation membrane and purified by chromatography on silica gel using mixtures of ethyl acetate and hexane as eluent to give tert-butyl N-(5-bromo-3-methyl-pyrazin-2-yl)-carbamate as a white solid (140 mg, 68%). .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.30 (s, 1H) 6.65 (br s, 1H), 2.55 (s, 3H), 1.55 (s, 9H).
Example P5: Preparation of 3-trifluoromethyl-2-aminopyrazine
(22) ##STR00027##
Step 1: Preparation of tert-butyl N-(3-trifluoromethylpyrazin-2-yl)-carbamate
(23) ##STR00028##
(24) Diphenylphosphoryl azide (3.47 g, 12.6 mmol) was added to a stirred solution of 3-trifluoromethylpyrazine-2-carboxylic acid (1.92 g, 9.70 mmol) and triethylamine (1.28 g, 12.6 mmol) in tert-butanol (9.6 ml, 100 mmol) and toluene (19.2 ml). The resulting mixture was heated at 90° C. for 4 hours and then allowed to cool. It was washed with 2M aqueous sodium bicarbonate, then dried through a phase-separation filter and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate in hexane as eluent to give tert-butyl N-(3-trifluoromethylpyrazin-2-yl)-carbamate containing 3-trifluoromethyl-2-aminopyrazine (2.0 g) as a colourless oil which slowly crystallised to give a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.70 (s, 1H), 8.40 (s, 1H), 7.20 (br s, 1H), 1.55 (s, 9H).
(25) Step 2: Preparation of 3-trifluoromethyl-2-aminopyrazine
(26) ##STR00029##
(27) Trifluoroacetic acid (1.1 ml, 14 mmol) was added in portions to a stirred solution of the crude tert-butyl N-(3-trifluoromethylpyrazin-2-yl)-carbamate (0.92 g, ca. 3.5 mmol) in 1,2-dichlorethane (9.2 ml) at room temperature. The resulting mixture was heated under reflux for 2 hours, allowed to cool, then washed with saturated aqueous sodium bicarbonate and dried through a phase-separation filter. Concentration under reduced pressure then gave 3-trifluoromethyl-2-aminopyrazine (0.48 g) as a yellow solid
(28) .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.25 (s, 1H), 8.00 (s, 1H), 5.15 (br s, 1H).
Example P6: Preparation of tert-butyl N-(3-methyl-pyrazin-2-yl)-N-methyl-carbamate
(29) ##STR00030##
Step 1: Preparation of tert-butyl N-(3-methyl-pyrazin-2-yl)-N-methyl-carbamate
(30) ##STR00031##
(31) A solution of tert-butyl N-(3-methyl-pyrazin-2-yl)-carbamate (1.05 g, 5.0 mmol) in dry DMF was added dropwise to a stirred suspension of sodium hydride (220 mg, 5.5 mmol) in dry DMF at room temperature (total volume of DMF ˜10 ml) (effervescence). The resulting mixture was stirred at room temperature for 30 minutes, then methyl iodide (3.6 g, 25 mmol) was added in one portion. The reaction mixture was stirred for 2 hours, then quenched with water and extracted with ethyl acetate. The extracts were washed with water and brine, then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified mass directed reverse phase HPLC to give tert-butyl N-(3-methyl-pyrazin-2-yl)-N-methyl-carbamate (24 mg, 2%) as an oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ7.35 (d, 1H), 7.00 (d, 1H), 3.55 (s, 3H), 2.50 (s, 3H), 1.55 (s, 9H).
Example P7: Preparation of 2-amino-3-trifluoromethyl-5-bromopyrazine
(32) ##STR00032##
Step 1: Preparation of 2-amino-3-trifluoromethyl-5-bromopyrazine
(33) ##STR00033##
(34) A solution of bromine in dichloromethane (10 ml) was added in portions to a stirred solution of 2-amino-3-trifluoromethylpyrazine (1.5 g, 9.2 mmol) and pyridine (0.90 ml, 11 mmol) in chloroform. The resulting mixture was stirred at room temperature for 24 hours. Volatiles were removed under reduced pressure and the residue was purified by chromatography on silica gel using a gradient of ethyl acetate in isohexane as eluent to give 2-amino-3-trifluoromethyl-5-bromopyrazine (1.7 g, 77% yield) as an off-white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.30 (s, 1H), 5.13 (br s, 2H).
(35) Further examples of the invention can be prepared similarly using the methods described above. Table 2 below, shows the structure of these compounds and the physical characterising data obtained using one or more of methods as outlined below.
(36) TABLE-US-00002 TABLE 2 Characterising data for Compounds of formula (I) made by the methods above. Compound Data (400 MHz, CDCl.sub.3) ID Structure unless stated I1
Physical Characterisation
Compounds of the invention were characterised using one or more of the following methods.
NMR
(37) NMR spectra contained herein were recorded on either a 400 MHz Bruker AVANCE III HD equipped with a Bruker SMART probe or a 500 MHz Bruker AVANCE III equipped with a Bruker Prodigy probe. Chemical shifts are expressed as ppm downfield from TMS, with an internal reference of either TMS or the residual solvent signals. The following multiplicities are used to describe the peaks: s=singlet, d=doublet, t=triplet, dd=double doublet, m=multiplet. Additionally br. is used to describe a broad signal and app. is used to describe and apparent multiplicity.
(38) LCMS
(39) LCMS data contained herein consists of the molecular ion [MH+] and the retention time (tr) of the peak recorded on the chromatogram. The following instruments, methods and conditions were used to obtain LCMS data:
(40) Method A
(41) Instrumentation: Waters Acquity UPLC-MS using a Sample Organizer with Sample Manager FTN, H-Class QSM, Column Manager, 2×Column Manager Aux, Photodiode Array (Wavelength range (nm): 210 to 400, ELSD and SQD 2 equipped with a Waters HSS T3 C18 column (column length 30 mm, internal diameter of column 2.1 mm, particle size 1.8 micron).
Ionisation method: Electrospray positive and negative: Capillary (kV) 3.00, Cone (V) 30.00, Source Temperature (° C.) 500, Cone Gas Flow (L/Hr.) 10, Desolvation Gas Flow (L/Hr.) 1000. Mass range (Da): positive 95 to 800, negative 115 to 800.
The analysis was conducted using a two minute run time, according to the following gradient table at 40° C.:
(42) TABLE-US-00003 Time Solvent Solvent Flow (mins) A (%) B (%) (ml/mn) 0.00 95.0 5.0 0.7 1.75 0.0 100 0.7 1.76 0.0 100 0.7 2.0 0.0 5.0 0.7 2.01 95.0 5.0 0.7 2.11 95.0 5.0 0.7 Solvent A: H.sub.2O with 0.05% TFA Solvent B: CH.sub.3CN with 0.05% TFA
Method B (2 min Method)
Instrumentation: Either (a) Waters Acquity UPLC system with Waters SQD2 single-quad MS detector, Photodiode Array Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit (injection volume: 2 microliters, 1 min seal wash); or (b) Waters Acquity UPLC system with Waters QDa single-quad MS detector, Photodiode Array Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit (injection volume: 2 microliters, 1 min seal wash).
LC-Method:
Phenomenex ‘Kinetex C18 100A’ column (50 mm×4.6 mm, particle size 2.6 micron), Flow rate: 2 mL/min at 313K (40 Celsius),
Gradient (Solvent A: H.sub.2O with 0.1% Formic Acid; Solvent B: Acetonitrile with 0.1% Formic Acid):
The analysis was conducted using a two minute run time, according to the following gradient table at 40° C.
(43) TABLE-US-00004 Time Solvent Solvent Flow (mins) A (%) B (%) (ml/mn) Initial 70.0 30.0 2.000 1.20 10.0 90.0 2.000 1.70 10.0 90.0 2.000 1.80 70.0 30.0 2.000 2.00 70.0 30.0 2.000 2.20 70.0 30.0 2.000
Method C (1 min Method)
Instrumentation: Either (a) Waters Acquity UPLC system with Waters SQD2 single-quad MS detector, Photodiode Array Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit (injection volume: 2 microliters, 1 min seal wash); or (b) Waters Acquity UPLC system with Waters QDa single-quad MS detector, Photodiode Array Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit (injection volume: 2 microliters, 1 min seal wash).
LC-Method:
Phenomenex ‘Kinetex C18 100A’ column (50 mm×4.6 mm, particle size 2.6 micron), Flow rate: 2 mL/min at 313K (40 Celsius),
Gradient (Solvent A: H.sub.2O with 0.1% Formic Acid; Solvent B: Acetonitrile with 0.1% Formic Acid):
The analysis was conducted using a one minute run time, according to the following gradient table at 40° C.
(44) TABLE-US-00005 Time Solvent Solvent Flow (mins) A (%) B (%) (ml/mn) Initial 60.0 40.0 2.000 0.80 0.0 100.0 2.000 0.95 0.0 100.0 2.000 1.00 60.0 40.0 2.000 1.10 60.0 40.0 2.000 1.25 60.0 40.0 2.000
BIOLOGICAL EXAMPLES
(45) B1 Pre-Emergence Herbicidal Activity
(46) Seeds of a variety of test species were sown in standard soil in pots: Triticum aestivium (TRZAW), Avena fatua (AVEFA), Alopecurus myosuroides (ALOMY), Echinochloa crus-galli (ECHCG), Lolium perenne (LOLPE), and Setaria faberi (SETFA). After cultivation for one day (pre-emergence) under controlled conditions in a glasshouse (at 24/16° C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). The test plants were then grown in a glasshouse under controlled conditions (at 24/16° C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days, the test was evaluated (5=total damage to plant; 0=no damage to plant). Results are shown in Tables B1.
(47) TABLE-US-00006 TABLE B1 Control of weed species by compound of Formula (I) after pre-emergence application Com- pound Rate ID (g/ha) ECHCG LOLPE SETFA AVEFA ALOMY TRAZW I1 1000 2 1 3 1 0 0 I2 1000 2 0 3 0 0 0 I3 1000 3 0 4 1 0 0 I4 1000 3 0 4 1 0 3 I5 1000 2 1 3 0 0 0 I6 1000 3 0 5 1 0 0 I8 1000 2 1 4 0 0 0 I9 1000 1 0 4 0 0 0 I10 1000 2 0 2 0 0 0 I11 1000 3 0 4 0 0 1 I12 1000 2 0 3 1 0 0
B2 Post-Emergence Herbicidal Activity
(48) Seeds of a variety of test species were sown in standard soil in pots: Triticum aestivium (TRZAW), Avena fatua (AVEFA), Alopecurus myosuroides (ALOMY), Echinochloa crus-galli (ECHCG), Lolium perenne (LOLPE), and Setaria faberi (SETFA). After 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16° C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). The test plants were then grown in a glasshouse under controlled conditions (at 24/16° C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days, the test was evaluated (5=total damage to plant; 0=no damage to plant). Results are shown in Tables B2.
(49) TABLE-US-00007 TABLE B2 Control of weed species by compound of Formula (I) after post-emergence application Com- pound Rate ID (g/ha) ECHCG LOLPE SETFA AVEFA ALOMY TRAZW I1 1000 4 1 4 2 0 0 I2 1000 4 0 4 1 0 0 I3 1000 3 1 4 3 1 1 I4 1000 3 1 4 2 0 0 I5 1000 2 1 NT 1 0 1 I6 1000 4 2 5 3 1 1 I7 1000 2 1 4 1 0 0 I8 1000 4 1 5 2 1 1 I9 1000 2 0 3 2 0 0 I10 1000 3 0 2 1 0 0 I11 1000 5 1 5 4 0 1 I12 1000 3 1 4 2 1 1