JPH04178373A - 6-haloalkyl-3-phenyluracil derivative and production thereof - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula [Rf is 1-4C haloalkyl; G is H or methyl; X is H or halogen; Y is O or -N(R<3>), (R<3> is H, 1-4C alkyl, etc.); Z is H or nitro; R is H, CH(R<1>)CO2R<2>, (R<1> is H or 1-4C alkyl; R<2> is H, 1-6C alkyl, etc.) or CH(R<1>) CidenticalN]. EXAMPLE:3-[2-Fluoro-4-(ethoxycarbonylmethyloxy)phenyl]-6-trifluorometh yl-2,4(1 H,3H)-pyrimidinedione. USE:A herbicide. PREPARATION:A 6-haloalkyl-1-methyl-3-phenyluracil derivative shown by formula II is reacted with a nitrating agent (e.g. nitric acid) in a solvent such as sulfuric acid at -20 to 50 deg.C to give a compound shown by formula I.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides 6-haloalkyl-3-
This invention relates to novel intermediates used in the production of phenyluracil derivatives (described in Japanese Patent Application No. 2-168683) and their production methods.

[Conventional technology and issues]

Conventionally, known technologies that describe uracil derivatives having a haloalkyl group at the 6-position and a substituted phenyl group at the 3-position include U.S. Patent No. 3580913, U.S. Patent No. 3981715, and U.S. Patent No. 38694.
57, U.S. Pat. No. 3,635,977, JP-A-61-221178, JP-A-63-41466, JP-A-63-107967, Japanese Patent Application No. 1987-1
No. 68683, International Patent Application No. 88/10254, Journal of Heterocyclic Chemistry, No. 9
Vol. 513, 1972 (Albert W, L.
Utz, et al., J.

Heterocyclic Chem,, 9.51
3 (1972)) is known.

However, these methods are not necessarily satisfactory as methods for producing uracil derivatives having a substituted phenyl group at the 3-position and a haloalkyl group at the 6-position, and a more advantageous production method is desired.

On the other hand, U.S. Patent No. 4734124, Japanese Patent Application Publication No.
-308278, JP-A-2-229156, and European Patent Publication No. 360072 disclose a manufacturing method for converting a benzene ring bonded to a heterocycle such as a tetrazolinone ring, an oxazolinedione ring, a pyrazole ring, or a dimethylmaleimide ring into a benzene condensed ring. is disclosed, or if it is a heterocycle or a uracil ring, nothing is known.

[Means to solve the problem]

The present inventors have discovered that 6-haloalkyl- is useful as a herbicide.
3-Phenyluracil derivative (Patent application No. 2-168683
As a result of intensive study on the manufacturing method of the method (described in No. 1), a new manufacturing method and manufacturing intermediate represented by scheme (1) were discovered, and the present invention was completed.

(Hereinafter, blank spaces) H3CH3 [In the formula, R1 represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R')-(R3 is hydrogen represents a hydrogen atom, CH(R')CO□R2 (however,
R1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, or a tetrahydrofurfuryl group. ) or CH(R')C=N
(However, R1 represents the same meaning as above.)
a is CH(R')CO□R2 (wherein, R1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R2 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or 2 to 6 carbon atoms;
4 represents an alkenyl group or a tetrahydrofurfuryl group. ) or CH(R')C=N (however, R1 represents the same meaning as above), and J is 01-C, an alkyl group, a C2-C5 alkenyl group, a C3-C5 alkynyl group, (03 -C6 cycloalkyl) C1-C2 alkyl group, 01-C6 haloalkyl group, C1-C6 haloalkenyl group, C1-C6 haloalkynyl group, cyanomethyl group, (C, -C3 alkoxy)01-C2 alkyl group,
-CH2co□A2+ (However, A2+ is a hydrogen atom, 01
~C5 represents an alkyl group, a sodium atom, a phenyl group optionally substituted with a halogen atom, or a benzyl group optionally substituted with a halogen atom. ), -CH2A24(A22)A” (However, A22 and A
23 each independently represents a hydrogen atom or an 01-C3 alkyl group. ), an optionally substituted benzyl group (however, substituents include 01-C4 alkyl group, 01-C4 haloalkyl group, 01-C4 alkoxy group, (C, -C4
alkoxy) carbonyl group, (C.

~C3 alkoxy)01~C2 alkyl group, represents a halogen atom. ) or -CH2A24 (however, A24 is an optionally substituted 2-pyridyl group (however, the substituent is 0
Represents a 1-C4 alkyl group or a halogen atom. ), an optionally substituted 2-pyridazyl group (however, the substituent represents a C3-C4 alkyl group or a halogen atom),
Represents a 3-isothiazole group or a 3-isoxazole group. ) represents. ] In the present invention, as shown in Scheme (1), after producing a uracil ring having a haloalkyl group at the 6-position in the initial stage of the reaction, a substituent on the phenyl group at the 3-position is added to the uracil ring. By controlling the reaction in stages so as not to affect the reaction, the desired formula (VII) can be produced in good yield.

Furthermore, since the substituent J (having the same meaning as above) can be introduced in the final step, compounds having J, which is unstable in conventional production methods, can be obtained in high yield.

Each process can be carried out sequentially, or can be carried out continuously by selecting conditions.

Each manufacturing method will be explained in detail below.

■Production method of compounds (II) to (III) Usually, (!-Ra(XI) is 0.5 to 1 for compound (II).
．． 5 equivalents, preferably 0.9 to 1.2 equivalents, and a base of 0.8 to 3.0 equivalents, preferably 1.0 to 2.4 equivalents, at -20°C to 120°C in a solvent. Preferably, the compound (III
) can be obtained.

The leaving group β of the 1-Ra compound (XI) is preferably a chlorine atom, a bromine atom, a chlorine atom, a methanesulfonyloxy group, a paratoluenesulfonyloxy group, etc. For example, as A-Ra, , BrCH2C02C
21-15, CH35O□0CH2C02CH3, Br
CH(CH3)C0□C,H5, CICH2CO2CH
I can give something like 3.

As a solvent, aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene, /'% logenated hydrocarbons such as chloroform and methylene chloride, and diethyl. Ethers such as ether, dioxane and tetrahydrofuran, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile and isobutyronitrile, formamide, N,N-dimethylformamide, N
- Acid amides such as methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, water, and mixtures thereof, preferably the above, nitriles, acid amides, aromatic hydrocarbons, ketones, and sulfur-containing compounds. Compounds and mixtures thereof.

As a base, inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, potassium hydroxide, sodium hydroxide, triethylamine, pyridine,
Examples include nitrogen-containing organic bases such as 4-(N,N-dimethylamine)pyridine and 1,4-diazabicycloC2,2,23octane, and preferably the above-mentioned inorganic bases.

After the reaction is completed, the reaction solution is concentrated and then poured into water to dilute the solution p.
Adjust H to acidic. The crude crystals can be collected by filtration as they are, or after extraction with an organic solvent and washed with a dilute alkaline aqueous solution, dilute acidic aqueous solution, or water as necessary, the extract can be subjected to conventional post-treatments such as concentration and drying to obtain the target compound. obtain. Usually, it can be used in the next reaction without any special purification.

■ Process for producing compounds (III') to (IV) Compounds (
III), the methylating agent is usually used in an amount of 0.5 to 5 equivalents,
Preferably 0.9 to 2 equivalents are used, and the base is usually used in an amount of 0.9 to 2 equivalents.
5 to 5 equivalents, preferably 0.9 to 2 equivalents, in a solvent at a temperature of usually -20°C to 100°C, preferably room temperature to 80°C, for usually 1 hour to 48 hours, preferably 2 hours. The compound (m
Can you get it? As a methylating agent, methyl chloride,
Methyl iodide, methyl bromide, dimethyl sulfate, diazomethane, etc. are used, and methyl iodide and dimethyl sulfate are preferred.

As a base, inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, potassium hydroxide, sodium hydroxide, pyridine, triethylamine,
Examples include nitrogen-containing organic bases such as 1,4-diazabicyclo[2°2.2]octane, and preferably the above-mentioned inorganic bases.

As a solvent, aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, halogenated hydrocarbons such as chloroform, methylene chloride, diethyl ether, Ethers such as dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and isobutyronitrile; acid amides such as formamide, N,N-dimethylformamide, and N-methylpyrrolidone; Examples include sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, water, and mixtures thereof, and preferably the above-mentioned acid amides, ethers, aromatic hydrocarbons, sulfur-containing compounds, water, and mixtures thereof.

After the reaction is completed, the reaction solution is concentrated if necessary and then poured into water to obtain crude crystals, or water is added and extracted with an organic solvent.

Furthermore, after washing with a dilute alkaline aqueous solution, dilute acidic aqueous solution, saturated saline, or water as required, the extract is subjected to usual post-treatments such as drying and concentration to obtain a composite. Usually, it can be used in the next reaction without any special purification.

■ Process for producing compound (IV) to (V) Compound (IV)
Using 0.5 to 1.5 equivalents, preferably 0.8 to 1.1 equivalents of the nitrating agent, in a solvent at -20°C to 50°C.
Compound (V) can be obtained by reacting C1 preferably at -10°C to 30°C for 10 minutes to 8 hours, preferably 30 minutes to 4 hours.

As the nitrating agent, nitric acid, potassium nitrate, acetyl nitrate, nitronium trifluoro-tetramethane sulfonate, nitronium tetrafluorophorate, alkyl nitrate, etc. are used, and preferably nitric acid and acetyl nitrate are used.

As a solvent, acids and acid anhydrides such as sulfuric acid, acetic anhydride, acetic acid, anhydride 1-1) fluoroacetic acid, chloroform, dichloromethane, etc., /'% halogenated hydrocarbons, tetrahydrofuran, diethyl ether, dioxane, and other ethers. kind,
Water or mixtures thereof are used, preferably acids and acid anhydrides.

After the reaction is completed, the reaction solution is concentrated if necessary and then poured into ice water to obtain crude crystals, or ice water is added and extracted with an organic solvent.

Furthermore, after washing with a dilute aqueous alkaline solution, saturated saline, or water as necessary, the extract is subjected to usual post-treatments such as drying and concentration to obtain a composition. Usually without adding special purification,
Can be used for the next reaction.

■ Process for producing compounds (V) to (VI) a) To compound (V), a combination of iron, zinc, tin, tin (II) chloride, etc., and acids such as hydrochloric acid, acetic acid, etc. as a metal reagent reducing agent, 1 to 15 equivalents, preferably 1 to 10 equivalents, acetic acid, water, alcohols such as methanol and ethanol, ethers such as dioxane and tetrahydrofuran,
Using aromatic hydrocarbons such as toluene and xylene, esters such as ethyl acetate and butyl acetate, or mixtures thereof as a solvent, the temperature is 20°C to 150°C, preferably 60°C.
Compound (VI) can be obtained by reacting at 100°C to 100°C for 10 minutes to 8 hours, preferably 30 minutes to 5 hours.

After the reaction is completed, the insoluble matter is removed, and if necessary, the target product adsorbed on the insoluble matter is extracted with an organic solvent.

Furthermore, after washing these organic layers with a dilute aqueous alkaline solution, saturated saline, or water as necessary, the extract is subjected to usual post-treatments such as drying and concentration to obtain a composition. Usually, it can be used in the next reaction without any special purification.

b) using 0.5 to 20% by weight, preferably 1 to 10% by weight of palladium carbon, platinum (IV) oxide, Raney nickel, etc. as a heterogeneous hydrogenation catalyst with respect to compound (V), Ethers such as tetrahydrofuran, dioxane, and ether, alcohols such as methanol and ethanol, acetic esters such as ethyl acetate and butyl acetate, water, acetic acid, hydrochloric acid, cyclohexane, N, N-dimethylformamide, or a mixture thereof as a solvent. Compound (VI) can be obtained by adding hydrogen at normal pressure to 100 atm, preferably at normal pressure to 30 atm.

In addition, sodium hydroxide is added to the system to adjust hydrogenation.
Alkali such as potassium hydroxide, potassium carbonate, and sodium phosphate; inorganic or organic sulfur compounds such as sodium sulfite, hydrosulfide, sodium hydrogen sulfide, sodium thiocyanate, thiophene, thiazole, 2-aminobenzothiazole, and 2-aminothiazole; , an organic cyano compound such as dicyandiamide, diaminomaleonitrile, cyanoacetic acid ester, or a mixture thereof.
It can be added in an amount of 1 to 40% by weight, preferably 1 to 20% by weight.

After the reaction, the catalyst and insoluble matter are removed, and the solvent is distilled off to obtain a composite. If necessary, this is purified by solvent or extraction and subjected to usual post-treatments to obtain the desired product. Usually, it can be used in the next reaction without any special purification.

■ Process for producing (Vll) from compound (Vl) Compound (V
Against I)! -J (compound xII) from 0.5 to 2.0
equivalents, preferably 0.9 to 1.2 equivalents, and 0.9 to 1.2 equivalents of the base.
5 to 2.2 equivalents, preferably 0.9 to 1.5 equivalents in the solvent used -20°C to 100°C1 preferably 0°C to 8
Compound (VII) can be obtained by reacting at a temperature of 0°C for usually 30 minutes to 24 hours, preferably 1 to 6 hours (A and J have the same meanings as above).

As a solvent, aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as hensen, toluene, xylene, chlorobenzene, chloroform, methylene chloride, etc., and diethyl ether. , dioxane, ethers such as tetrahydrofuran, ketones such as acetone, methyl ethyl ketone, nitrites such as acetonitrile, isobutyronitrile, formamide, N,N-dimethylformamide, N-
Examples include acid amides such as methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, water, and mixtures thereof, preferably the above-mentioned nitriles, acid amides, aromatic hydrocarbons, ketones, and sulfur-containing compounds. and mixtures thereof.

As a base, inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, potassium hydroxide, sodium hydroxide, triethylamine, pyridine,
Examples include nitrogen-containing organic bases such as 4-(N,N-dimethylamino)pyridine and 1,4-diazabicyclo(2,2°2)octane, and preferably the above-mentioned inorganic bases.

After the reaction is completed, the reaction solution is concentrated and then poured into water, and the crude crystals are filtered as they are or extracted with an organic solvent.

Furthermore, after washing with a dilute alkaline aqueous solution, dilute acidic aqueous solution, or water as necessary, the extract is subjected to conventional post-treatments such as drying and concentration to obtain the target compound.

■Production method of compound (IX) and (X) to (III) Usually, the amount of compound (X) to compound (IX) is 0.5 to
1.5 equivalents are used, preferably 0.9 to 1.1 equivalents.

Although the reaction proceeds in the presence of a base and without a solvent, it is usually accelerated by using a solvent. As a solvent, aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, halogenated hydrocarbons such as chloroform, methylene chloride, diethyl ether, dioxane, etc. Ethers such as tetrahydrofuran, acetone,
Ketones such as methyl ethyl ketone, nitriles such as acetonitrile and isobutyronitrile, pyridine, N, N-
Tertiary amines such as diethylaniline, formamide,
Examples include acid amides such as N, N-dimethylformamide and N-methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, water and mixtures thereof, and preferably the above-mentioned aromatic hydrocarbons, acid amides, and Examples include sulfur compounds and mixtures thereof.

The base is used in an amount of 0.5 to 2 equivalents, preferably 0.8 to 1.5 equivalents, based on compound ([X). Pyridine, triethylamine, 1,4-diazabicyclo[2,
2,2] Nitrogen-containing organic bases such as octane, inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, preferably sodium hydride and sodium hydroxide. , potassium hydroxide.

The reaction temperature is usually -70 to 80°C, preferably -20°C.
It is carried out at room temperature from °C.

The reaction time usually takes 10 minutes to 6 hours, preferably 30 minutes to 2 hours.

After the reaction is complete, add mineral acids such as hydrochloric acid, acetic acid, trifluoroacetic acid,
The compound (II
I) is obtained.

The production of the present invention and the production of its intermediates will be specifically described below as examples, but the present invention is not limited thereto.

(Hereafter, blank space) Example l-1 3-(4-(ethoxycarbonyl-1-ethyloxy)
phenyl)-6-trifluoromethyl-2,4(LH,
Synthesis of 3H)-pyrimidinedione 3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(IH,
0.26 g of potassium carbonate in a mixture of 0.46 g of 3H)-pyrimidinedione and 10 ml of anhydrous acetonitrile;
0.34 g of α-bromopropionic acid ethyl ester was added, and the mixture was stirred at room temperature for 30 minutes and then refluxed for 1 hour. After cooling, the solvent was distilled off, water was added, and the mixture was washed with ethyl acetate.

Furthermore, the aqueous layer was made acidic with hydrochloric acid and extracted again with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 0.36 g of the target compound as brownish white crystals. obtained as.

Melting point 153-155°C 'H-NMR (CDCA 3) δ (ppm):
1.21 (3H, t, J=7Hz).

1.58 (3H, d, J=6Hz), 4.12 (
2H, q, J・7Hz).

4.65 (IH, Q, J=6Hz), 6.07 (
IH, S).

6.65-7.15 (4H, m), 10.05 (L
H, or s) Example 1-2 3-(4-(ethoxycarbonylmethyloxy)phenyl)-6-)lifluoromethyl-2,4(IH,3H
)-pyrimidinedione synthesis 3-(4-human-7xyphenyl)-6-)lifluoromethyl-2,4(IH,3H
17 g of potassium carbonate O and 0.203 g of ethyl bromoacetate were added to a mixture of 0.30 g of )-pyrimidinedione and 10 ml of anhydrous acetonitrile, and the mixture was refluxed for 3 hours. After distilling off the solvent, water was added and insoluble materials were removed, and the resulting aqueous solution was adjusted to pH=1 with hydrochloric acid. The precipitated solid was filtered, washed with water and dried to obtain 0.20 g of the target compound.
was obtained as a solid.

Melting point 177-179°C 'H-NMR (CDCj73) δ (plum):
1.30 (3H, t, J=7Hz).

4.24 (2H, q, J=7Hz), 4.57 (
2H, s).

6.12 (IH, s), 6.75-7.20 (4
H, m).

9.60 (IH, br s) Example 1-3 3-(4-(methoxycarbonylmethyloxy)phenyl)-6-trifluoromethyl-2,4(IH, 3H)
-Synthesis of pyrimidinedione 3-(4-hydroxyphenyl)-6-4lifluoromethyl-2,4(IH,3H)
Using 2.85 g of -pyrimidinedione, 1.14 g of methyl chloroacetate, 1.60 g of potassium carbonate and 50 ml of acetonitrile, 2.0 g of the target compound was obtained as a brownish solid in the same manner as in Example 1-2.

Melting point 210-212°C'H-NMR (DMSO-66) δ(1)pm):
3.73 (3H, s).

4.63 (2H, s), 6.03 (IH, s)
.

6.75-7.28 (5H, m) Example 1-4 3-[2-fluoro-4-(methoxycarbonylmethyloxy)phenyl)-6-trifluoromethyl-2,4
Synthesis of (IH,3H)-pyrimidinedione H2 CF, C=CHC0□C2H9 Add 0.726 ml of trichloromethyl chloroformate to a mixed solution of 2 g of 2-fluoro-4-methoxycarbonylmethyloxyaniline and 20 ml of anhydrous chloroform at room temperature. Added gradually. After refluxing for approximately 90 minutes until the solution became homogeneous, the solvent was distilled off and 2.2 g of 2-fluoro-
4-methoxycarbonylmethyloxyphenyl isocyanate was obtained.

Next, 60% pure sodium hydride was added to a mixture of 1.85 g of ethyl 3-amino-4,4,4-trifluorocrotonate and 5 ml of anhydrous N,N-dimethylformamide.
．． 404 g was gradually added under water cooling.

After stirring at room temperature for about 30 minutes, cool to 0°C again.
The previously prepared mixed solution of 2-fluoro-4-methoxycarbonylmethyloxyphenyl isocyanate and anhydrous tetrahydrofuran was added dropwise over about 10 minutes. When the temperature of the reaction solution rose to room temperature, it was poured into water, washed with ether, and the aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate.

Furthermore, after drying with anhydrous sodium sulfate, the solvent was distilled off and the resulting composite was subjected to preparative thin layer chromatography (developing solvent,
Purification was performed using ethyl acetate:hexane (2:3) to obtain 0.54 g of the target compound as white crystals.

Melting point 169-172°C 'H-NMR (DMSO-d6) δ (ppm):
3.76 (3H, s).

4.60 (2H, s), 6.06 (IH, s)
.

6.50-7.40 (4H, m) At the same time, 60 μm of white solid was obtained near the target compound on preparative thin layer chromatography, and as a result of analysis, 3-[2-fluoro- 4-(Ethoxycarbonylmethyloxy)phenyl]-6-trifluoromethyl-2
, 4(LH,3H)-pyrimidinedione.

Melting point 133-136°C 'H-NMR (DMSO-d,) δ (ppm): 1.
30 (3H, t, J・7Hz), 4.25 (2
H, Q, J=7Hz).

4.59 (2H, s), 6.14 (IH, s
).

6.47-7.37 (4H, m) Example 2-1 3-C4-(methoxycarbonylmethyloxy)phenyl)-1-methyl-6-trifluoromethyl-2,4
Synthesis of (IH,3H)-pyrimidinedione CH3 "3-(4-(methoxycarbonylmethyloxy)phenyl)-64lifluoromethyl-2,4(IH,3H)
1.6 g of methyl iodide was added to a mixture of 1.95 g of -pyrimidinedione, 9 ml of N,N-dimethylformamide, and 1.2 g of potassium carbonate, and the mixture was stirred at room temperature for 12 hours. The reaction solution was poured into water, and the precipitated solid was filtered, washed with water, and dried to obtain 1.72 g of the target compound as a white solid.

Melting point 147-149°C 'H-NMR (CDCA 3) δ (ppm):
3.50 (3H, br s).

3.77 (3H, s), 4.60 (2H, s
).

6.37 (IH, s), 6.80-7.25 (
4H, m) Example 2-2 Synthesis of 3-[2-fluoro-4-(methoxycarbonylmethyloxy)phenylcou-1-methyl-6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione CH3 3-[2-fluoro-4-(methoxycarbonylmethyloxy)phenyl)-6-trifluoromethyl-2,4
(IH,3H)-pyrimidinedione 0.29g, N,
2 ml of N-dimethylformamide and 0 potassium carbonate
．． Add 0.23 g of methyl iodide to 17 g of the mixture;
Stirred at room temperature for 24 hours. The reaction solution was poured into water and extracted with ethyl acetate.

Furthermore, the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. When the solvent was distilled off, 0.29 g of the target compound was obtained as a viscous, transparent oil.

'H-NMR(CD(J'2) δ(ppm):
3.47 (3H, br s).

3.75 (3H, s), 4.56 (2H, s
).

6.23 (IH, s), 6.55-7.25 (
3H, m) Example 2-3 3-C4-(ethoxycarbonylmethyloxy)phenylcou 1-methyl-6-trifluoromethyl-2,4
Synthesis of (IH,3H)-pyrimidinedione CH.

3-(4-(ethoxycarbonylmethyloxy)phenyl)-6-trifluoromethyl-2,4(LH,3H
)-pyrimidinedione 0.11 g 5N, N-dimethylformamide 1.5 ml, potassium carbonate 0.064 g
and 0.087 g of methyl iodide, Example 2-
In the same manner as in 2, 0.080 g of the target compound was obtained as white crystals.

Melting point 106-109°C 'H-NMR (CD(J'3) δ(1)I)m)
: 1.25 (3H, t, J=7Hz).

3.45 (3H, br s), 4.27 (2H, q
, J=7Hz).

4.51 (2H, s), 6.20 (IH, s).

6.60-7.20 (4H, m) Example 2-4 3-(4-(Ethoxycarbonyl-1-ethyloxy)phenylcou-1-methyl-6-trifluoromethyl-
Synthesis of 2,4(IH,3H)-pyrimidinedione CH3 □ 3-(4-(ethoxycarbonyl-1-ethyloxy)
phenyl)-6-dolifluoromedyru2.4 (I
H,3H)-pyrimidinedione 0.29 g, N,N-
5 ml dimethylformamide, 0.16 potassium carbonate
Example 2-
In the same manner as in 2, 0.25 g of the target compound was obtained as a viscous oil.

'H-NMR (CDCβ3) δ(1)I)m):
1.23 (3H, t, J=7Hz) 1.58 (3H
, d, J=7Hz), 3.45(31
i, br s).

4.16 (2H, q, J=7Hz), 4.67
(1) 1, q, J=7Hz) 6.22 (LH,
s), 6.69 to 7.30 (4H, m) Example 3-1 3-[3-nitro-4-(methoxycarbonylmethyloxy)phenylcou 1-methyl-6-trifluoromethyl-2,4 Synthesis of (IH,3H)-pyrimidinedione CH3 □ C1(3 3-(4-(methoxycarbonylmethyloxidi), phenylcou 1-methyl-6-trifluoromethyl-2,4
-(IH,3H)-pyrimidinedione, 1.13 g, was dissolved in 12 ml of 95% sulfuric acid. The mixed solution is 0-5
After cooling to °C, 0.24 ml of 60% nitric acid was slowly added dropwise. After the addition, the reaction solution was stirred at room temperature for 30 minutes.

Furthermore, the reaction solution was poured into ice water and stirred.

The precipitated solid was filtered, washed with water, and dried to obtain 0.87 g of the target compound as a brownish solid.

Melting point 166-168°C 'H-NMR (CDCj2, I) δ (ppm)
: 3.54 (3H, brs).

3.78 (3H, s), 4.78 (2t (, s)
, 6.30(it(,s).

7.02 (IH, d, J・9Hz).

7.35 (IH, dd, J=9.2Hz).

7.75 (IH, d, J・2Hz).

Example 3-2 3-[2-Fluoro-5-nitro-4-(methoxycarbonylmethyloxy)phenylcou 1-methyl-6-trifluoromethyl-2,4 (IH.

Synthesis of 3H)-pyrimidinedione CH3 CH.

3-[2-Fluoro-4-(methoxycarbonylmethyloxy)phenyl]-1-methyl-6-1.lifluoromethyl-2,4(IH,3H)-pyrimidinedione 0.
In the same manner as in Example 3-1, 0.16 g of the target compound was obtained as amber crystals using 24 g of 609 stone nitric acid, 0.049 ml of nitric acid, and 3 ml of 95% sulfuric acid.

Melting point 77-80°C' H-NMR (CDCx 3 ) δ (ppm)
: 3.50 (3) (, br s).

3.77 (3t(,s), 4.74(2H,s)
, 6.26(It(,s).

6.76 (IH, d, J・11Hz).

7.83 (1, H, d, J=7tlz) Example 4-
1 3~(3-sai xo 2H-1,4-henzosai xazine-
6-yl)-1-methyl-6-trifluoromethyl-2
,4(IH,3H)-pyrimidinedione synthesis C(]3 □ 1H・3-[3-nitro-4-(methoxycarbonylmethyloxy)phenyl-1-methyl-6-trifluoromethyl-2,4( IH,3H)-pyrimidinedione 0.50
g, a mixed solution of 5 ml of ethyl acetate/L and 3 ml of citric acid was mixed with 0.6 g of iron powder preheated to 80°C.
It was gradually added dropwise into a mixture of 9 g and 2 ml of 5% acetic acid aqueous solution. After the dropwise addition, the reaction mixture was vigorously stirred at 70°C for 45 minutes, filtered while hot, and insoluble matter was extracted several times with hot ethyl acetate. The organic layer was washed successively with water, a saturated aqueous sodium bicarbonate solution, and water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 0.32 g of the target compound as a white solid.

Melting point 257-259°C 'H-NMR (CDCA 3) δ(1)I)m)
: 3.50 (3H, brs).

4.48(2)(,s), 6.26(IH,s
).

6.40-7.05 (3t(,m).

8.85 (LH, br s ) Example 4-2 3-(7-fluoro-3-year-old xo-2H-1,4-benzoxazin-6-yl)-1-methyl-6-trifluoromethyl-2 ,4(])(,3H)-Synthesis of pyrimidinedione C11°H3 3-[2-fluoro-5-diI helo-4-(methoxycarbonylmethyloxy)phenyl]-1-, methyl-6
-trifluoromethyl-2,4 (IH.

A mixed solution of 0.110 g of 3F()-pyrimidinedione, 3 ml of ethyl acetate, and 2 ml of acetic acid, and 0.14 g of iron powder.
0 g, and 2 ml of a 5% acetic acid aqueous solution in the same manner as in Example 4-1 to obtain 0.090 g of the target compound as white crystals.

Melting point 219-222°C' H-NMR (CDCA3) δ (ppm)
: 3.50 (3H, s).

4.52 (2H, s), 6.27 (IH, s>
.

6.59 (IH, d, J=8Hz), 6.74
(l)l, d, J=101(z).

9.30 (IH, br s ) Example 5-1 3-(3-oxo-4-propargyl-2H-1,4-
Synthesis of benzoxazin-6-yl)-1-methyl-6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione H3 C1(3 □ 3-[3-oxo-2H-1,4-henzo Talented Gisashin
6-yl)-1-methyl-6-trifluoromethyl-2
, 0.160 g of 4(IH,3H)-pyrimidinedione,
0.019 g of 60% purity sodium hydride was gradually added to a mixed solution of ml of N,N-dimethylpolamide while cooling with water. After 20 minutes, 0.056 g of propargyl bromide
was added and stirred at room temperature for 3 hours.

Next, the reaction mixture was poured into water, and after stirring, the precipitated solid was collected by filtration, washed successively with a saturated aqueous sodium bicarbonate solution and water, and then dried.

Further, the mixture was washed with isopropyl ether and hexane, and then dried to obtain 0.080 g of the target compound as a white solid.

Melting point 207-210'C'H-NMR (CD(J! 3) δ(pl)m)
: 2.23 (IH, t, , J=2H2).

3.50 (3H, br s ), 4.56 (2
H, d, J=2Hz).

4.58 (2H, s), 6.28 (IH, s
).

6.15-7.15 (3H, m) Example 5-2 3-(7-fluoro-3-oxo-4-propargyl-
2H-1,4-benzoxazin-6-yl)-1-methyl-6-trifluoromethyl-2,4(IH,3H)
-Synthesis of pyrimidinedione H3 H3 3-(7-fluoro-3-oxo-2H-1,4-benzoxazin-6-yl)-1-methyl-6-trifluoromethyl-2,4(IH,3H) -pyrimidinedione 0.34g, N,N-dimethylformamide 3.4m
55% purity sodium hydride in a mixed solution of 0.040
g was added at room temperature.

The reaction mixture was cooled to below O'C and 0.110 g of propargyl bromide was added dropwise. After stirring for several hours, the reaction mixture was poured into ice water, extracted with ethyl acetate, washed successively with water and saturated brine, and the organic layer was dried over anhydrous sodium sulfate.

Furthermore, the mixture obtained by distilling off the solvent was subjected to preparative thin layer chromatography (developing solvent: ethyl acetate/hexane = 1:
The solid obtained by purification in step 1) was washed with isopropyl ether to obtain 0.28 g of the target compound as white crystals.

Melting point 158-160°C 'H-NMR (CDCff 3) δ (ppm):
2.31 (IH, t, J=2Hz).

3.60 (3H, s), 4.69 (2H, d,
J=2Hz).

4.73 (2H, s), 6.43 (IH, s).

7.01 (IH, d, J=10Hz).

7.15 (LH, d, J=7Hz) Example 5-3 3-(7-fluoro-3-oxo-4-methoxymethyl-2H-1,4-benzoxazin-6-yl)-1-
Methyl-6-trifluoromethyl-2,4(18,3H
)-pyrimidinedione synthesis H3 H3 ■ 3-(7-fluoro-3-oxo-2H-1,4-benzoxazin-6-yl)-1-methyl-6-trifluoromethyl-2,4(IH, 3H) -pyrimidinedione O, 100g, N,N-dimethylpolamide 2m
l mixed solution and 0.011 g of 60% sodium hydride,
Using 0.025 g of tetramethyl methyl ether, 0.050 g of the target compound was obtained as a white solid in the same manner as in Example 5-2.

Melting point 96-100°C')]-NMR (CD(J',) δ(ppm)
: 3.34 (3H, s).

3.52 (3H, br s), 4.63 (2H, S
).

5.20 (2H, S), 6.27 (11 (, S).

6.80 (IH, d, J=lOHz).

7.10 (IH, d, J=8Hz) Example 6-1 Synthesis of 3-(4-methoxyphenyl)-6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione 3-amino-4 , 4.0 g of ethyl 4,4-trifluorocrotonate, 20 ml of N,N-dimethylformamide
Add 55% pure sodium hydride to a mixed solution of 0.5% pure sodium hydride at room temperature.
950 g was added gradually. After stirring for 1 hour, 4-methoxyphenylcarbamic acid ethyl ester 4.27
g and heated at 110°C for 4 hours.

Next, the reaction mixture was poured into water, washed with ethyl ether, and the aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate.

The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off. The resulting particles were washed with isopropyl ether to obtain 3.05 g of the target compound as ocher crystals.

Melting point 224-228°C 'H-NMR (CD(J'3) δ (ppm):
3.76 (3H, s).

6, 10 (IH, s),, 6.64-7.26 (4
H, m).

9.96 (IH, br s) Example 6-2 Synthesis of 3-(4-methoxyphenyl)-6-)lifluoromethyl-2,4(IH,3H)-pyrimidinedione] UCF3
C=CI(Co2C2H5 3-amino-4,4,4-)ethyl fluorocrotonate 8.0 g, N,N-dimethylformamide 20 ml
2.4 g of sodium methoxide was gradually added to the mixed solution at room temperature. After stirring for 15 minutes, 8.52 g of 4-methoxyphenylcarbamic acid ethyl ester was added, and the mixture was heated at 115°
The mixture was heated for 7 hours.

Next, the reaction mixture was poured into water, washed with ethyl ether, and the aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate.

Furthermore, after washing the organic layer with water, drying with anhydrous sodium sulfate,
After distilling off the solvent, the residue was washed with isopropyl ether to obtain 4.42 g of the target compound as white crystals.

Example 6-3 Synthesis of 3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione 3-(4-methoxyphenyl)-6-trifluoromethyl-2, A mixed solution of 1 g of 4(IH,3H)-pyrimidinedione and 40 ml of anhydrous methylene chloride was added under a nitrogen atmosphere to -
The mixture was cooled to 60 to -70°C, and 7 ml of a 1Mo1 solution of boron tribromide (CH2C12) was slowly added dropwise. The mixture was left to stir until it reached room temperature, and was further stirred for 2 days.

Next, the reaction mixture was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous sodium sulfate.

Furthermore, the granules obtained by distilling off the solvent were washed with isopropyl ether to obtain 0.65 g of the target compound as ocher crystals.

Melting point 292-294℃'l(-NMR(DMSO-d, ) δ(pp
m): 6.00 (IH, s).

6.53-7.13 (4H, m), 7.36 (IH
, br s).

12.39 (IH, br s) Example 6-4 Synthesis of 3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione 3-(4-methoxyphenyl) -6-trifluoromethyl-2,4(IH,3H)-pyrimidinedione 4.4g
A mixed solution of 40 ml of anhydrous methylene chloride was cooled in a dry ice-acetone bath, and 5.8 g of boron tribromide was added dropwise. The mixture was left to stir until it reached room temperature, and was further stirred for one day.

Next, the reaction mixture was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous sodium sulfate.

Furthermore, after distilling off the solvent, the mixture was washed with isopropyl ether and dried to obtain 2.85 g of the target compound as crystals.

Example 7-1 Synthesis of 3-fluoro-4-nitrophenoxyacetic acid methyl ester 3.45 g of chloroacetic acid methyl ester in a mixture of 5 g of 3-fluoro-4-nitrophenol, 4.4 g of potassium carbonate, and 10 ml of 5N, N-dimethylformamide. was slowly added dropwise at room temperature. After stirring for - days, the reaction mixture was poured into water, and the precipitated solid was washed successively with a dilute aqueous alkaline solution and water, and then dried. The resulting mixture was washed with isopropyl ether to obtain 6.03 g of the target compound as a solid.

Melting point 88-91°C 'H-NMR (CDCA 3) δ(1)pm):
3.83 (3H, S).

4.74 (2H, S), 6.46-7.22 (2H
, m).

7.82-8.37 (It(, m) Example 7-2 Synthetic iron powder of 3-fluoro-4-aminophenol 14.
A mixture of 2 g and 16 ml of 5% aqueous acetic acid solution was heated to 80°C, and 3-fluoro-4-nitrophenol 4 was added into it.
A mixed solution of g1 16 ml of ethyl acetate and 16 ml of acetic acid was slowly added dropwise. After the dropwise addition, the mixture was vigorously stirred at 70°C for 20 minutes.

The reaction mixture was then filtered while hot, and the insoluble matter was extracted with hot acetic ethyl ester.

Further, the organic layer was passed through Celite, washed with water, and dried over anhydrous sodium sulfate. After evaporating the solvent, the resulting composite was washed with isopropyl ether and hexane to obtain the target compound 2.
1 g was obtained as light yellow crystals.

Melting point 138-140°C'H-NMR (CDCf,) δ (ppm):
5.12 (2H, br s).

6,16-6.92 (4H, m) Example 7-3 3 Synthesis of fluoro-4-aminophenoxyacetic acid methyl ester 3-fluoro-4-ditrophenoxyacetic acid methyl ester 4.84 g, methyl alcohol 60ml, water 0,
A mixture of 15 ml of platinum (IV) oxide and 0.097 g of platinum (IV) oxide was allowed to absorb 1.561 g of hydrogen over 40 minutes while stirring.

Next, the reaction mixture was filtered through Celite, the solvent was distilled off, and then dried using a vacuum pump to obtain 4.03 g of the target compound as pale reddish-purple crystals.

Melting point 70-73°C 'H-NMR (CDCl23) δ(pI)m):
3.18 (2H, br s).

3.73 (3H, s), 4.46 (2H, s).

6.29-6.82 (3H, m) Example 7-4 Synthesis of 3-fluoro-4-aminophenoxyacetic acid methyl ester 1.97 g of 3-fluoro-4-aminephenol.

A mixture of 2.25 g of potassium carbonate and 5 ml of N,N-dimethylformamide' was stirred at 50 to 55°C for 30 minutes, and then 1.60 g of methyl chloroacetate was added dropwise and stirred for 4 hours.

Next, the reaction mixture was poured into water, and the precipitated solid was washed successively with a dilute alkaline aqueous solution and water, dried, and then subjected to silica gel column chromatography (eluent: chloroform).
Purification was performed to obtain 0.98 g of the target compound as a light brown solid.

Next, examples of the present invention, including the compounds synthesized in the above examples, are shown in Tables 1 to 4, respectively, or the compounds of the present invention are
It is not limited to these.

Table 1 Rf CF3F NH CF, HNCH3 CF3F NCH3 CF3HN5O2CH3 CF3F N5O2CH3 CF3F NCOCH5 CF3F NCOCH3 CF3HN5O2Et CF3F N5O2Et CF+ F NBu'CF3
8 NBu' CF3F NEt CF3HNEt CF3 F NPr'CF3
HNPr' CF3CF2HNH CF3CF2F NH Table 1 (Continued) Rf CF2
HNBU' HCF2F NSO□Et HCF2HNSO□Et HCF2CI NH CF, CF2Cl NH CF3F NHCHO CF3HNHCHO HCF2F NHCHO HCF2HNHCHO CF, CF2F NC0 CH5CF2HNHC )10 Table 2 H CF, FOCH2C02H CF, FOCH2C02CH.

CF, F OCH2C0□Et CF3 F OCH2C0□Pr”CF3 F
OCH2CO2Pr'CFp F OCH2Co
2Bu'CFs F OCH2C02BLI'CF
3 F OCH2C02BLI'CF, F
OCH, CO□Bυ1CF3 F OCH2C02
-VinylCF3F OCH2C0□-Allyl
CF, FOCH2C0□-THFCF2F
OCH(CH3)Co2H Table 2 (continued) CF, F OC) I(CH3)CO2EtC
F-F OCH(CH3)CO2Pr'CF,
F OCH(CH,)C02Bu'CF3F
OC)l(CH3)Co□Bu”CF3P OC
H(CH3)C02Bu'CF3F OCR(CH
,)Co□Bu″CF, F OC1((CH
3) COJu'CF3F OCH(CH3)C02
-VinylCF3FOCH(CH-)-
AllylCF3FOC)I(CH3)-THF
CF3HOCH2C02H CF, HOCH2C0□C1 (3CFs
HOCH2CO2巳tCF3 HOCF(2c
O□Pr'CF3 [(OCH2CO2Pr”CF
s HOCH2C02BLI"Table 2 (continued) CF3 HOCH2C0Ju' CF3 HOCH2C0□-V+nylCF=
HOCH2CO2-A11ylCF, HOCH
2C02-THFCF, HOCH(CH3)C0
2HCF, HOCH(CH3)C02CH3CP
2HOCH(CH2)CO□Et CP-HOCH(CH-)CO2Pr"CF= H
OCH(CH=)CO2P r 'CF2 HOC
H(CHa)CO2Bu″CF, HOCH(CH
i) C02EtCF= HOCH(CHi)COJ
u'CF2 HOCH(CH-)CO2BLI'C
Fx HOCH (CHz) COz-VinylCF
2 HOCH(CHi)CO2-AllylCF,
HOC) I(CH3)Co2-THF Table 2 (continued) HCF2F OCH2C02CH3HCF2F
OCH2C0□Et HCF2 HOC) I2CO2CH3HCF2HOC
)12cO□Et CF3CF2F OCH2C02CH3CF, CF
2F OCH2C0□EtCF3CF2 HOC
H2C02CH3CFICF2 HOCR2C0Jt HCF2F OC1((CH3)CO,CI(38
CF2HOC) ((C1(3)CO2EtCF, CF2
F OCH(CH3)C02CH3CFiCF2H
OC) ((CI-1i)CO2EtCF, C1O
C) (2C02CH2CF, CI OCH,
, C02EtCF= C1OCH2CO2Pr'C
Fp CI OCH(CH3)C02CH3C
F2CI OCH (CH3) CO2Et Table 2 (continued) RfXYR CF3Br OCH2C02CH3CF3 B
r OCH2C02EtCF3 Br O
C1(2co2Pr'CF3Br OCH(CHs
)C0□CH3CF= Br OCH(CH=
)Co2EtCF, Br OC1((Pr')Co
2EtCF, I OCH2C0□EtCF3
F NHCH2C0□ CF3F NHCH2C0□H CF3F NHCH2C02Et CF, F NHC82CO□Pr'CF 3
F NHCH2CO2P r ”CF-F N
HCH2C02BU″CF= 'F NHCH
2C0Ju'CF, F NHCH2C0Ju
'CF-F NHCH2C0□Bu'CF3
F NHCH2C0□-VinylCF, F
NOCH2C02-AIIYI Table 2 (continued) RfXYR CF3F NHCF (2CO7-THFCF,
F NACCH2C02HCF, F
NAc CH2C02CH3CF, F
NAc C) 12CO2EtCF2 F
NACCH2C0zPr'CF3 F NAC
CH2C0□BU”CFz F NACCH2C
02BU'CF3F NACCI(2CO2-TH
FCF, F NAc CH(CHs)C
02HCF3F NAc CH(CH3)C0
□CH3CF, F NAc CH(CH
2) Co2EtCF= F NFm CH
2C0□HCF3P NFm CH2C0□C
H.

CF3F NFm CH2C02EtCFI
F NFm CH2CO2Pr'CF+
F NFm CH2C0Ju”CF3
F NFm CH2C0Ju'CF=
F NFm CH(C)Is)CO□H 2nd
Table (continued) RfXYR CF3F NFm CH(CH,)Co2CH
3CF3F NFm CH(CHs)Co2E
tCF, F NFm CH2C0□-T
HFCF3F N5O2CH, C0□CH3CF,
F N5O2CH, CH2C02CH.

CF, F NSO□CH, CH2C02EtC
F3 F N5OzCHi C82CO□Pr
'CF2 F NSO2CH3CH2C0Ju'
CF3 F N5OzCHs CH2C0J
u”CF, F N5O2CH, CH2C0□
-THFCF3F NSO2CH3CH(CH3)C
02HCF3F NSO2CH3CH(CH3)Co
□CH3CF, F NSO□CH,CH(C
Ha) Co2EtCF2 F N5O2Et
CH2C02HCF, F NSO□Et
CH2C02CH3CF3P N5O2Et
CH2C02EtCF2 F NSO□Et
CH2CO2Pr'CF2 F N5O2Et
CH2C02BU'Table 2 (continued) RfXYR CF3 F N5OzEt CH2C02Et
CF, F NSO□Et CH2C0□-T
HFCF3F NSO□Et CH(CH,)C0
2HCF3F NSO□Et CH(CH3)Co
□CH3CF, IF NSO□Et CH(CH,
)CO2EtHCF2F NHCH2C0,H HCF2 F NHCH2C02CH3CF2F
NHCH2C0□Et HCF2F NHCH(CH,)C02HCF3F
NHCH(CH2)CO2CO.

HCF2F NHCH(CH,)Co2EtCF3C
F2 F NHCH2C0tHCF, CF2F
NHCH2C0, CH3CF, CF2F NHCH2
C02EtCF, CF2F NHCH(CH3)C0
□CH3CF2 F NHCH(CHa)CO2C
O-CFaCF2F NHCH(CH,)CO2Et
HCF2F NAc CH2C02CH.

Table 2 (continued) RfXYR HCF2 F NACCH2C02EtCF3C
F2 F NACCH2C02CH3CF3CF2
F NACCH2C02EtHCF2F NF
m CH2C0□CH3HCF2F NFm
CH2C02EtCF3CF2 F NFm
CH2C0□CH3CF, CF2F NFm
CH2C02EtHCF2 F NSO□CH
3CH2C02CH3HCF2F N5O2CH3C
H2CO□EtHCF2F N5O2Et CH2
C02CH3HCF2F NSO□Et C1hC
O2EtCF3CF2F N5O2CH, CH2C0
□CH.

CF, CF2F N5O2CH2CH2CO2EtC
F2CF2F N5O2Et CH2C02CH3
CF3CF2F N5O2Et CH2C0□Et
CF3F NCH3CH2C0□H CF3F NCH2CH2CO2CH3 Table 2
(continued) CF3 F NEt CH2C02EtHC
F2F NCH3CH2C02HHCF2F NC
)(3CH2CO2CH3HCF2F NC)I3C
H2CO□EtCF3CF2F NCH3CH2C0
2HCF3CF2 F NCH3C)12CO2C
H3CF3CF2F NCH3CH2C0□EtCF
3HNHCH2C0□H CF3 HN)l CH2CO2C
)i 3CF, HNHCH2C0□EI CF3HNHCH2CO2Pr' CF3 HNHCH2CO2Pr"CF3 H
NHCH2C0□BU″CF3HNHCH2C02Bu
'CFi HNHCH2C0Ju 'CF3 H
NHCH2C0□Bu'CFs HNHCH2C0
□-V+nylCFs HNHCH2CO2-A1
1yl Table 2 (continued) RfXYR CF3HNHCH2C02-THF CF, HNACCH2C02H CF3HNACCH2C0□CH3 CF3HNAc CH2C02EtCF3 H
NACCH2CO2Pr'CF3 HNACCH2
C0□Bu'CFs HNACCH2C02BU
'CF, HNAc CH2C0□-THFC
F3HNAc CH(CH3)C02HCF3HN
Ac CH(CH3)C02CH3CF, H
NAc CH(CH3)C02EtCFs H
NFm C1-12co2HCF3 HNFm
CH2C0□CH3CF2HNFm CH2
C02EtCFz HNFm CH2C0Ju
'CF3HNFm CH2C02Bu''CF3
HNFm CH2C0Ju'CF3HNFm
CH(CH3)C02H Table 2 (continued) RfXYR CF3 8 NFm CH(CH3)C0
□Ct(3CF3HNFm CH(Cf(3)C0
□EtCF3HNFm C)12cO7-T)IF
CF3HN5O2CH3CH2CO2HCF3HN5O
2CH3CH2CO2HCF3HN5O2CH3CH2
CO□EtCF3HNSO2CH3CH2CO2Pr'
CF3HN5O2CH:l CH2C02BIJ'C
F3 HNSO2CH3CH2C02Bu''CF3
HN5O2CH, CH2C02-THFCF3HN5O
2CH3CH(C)13)C02HCF3HN5O2C
H3CH(CH3)CO2CH3CF3 HN5O
2CH,CH(CH3)C0□EtCF3HNSO□E
t CH2C0□HCF2 HN5O2Et
CH2C0□CH3CF3 HN5O2Et C
H2C02EtCF3 HN5O2Et CH2
CO2Pr'CF, HN5O2Et CH2C
0□Bu"Table 2 (continued) RfXYR CF3 HNSO□Et CH2C02BIJ'
CF3HNSO□εt CH2C02-TI-IPC
F, HNSO□Et CH(CH3)C02H
CF, HNSO□Et CH(CH3)C02
CH3CF, HN5O2Et CH(CH,)
C02EtHCF2HNHCH2C0□H )ICF2HNHCH2C02CH3 HCF2HNHCH2C0□Et HCF2HNHCH(CH3)C02HCF2HNHC
H(CH3)C02CH3HCF2HNHCH(CH,
+) CO2EtCF3CF, HNHCH2C0□H
CF, CF2HNHCH2C0□CH3CF3CF2H
NHC1(2CO□EtCF3CF2HNHCH(C)
13) CO□HCF3CF2HNHCH(CH3)C0
2CH3CF3CF2HNHCH(CH3)C02Et
HCF2 HNACCH2CO2CH3 Table 2
(continued) RfXYR HCF2 HNACCH2C0□EtCF3CF2
HNACCH2C02CH3CF3CF2HNAc
CH2C02EtHCF2HNFm CH
2C0□CH3HCF2HNFm CH2C02E
tCF3CF2HNFm CH2C02CH3CF
3CF2HNFm CH2C02EtHCF2HN
5O2CH3CH2C02C)13HCF28 N
SO□CH3CH2C0□EtHCF2HN5O2Et
CH2Co2CH.

HCF2HN5O2Et CH2C02EtCF3C
F2 HNSO2CH3CH2C02C)+3CF3
CF2HNSO2CH3CH2C02EtCF3CF2
HN5O2Et cH2cO2cH3CF3CF2H
NSO□Et CH2C0□EtCF3HNCH3C
H2Co□H CF3HNCH3CH2C02CH3 CF3HNCH3CH2C02Et Table 2 (continued) RfXYR CF3HNEt CH2C02EtHCF2HN
C)]3CH2CO2H HCF2HNCI(3CH2CO,C02HCF2HN
CH3CH2C02Et CF3CF2HNCH3CH2C02HCF3CF2
HNCH3CH2C0□CH3CF3CF2HNCH
,CH2C0□EtCF3F OCH2CmiN CF3F NHCH2CyoN CF3 F NACCH2CmiNCF3
F N5O2C1 (3CH2C=NCF3CI
NHCH2C02Et CF, CI NAc CH2C02EtC
F3CI NFm CH2C0□EtCF3
CI N5O2CH3CH2CO2EtCF3
CI N5O2Et CH2C02EtCF3C
I NCH3CH2C02EtCF3Br NHC
H2C02Et Table 2 (continued) RfXYR CF3 Br NAc CIhC02EtC
F3 Br NFm CH2C02EtCF
3 Br N5O2CH3CH2CO□EtCF
3HOC02CH3 CF3HNHC02CH3 CF, HNAc C02CH3CFI
HNSO□CH3CH2C:N (hereinafter, blank) Table 3 CH3 fXYR CF, F OCH,CO,H CF3FOCH2C02CH3 CF, F OCH2C02Et CF, F OCH2C0□Pr'''CF3 F
OC82CO□Pr'CF3 F OCHzC
OJu” CFa F OCH2C02Bu'CFs F
OCH2C0Ju' CF3 F OCH2C0□Bu'CFa F
OCH2C02-VinylCF, F, OCH2C
0□-AllyICF2 F OCH2C0□-T
HFCF, FOCH(CH,)Co2H
3 Table (continued) fXYR CF, F OCH(CH3)C02CH3C
F3F OCR (CH3) C0□EtCF3F
OCH(CH3)CO2Pr'CF3F OCR
(CH3)CO2Pr'CF3F OCH(CH3
)C0□Bu”CF3F OCH(CH3)C0□
Bu'CF3F OCH(CH3)C02BLl'
CF3F OCH(CH3)C02Bu'CF3F
OCR(CH3)CO2-VinylCF3
FOCH(CH3)-A11ylCF3F
OCH(CH3)-THFCF3HOCH2C0□H CF3HOCH2C0□CH3 CF3HOCH2C02Et CF3HOCH2C02P r' CF3 HOCH2CO2Pr'CF3HOCH2C02BU' CF3 HOCH2C02BU' 3rd Table (continued) fXYR CFa HOCH2C0Ju' CF3 HOCH2C02Bu' CF3 HOCH2C02-VinylCF, HO
CH2CO2-A11yl CF3HOCH2C0□-THF CF, HOCH(CH3)Co□HCFs
HOCH(CH2)CO2CH3CF, HOCH
(CHs)CO, EtCF, HOCH(CHs)
CO□Pr”CF3HOCH(CH3)C0Ju' CF2 HOCH(CH3)C0□Bu”CFs
HOCH(CH3)C0Ju'CF2 HOC
H(CHj)CO2BU'CFs HOCH(CH
a) CO□Bu'cF, HOCH(CH2)CO
,-VinylCFa HOCH(CH3)C0□
-AllyICF a HOCH(CH2)Co
2-THFHCF2F OCH2C02CH.

HCF2HOCH2C02CH3 HCF2)(OCR2C0□Et CF3CF2 F OCR2C02C1(3CF
3CF2 F OC82CO2EtCF, CF2
HOC1(,C02CH3CF3F2HOCH2C0□
Et HCF2 F OCH(CH2)Co□C1(3
HCF2HOCH(CH3)C0□EtCF, CF2F
OCH(CH3)Go□CH.

CF, CF2HOCF((CH3)Co□EtCF,
CI OCH2C07CI (3CF2 C
1OCH2C02Et CF, C1OC82CO□Pr'CF, C
1OCH(CH2)CO2CH3CF, CI
OC) ((CH,)Co□EtCF, CI
OCH(Pr')C0□EtCF, Br
OCH2Co2CH3 Table 3 (continued) CF3 Br OCH2CO2Pr'CF3B
r OCH(CH3)C02CH3CF3Br
OCH(CH3)C0□EtCF3Br OCH
(Pr')C0□HCF, I OCH2C0
□EtCF3F Nl(CI(2CO□HCF,
F NHCH2C02CH3CF3F N
HCH2C0□Et CF= F NHCH2CO2Pr'CF3F
NHCH2C02Pr”CF, F N
HCH2C02Bu″cF2F NHC)12cO
□Bu'CF3F NHCH2C0□Bu'CF3
F NHCH2C0□Bu'CFI F
NHCH2C0□-VinylCF, F N
HCH2CO2-A11yl Table 3 (continued) fXYR CF3 F NACCl-12C02HCF,
F NAc CH2C0□CH3CF,
F NAc CF(2CO□EtCF3
F NACCI"l2CO□Pr'CF3
F NACCH2C02BU″CF3 F
NACCH2C0Ju'CF3F NACC
H2C0□-THFCF3 F NACCH (
CH3)Co2HCF3F NAc CH(C
H3) C02CH.

CF3F NAc CH(CH3)C0,Et
CF, F NFm CF (2CO, HC
F2 F NFm CH2C02CHsC
F, F NFm CH2C0□EtCF
I F NFm CH2C0□EtCF3
F NFm CH2C0□Bu”CF3
F NFm CH2C02BU'CF=
F NFm CH(CH3)C02HC
F= F NFm CH(CH3)C02
CH-Table 3 (continued) fXYR CF3F NFm CH(CH3)C0□Et
CF3F NFm CH2C0□-THFCF
3F N5O2CH3CH2CO, HCF3F
N5O2CH, CH2C0□CH3CF3F N
5O2CH, CH2C0□EtCF3 F N
5OzCHz CH2CO2Pr'CF3 F
N5OzCHz CH2C02BU'CF3
F NSO2CH3CHzCOJu”CF,
F N5O2CH, CH2C02-THFCF3
F N5O2CHs CH(CHs)C0□HC
F, F N5O2CH,CH(CH,)CO
□CH.

CF3F N502CH, CF((CH3)Co2
EtCF, F Nso, EtcH,co
2uCF3F N5OJt CH2C02CHsC
F, F N5O2Et CH2C0□EtC
F3 F N5O2Et CH2CO2Pr
'CF3F NSO□Et CH2C02Bu''
'CF3 F N5O2Et CH2C02
BU' Table 3 (continued) fXYR CF, F N5O2Et CH2C0□-T
HFCF, F NSO□Et CH(CH3
)C0□HCF3F N5O2Et CH(CH3
)C0□CH3CF, F NSO□Et C
H(CH3)C0□EtHCF2F NHCH2C
0□H HCF2F NHCH2C0□CH3HCF2F
NHCH2C02EtHCF2 F NHC
H(CH3)C02HHCF2'F NHCH(C
H3) C02CH.

HCF, F NHCH(CH,)C0□EtC
F3F2F NHCH2C0□HCP, CF2F
NHCH, C02CH2CF, CF2F NH
C) 12CO2EtCF3CF2 F NHCH
(CH3)C0□HCF, CF2F NHCH(C
H3) C02CH.

CF, CF2F NHCH(CH3)C0□EtC
F3F NAc CH2C0□CH.

HCF2 F NAC, CH2CO2Et 3rd
Table (continued) CF3CF2F NAc CH2C02CH3
CF3CF2 F NACCl-12cO2Et
HCF2 F NFm CH2C02CH-
HCF2F NFm CH2C02EtCF,
CF2 F NFm CH2C02CH.

CF, CF2F NFm CH2C0□EtH
CF2F N5O2CH3CH2CO□CH3HC
F2F NSO□C)13C)12CO2EtHCF
2 F N5O2Et CH2C0□CH3H
CF2F NSO□Et CH2C02EtCF3
CF2F NSO□CH3CH2C02CH.

CF, CF2F NSO□CH3CH2C02EtC
F, CF, F NSO2εt CH2C02C
H3CF3CF2F NSO□Et el(2CO
□EtCFs F NCH3CH2C0□HC
F3F NCH, CH2C0□CH3CF3
F NCH3CH2C02EtTable 3 (continued) HCF2F MCI(3CH2CO2HHCF2F
NCH3CH2C0□CH3HCF2 F
NCI (3CH2CO2EtCF, CF2F N
CH,CH2Co2HCF3CF2F NCH,C
H2C02C1-13CF3CF2F NCH, 3
CH2CO2EtCF3HNHCH2C02)I CF, )l NHCH2C0□CH3CF3
HNHC) (2c02Et CF3HNHCH2C0□Pr” CF3 HNHCH2CO2Pr”CF, H
NHCH2C02Bu'CF3 HNHCH2C0
2Bu'CF3 HNHCH,, C02Bu'CF
, HNHCH2C02Bu'CF3HNHCH2
C0□-V+nylCF3 HNHCH2Co2-
A11ylCF3HNHCH2Co2-THF CF= HNACCH2C0□CH3CF,
HNAc CH, C02EtCF3 HNA
cCF(2cO2Pr'CF3 HNACCH2C
02Bu”CF3 HNAG CH2C02
Bu'CF, HNAc CH2C02-T
HFCF3HNACCH(CH3)C02HCF3HN
Ac CH(CH3)C02CH3CF,
HNAc CH(CHs)C02EtCF3
HNFm CH2C0□HCF3HNRm
CH2C02CH3CF3HNFm CH2
C0□EtCI”l HNFm CH2CO
2Pr'CF2 HNFm CH2C0□B
u″CFs HNFm CH2C0Ju'C
F3HNFm CH(CHs)C02ECF3H
NFm CH(CH,)C02CH3CF,
HNFm CH2C02-THFCF, H
N5O2C) I3CH2CO□HCF3HNSO2CH
3CH2C02C)13CF3HNSO□CH3C)I
2COJtCF3 HNSO□CH3CF(2cO
□Pr'CF3HN5O2CHz CH2C0□Bu
'CF3HN5O2CH, Cl-12CO□Bu'''C
F, HN5O2CH,CH2Co2-THFCF
2HN5O2CH2CH(CH2)CH2C0□
HN5O2CH3CH(CHs)CO2CH3CF3
HN5O2CH,CH(CI-1,)C02EtC
F3 HN5O2Et CH2Co2)ICF,
HNSO2εt CH2C02CH3CF3H
NSO□Et CH2C0□EtCF3 HNS
O□Et CH2C0Ju'CF3HN5O2Et
CH2C02Bu・CFs HN5O2Ej
CH2C0□Bu' Table 3 (continued) CF2 HN5O2Et CH2Co□-TH
FCF3)I N5O2Et CH(CH3)C
o2HCF3HNSO, Et CH(CH3)C0
□CH3CF, HNSO□Et CH(CI
-13) C02EtCF2HNHCH2C02H HCF2HNHCH,C02CH3 HCF2)I NHCH2C0□EtHCF2
HNHCH(CH3)C02HHCF2HNHCH(C
H3)C02CH3HCP2HNHCH(CH,)C0
2HCF3CF2HNHCH2C02H CFICF2)I NHCH2C02CH3CF3
CF2 HNHCH2C02EtCF, CF3I
NHCH(CH3)C02HCF3CF2HN)(C
H(CH3)C02CH.

CF2CF2ONHCH (CI-13) C02EtCF
2HNACCH2C02CH.

Table 3 (continued) fXYR CF2CF2ONAc CH2C0□CH3CF3
CF2 HNACCH2C02EtHCF2 HN
Fm CH2C02C)+3HCF2 HNFm
CH2Co2EtCF3CF2 HNFm
CH2C02CH3CF3CF2HNFm CH
2C02EtHCF2HN5O2CH, Cl-12CO
□CH3HCF2HN5O2CH3CH2CO□EtH
CF2 HN5O2Et CH2C02CH3HC
F2HNSO□Et CH2C0□EtCF3CF2
HN5O2CH3CH2CO□CH3CF=CF2
HNSO□CH3CH2C0□EtCF3CF2
HNSO□Et CH2C02CH3CF, CF2
HN5O2Et CH2C02EtCF,
HNCH3CH2C02HCF, HNCH,CH
2C0□C1 (3CF38 NC)1. CH
2C02Et Table 3 (continued) fXYR HCF2HNCH, CH2C02H HCF2 HNCH, CH2C02CH31 (CF3
I NCH3CH2C0□EtCF3CF2HNC
H,CI(2CO□HCF,CF3I NCH,C
H2C0□CH3CF3CF2HNCH3CH2C07
EtCF, CI NHCH2C0□EtCF
3CI NAc CH2C0□EtOF,
CI NFm CH, C02EtCF,
CI N5O2CH3CH2CO2EtCF3CI
N5O2Et CH2C02EtCF3CI
NCH, CH2C02EtCF, Br N
HCH2C0□EtCF3 Br NAc
CH2C0□EtCF, F NHH CF, F OR CF3F NAc H CF, F NCH,H Table 3 (continued) CF3F NPm H CF3F NSO□C83H CF, F NSO□Et HCF3 F
NBu' HCF3HNHH CF, HOH CF, HNAc H CF2HNCH3H CF3 HNFm H CF, HNSO□CH3H CF3HNSO□Et H CF2 HNBu' H CF, CI NHH CF, Cl0H CF3Br N HH CF 3 Br OH CF, F OC82CmiNCF, F
N5O2CH, C02CH3CF2 HOC
H2C=N CF, HNHCH2C=N CF, HNAc CH2C=NCF,
HN5O2CH3CH, C=N (blank below) Table 4 CH3 CP3F OCR2C0□H CF3F OCH2C0□CH3 CF3F OCH2C0□Et CF3 F OCH2C0□Pr″CF3 F
OC82CO2Pr'CF3 F OCH2C0
Ju"cF's F OCH2C02Bu"C
F3 F OCH2C02BU'CFI F
OCH2C02Bu'CF3 F OCH2C02
-VinylCF, FOCH2C0□-All
y1cF3F OCH2C0□-THF Table 4 (continued) fXYR CF2F OCR(CH3)C02CH3CF2F
OCR(CH3)C0□HCFz F
OCH(CH3)C02Bu'CF3F OC3(
CH3)CO□Pr'CF, F OCH(C
H2) C02Bu'CF, F OCH(CH
3) C02Bu'CF, F OCH (CHs
)Co2Bu'CFs F OCH(CHl)
Co2Bu'CFs F OCH(CHs)C
O2-VinylCFs F OCH (CHz
)-AllylCF3F OCR(CH2)-TH
FCFs HOCH2C0□H CF, HOCH2C0,CH.

CFs HOCH2C0zEt CF, HOCH2CO2Pr' CFi HOCHzCOiPr" CFs HOCHzCOJu" Table 4 (continued) CFI HOCl-12cOJu'CF3 H
OCH2C0Ju' CF3 HOCH2C02-VinylCF3HO
CH2C0□-Allyl CF, HOCH2C0□-THFCF, H
OCH(CH3)C0□HCFz HOCH(CH
3) C02CH3CF2 HOCH(CH,)Co
□EtCF, HOCH(CH3)CO2Pr″C
Fs HOCH(Ctla)C02Bu'CF2H
OCR(CH3)COJu.

CF3 HOCH(CH2)Co2Bu'CFs
HOCH(CHz)C02u'CF2 HOC
H(CI2)C02Bu'CFz HOCH(CH
3) C02-VtnylCF, HOCH(CH2
)Co□-AllyICF3HOCH(CH,)CO2
-THF Table 4 (continued) RfXYR HCF2F OCH2C02Et HCF2HOCH2C0□CH3 HCF2HOCH2C0□Et CF, CF2F OCH2C0□CH3CF3CF
2F OCH2C0□EtCF, CF2OOCH,
C02C1(.

CF, CF2OOCH2C0□Et HCF2F OCH(CH3)C02CH3CF2
HOCH(CH3)C0□Et CF3CF2F OCR(CH,)CO2CH3C
F3CF2HOCH(CHs)C0□EtCF,
C1OCH2C0, CH3CF, C1OCH2C
0□Et CF, C1OCH2C0□Pr'CF3Cl
OCH(CH3)C02CH3CF3 C1OC
H(CI(a)COJtCF= C1OCH(Pr
') COJtCF, Br OCH2C02C
H.

Table 4 (continued) CF3Br OCH2CO2εt CF3 Br OCH2C0□Pr 'CF3B
r OCH(CH3)C02CH3CF3Br O
CH(CH3)C0□EtCF3 Br OCH
(Pr')C0□EtCF3I OCH2C0□E
t CF2 F NHCH2C02HCF,
F Nl(CH2C0□CH3CF2 F
NHCH2C02EtCF=F, NHC
H2CO2Pr'CF3F NHCH2CO2Pr
"CF, F NHCH, C02Bu" CF,
F NHCH2C0□Bu'CF2F
NHCH2C0Ju' CF, F NHCH2C0□Bu'CF2
F NHCH2C0□-Vtny ICF,
F NHCH2C0□-Allyl Table 4 (continued) RfXYR CF3'F NAc CH2C0□HCF,
F NAc CH2C02CH3CF3F
NAc CH2C0□EtCF3 F
NACCH2C0zPr'CF3F NAc
CH2C0□Bu'CF3 F NACC
H2C02BIJ'CF= F NACCH2
C02-THFCF2F NAc CH(CH
3) C02HCF3F NAc CH (CHs
)C02CH3CF3 F NACCH(CH
3) C0□EtCF, F NFm CH
2C02HCF, F NFm CH2C
02CH.

CF= F NFm CH2C0□EtC
Fa F NFm CH2CO2Pr'C
F3 F NFm CH2C0Ju”CF
a F NFm CH2C02BU'CF
, F NFm CH(CH,)Co□H
CF, F NFn+ CH(CH3)C
02C) 13CF3 F NFm CH2
C02-THFCF3F NSO2CH3CH2C
0,HCF, F NSO,C) (2CH2C
O2CH.

CF, F N5O2CH, CH2C02Et
CF:l F N5O2CHz CH2C0
□Pr'CFa F N5O2CHz CH
2C0□Bu'CF2 F N5O2CHz
CH2C0□Bu”CF, F N5O2C
Hs CH2C0□-THFCF, F N
SO,CH,CH(CH2)CO2HCF, F
N5O2CH, CH(CH2)Co□CH.

CF3F N5O2CH3C1 ((CHa)C0□
EtCF= F N5O2Et CH2C0
JCF, F NSO□Et CH2C0z
CHsCF, F NSO□Et CH2C
0□EtCF2 F N5O2Et CH2
C0□Pr'CFa F NSO□Et C
H2C0Ju"CF2 F N5O2Et
CHxCOJu'CF, F N5O2Et
CH(CH3)Co2)ICF3F NSO
□Mi t el ((CH3)CO2CH:1CF3F
NSO, Et CH(CH3)C02EtH
CF2F NHCH2C0□HHCF2F
Nl(CH2C02C1(3HCF2F NH
CH2C02EtHCF2F NHCH(CH3
)C02HHCF, F NHCH(CH3
)C02C)(3HCF2F NHCH(CH3
)Co□EtCF3CF2F NHCH2C0□
HCF3CF2F NHCH2C02CH.

CF, CF2F NHCH2C02EtCF3C
F2 F NHC)I(CHI)CO2)IC
F3CF2 F NHCH(CH3)Co□C
H3CF, CF2F NHCF ((CHC02E
tCF3 F NACCH2CO2CH3 Table 4 (continued) fXYR CF3CF2F NACC1-12CC12CH.

CF3CF2 F NACCH2C0zEtHC
F2 F NFm CF I...
Co2CH3HCF2FNFmCH
2C02EtCF3CF2F NFm CH2
C02CH3CF3CF2F NFm ClixcO2EtHCF2F N5O2CH3CH2CO
2CH3HCF2F N5O2CH3CH2Co2
EtHCF2 F N5O2Et C) 12cO
2cH3HCF2 F N5O2Et CH2C
02EtCF3CF2F N502CH3C) I2C
02CH3CF, CF2F N502CH3C) 12
co2EtCF3CF2F N5O2Et C1(
2CO2C1 (3CF3CF2F N5O2Et
C) 12cO2EtCF3F NCH3CH2C0
2HCF3F NCH3C1 (2C02C1 (3C
F3F NCH,C1(,CO,EtCF,
F NEt Cll, Co2Et Table 4
(continued) HCF2F NCH3CH2C02HHCF2F
NCH,CI(2CO□CH3HCF2F N
CH, CH2C0□EtCF3CF2 F NC
H3CH2C02HCF3CF2 F NCH3
CH2C02CH3CF, CF2F NCH3CH
2C0□EtCF3HNHCH2C02H CF3HNHC) (2C02CHj CF, HNHCH2C0□Et CF, HNHCH2C0□Pr'CF2HNHC
H2CO2Pr” CFs HNHCH2C0□Bu”CF3HNHC
H2C0□Bu' CFs HNHC)]zCO□Bu'CF=
HNH'CH2C0Ju'CF3 HNHCHzC
Oz-VinylCF3HNHCH2C0□-Ally
1 Table 4 (continued) CF3 HNACCH2C02 CF3HNAc C) I2C02CH-CF3HN
Ac CH2C02EtCF3 HNACCH
2CO2Pr'CFz HNAc C)12c
OJu'CF3 HNACCH2C02BIJ'C
F3HNACCH2C02-THF CF3 HNACCH(CH3)Co2HCF3
HNAG CH(CH3)C02CI(3CF
, HNAc CH(C)(,)CO,EtC
F3HNFm CH2C02H CF3HNFm CH2C02CH, +CF2
HNFm CH2C02EtCFa HNF
m CH2CO2Pr'CF2 HNFm
CF(2CO2BU″CF3 HNFm C
H2C02Bu'CF3 HNFm C8(C
Ha) CO2H Table 4 (continued) RfXYR CF3 1(NFm CH(CH3)C02Et
CF 3HNFm CH2C0□-THFCF31
(N502C)I3C82CO□HCF31(N5O2
CH3C)]2CO□CH3CF3 HN5O2C
1 (3C82C02EtCF3 HNSO□CH3
CH2C0□Pr'CF3HN5O2C1 (3CH2C
OJu'CF3HN502C)13C)I2CO2Bu
″′CF3 HN5O2CH3C)12CO□-T
)IPCF38 NSO□C)13C)l(CH3
)CO2HCF3HN5O2CH3C1((CH3)C
O□CH3CF, HN5O2CH,C)! (C.I.
(3) C02EtCF3 HNSO□Et CH
2Co2HCF3 HNSO□Et C1-12
CO□CH3CF3 HNSO□Et C1hC
O, EtCF3 HNSO□Et CH2C0□
Pr'CF3HN5O3Et CH2C0□BU"Table 4 (continued) RfXYR CF3 HN5O2Et C)12CO2-T
HFCF3HN5O2Et CH(CI-13)C
O2HCF3HN5O2Et CH(CH3)C0
2CH3CF3HN5O2Et CH(CI-13
)C02EtCF2HNHCH2C02H HCF2HNHCH2Co2CH5 HCF2HNHC) (,C02Et HCF2HNHC)1(C)(3)Co2)()(CF
28 NHC)1(CJ(3)CO2C)I3HC
F2 HNHC1((CI(3)C02HCF3CF
2HNHC1(2CO21(CF3CF2HNHCH2
Co2CH5CF3CF2HNHCH2C02Et CF3CF2HNHCH(CH3)C02HCF3CF
2HNHCH(CH3)C02C)I3CF3CF2H
NHCH(CH3)C02EtHCF2HNAc
CH2C02CH3HCF2 HNACCH2C02
Et Table 4 (continued) CF3CF2 HNACCH2C0□C113CF3
CF2 HNACC1hCO2EtHCF2HNFm
CF(2CO□CH3HCF2HNFm C
H2C0□EtCF, CF2 HNFm CH2
C02CH3CF, CF2 HNFm CH2C
0□EtHCF2HN5O2CH, CH2C0□CH.

HCF2HNSO□CH3CH2Co□EtHCF2
HN5O2Et CH2C02CHsHCF2HN
SO□Et CH2C0□EtCF3CF2HN5O
2CH, CH2C0□CH3CF, CF2HN5O2C
H, CH2C02EtCF3CF2 HN5O2Et
CH2C02CH-CF3CF2HN5O2Et
CH2C02EtCF3HNCF(, CH2C0□H CF3HNCH3CH2C02CH.

CF3HNCH3CH2C02Et Table 4 (continued) RfXYR HCF2 HNCH3CHpCO2H) (CF2HN
CH,CH2C02C)I3)(CF2HNC)(3C
1(2CO2EtCF3CF2 HNCI(, CI(
2CO2HCF3CF21 (NCH3CH2C02CI
(3CF3CF2HNCH3CH2C02EtCF3C
I NHCH2C02EtCF3CI NAc
CH2C02EtCF, CI NFm
CH2C02EtCF3CI N5O2CH,
CH2C02EtCF3 CI N5O2Et
CH2C02EtCF3CI NCH3C1(2
C02EtCF3Br NHCH2C02EtCF
s Br NAc CH2C0zEtCF3
F NHH CF, F OR CF3F NAc H CF3F NCH,H Table 4 (continued) CF3 F NFIII HCF3
F N502C83HCF3 F N5O
2Et HCF3 F NBu' HC
F, HNHH CF, HOH CFJ HNACH CF38 NCH,H CFs HNFm H CF, HN502CH3H CFz HN5O2Et H CFs HNBu' H CF, CI NHH cps C1OH OF, Br 'NHH CF s Br OH CF3'F OCH2CmiN Table 4 (continued) ) CFz F NACCH2CmiNCF3F
N5O2C)I3C)12c=NCF3 HOC
1(2CmiN CF, HNF(CH2CmiN CF3HNAc CH=CH2 (hereinafter, blank) The symbols in the table have the following meanings.

Et: C2H6 Pr'': 0H2CH2CH3 Pr’: CH(CH3)2.

Bu”: CH2CH2CH2CH3Bu”:
CH(CH3)CH=CH1Bυ': CH2C
l(CH3)2Bu': C(CH2)3 Vinyl: CH=CH2 A11yl: CH2CH=CH2Ac: C
0CHa

Claims (7)

[Claims] (1) Formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, G represents a hydrogen atom or a methyl group, and represents a hydrogen atom or a halogen atom, Y represents an oxygen atom or -N
(R^3)-(R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group, or an ethanesulfonyl group), and Z represents a hydrogen atom or a nitro represents a group, R is a hydrogen atom, CH(
R^1) CO_2R^2 (However, R^1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R^2 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or 2 carbon atoms. ~
4 represents an alkenyl group or a tetrahydrofurfuryl group. ) or CH(R^1)C≡N (wherein R^1 represents the same meaning as above). ] A 6-haloalkyl-3-phenyluracil derivative represented by: (2) Formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R^3)- (R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group or an ethanesulfonyl group). ] A 1-H-6-haloalkyl-3-phenyluracil derivative represented by the formula (VI) l-Ra(VI) [wherein, Ra is CH(R^1)CO_2R^2 (however,
R^1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R^2 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, or a tetrahydrofurfuryl group. represents. ) or CH(R^1)C≡
N (where R^1 represents the same meaning as above), l is a halogen atom, methanesulfonyloxy group, ethanesulfonyloxy group, benzenesulfonyloxy group,
Represents a paratoluenesulfonyloxy group, a paranitrotoluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group. ] Formula (III) is characterized by reacting with a compound represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) [R_f, X, Y and Ra represent the same meanings as above. ]
A method for producing a 1H-6-haloalkyl-3-phenyluracil derivative represented by: (3) Formula (III): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R^3)- (R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group or an ethanesulfonyl group), R is a hydrogen atom, CH(R^1)CO_2R
^2 (However, R^1 is a hydrogen atom or a carbon atom number of 1 to 4
represents an alkyl group, R^2 is a hydrogen atom, and the number of carbon atoms is 1
-6 alkyl group, alkenyl group having 2 to 4 carbon atoms, or tetrahydrofurfuryl group. ) or CH(
R^1) C≡N (however, R^1 represents the same meaning as above). ] Formula (IV) is characterized by methylating a 1H-6-haloalkyl-3-phenyluracil derivative represented by: ▲There are numerical formulas, chemical formulas, tables, etc.▼(IV) X, Y and R represent the same meanings as above. ] A method for producing a 6-haloalkyl-1-methyl-3-phenyluracil derivative represented by: (4) Formula (IV): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(IV) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R^3)- (R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group or an ethanesulfonyl group), R is a hydrogen atom, CH(R^1)CO_2R
^2 (However, R^1 is a hydrogen atom or a carbon atom number of 1 to 4
represents an alkyl group, R^2 is a hydrogen atom, and the number of carbon atoms is 1
-6 alkyl group, alkenyl group having 2 to 4 carbon atoms, or tetrahydrofurfuryl group. ) or CH(
R^1) C≡N (however, R^1 represents the same meaning as above). ] Formula (V) is characterized by nitrating a 6-haloalkyl-1-methyl-3-phenyluracil derivative represented by: ▲There are numerical formulas, chemical formulas, tables, etc.▼(V) R_f, X, Y and R represent the same meanings as above. ] A method for producing a 6-haloalkyl-1-methyl-3-phenyluracil derivative represented by: (5) Formula (V): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(V) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R^3)- (R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group or an ethanesulfonyl group), Ra is CH(R^1)CO_2R^2 (however, R^1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R^2 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, represents an alkenyl group or a tetrahydrofurfuryl group having 2 to 4 carbon atoms) or CH(R^1)
C≡N (where R^1 has the same meaning as above). ] Formula (VI) is characterized by reducing and ring-closing a 6-haloalkyl-1-methyl-3-phenyluracil derivative represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VI) R_f, X, Y and R^1 represent the same meanings as above. ] A method for producing a 6-haloalkyl-1-methyluracil derivative represented by: (6) Formula (VI): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VI) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or -N(R^3)- (R^3 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an acetyl group, a methanesulfonyl group or an ethanesulfonyl group),
R^1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. ] A 6-haloalkyl-1-methyluracil derivative represented by the formula (XII) l-J(XII) [wherein J is a C_1 to C_5 alkyl group, C_2 to C_
5 alkenyl group, C_3-C_5 alkynyl group, (C_
3-C_5 cycloalkyl) C_1-C_2 alkyl group, C_1-C_6 haloalkyl group, C_1-C_6 haloalkenyl group, C_1-C_6 haloalkynyl group, cyanomethyl group, (C_1-C_3 alkoxy)C_1-C
_2 alkyl group, -CH_2CO_2A^2^1 (however, A^2^1 is a hydrogen atom, C_1 to C_5 alkyl group,
Represents a sodium atom, a phenyl group optionally substituted with a halogen atom, or a benzyl group optionally substituted with a halogen atom. ), -CH_2CON(A^2^
2) A^2^3 (however, A^2^2 and A^2^3 each independently represent a hydrogen atom or an alkyl group of C_1 to C_3), an optionally substituted benzyl group (however, , the substituent is a C_1-C_4 alkyl group, C_1-C_
4-haloalkyl group, C_1-C_4 alkoxy group, (C
_1-C_4 alkoxy) carbonyl group, (C_1-C
_3 alkoxy) C_1 to C_2 alkyl group, represents a halogen atom. ) or -CH_2A^2^4 (However, A
^2^4 is an optionally substituted 2-pyridyl group (however, the substituent represents a C_1 to C_4 alkyl group or a halogen atom), an optionally substituted 2-pyridazyl group (however, the substituent is C_1 to C_4 alkyl group or halogen atom), 3-isothiazole group or 3-
Represents an isoxazole group. ), l represents a halogen atom, a methanesulfonyloxy group, an ethanesulfonyloxy group, a benzenesulfonyloxy group, a paratoluenesulfonyloxy group, a paranitrotoluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group. ] The compound represented by the formula (
VII): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VII) [In the formula, R_f, X, Y, R^1 and J represent the same meanings as above. ] A method for producing a 6-haloalkyl-1-methyluracil derivative represented by: (7) Formula (IX): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(IX) [In the formula, R_f represents a haloalkyl group having 1 to 4 carbon atoms, and R' represents an alkyl group having 1 to 6 carbon atoms. group, phenyl group or benzyl group. ] A β-aminocrotonic acid ester having a haloalkyl group at the β position represented by the formula (X): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(X) [In the formula, X represents a hydrogen atom or a halogen atom. , Y represents an oxygen atom or -N(R^3)- (R^3 represents an alkyl group having 1 to 4 carbon atoms, an acetyl group, a formyl group, a methanesulfonyl group or an ethanesulfonyl group), and R is a hydrogen atom, CH(R^1)CO_2R^2 (where R^1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R^2 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. represents a group, an alkenyl group having 2 to 4 carbon atoms, or a tetrahydrofurfuryl group) or CH(R^1)
C≡N (where R^1 has the same meaning as above). [In the formula, R_f, X, Y and R are It has the same meaning as above. ] A method for producing a 1H-6-haloalkyl-3-phenyluracil derivative represented by: