FI92394C - 5-Amino-1,2,4-thiadiazol-3-yl-iminokarbonyyliyhdiste - Google Patents

Description

χ 92394 5-Aitiino-1. 2.4-thiadiazol-3-yl-iminokarbonvvliyhdiste

The present invention relates to 5-amino-1,2,4-thiadiazol-3-yliminocarbonyl derivatives and to a process for their preparation. These compounds are useful as selected products for the preparation of antibacterial 3-propenyl cephem derivatives.

Description of the prior art

Cephem derivatives having an anunone group are previously known from Japanese Laid-Open Publication Nos. 174,378 / 83; 198.490 / 83; 130.295 / 84; 172.493 / 84; 219.292 / 84; 97.983 / 85; 197.693 / 85; 5,084 / 86; and so on.

Japanese Laid-Open Publication Nos. 172,493/84 and 5,084 / 86 specifically describe cephem derivatives having axnm at the i opr openy y 1 i r y hma 3-position.

Summary of the Invention

The present inventors have shown that cephem derivatives having an ammoniopropenyl group in the 3-position and a fluoro-substituted lower alkoxyimino group or a cyano-substituted lower alkoxyimino group in the 7-position side chain have excellent antibacterial activity. These compounds, their preparation and use are described in more detail in the parent application (No. 87,449, Patent No. 89169).

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS 4a

The compounds of the invention may be used as an optional product in the preparation of 3-propenyl cephem derivatives of formula (I).

2 92394 N-TT-C-CONHy ^ S ^ Η, Ν- ^ ε ^ A J-ff ^ CH = CHCH, -A (I) xO -R, O COO- wherein R2 is a fluoro-substituted methyl group, and A is cyclic or an acyclic ammonium group.

Namely, the compounds of formula (I) and their pharmaceutically acceptable salts can be prepared individually by administering a compound of formula (II): N ~ TpC-CONH '^ - rS>, η <Ps · ^ fi-N'f # NCH = CHCHtX m, H'N b XO-R, COOH (Π) wherein R 2 is a fluoro-substituted methyl group and X is a halogen atom, or a corresponding compound in which the amino and / or carboxyl groups are protected by protecting groups, or a corresponding salt, to react the compound with a compound of formula (III): A '(III) wherein A' is an amine corresponding to A, with a compound in which the functional groups are protected with protecting groups .. or salts thereof; after which, if desired, po IStctada SUOId "groups.

A compound of formula (II) which is an intermediate; a substance in which the amino and / or carboxyl group (s) is (are) protected or the salts of this compound are all new compounds. These compounds can be prepared by the following method. In other words, compounds 3 92394 can be prepared by administering a compound of formula (IV):

N - ~ - C - COOH

A N N (IV) H2N '\ o - Rx wherein Rj has the same meaning as above, a reactive acid derivative thereof, a compound in which the amino group is protected by a protecting group, or a salt of the compound, is reacted with a compound of formula (V):

H-N

y_ ^ s> I (V)

v I CH = CHCH2X

COOH

wherein X has the same meaning as above, with a compound in which the carboxyl group is protected by a protecting group, or a salt thereof, optionally deprotected, and / or converted into another halogen atom of the symbol X.

The above reaction can be carried out under conventional N-acylation reaction conditions. For example, the reaction may be carried out at -50 ° C to 50 ° C in an inert solvent such as tetrahydrofuran, ethyl acetate, acetone, Ν, Ν-dimethylformamide, acetonitrile, dioxane or a mixture of these solvents.

Examples of the reactive acid derivative of the compound of the formula (IV) include an acid halide such as acid chloride, acid bromide, etc., symmetrical acid anhydride, mixed acid anhydride, active ester, active acid amide or the like.

When a free carboxylic acid of the formula (IV) or a salt thereof is used, the reaction is preferably carried out in the presence of a conventional condensing agent such as Ν, Ν-dicyclohexylcarbodiimide, p-toluenesulfonic acid or the like.

The conversion of a halogen atom of the symbol X into another halogen atom is carried out in a conventional manner. For example, a compound of formula (II) wherein X is an iodine atom can be prepared by reacting a compound of formula (II) wherein X is a chlorine atom with an alkali metal iodide.

The present invention relates to intermediates of formula (VI) below which are novel compounds of myGs.

ff ---- ^ ™ JL? N (VI)

H2N OCH2F

wherein Rg is a carboxyl group, a halocarbonyl group, a carbamoyl group, a cyano group, a compound in which the amino and / or carboxyl group (s) is (are) protected, or a salt thereof.

Suitable protecting groups for amino and carboxyl groups are the same as those already mentioned in connection with the compounds of the formula (II).

The above compounds can be prepared by the following method.

5 92394 NC - C - CONH,

S

'% H (VII>

V H N ^ S / N \ <XIVI

H2N OH

NC - C - CONH- (^ och2f iVIII)

▼ N -ir "C - COX

NC - C - CN AS / N N

J (IX) H2N \ ch2f ^ OCH2F - (x: halogen atom) / (XV) i /

V N -π— C - COOH

H-N 11 .N [J

2 \ c. c - CN \ (XIII)

»(X) OCH2F

nOCH2F

N -π C .— CONH-

Aixl

»Η N X

n2 OCH ^ F

N | T C CN (X T T)

Jl n n ^ (XII)

H-N N

4 ^ OCH2F

(XI) 6 92694

A compound of formula (VIII) may be prepared by reacting a compound of formula (VII) with halofluoromethane in an inert solvent.

Examples of halofluoromethane include bromofluoromethane, iodofluoromethane and the like.

The reaction is filtered at a temperature in the range of -30 ° C to 100 ° C.

A compound of formula (IX) may be prepared by reacting a compound of formula (VIII) with a dehydrating agent in an inert solvent. As the reaction temperature, room temperature or a higher temperature is preferably used. As the dehydrating agent, oxophosphorus chloride, thionyl chloride, etc. can be used.

A compound of formula (X) may be prepared by reacting a compound of formula (IX) with ammonia and / or an ammonium salt in an inert solvent such as water, lower alcohol, acetone, chloroform, etc. A suitable reaction temperature range is -20 ° C. and between room temperature. As the ammonium salts, ammonium chloride, ammonium acetate, ammonium sulfate and the like can be used.

A compound of formula (XI) may be prepared by reacting a compound of formula (X) with a halogenating agent such as gaseous bromine, gaseous chlorine, etc. to enhance halogenation, after which it is reacted with an alkali metal thiocyanate, preferably in the presence of a base. is between -20 ° C and room temperature. As the alkali metal thiocyanate, potassium thiocyanate, sodium thiocyanate and the like can be used.

A compound of formula (XII), a compound in which the amino group is protected or a salt thereof can be prepared by hydrolyzing a compound of formula (XI), a compound in which the amino group is protected or a salt thereof, in the presence of an oxidizing agent or a base followed by protecting groups. when deleted.

The reaction can be carried out at 0 ° C to 70 ° C in water, a buffer solution or in a mixed solvent with a lower alcohol.

7 92394

Hydrogen peroxide, oxygen, etc. can be used as the oxidizing agent? mixed with sodium hydroxide, potassium hydroxide, etc. as a base. A compound of formula (XIII), a compound in which the amino group is protected or a salt thereof can be prepared by hydrolyzing a compound of formula (XII), a compound in which the amino group is protected or a salt thereof, in the presence of a base, followed by deprotection if desired. . The bases, solvents, reaction temperatures, etc. may be the same as in the reaction sequence, Formula (XI) to Formula (XII). A compound of formula (XIII), a compound in which the amino group is protected or a salt thereof may be further prepared by reacting a compound of formula (XIV) in which the amino and / or carboxyl groups are protected with halogen fluoromethane, after which the protecting group may be remove.

Examples of halofluoromethane include bromofluoromethane, iodofluoromethane and chlorofluoromethane.

The reaction can be carried out in an inert solvent at -30 ° C to 100 ° C in a reaction lamp.

Examples of the inert solvent include sulfoxides such as dimethyl sulfoxide, etc., amides such as N, N-dimethylacetamide, formamide, hexamethylphosphoryl triamide, etc., ketones such as acetone, etc., or a mixture of these solvents.

A compound of formula (XV), a compound in which the amino group is protected or a salt thereof can be prepared by reacting a compound of formula (XIII), a compound in which the amino group is protected or a salt thereof with a halogenating agent.

Examples of the halogenating agent include phosphorus pentoxide, thionyl chloride, thionyl bromide, oxyphosphorus chloride and. like.

The reaction described above can be carried out in an inert solvent such as dichloromethane, tetrahydrofuran, ethyl acetate, chloroform or a mixture of these solvents at a reaction temperature of -50 ° C to 50 ° C.

The present invention is illustrated in more detail by the following examples of β 92394.

Example 1

Ethyl 2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetate 0 / 7Λ-N-t--C-COOC2H5 Ø-chn-^ F ^ A, noch2f

Ethyl 2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-hydroxyiminoacetate (60.4 g) was dissolved in dimethyl sulfoxide (210 ml), followed by the addition of potassium carbonate (96.48 g) with cooling. The solution was stirred for 10 minutes. Bromofluoromethane (19 g) was then added and the solution was stirred for 3 hours at room temperature. Ethyl acetate (1 liter) was added to the reaction solution, and the solution was washed with water and saturated brine, followed by drying over anhydrous magnesium sulfate. The solvent was distilled off, and ethanol (120 ml) was added to the portion. The formed crystals were collected by filtration and washed with ethanol to give the title product (58.2 g).

Example 2 2- (5-Tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoro-methoxyiminoacetic acid

Ύ M-n — C-COOH

o-imAyή 6 ^ β 92394

To a mixture of sodium hydroside (2.04 g), ethanol (146 ml) and water (29 ml) was added the compound prepared in Experiment 1 (17.87 g), after which the solution was stirred for 20 minutes at reflux temperature. The solution was concentrated under reduced pressure, followed by the addition of ethyl acetate (200 ml) and 1N hydrochloric acid (77 ml). The ethyl acetate layer was separated and washed with saturated brine, followed by drying by adding anhydrous magnesium sulfate. The solution was distilled off to obtain crystals. The crystals were broken by the addition of petroleum ether and collected by filtration to give the title product (16.55 g).

Example 3 p-Methoxybenzyl 7β- (2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetamido) -3 - ((Z) -3-chloro- 1-propen-1-yl) -3-cephem-4-carboxylate O Νχ ° 'ΟΟΝΗγ-Γ5Ί Γα OK S \ oh /. Dimethylformamide (348 μl) and tetrahydrofuran (4.1 ml) were cooled to -10 ° C, and phosphorus oxychloride (418 μl) was added thereto, followed by stirring for 90 minutes while cooling. To this solution was added the compound prepared in Experiment 2 (1.73 g) in tetrahydrofuran (5.5 ml) while cooling to -10 ° C, and the resulting solution was stirred for 90 minutes under ice-cooling. The reaction solution was cooled to -20 ° C, and a mixture of p-methoxybenzyl 7-amino-3 - ((Z) -3-chloro-1-propen-1-yl) -3-cephem-4-carboxylate hydrochloride was added thereto. (1.78 g), N- (trimethylsilyl) acetamide (2.95 g), ethyl acetate (18 ml) and tetrahydrofuran (5.5 ml), and the resulting solution was stirred for 10 hours at 92-94 ° C at -10 ° C. Ethyl acetate (100 ml) was added to the reaction solution, and the resulting solution was washed several times with water, saturated aqueous sodium hydrogencarbonate solution and magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title product (2.65 g).

Example 4 p-Methoxybenzyl 7β- (2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetamido) -3 - ((E) -3-iodo- 1-propen-1-yl) -3-cephem-4-carboxylate SN-C-CONH-wS ^ n / s & ii w I sOCH, F COOCH, - ^ - OCHs

The compound prepared in Experiment 3 (10.11 g) was dissolved in acetone (212 ml), and sodium iodide (9.03 g) was added thereto under ice-cooling. The resulting solution was stirred for 15 minutes under ice-cooling, and then for 90 minutes at room temperature. The solvent was evaporated off and the residue was extracted with ethyl acetate (500 ml). The extract was washed saturated. aqueous sodium thiosulfate solution and saturated brine, followed by drying over anhydrous magnesium sulfate. The dry extract was concentrated under reduced pressure, and n-hexane was added thereto. The resulting precipitate was collected by filtration to give the title product (10.92 g).

Example 5 p-Methoxybenzyl 7 / 5- (2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -difluoromethoxyiminoacetamido) -3 - ((Z) -3-chloro- 1-propen-1-yl) -3-cephem-4-carboxylate 92394 Λ'oCHFj COOCH, -O-OCHj

In the same manner as in Experiment 3, 2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-difluoromethoxyiminoacetic acid (2.00 g) was reacted with p-methoxybenzyl 7-amino-3 - ((Z) -3-chloro-1-propen-1-yl) -3-cephem-4-carboxylate with hydrochloride (1.795 g) to give the title product (3.17 g).

Example 6 p-Methoxybenzyl 7β- (2- {5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-difluoromethoxyiminoacetamido) -3 - ((E) -3- iodo-1-propen-1-yl) -3-cephem-4-carboxylate 2 m-C-CONH (O-CH), COOCl-O-OCH

In the same manner as in Experiment 4, the compound prepared in Experiment 5 (3.00 g) was reacted with sodium iodide (2.62 g) to give the title compound (2.92 g).

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oo »o χ -» f- _ · o - ^ z ii 9 ^ c_i, ii'- '* - * l ί -Ϊ w' m W Ift ε Ξ = o? s. g = 5 - ^ .Οβι · β.00.Ν

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Example 7 2- (5-Tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoro-methoxyiminoacetylic acid hydrochloride Hydrochloride-N -? - c-coa O "? ® * Un ». Ha

A S OCHiF

Phosphorus pentachloride (395 mg) was dissolved in dichloromethane (2.9 ml) and cooled to -5 ° C. Lisattiin the test in a solution-prepared compounds on SA 2 (627 mg) and the solution was stirred kanden and a half hours y1la said temperature. The reaction solution was added to a mixture of n-hexane (9.4 ml) and n-octane (9.4 ml). The precipitated crystalline material was collected by filtration and washed with n-octane to give the title compound (325 me).

Melting point: 139 - 140 ° C (decomposes'

Mass spectrum (m / 'e): M ..... 480 (Cl), 482 (Cl)

Infrared Absorption Spectrum (cm -1, Nujol): 1795, 1780, 1740, 1630 NMR Spectrum (δ, DMSC-d 6): 5.79 (2R, d, J = 54 Hz), 7.31 (15 H, s), 10.09 (1H, s)

Example 8 2- (5-Tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetic acid ethyl ester N-s-C-COOCiH,

Η; Ν · ^ ε-Ν N

b "OCH, P

is 92394

The compound prepared in Experiment 1 (2.00 g) was stirred in trifluoroacetic acid at room temperature for 30 minutes. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title product (405 mg).

Melting point: 172-173 ° C

Infrared Absorption Spectrum (Nujol): 1730, 1615 NMR Spectrum (, DMSO-d 6): 1.28 (3H, t, J = 7.0 Hz), 4.34 (2H, q, J = 7.0 Hz), 5.83 (2H, d, J = 54.5 Hz), 8.27 (2H, brs)

Example 9 2- (5-Amino-1,2,4-thiaziazol-3-yl) - (Z) -2-fluoromethoxy-aminoacetic acid

N -! - C-COOH

H.N'V k0CHjP

The compound prepared in Experiment 12 (200 mg) was suspended in a mixture of ethanol (6 ml) and water (2 ml). A 1N aqueous sodium hydroxide solution (1.75 ml) was added thereto, and the mixture was stirred at 60 ° C for 1 hour. Ethanol was distilled off from the reaction solution, and the pH of the solution was adjusted to 2 using 1 N chloro-hydrogen chloride. The slurry solution was purified by passing "Dia-Ion SP207" (a trademark of a nonionic adsorption resin manufactured by Mitsubishi Chemical Industries, Ltd.) to give the title product (3C mg).

iTu TaDUr. a SDSOrp * iOSpcKtl i iciT; , N J j Oi /; -L / 0, x € 2C NMR Spectrum (δ, DMSO-d 6): 5.74 (2H, d, J = 55 Hz), 8.24 (2H, br)

Example 10 16 92394 p-Methoxybenzyl 1β- (2- (5-tritylamino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetamido) -3 - ((Z) -3- chloro-l-propen-l-yl) -3-cephem-4-carboxylate

O N-rC-CONH ^ -C1 Qh | hi / s'N n-OCHiF j- N

fhfr COOCH, - <f [yocHJ

To a mixture of ethyl acetate (37 ml), tetrahydrofuran (5 ml) and dichloromethane (15.7 ml) was added N- (trimethylsilyl) acetamide (8.17 g) and p-methoxybenzyl 7-amino-3 - ((Z ) -3-chloro-1-propen-1-yl) -3-cephem-4-carboxylate hydrochloride (3.33 g), the solution was cooled to -20 ° C, after which the compound deprotected in Experiment 11 was added. (3.80 g) was stirred at 10 ° C for 1 hour. Ethyl acetate (500 ml) was added to the reaction solution, and the mixture was washed several times with water, saturated aqueous sodium chloride solution, 1N hydrochloric acid and saturated salt to give a solution of water, followed by the addition of aqueous sodium hydroxide. Liuctin was evaporated ir. The residue and the residue were purified by silica gel column chromatography to give the title product (4.33 g).

The inir crab absorption spectrum and NMR spectrum of the product were equal to the values of the compound prepared in Experiment 3.

Example 11 2-Cyano-2-fluoromethoxyiminoacetamide NC-C -CONH,

OF

^ OCH2P

92394 17 2-Cyano-2-hydroxyiminoacetamide (22.6 g) was dissolved in dimethyl sulfoxide (100 ml), followed by the addition of potassium carbonate (55.2 g) with stirring at room temperature, and stirring was continued for 20 minutes. Fluorobromomethane (27 g) was dissolved in dimethylformamide (20 ml) and added to the solution, after which the solution was stirred for 20 hours at room temperature, after which it was allowed to cool. The reaction solution was added to ice water (1 liter) and extracted twice with ethyl acetate (150 ml). The organic layer was washed twice with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was distilled off. The residue was washed with ethyl ether and dried to give the title product (14.4 ° C).

Melting point: 124-125 ° C

Infrared Absorption Spectrum (cm -1, Nujol): 3410, 3290, 3150, 1690, 1590 NMR Spectrum (ε, DMSO-d 6): 5.94 (2H, d, J = 54.0 Hz), 7.85 - 9.40 (2K, b).

Example 12 2-Fluorimethoxyiminoproparidinitrile

NC- C - CN

II

OF

'^ OCH2F

A mixture of the compound prepared in Experiment 14 (14.0 g), acetonitrile (15 mL), sodium chloride (15 g) and phosphoryl chloride (14 mL) was refluxed for 2 hours. Phosphoryl chloride (5 ml) was added to the mixture and heating was continued for 2 hours. The reaction solution was cooled and added to ice water (200 ml), after which the solution was stirred at room temperature for one hour. the solution was extracted twice with methylene chloride 18

O ') * v O A

y C. U.y 'f (50 ml). The extract was washed with 5% aqueous sodium bicarbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated off. The resulting oily product was distilled under reduced pressure to give a colorless oily title product (9.1 g).

Boiling point: 69-70 ° C / 25 mmHg NMR Spectrum (ε, CDCl 3): 5.85 (2H, d, J = 52.0 Hz)

Example 13 2-Cyano-2- [1] ormethoxy-iminoacetamidine h2n.

C - C - C N

HN · ||

OF

^ och2f

A mixture of 28% ammonia (50 ml), ammonium chloride (6 g ') and ethanol (5 C ml) was cooled to -5 ° C and the compound prepared in Experiment 16 (9.1 g) was added with stirring, followed by stirring was continued at the same temperature for 3 hours, water (100 ml) was added to the reaction solution, the solution was extracted three times with methylene chloride (50 ml), the extract was dried over magnesium sulfate and the solvent was distilled off. .

A portion of the product was dissolved in ethanol, and acetic acid was added dropwise with stirring. The precipitate formed was collected by filtration and washed with eLanol, and when the physical characteristics of the product were obtained, the physical characteristics of the acetate belong to the acetate.

Melting point: 125-127 ° C

Infrared Absorption Spectrum (cnT *, Nujol): 3200, 1670, 1570 NMR Spectrum (¢ δ, DMSO-d 6): 1.90 (3H, s), 5.95 (2H, d, J = 54.0 # Hz), 7.40 (3 H, b)

Example 14 2- (5-Amino-1,2,4-thiadiazol-3-yl) - (E) -2-fluoromethoxyimino-acetonitrile n - n-c-cn

i II

N N

H2N '^ \ s // \

'OCH2 F

The compound prepared in Experiment 17 (3.0 g) was dissolved in methanol (50 ml) and triethylamine (4.2 g) was added thereto. The solution was cooled to -5 ° C and bromine (3.5 g) was added dropwise. Then, potassium thiocyanate (2.1 g) in methanol was added to the solution at -3 ° C and -5 ° C, and the solution was stirred at this temperature for 2 hours. I drive. The precipitate formed was collected by filtration and washed with water and methanol. The precipitate was recrystallized from acetone to give the title product (3.4c).

Melting point: 236-238 ° C

Infrared Absorption Spectrum (cm -1, Nujol): 3450, 3250, 3075, 1610, 1520 NMP spectra (ε, D.MSO-d 6) · 6.02 (2H, d, J = 54.0 Hz), δ 32 (2H, b)

Example 15 2- (S-allyl-amino-1,2,4-liadiazol-3-yl) - (2) -2-fluoromethoxy-1-yl] -N-t-CL 2; Ϊ. U 1

N - n-c-— CONH O

Π I

Ann h7n \ / x

2 Ns' OCH2F

ό Ο ί .. Λ 20 s L · \ J /

To an aqueous solution of sodium hydroxide (0.23 g) (18 ml) was added 35% aqueous hydrogen peroxide solution (7.4 ml). The compound prepared in Experiment 18 (2.0 g) was added thereto with stirring at room temperature. The solution was stirred for an additional 8 hours at 25 ° C to 30 ° C. The precipitates formed were collected by filtration, washed with water and acetone and dried to give the title product (1.3 g).

Melting point: 210-211 ° C

Infrared absorbed spectra (cm -1, Nu jol): 3450, 3260, 3180, 1690, 1610 NMR spectra (δ, DMSO-d 6): 5.73 (2H, d, J = 55.0 Hz), δ , 69 (2H, br), 7.9 δ (1H, br), 8.10 (1H, br).

Example 16 2- (5-Amino-1,2,4-thiadiazol-3-yl) - (Z) -2-fluoromethoxyiminoacetic acid

N-π- C -COOH

I 0 11

An n

/ \> S v'OCH2F

h2n

The sequence consisting of the compound prepared in Experiment 19 (1.1 g) and 2N aqueous sodium hydroxide solution (10 ml) was stirred at 5 ° C for 5 hours. The reaction mixture was cooled, adjusted to pH 1.0 with concentrated hydrochloric acid, and extracted with ethyl acetate (20 mL). Anhydrous magnesium sulfate was added to the extract, dried, and the solvent was removed. The residue was washed with isopropyl ether to give the crude product (0.8 g). The crude product was subjected to lid-on-phase silica gel column chromatography to give the title product (0.4 g).

The infrared and NMR spectra of the product were identical to the values of the compound prepared in Experiment 13.

Claims (4)

1. Where R6 is a carboxyl, halocarbonyl, carbamoyl or syano, compound, said amino and / or carboxyl group is protected by a protecting group, or a salt of these ice compounds . A 5-amino-1,2,4-thiadiazol-3-yl-iminocarbonyl compound of the following formula: 2. A process for preparing a 5-amino-1,2,4-thiadiazol-3-yl imino compound of the following formula; -C-COOH Jf NN h2 / s / 25 wherein said amino and / or carboxyl group is protected by a protecting group, or for the production of a salt of these - C -: - COOH // ^ INN H 2 6; / · 4 remove the protecting groups; or (2) hydrolyzing a compound of the following formula: N -rr- C -CONH 5 // vT in JL NI * h 2 n 2 s 2 and 2 f a base, whereupon the protection group is eliminated if necessary.