JPH0222266A - N-containing heterocyclic compound - Google Patents

Abstract

NEW MATERIAL:An N-containing heterocyclic compound expressed by formula I [R<1> is aryl substituted by nitro or halo(lower)alkyl; R<2> is amino which may be substituted by lower alkyl or cycloalkyl, N-containing heterocyclic ring which may be substituted by lower alkyl, hydroxy or hydroxy(lower)alkyl or halogen; R<3> is H or lower alkyl; R<4> is aryl; A is lower alkylene; X is CH or N; n is 0 or 1] and salts thereof. EXAMPLE:3-Bromoacetylamino-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine. USE:Useful as a treating drug for cerebrovascular diseases, e.g., cerebral hemorrhage, cerebral infraction or transient cerebral ischemic attack. PREPARATION:For example, a compound expressed by formula II is reacted with a compound expressed by formula III in a solvent to afford the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel N-containing heterocyclic compound useful for the treatment of cerebrovascular diseases, and is used in the medical field.

[Means for solving the problems] The N-containing heterocyclic compound which is the object compound of this invention is:
It is represented by the following general formula [I].

[In the formula, R1 is an aryl group substituted with nitro or halo(lower) alkyl, R2 is an amino group optionally substituted with lower alkyl or cycloalkyl; or halogen, R3 is hydrogen or a lower alkyl group, R4 is an aryl group, A is a lower alkylene group, X is N or C)l, n means an integer 0 or 1 ] The target compound [11 or a salt thereof can be produced by the production method explained in the following reaction formula.

Production method' R2-A-COOH[Il[
] [La] or a salt thereof [IV] or a salt thereof [I] or a reactive derivative thereof at the amino group or a salt thereof [Ib] or a salt thereof [Ib] or a salt thereof [1c] or a salt thereof [wherein R5 and R6 each mean hydrogen, a lower alkyl group or a cycloalkyl group, or R and R6 jointly with the nitrogen atom to which they are attached lower alkyl, hydroxy or form an N-containing heterocyclic group optionally substituted with hydroxy (lower) alkyl, R7 is hydrogen or an amine protecting group, Y is a leaving group, R1, R2, R3, R', A and Each X has the same meaning as before. Details of the various definitions mentioned in this specification and preferred examples thereof are explained below.

As used herein, "lower", unless otherwise specified, shall mean groups having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.

Suitable "aryl groups" include phenyl, naphthyl,
Examples include groups such as tolyl, xylyl, mesityl, cumenyl, etc., but preferred are phenyl group and tolyl group.

Suitable halo(lower) alkyl groups include chloromethyl, difluoromethyl, trifluoromethyl, bromomethyl, 2-chloroethyl, and the like.

Suitable lower alkyl groups include methyl, ethyl,
Mention may be made of straight or branched alkyl groups such as propyl, isopropyl, butyl, tertiary butyl, benthexyl, etc., among which preferred are C1-C
4 alkyl group, most preferably methyl group.

Suitable monocycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohebutyl, cyclooctyl, adamantanyl, and the like.

Suitable "N-containing heterocyclic groups" include saturated 5- or 6-membered N-containing, or N- and S-containing, such as piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, etc. or N- and O-containing heterocyclic groups.

Suitable 1-hydroxy (lower) alkyl groups include hydroxymethyl, hydroxyethyl, hydroxypropyl, and the like.

Suitable "halogens" include fluorine, chlorine, bromine or iodine.

Suitable 1-lower alkylene groups include methylene, ethylene, propylene, methylmethylene, tonomethylene, tetramethylene, pentamethylene, and the like.

Preferred examples of "aryl groups substituted with nitro or halo (lower) alkyl" include phenyl groups substituted with nitro, such as phenyl groups substituted with no halo (lower) alkyl, such as chloromethylphenyl, trifluoromethylphenyl, etc. etc.

Preferred examples of "amine groups optionally substituted with lower alkyl or cycloalkyl" include amino groups such as mono- or di-lower groups such as methylamino, ethylamino, propylamine, dimethylamine, diethylamino, methylethylamino Examples include alkyl-substituted amino groups, such as mono- or di-cycloalkylamino groups such as cyclopentylamino, cyclohexylamino, and adamantanylamino.

The term "N-containing heterocyclic group optionally substituted with lower alkyl hydroxy or hydroxyl (lower alkyl)" refers to the above-mentioned N-containing heterocyclic groups, such as 4-methylbiperazin-1-yl, 2,5 Examples include lower alkyl-substituted heterocyclic groups such as -dimethylpyrrolidin-1-yl, hydroxy-substituted heterocyclic groups such as hydroxypyrrolidinyl, and hydroxy (lower) alkyl-substituted heterocyclic groups such as hydroxymethylpyrrolidinyl. .

Preferred ft'7mino-protecting groups include acyl groups, such as lower alkoxycarbonyl groups such as tertiary-butoxycarbonyl, substituted or unsubstituted aralkoxy groups such as benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, etc. Examples include groups that can be easily introduced or removed, such as carbonyl groups.

Suitable leaving groups include acid residues such as halogens such as chlorine, bromine, fluorine and iodine, sulfonyloxy groups such as mesyloxy, tosyloxy, phenylsulfonyloxy, and the like.

Suitable salts of the target compound [I] are commonly used non-toxic pharmaceutically acceptable salts, such as formate, acetate, fumarate, trifluoroacetate, maleate, tartrate, methanesulfonic acid. salts, organic acid addition salts such as benzenesulfonates, toluenesulfonates, inorganic acid addition salts such as hydrochlorides, hydrobromides, sulfates, phosphates, amino acids such as aspartates, glutamates, etc. Examples include salts such as

Compounds [I al to [I c] are included within the scope of compound [1], and therefore these compounds [! a] or [
For suitable salts of [IC], the target compound [11
You can refer to the example given in .

The method for producing the object compound of the present invention will be explained in detail below.

1 target compound [I al or its salt is the compound [1 []
Alternatively, it can be produced by reacting a reactive derivative thereof at the amine group or a salt thereof with the compound [I[] or a reactive derivative thereof at the carboxy group or a salt thereof.

Suitable reactive derivatives of the amino group of compound [1] include the base-type imino group of Ship, which is produced by the reaction of compound [1] with a carbonyl compound such as an aldehyde, a ketone, etc., or its enamine-type tautomerism. Silyl derivatives produced by the reaction of the compound [ffl with silyl compounds such as bis(trimethylsilyl)acetamide, mono(trimethylsilyl)acetamide, bis(trimethylsilyl)urea, etc.] Reaction of the compound [ffl with trichloride, phosgene Examples include derivatives produced by.

Suitable salts of the compound [nl and its reactive derivatives are
Reference may be made to the salts exemplified for compound [I].

Suitable reactive derivatives of the carboxyl group of compound [11[] include acid halides, acid anhydrides, activated amides, activated esters, and the like.

Suitable examples of such reactive derivatives include acid chlorides; acid azides; substituted phosphoric acids such as dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, dibenzyl phosphoric acid, halogenated phosphoric acid, dialkyl phosphorous acid, sulfurous acid, thiosulfuric acid, Sulfuric acid, sulfonic acids such as methanesulfonic acid, aliphatic carboxylic acids such as acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, impentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, or such as benzoic acid, etc. mixed acid anhydrides with acids such as aromatic carboxylic acids; symmetrical acid anhydrides; activated amides with imidazoles, 4-substituted imidazoles, dimethylpyrazoles, triazoles or tetrazoles; or e.g. cyanomethyl esters, methoxymethyl esters, Dimethyliminomethyl [(CH3)2
1CH-conister, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthioester, p-nitrophenyl deoester , p-talesyl thioester, carboxymethyl thioester, pyranyl ester, pyridyl ester, piperidyl ester, 8
-activated nistyl, such as quinolyl thioester, or for example N,N-dimethylhydroxylamine, 1-hydroxy-2-(IH)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-IH-benzotriazole Examples include esters with N-hydroxy compounds such as. These reactive derivatives can be arbitrarily selected from among them depending on the type of compound [ml] to be used.

Suitable salts of the compound [■] and its reactive derivatives include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, ammonium salts such as trimethylamine salts, triethylamine salts, etc. salt, pyridine salt, picoline salt,
Examples include base salts such as organic base salts such as dicyclohexylamine salt and N,N'-dibenzylethylenediamine salt, and acid addition salts as exemplified for compound [1].

The reaction is usually carried out in a conventional solvent such as water, an alcohol such as methanol or ethanol, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, or pyridine. However, the reaction can be carried out in any other organic solvent as long as it does not adversely affect the reaction. These conventional solvents may be used in mixtures with water.

When the compound [1[] is used in the form of the free acid or its salt in this reaction, N,N'-dicyclohexylcarbodiimidosyl-N'-morpholinoethylcarbodiimide;N-cyclohexyl-N'-(4-diethylaminocyclohexyl)carbodiimide; N. N'diethylcarbodiimide, N. N'-diisoprobylcarbodiimide (dimethylaminobrobyl)carbodiimide; N.

N'-carbonylbis-(2-methylimidazole)
;pentamethyleneketene-N-cyclohexylimine;
diphenylketene-N-cyclohexylimine;ethoxyacetylene;1-alkoxy-1-chloroethylene;
Trialkyl phosphite; Ethyl polyphosphate; Isopropyl polyphosphate: Phosphorus oxychloride (phosphoryl chloride); Phosphorus trichloride;
Phosphoryl diphenylazide; thionyl chloride; oxalyl chloride; lower alkyl heroformates such as ethyl chloroformate, isopropyl chloroformate; triphenylphosphine; 2-ethyl-7-hydroxybenzisoxazolium salt; 2-ethyl-5 - ( m -sulfophenyl) isoxazolium hydroxide inner salt; 1-(
p-chlorobenzenesulfonyloxy)-6-chloro-
IH-benzotriazole, N. Preferably, the reaction is carried out in the presence of a conventional condensing agent such as the so-called Vilsmeier reagent prepared by the reaction of N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorous oxychloride, and the like.

The reaction also includes alkali metal bicarbonates, tri(lower)alkylamines, pyridine, N-1)alkylmorpholines, N. It may be carried out in the presence of an inorganic or organic base such as N-di(lower)alkylbenzylamine.
Liquid bases can also be used as solvents.

Although the reaction temperature is not particularly limited, the reaction is usually carried out under cooling or heating.

Production Process 1 The target compound [Ib] or a salt thereof can be produced by reacting a compound [IV] or a salt thereof with a compound [V] or a salt thereof.

Examples of suitable salts for compounds [IV] and [V] include those exemplified for compound [1].

This reaction is usually carried out using water, alcohols such as methanol, ethanol, isopropyl alcohol, dioxane, tetrahydrofuran, N,N-dimethylformamide, methylene chloride, chloroform, tetrachloromethane, or other conventional solvents that do not adversely affect the reaction. It can be carried out in mixtures of these.

The reaction temperature is not particularly limited, and the reaction can be carried out at low temperature, under heating, or under heating.

This reaction is carried out using an inorganic base such as an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide, an alkali metal carbonate or hydrogen carbonate such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. , such as triethylamine, pyridine, N. The reaction can also be carried out in the presence of an organic base such as a tertiary amine such as N-dimethylanidine.

This reaction can also be carried out in the presence of an alkali metal halide such as sodium iodide or potassium iodide.

The main target compound [1c] or a salt thereof is the compound [1[a]
Alternatively, it can be produced by reacting a salt thereof with compound [V] or a salt thereof.

This reaction can be carried out in substantially the same manner as Production Method 2, and therefore, the description of Production Method 2 may be referred to for the reaction method of this reaction and reaction conditions such as base, solvent, reaction temperature, etc.

In this reaction, a compound in which R7 is an amine protecting group [
Ic] is obtained, by subjecting the compound [Ic] in which R7 is an amine protecting group to the elimination reaction of the amine protecting group described in the reaction formula below, the target compound [Ic] in which R7 is hydrogen is obtained. can be manufactured.

[Id] or a salt thereof [Ie] or a salt thereof (wherein R7a means an amine protecting group, R1R2R3
, R4, A and X each have the same meaning as before).

For suitable salts of compounds [Idco and [Ie], compounds [! You can refer to the example given here.

This elimination reaction can be carried out by a conventional method, such as hydrolysis, reduction, etc.
For the reaction conditions such as base, catalyst, solvent, reaction temperature, etc., refer to the reaction method and reaction conditions of the conventional method for removing the amino protecting group.

Furthermore, such reactions are also encompassed within the scope of this manufacturing method.

Among the raw material compounds for the above production method, some of them are new and can be produced by the production method explained in the reaction formula below.

[■] or a reactive derivative thereof in a carboxy group or a salt thereof [■] or a salt thereof [H] or a salt thereof (wherein R8 means an esterified carboxyamino group, R1, R3, R4 and X each have the same meaning as before).

Suitable ester moieties of the esterified carboxyamino group include, for example, lower allyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, tertiary-jf ester, pentyl ester, hexyl ester, etc. For example, iodoethyl ester, dichloroethyl ester, trichloroethyl ester, trifluoromethyl ester-terminated mono (or di or tri) 0 (lower) alkyl ester, such as hydroxymethyl ester, hydroxyethyl ester, hydroxypropyl ester, hydroxybutyl ester. Hydroxy (lower) alkyl esters such as benzyl ester, 4-nitrobenzyl ester, triple ester, etc., lower alkenyl esters such as vinyl ester, allyl ester, and the like.

The method for producing the raw material compound [I] will be explained in detail below.

1 Production 1st step The compound [■] or a salt thereof is produced by subjecting the compound [■] or a reactive derivative thereof in a carboxy group or a salt thereof to a reaction for introducing an esterified carboxyamino group. be able to.

For suitable reactive derivatives at the carboxy group of compound [■], refer to those exemplified for compound [11].

For suitable salts of compound [■], compound [11[
] Please refer to the examples given below.

For suitable salts of compound [■], refer to those exemplified for compound [■].

This reaction involves reacting a compound [■) with a reactive derivative thereof or a salt thereof at the co- or carboxy group with an azide compound such as diphenylphosphoryl azide, sodium azide, etc., and then reacting the resulting compound with an alcohol to introduce an ester moiety. It is done by doing.

The former reaction is preferably carried out in the presence of a base such as triethylamine, pyridine and the like.

These reactions are usually carried out sequentially in solvents such as butanol, benzene, toluene, tetrahydrofuran, and the like.

Although the reaction temperature is not particularly limited, it is preferable to carry out the reaction at room temperature, under heating, or under heating.

Second step Compound [I] or a salt thereof can be produced by subjecting compound [I] or a salt thereof to an ester group elimination reaction.

The elimination reaction in this production method can be carried out by conventional methods such as hydrolysis, reduction, etc.

Hydrolysis is preferably carried out in the presence of an acid such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, or a base such as sodium hydroxide, sodium ethoxide, triethylamine.

Reduction can be carried out by conventional methods such as chemical reduction, catalytic reduction, etc.

This reaction is usually carried out in a solvent such as ethanol or benzene, which does not adversely affect the reaction.
The reaction can be carried out in any other solvent.

The reaction temperature is not particularly limited, and the reaction can be carried out under cooling or heating.

The compound obtained by the above production method can be prepared by conventional methods such as extraction using an appropriate solvent, color! - It can be separated from the reaction mixture and purified by methods such as chromatography, reprecipitation, and recrystallization.

Each of the target compound [1] and the starting compound may contain one or more stereoisomers based on the asymmetric carbon atom, and all such isomers and mixtures thereof are included within the scope of the present invention.

The object compound CI of this invention and its salts are used in the form of conventional pharmaceutical preparations in solid, semisolid or liquid form, mixed with organic or inorganic carriers or excipients suitable for external, oral or parenteral use. can do. The active ingredient can be, for example, a tablet, pellet, capsule, patch, suppository, solvent,
It may be mixed with the usual non-toxic, pharmaceutically acceptable carriers for emulsions, suspensions, and any other forms suitable for use, such as water, dextrose, lactose, gum acacia, etc. , gelatin, mannitol, starch paste, magnesium trisilicate,
Talc, cornstarch, keratin, colloidal silica,
Potato starch, urea and other carriers suitable for the production of solid, semi-solid or liquid formulations can be used, with the addition of auxiliaries, stabilizers, thickeners and coloring and flavoring agents. The pharmaceutical composition can also contain preservatives and bacteriostatic agents to stabilize the active ingredient in the desired dosage form. The amount of active compound of interest in the pharmaceutical composition is that amount sufficient to produce the desired therapeutic effect on the disease process or condition.

The dosage or therapeutically effective amount of the object compound of this invention [1F will vary depending on the age and symptoms of each individual patient to be treated;
/kg, more preferably 1 to 50a+g/kg, is administered as a daily dosage for the treatment of diseases.

The pharmaceutical compositions of this invention contain from about 0.01 mg to about 500 mg of active ingredient per oral and parenteral unit dose.
Compound [11 or a salt thereof] of g.

[Effects of the Invention] In order to demonstrate the usefulness of the target compound [I], the results of pharmacological tests will be explained below.

Kusabai Sumi 1 (A) 2-Methyl-3-morpholinoacetylamino-4
-(3-nitrophenyl)-6-phenylpyridine (B) 6-methyl-4-(3-nitrophenyl)-5-
[: (pyrrolidin-1-yl)acetylaminoco-2
- Phenylpyrimidine hydrochloride test, anoxic treatment (gas 1
One pair of ICR male medium mice of the same age (1 week after birth) was kept in a sealed glass chamber with circulating nitrogen gas, and the survival time was measured.

Thirty minutes before the experiment, one mouse was pretreated by intraperitoneal administration of the test compound and another was pretreated with vehicle only.

Test Results Treatment of mice with a test compound can result in an increase in the survival time of the animals subjected to anoxia.

As is clear from the above test results, the N-containing heterocyclic compounds [I] of the present invention and their salts are effective in preventing cerebrovascular diseases such as cerebral hemorrhage, cerebral infarction, hyperischemic attack, etc. Useful for treatment.

[Example] The present invention will be described in more detail below with reference to Production Examples and Examples.

(Leaving space below) n: Number of test groups * Hp < 0.05 (compared with control) **: p < O, OL (compared with control) 1. Methyl fluoromethylphenyl-5-pyrimidinecarboxylate (1
A suspension of 2 g) and sodium hydroxide (2.58 g) in methanol and water is refluxed for 10 hours. After distilling off the solvent, the residue is dissolved in a suspension of water and chloroform under stirring. The aqueous layer was separated and adjusted to pH 3.0 with 10% hydrochloric acid. The resulting precipitate is collected by filtration, washed with water, and dried under vacuum to obtain 6-methyl-2-phenyl-4-(3-trifluoromethylphenyl)-5-pyrimidinecarboxylic acid (7.09 g).

mp i 197-199℃ IR (streak seal): 1710. 1120
am-1HMR (DMSO-ds, S)'
2-70 (3H1s), 7.5-8.35 (7
H, m), 8.4-8.7 (2H, m) MASS
: 358 (M") Calculated value as elemental analysis "19H13F3N20□: C
63,69,H3,66,N 7.82 Actual value 2C63
,89,H3,54,N 7.821 product ±1 2-methyl-4-(3-nitrophenyl)-6-phenyl-3-pyridine carbon # (10,7 g), triethylamine (3,3 g) and diphenyl A warm mixture of phosphoryl azide (8.98 g) in tert-butanol (1 oomQ) is refluxed for 14 hours. After evaporating the solvent, the residue is dissolved in a suspension of chloroform (roomQ) and a saturated aqueous solution of sodium bicarbonate (100 mQ) under stirring. The organic layer is separated, washed successively with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography using silica gel (250 g) and eluted with chloroform. Both fractions containing the target compound were combined and concentrated under reduced pressure to give 3-tert-butoxycarbonylamino-2-methyl-4-(3
-nitrophenyl)-6-phenylpyridine (9,64
g) is obtained.

mp: 153℃ (decomposition) IR (streak seal) '3250. 1680.
1520. 1340 cm-INMR (CDCl
2. δ): 1.35 (9H, s), 2.66
(3H, s).

5.97 (IH,s), 7.3-8.45 (9
H, m), 7.54 (IH, s) MASS (M/Z): 405 (M”) Production example 2
The following compounds (Production Examples 3 to 5) are obtained in the same manner as above.

K product ■1 5-tertiary poxylponylamino-6-methyl-2
-Phenyl-4-(3-trifluoromethylphenyl)
Pyrimidine.

mp: 150-151℃ IR (Stripe 1-L)' 3320. 1690
cm'NMR (CDC1a, l; ): 1.37
(9H9s), 2-63 (3H1s).

6.05 (IH, s), 7.4-8.2 (7H,
m), 8.4-8.7 (2H, m) MASS: 429 (M”) Elemental analysis Calculated value as 23H22F3N302:
C64, 33, H5, 16, N 9.78 Actual value F C
64,82,H5,18,N 9.88 Production Example 4 5-Tertiary butoxyluponylamino-4(3-nitrophenyl)-2-phenylpyrimidine.

mp: 164-165℃ IR (Stripe 1-L)' 3200. 1710.
1350 cm-INMR (CDCl2.8):
1.45 (9H, s), 6.45 (IH, s)
.

7.45-8.73 (9H, m), 9.30 (
LH, s) MASS (M/Z): 392 (M”
) manufactured by 1dl 5-tertiary butoxylponylamino-6-methyl-4
-(3-nitrophenyl)-2-(p-tolyl)pyrimidine mp: 285-287°C (decomposition) IR (stinyl9-yl)' 3300. 1685.
1610. 1525. 1350cm-INMR (
DMSO-d6. δ): 1.3 (9H, s),
2.42 (3H, s).

2.58 (3H,s), 7.42.8.41 (4
H, ABq, J=8Hz) 7.7~8.8 (4H, m
), 9.11 (IH, bs) Production Example 6 3-tertiary poxylponylamino-2-methyl-4
-(3-nitrophenyl)-6-phenylpyridine (9
, 6 g) and concentrated hydrochloric acid (5,Q5IILII) in ethanol (96 mQ) is refluxed for 1.5 hours.

The solvent was distilled off, and the residue was dissolved in chloroform (100IIIQ
) and water (100 mQ). This solution was adjusted to pH 10.0 with a 4N aqueous sodium hydroxide solution. The organic layer is separated, washed with brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue was triturated in diethyl ether to give 3-amino-2-methyl-4
-(3-nitrophenyl)-6-phenylpyridine (5
, 17g).

mp: 154.5-157°C IR (sudicol): 3460. 3370.
3350. 1620. 1520°1350co+
-1 NMR (CDC13,l; ): 2.58 (3H,
s), 3.74 (2H9br s), 7.2
-8.5 (9H, m), 7.33 (LH,
s) MASS (M/Z): 305 (M'') The following compounds (Production Examples 7 and 8) are obtained in the same manner as in Production Example 6.

Production Example 7 5-Amino-6-methyl-2-phenyl-4(3-trifluoromethylphenyl)pyrimidine.

mp: 145-147°C IR: 3360. 1610
am-'NMR (CDC13, f; )' 2.5
3 (3H1s), 3.80 (2H9s>.

7.3-8.5 (9H, +n) MASS: 329 (M) Elemental analysis”18
Calculated value as H14F3N3: C65,65,)!
4.28. N 12.76 Actual value: C65,64
, H4,30,N 12.6g produced ±1 5-amino-4-(3-nitrophenyl)-2-phenylpyrimidine.

mp' 155-156℃ IR (S9a-4)' 3450. 3370.
1605. 1350 am-'NMR (CDC1
s, 8): 3.75 (2H, br), 7.40
-7.85 (4H, m), 8.20-8.50 (
5H, m), 8.75-8.82 (LH, m) MASS (M/Z): 292 (M”) Juseibo 1 In the same manner as in Production Examples 2 and 6, 3-amino-2-methyl -4-(4-nitrophenyl)-6-phenylpyridine is obtained.

ff1p: 277°C (decomposition) IR (streak 1-l): 3460. 3380.
1590. 1510°1350 cm' NMR (CDCl2.δ): 2.59 (3H,s
), 3.78 (2H.

br s), 7.3-8.55 (9H, m), 7
．． 38 (IH,s)MASS (M/Z): 30
5 (M”) 3-amino-2-methyl-4-(3-nitrophenyl)
-6-phenylpyridine (Ig), toluene (10+1
111) and pyridine (0.31 g),
Toluene (2mQ) of bromoacetyl bromide (0.7g)
Add the solution at 15°C. After stirring at room temperature for 7 hours, the reaction mixture was mixed with ethyl acetate (501111) and ice water (20 mQ).
The organic layer is separated, washed successively with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The solvent is evaporated under reduced pressure and the residue is triturated in diethyl ether to give 3-bromoacetylamino-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine (1.15 g).

mp: 198-199.5℃ IR (lined) i 3240. 1650.
1530. 1350 cm-'NMR (DMSO
-ds, δ): 2.53 (3H, s), 3.9
1 (28°s), 7.4-8.46 (9H, m)
, 7.93 (IH,s), 10.09 (IH,s
) MASS (M/Z): 425. 427 (M
) The following compounds (Examples 2 to 7) were prepared in the same manner as in Example 1.
get.

Naogi 1 3-Bromoacetylamino-2-methyl-4-(4-nitrophenyl)-6-phenylpyridine.

mp: 209-212°C (decomposition) IR (nujol): 3225. 1670.
1515. 1315 cm-INMR (DMSO
-ds, S)' 2.54 (3H1s), 3.9
6 (2H9s), 7.4-8.5 (9H, m>,
7.86 (1)1. s), 10. IL(IH,s
) MASS (1'l/Z): 425.427 (M
”) Taihuangbo 1 3-(3-bromopropionylamino)-2-methyl-
4-(3-nitrophenyl)-6-phenylpyridine.

mp: t98-200℃ IR (line 1-l): 3230. 1650.
1530. 1350 cm-'NMR (DMSO
-ds, δ): 2.54 (3H, s), 2.5
6-3.1 (2H, m), 3.45-4.0 (2
H, m>, 7.35-8.5 (98゜m),
7.88 (IH,s), 9.81 (IH,s
) MASS (M/Z): 439. 4
41 (M) Encounter 1 3-(2-bromopropionylamino)-2-methyl-
4-(3-nitrophenyl)-6-phenylpyridine.

mp: 202-207.5°C IR (sujiwor): 3200. 1645.
1525. 1345 am-'NMR (CDCl
2.8 ) : 1.76 (31(,d,J=
7t(z), 2.61(3H,s), 4.4(
IH, q, J=7Hz>, 7.3-8.4 (9)1
゜a+), 7.74 (IH, s) MASS (M/Z) i 439.441 (M”)
Elemental analysis: Calculated value as C2, H18N303Br:
C57,29,H4,12,N 9.54 Actual value:
C57,29,H4,02,N 9.38 members ■1 5-bromoacetylamino-6-methyl-4(3-nitrophenyl)-2-phenylpyrimidine.

mp: 206-209°C (decomposition) IR (Xdi1-4)' 3220. 1660.
1520. 1345 cm-1HMR (DMSO
Js, 8)' 2.57 (3H,s), 4.02
(2H.

s), 7.45-8.8 (9H, m) MASS
(M/Z): 426.428 (M") 1j".

5-bromoacetylamino-4-(3-nitrophenyl)-2-phenylpyrimidine.

mp: 219-220℃ IR (Sugital)' 1670. 1350
am-'NMR (CDC1s, 8)' 3.92
(21(,s), 7.42-7.90(4H,m),
8.20-8.70 (5H, m), 9.05 (
IH,s).

10.25 (LH, s) MASS <M/Z): 412.414 (M”)
5-Bromoacetylamino-6-methyl-2-phenyl-4-(3-triple-ometherphenyl)pyrimidine.

mp: 164-165°C IR (sugital): 3220. 1655
am-1HMR (CDCl2.8) 7 2.
60 <3H,s), 3.93 <21(,s
).

7.4-8.1 (7H, m), 8.4-8.7 (
2H,m) Elemental analysis: Calculated value as C2oH15BrF3N30: C53,35,H3,36,N 9.3
3 actual measurements: C53,64, H3,25, N 9.38
Methylene chloride (5 relatives) of 3-bromoacetylamino-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine (0.5 g) and morpholine (0.25 g)
The mixture is stirred at room temperature for 8 hours. The reaction mixture is poured into a mixture of methylene chloride (5 mQ) and water (10 mQ). The organic layer is separated, washed with water, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified with silica gel (25
g) and eluted with a mixture of methanol and chloroform. The fractions containing the target compound are combined and concentrated under reduced pressure. The residue is recrystallized from ethanol to obtain 2-methyl-3-morpholinoacetylamino-4-(3-nitrophenyl)-6-phenylpyridine (41Fung).

mp: 167-168°C IR: 3550. 3330.
1690. 1520°1355 am-1 NMR (CDC1a, S) = 2-3-2-6
(4H9m), 2-62 (3Ls), 2
．． 97 (2H,s), 3.45-3.72 (4
H, m), 7.25-8.3 (9H, m),
7.5 (IH,s), 8.66 (IH,s)M
ASS (M/Z): 432 (M) Elemental analysis "24'24'404, calculated value: C66,65
, H5,59, N 12.96 Actual value F C66,66
, H5,44,N 13.06 The following compounds (Examples 9 to 29) are obtained in the same manner as in Example 8.

X irises ±1 2-methyl-3-[(4-methylbiperazin-1-yl)acetylamino]-4-(3-nitrophenyl)-6
-Phenylpyridine.

mp: 103-106°C IR (2 di 1-x): 1660. 1520.
1350 cm-1HMR(CDCl2.δ)'
2.1-2.75 (8H, m>, 2.26 (3H
,s), 2.63 (3H,s), 2.98 (2
H,s), 7.2-8.35 (9H,m), 7.
54 (IH, s), 8.76 (1)! , s) M.A.
SS (M/Z): 445 (M'')

rnp: 120-121°C IR(v;a-L>' 3250. 1665.
1520. 1350 cm-'NMR (CDCl
2. δ): 1.56-1.98 (4H, m>, 2.
36-2.76 (4H, m), 2.65 (38
,s), 3.16 (2H,s).

7.35-8.44 (9H, s), 8.77 <
IH, s) MASS (M/Z): 416 (M”
) Elemental analysis "24'24N403, calculated value: C
69,21,H5,81,N 13.45 Actual value: C
69,54,)+5.57. N 13.46 U 2-Methyl-4-(3-nitrophenyl)-6-phenyl-3-piperidinoacetylaminoviridine.

mp: 125.5-127℃ IR (Stripe a-L): 3340. 1680.
1520. 1345 cm-INMR (CDCl
2. δ): 1.25-19 (6H, m), 2.
2-2.65 (4H, m), 2.64 (3)1. s
), 2.92 (2H,s), 7.35-8.45
(9H, m>, 7.55 (LH, s), 8.9
5 (LH,s)MASS (M/Z): 430
(M”) Elemental analysis “2JH26N403, calculated value i C69,75,H6,09,N 13.01 Actual f
tTJ flM[2 C69,80,H5,69,N
13.03 Snail 2-methyl-4-(3-nitrophenyl)-6=phenyl-3-thiomorpholinoacetylaminopyridine and its hydrochloride.

The physical property values below are for the hydrochloride.

mp: 210-215℃ (decomposition) IR (XE; i-4>' 3350 (br)
, 1700. 1630. 1610°1520,
1375 am-1 NMR (DMSO-ds, 8)' 2.63 (3
H1s), 2.65-3.65 (8H, m), 4.1
5 (2H, s), 7.35-8.45 (9H, m
>.

7.96 (IH,s), 11.05 (IH,s)
MASS (M/Z) 7448 (M”) 3-[(N,N-dimethylamino)acetylaminoco-
2-Methyl-4-(3-nitrophenyl)-6-phenylpyridine.

mp: 148-149℃ IR (Stripe 3-L)' 3270. 1670.
1520. 1350 cm-1 HMR (CDCl
2. δ): 2.23 (6)1. s), 2.63
(3H, s).

2.92 (2H,s), 7.25-8.35 (
9H, m), 7.5 (IH, s), 8.75
(IH,s)MASS (M/Z): 390 (M
") Elemental analysis" Calculated value as 22H22N403:
C67, 68, H5, 68, N 14.35 Actual value:
C67,87, H5,52, N 14.47 Example 14 3-[(adamancun-1-ylamino)acetylaminoco-2-methyl-4-(3-nitrophenyl)-6-
Phenylpyridine.

mp: 190-191℃ IR: 3250. 1660.
1525. 1350 cm-'NMR (CDC1
3,S)' 1.2-2.2 (15H1m), 2
．． 63 (3H, s), 3.24 (2H, s), 7
．． 25-8.4 (9H, m).

7.56 (IH,s), 9.32 (IH,s)M
ASS (M/Z): 496 (M”) Elemental analysis”3
Calculated value as 0H32N403: C72,56,H
6,49,N 11.28 Actual value: C72,99,H
6,33,N 11.32 Example 15 2-Methyl-3-(3-morpholinopropionylamino)-4-(3-nitrophenyl)-6-phenylpyridine.

mp: 142-144℃ IR (Sujoor): 3240. 1630.
1520. 1345 am-'NMR (CDCl
2. δ): 2.2-2.85 (81, m), 2
．． 64 (3Ls>, 3.4-3.8 (4H, m)
, 7.35-8.43 (98, m).

7.58 (IH,s), 10.35 (1)1. s
) MASS (M/Z): 446 (M") Elemental analysis "25'26N404, calculated value: C67,25
, H5, 87, N 12.55 Actual value: C66, 8L
, H5,65,N 12.48 Higashigoshoku group 2-methyl-3-(2-morpholinopropionylamino)-4-(3-nitrophenyl)-6-phenylpyridine.

mp: 177-178°C IR (Stripe 1-L)' 3325. 1690.
1525. 1340 am-INMR (CDCl
2. δ): 1.13 (31(,d,J=7)1z
), 2.34-2.66 (41(,m), 2.6
3 (3H, s), 3.0 (LH, q.

J=7Hz>, 3.5-3.85 (4H, m),
7.4-8.53 (9H.

m>, 7.57 (IH,s), 8.79 (11
(,s)MASS (M/Z) = 444 (
M-2) Elemental analysis Calculated value as 25H26N404: C67,25, H5,87, N 12.55 Actual value i C66,75, H5,64, N 12.47 Five dog dishes H 2-Methyl-3- Morpholinoacetylamino-4-(4
-nitrophenyl)-6-phenylpyridine.

mp: 154-156°C IR (sugital) = 3280. 1670.
1350 cm-'NMR (CDCl2.δ):
2.3-2.55 (4H, m), 2.62 (3H
.

s), 3.0 (2H, s), 3.45-3.
8 <48. m>, 7.27-8.37 (9H,
m), 7.5 (LH,s), 8.58 (I
H, s) MASS (+(/Z): 432 (M”
) Elemental analysis "22'24N404・1/8 Calculated value as EtOH: C66,46,H5,69,N 12.
78 actual measurement value: C66, 46, H5, 98, N 12.
48
-nitrophenyl)-2-phenylpyrimidine.

filp: 145-147°C IR (Sugital)' 3330. 17,00
．． 1525. 1350 cm-'NMR (CDC
l2. δ): 2.33-2.8 (4H, m),
2.6 (3H.

s), 3.1 (2H, s), 3.5-3.9 (
4H, m>, 7.35-8.62 (9H, m),
8.9 (LH,s)MASS (M/Z): 43
3 (M) Elemental analysis Calculated value as 23H23N504: C63,73,H5,35,N 16.16 Actual value: C64,01,H5,30,N 15.98X
Dish length 6-methyl-5-morpholinoacetylamino-2-phenyl-4-(3-triple olomederphenyl)pyrimidine.

mp: 153-154°C IR (sudicol): 3330. 1680
cm-'NMR(CDCl2.8)=2.35-2.
6 (4H, m), 2.6 (3H.

s), 3.08 (2H, s), 3.5-3.75
(4H, m), 7.4-8.1 (7H, m),
8.35-8.6 (2H, m), 8.73 (IH,
s) MASS: 456 (M”) Calculated value as “24H23F3N402” elemental analysis:
C63.15, H5.0g, N 12.27 Actual value:
C63,00, H5,10, N 12.46-terminus 5-morpholinoacetylamine-4-(3-nitrophenyl)-2-phenylpyrimidine.

mp: 192-194°C IR: 1695. 1355
cm-1HMR (CDC13,l; )' 2.4
8-2.65 (4H1m), 3-20 (2H,s),
3.38-3.50 (48, m), 7.45-8
．． 70 (8B, m>, 9.55 (LH, s), 9
．． 80 (LH, s) MASS (M/Z): 41
9 (M”) 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-thiomorpholinoacetylaminopyrimidine.

mp: 146.5-147.5°C IR (sugital) = 3200. 1675.
1520. 1340 cm-1HMR (CDC13
, l; )' 2.47-3.05 (8H, m),
2.58<3H,s), 3.1 (2H,s), 7
．． 35-8.72 (9H, m).

8.86 (18,s) MASS (M/Z): 449 (M”) Elemental analysis: Calculated value as C23H23N503S: C61,
46, H5, 16, N 15.58 Actual value F C61,
75,H4,95,N 15.73 Dog Direct Injection η 6-Methyl-5-piperidinoacetylamino-4-(3
-nitrophenyl)-2-phenylpyrimidine.

mp: 145-147°C IR: 3320. 1680.
1520. 1350 cm'NMR (CDC13
,S)' 1.28-1.78 (6H9m), 2
．． 25-2.72 (4H, m), 2.5 (3H,
s), 3.02 (21(, s).

7.35-8.7 (9H) MASS (M/Z): 431 (M) Elemental analysis Calculated value as 24H25N503: C66,81
, H5,84, N 16.23 Actual value: C67,00
,H6,02,N 16.04 x 1 x 6-methyl-5-[(4-methylbiperazin-1-yl)acetylamino]-4-(3-nitrophenyl)-2
-Phenylpyrimidine.

mp: 159-161℃ IR (Stripe 1-L) j 3330. 32g0.
1690. 1520°1350 cm-1 NMR (CDCl2.8): 2.2-2.84
(8H, m), 2.27 (3H, s), 2.6 (
3H,s), 3.1 (2H,s), 7.33-8
．． 7 (9H, a+), 8.98 (IH, s) MA
SS (M/Z): 446 (M”) Elemental analysis”2
Calculated value as 4H28'603: C64,56,H
5,87,N 18.82 Actual value: C15,03,H
5,85,N 18.84 衷五MED6-Methyl-4-(3-nitrophenyl)-5-[(pyrrolidin-1-yl)acetylaminoco-2-phenylpyrimidine and its hydrochloride.

The physical property values below are for the hydrochloride.

rap: 181°C (decomposition) IR (sudicol); 3560. 3200.
1680. 1655. 1525°1350 cn+
-' NMR (DMSO-d6.δ); 1.67-2.13
(4H, m), 2.63 (3H, s), 3.0-
3.4 (4)1. m), 4.27 (2H,s).

7.4-8.63 (9H, m), 10.5 (IH
, s), 11.18 (IH, s) Elemental analysis "23H23N503・HCI・1/2H20
As, calculated value: C59,67, H5,44, N 1
5.13 Actual measurement value: C59,40,H5,43,N 1
5.19 6-methyl-s-[((3R)-3-hydroxypyrrolidin-1-yl)acetylaminoco-4-(3-nitrophenyl)-2-phenylpyrimidine and its hydrochloride.

The physical property values below are for the hydrochloride.

mp: 190°C (decomposition) IR (sudicol): 1695. 1610.
1520. 1350 am-1HMR (C20,
8) 72.2-4.4 (6H, m), 2.8 <
38. s).

4.66 (2H,s), 4.8-5.3 (1)
1. m), 7.3-8.6 (9H, m) MASS (M/Z) j 416 (M-17) Sad 1
6-Methyl-5-[((2S)-2-hydroxymethylpyrrolidin-1-yl)acetylaminoco-4-(3-
(nitrophenyl)-2-phenylpyrimidine and its hydrochloride.

The physical property values below are for the hydrochloride.

mp: 157-158°C (decomposition) IR (streak 1-l): 33G0. 1695.
1610. 1520°1345 am-' NMR (C20,l; )' 1.93-4.35
(6H1m), 2.77 (3H.

s), 3.7-4.3 (2B, m), 4.08
(2H,s), 4.5-4.8 (IH,m>, 7
．． 27-8.55 (9H, m) MASS (M/Z)
: 415 (M-32>膟輿p 6-methyl-5-C(N,N-dimethylamino)acetylamino]-4-(3-nitrophenyl)-2-phenylpyrimidine.

mp: 142-144°C IR (X di 1-4): 3290. 1690.
1530. 1350 cm-'NMR (CDCl
2.8) 72.32 (6H,s), 2.62 (
3H,s).

3.05 (2H,s), 7.35-8.73 (9
)1. m), 8.8-9.3 (IH, br) MASS (M/Z): 391 (M) Elemental analysis Calculated value as 21H21N503: C64,44
, H5, 41, N 17.89 Actual value: C64, 44
, H5, 19, N 17.91 5-[(adamancun-1-ylamino)acetylaminoco-6-methyl-4-(3-nitrophenyl)-2-
Phenylpyrimidine and hisohydrochloride.

The physical property values below are for the hydrochloride.

mp: 257-259°C (decomposition) IR (streak 3-l)' 1710. 1525.
1350 am-'NMR (DMSO-d6.δ)
'1.3-2.4 (15)1. m), 2.66
(3)1. s), 3.97 (2H, br),
7.4-8.8 (9H, m).

8.9-9.4 (2H, br) MASS: 496 (M”) Elemental analysis: Calculated value as C29H3oN503C1:
C65, 47, H5, 68, N 13.16 Actual value:
C65,25,H5,82,N 13.08X Direct Medicine 6-Methyl~4-(3-nitrophenyl)-5-[(2
, 5-dimethylpyrrolidin-1-yl)acetylaminoco-2-phenylpyrimidine and its hydrochloride.

The physical property values below are for the hydrochloride.

mp: 150'C IR: 1680. 1600.
1520,1345cm-'NMR(DMSO-d6
．． δ)' 1.23 (3H,s), 1.29 (
3H,s).

1.4-2.3 (4H, m), 2.64 (3H
, s), 3.2 to 3.75 (2H, m), 4.2
3 (2H,s), 7.3~8.57 (91,s+
).

9.8 (IH,br), 11.4 (IH,s)
MASS: 445 (M) 5g> and 2-morpholinoethyl chloride hydrochloride (0.28g), 3
-[N-Tertiary butoxycarbonyl-N-(2-morpholinoethyl)aminoco-2-methyl-4-(3-nitrophenyl)-6-yenylpyridine (0.6 g) is obtained.

IR (film): 1670. 1530.
1350 am-1HMR (CDCl2.8):
1.51 (9H, s), 2.0-2.8 (6H.

ei), 2.66 (3H,s), 3.35-3.
8 (6H, m), 7.25-8.4 (108,5
) (2) In the same manner as in Production Example 6, 3-[N-tert-butoxycarbonyl-N-(2-morpholinoethyl)aminoco-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine (0,6 g) Kara, 2-methyl-4-(3
-nitrophenyl)-6-phenyl-3-(2-morpholinoethylamino)pyridine (0.32 g) is obtained.

mp 7163.5-164.5℃ IR (Sugital)' 3350. 1520.
1350 cm-'NMR (CDC13,8)'
2.15-2.55 (6H9m), 2.45-2.
8 (2H, n+), 2.68 (3H, m), 3.
46-3.8 (4H, m).

7.2-8.5 (9H, m), 7.37 (IH,
s) MASS: 418 (M”) Calculated value as “24H26N403” elemental analysis: C6
8,88,H6,26,N 13.39 Actual value: C6
8,52,H6,26,N 13.22 -nitrophenyl)-2-(p-)lyl)pyrimidine is obtained.

NMR (CDCl2.8>' 1.51 (9H, s
), 2.0-2.8 (6H, m).

2.45 (3H,s), 2.67 (3H,s)
, 3.4-3.9 (6H.

m), 7.2-8.8 (88,m) From this compound, 6-methyl-4-(3-nitrophenyl)-2-(ptolyl)-5-(2 -morpholinoethylamino)pyrimidine is obtained.

rap: 139-141°C IR (sugital): 3360. 1520.
1350 am'''INMR (CDC13=8
): 2.2-2.65 (6M1m), 2.43 (
3H,s).

2.68 (3H,s), 2.65-3.0 (2H
, m), 3.5~3.85 (4H, m), 4.2~
4.58 (1M, m), 7.29.8.35 (
4H, ABq, J: 8Hz), 7. ! lr7.85
(IH, m), 8.15-8.55 (2H, m),
8.85-9.05 (IH, m) 5-[N-tert-butoxycarbonyl-N-(2-(1-pyrrolidinyl)ethyl)aminoco-6- Methyl-4-(3-nitrophenyl)-2-(
p-tolyl)pyrimidine is obtained.

NMR (CDCl2,8)' 1-4~1.9 (4
H, m), t, s (9M1m).

2.13-2.6 (4H, m), 2.45 (3
H,s), 2.63 (3H.

s), 7.2-8.8 (8H, m) From this compound, 6-methyl-4-(3-nitrophenyl)-2-(p-tolyl)-5-[ 2-(1-
pyrrolidinyl)ethylaminocopyrimidine is obtained.

NMR (CDCl2.nW): 1.5
-193 (4H, mn, 2.23-3.0(
8H, m), 2.43 (38, s), 2.66
(3M, s), 4.29-4.63 (IH, m>,
7.3.8.35 (4H, ABq, J=8Hz).

7.52-7.88 (IH, m), 8.15-8.
56 (4H, m), 8.86-9.06 (IH,
m) 2-methyl-3-morpholinoacetylamino-4-(3
-nitrophenyl)-6-phenylpyridine (2,8g
) in ethanol (lomQ ) solution of 2
0% hydrogen chloride (4 ml) was added at 10°C under water cooling, and the reaction mixture was stirred at the same temperature for 1 hour. Filter the precipitate and add water (
7,2m11) to give 2-methyl-3-morpholinoacetylamino-4-(3nitrophenyl)-6
-Phenylpyridine dihydrochloride (0.87 g) is obtained.

mpi 187-188°C (decomposition) IR (streak 1-l): 3350. 1700.
1620. 1530°1350 am' NMR (DMSO-d6.δ)' 2.65 (3H
,s), 3.0-3.4(4H,m), 3.6-4
．． 0 (4H, m), 4.16 (2H, s).

7.35-8.45 (9H, m), 7.96 (I
H, s), 11.14 (LH, s) MASS (M/Z) 2 432 (M”) Elemental analysis: C24H24N404-2HC1・2.5H
20, calculated values: C52,37,H5,67,N
10.18°C112,88 Actual value: C52,20, H5,84, N 10.15
CI 12.91 The following compound was obtained in the same manner as in Example 33.

(1) 6-methyl-4-(3-nitrophenyl)-2-
(p-tolyl)-5-(2-morpholinoethylamino)
Virimidine dihydrochloride.

mp: >180℃ (decomposition) IR (suji meal)' 3250. 1610.
1520. 1510. 1360cm-'NMR (
DMSO-d6. δ): 2.35 (3H, s),
2.66 (3H, s).

2.7-3.36 (8H, m), 3.65-4.
0 (4H, m), 7.25°8.18 (4H,
ABq, J=8Hz), 7.66~7.93 (IH
, m).

8.1~8.4 (2H, m>, 8.56~8.7
4 (IH, m) MASS: 433 (M
) (2) 6-methyl-4-(3-nitrophenyl)-
2-(p-)lyl)-5-(2-(1-pyrrolidinyl)
Ethylaminocopyrimidine dihydrochloride.

mp: >190°C (decomposition) IR (KBr): 1610.1525.1500.
1350cm-'NMR (DMSO-ds, 8)'
1.55~2.2 (4M1m), 2.38 (3H
-s), 2.4-3.8 (8H, m), 2.71
(3H,s), 7.32°8.24 (4H,AB
q, J=8Hz), 7.7-8.1 (IH, m).

Claims (1)

[Claims] General formula▲ Numerical formulas, chemical formulas, tables, etc.▼ [In the formula, R^1 is an aryl group substituted with nitro or halo (lower) alkyl, R^2 is lower alkyl or cycloalkyl] an optionally substituted amino group; an N-containing heterocyclic group optionally substituted with lower alkyl, hydroxy or hydroxy (lower) alkyl; or halogen; R^3 is hydrogen or a lower alkyl group; R^4 is aryl group, A is a lower alkylene group, X is N or CH, n means an integer 0 or 1] and salts thereof.