JPS6056980A - Preparation of 7-deazapurine derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an antitumor agent, etc. by the use of inexpensive raw materials in a short manhour in high yield by simple and easy reaction operations and workability by advantageous facilities, by reacting a 7-deazapurine derivative with an amine. CONSTITUTION:A 7-deazapurine derivative shown by the formula I (X is O, or S; R1 is H, alkanoyl, or aroyl; R2 and R3 are alkyl, alkenyl, etc. wherein methylene is in alpha-position, or R2, R3 and neighboring N may form cyclic amino group) is reacted with an amine shown by the formula II (R4 and R5 are H, hydro- carbon residue which may contain substituent group, or R4, R5, and neighboring N may form cyclic amino group) in a solvent such as water, methanol, etc. in the presence of a base (NaOH, triethylamine, etc.), to give the titled compound shown by the formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 7-deazapurine derivatives and bulk thereof.

Among the 7-deazapurine derivatives that can be produced by the method of the present invention, supermodified bases (eg, q base).

PreQ4 base) is a specific tRlfA (tRNATy base)
r.

tRNA""', tRNA"pTh and tRNA"")
It is widely distributed in nature as a component of the first character of the anticodon, and is thought to play an important role in protein synthesis by recognizing genetic information from mRNA. On the other hand, with the recent development of basic biochemical research on tRNA, cancer cells. tR of base? Incorporation into the iA precursor is not complete, and q-deficient tRNAs are universally present.
It has become clear that A returns to normal tRHA, and that this uptake phenomenon by cancer cells is also observed for certain 7-deazapurine derivatives.
↓9 metabolism, voLx7. R time special issue [Cancer '80 J p
, 127-136 (1980)).

Recently, the chemical synthesis of q bases has been reported by Goto et al. (Yl, 0kada et aL, Jour
nal ofBlologioal Chemistry
y, 254, 3067 (1979)] requires a long process and a special reaction, and cannot be said to be completely satisfactory from an industrial perspective.

Therefore, the present inventors conducted various studies in order to establish an advantageous method for the industrial production of 7-deazapurine derivatives, and found that by performing a substitution reaction at the 7-position of the derivative, the objective As a result of further research based on this finding, the present invention was completed.

The present invention is based on (1) the general formula [wherein, represents an aμky group, an alkenyl group or an aralkyl group, respectively, and R2 and 13
X may form a cyclic amino group together with the adjacent nitrogen atom. ] A 7-deazapurine derivative represented by the general formula 1% ( ) [wherein R4 and R5 represent a hydrogen atom or a hydrocarbon residue which may have a substituent, and R4 and R5 are in contact with 9 may form a cyclic amino group together with a nitrogen atom [7]. [In the formula, X, R□, duck and R5 have the same meanings as above. ] and (2) a method for producing a 7-deazapurine derivative represented by the general formula A! which may have an L' group or a substituent! J-/L/ groups are shown respectively. However, when R6 is a hydrogen atom, R6 is not an ary μ group which may have a substituent. ] or a salt thereof.

In the above formula, the alkanoyl μ group represented by R1 is preferably a prime number of 1 to 1B, and j thereof is formyl, acetyl p, propioni/L/.

Butyryl) Isoguchiri μ, Valeri/L/, Isoparelli/
L/, pipaloy IL/, hexanoyl μ, heptanoyl.

Octanoiμ, 2-ethylphexanoiμ, nonanoi〃,
Dekanoi/I/I Undecanoi A/, Tridecanoi/I
/, tetodecanoyl μ, pentadecanoyl, hexadecanoyl μ, hedetadecanoyl μ, octadecanoy μ, and octadecanoy μ, among which those having 41 to 10 carbon atoms are preferably used. For alloys /L/, those with order prime numbers 7 to 12 are preferable, examples of which include Benchii μ, Truoi p, Naphtoi l/, among others, Benchii /
The l/ group and the like are conveniently used.

The groups represented by R2 and R3 may be the same or different members (, As an alkyl group having a methylene group at the 0-position, an alkyl group having about 1 to 10 carbon atoms, such as meflV, ethyl, n- Propy/L/, n-crochet μ, isocropper/L/, pliers μ, isobenchi μ, hexy/L/, isohexyl,
Examples include hedeti P, octiμ, )2μ, deS//l/ groups, and among them, an alkyl group having about 1 to 6 carbon atoms is conveniently used. As a kenyl group, a carbon number of 3 to 138 degrees, for example, A!Jl
v(2-probeni/l/), 2-butenyl, 2-pentenyl! , 2-hexenyl ρ, 4-propy/I/-2-pente=/I/, Vnnamyl, 2-noni/I/-2-gute-
Among these groups, γμ/I/P& having 3 to 9 carbon atoms is preferably used as rJ.These alkyl groups and 1μKenip groups can be
It may have ~3 11 groups, and examples of such substituents include alkyl groups having about 1 to 4 carbon atoms (e.g., methyl, ethyl, propy/L/, isopropy μ, guchi μ, isobuty μ, 5ea-buti" + tert-buti/L/).

A/L/joxy group having 1 to 4 carbon atoms (e.g., metquin,
Ethoxy, propoxy, 18o-deropoxyV, n-gutoxyγ, 180-ethoxy, 5ee-ethoxy.

tart-ethoxy group), a of about 1 to 4 carbon atoms! Kanoi/l' group (e.g., homyl, acetyp, propioni,
n-butyryμ, 1so-butyry/L/group), hydroxyl group,
Nitro groups, halogen atoms (e.g. fluorine, chlorine.

bromine, iodine), μ-hoki V group, cyano group, trifluoro-p
Methyl group, sialkylamino group (e.g. diethylamino,
diethylamino, dipropylamino, diisopropylamino, dibutylamino).

Alkalylamido groups (e.g., formamide, acetamide, propionylamide, butyrylamide).

(imbutyrylamide group), etc.

Aworki/L/Jin whose α-positions represented by R2 and R3 are methylene groups is, for example, ash 1r717-12
Bendi/I/l phenethyl, 3-phenyldep
Examples include piμ, naphthylμ methyl, naphthylethyl/l/ groups, and among them, benzyl group is conveniently used. These abp-kyl groups may also have substituents on the alkylene chain portion other than the α-position and the /i or ary-/l/(7enylv) ring portion, and such substituents include the above-mentioned substituents. Each of the groups exemplified for the alkyl group and the akenyl group is included.

Examples of the cyclic amino group formed by R2 and R3Y- together with the adjacent nitrogen atom include a 5- to 6-membered cyclic amino group, and a second ring heteroatom (e.g., N, 0). Examples of such cyclic amino groups include 1-pyrrolidiniμ, 1-pyrroliel, 1-imidazolidani/1/11-imidazoliniμ, 1-pifzolidiniμ, 1-piwozolinyl, mopholino, piperidino, 1-pivezini p group, etc. given,
The position adjacent to these cyclic amino group element atoms (e1
The substituent group may have a substituent other than the position (position), and examples of such substituents include the groups exemplified above for the Aμ/I/ group and the AμKenyl group.

In the above formula, the hydrocarbon residue in the hydrocarbon residue optionally having a substituent represented by R4 and R5 is
Kip group, αρheniV group, cycloalkyl/I′ group, cycloalkyl/L/ group, aralkyl group.

Examples include ary-/L/(aryl) group. Examples of alkyl groups include alkyl groups having 1 to 18 carbon atoms (e.g., methyl, ethyl, propy/L/, isopropy,
Butiμ, isobutiμ, geQ-butiμ, tert-
Buchi! , bench/L/l isopentyl, hexy/I/l
isohexy)v, hepti〃, octiμ, nonyl, deciρ
, undenyl, dodecyl/L/, tetwodecyl, hexade V/I/, octadecyμ, 1,2-dimethylpropyμ,
l-ethylpropyl, l,2,2-trimethyypropyμ
, 1-butylbutyl, 2-ethylhexyμ group). As an alkenyl lv group, for example, L prime number 1
~12 A〃Kenino 1/8 [Example, Vinyl, Ali/L/(
allyl), ]-]methyμvinyμ, 2-methyp
Vinyl ρ1-octeniμ, l-dece=/L/ group]. As a cycloalkyl/l' group, for example, a cycloafi/kyl group having 3 to 12 carbon atoms (e.g., cycloderopiμ, cycloguchip, cyclobenziμ, cyclohex!/f
i/, cyclohebuti μ.

cycloctyl, adamantyl fi/group).

As a cycloyivkeni/I/ group, for example, the prime number 3
~8 cycloalkeni AI (e.g., cyclobenteni μ, cyclohexentainyl, cyclohepteni μ, cycloocteni
, cyclopentadienyl/L/, cyclohexagenyl,
￥ cloheptadieneμ, V clooctadiene/L' group)
can be given. Examples of the Akki μ group include a C7-C13 group II, benzyμ, α-methypbenzyl, and phenethyl. diphenylmethy)va>. As an aryl group, even if the number of d elements is about 6 to 10, a! l −/i/ group (f'J, phenyl, a-naphthiμ, β-naphthi/l' group).

R4 and R5 may form a ring together with adjacent nitrogen atoms. Such a ring is preferably a 4- to lo-membered ring,
For example, azetidieμ, pyrrolidinyl, pyrrolinyl, pyloriμ, imidazolyρ, piozolyl, imidazoliniμ,
piperidino, mophorino, dihydropyridyl-tetwohydropyridyl, ff1J-methylpiperazini/l/,
N-ethylpiperazinyl, azacycloheptyl, azacyclodecyl μ, isoindo-/I/l indole, indolini μ.

Examples include isoindolinyl, azacyclononyl, azacyclodecyl, and the like.

These hydrocarbon residues represented by R4, R55L)
Alternatively, the ring formed by R4 and R5 together with adjacent crab atoms may have 1 to 3 substituents. Such substituents include, for example, alkyl μ groups having about 1 to 4 carbon atoms (e.g., methyl, ethyl, propyμ, isopropyμ, isobuty/l), 5ea-glutyl, tert-butyA/).
, having a hydroxyl group as a substituent and having an optional number of 1 to 4
alkoxy groups (e.g., methoxy, ethoxy, propoxy, 180-propoxy, n-butoxy, 180-butoxy, pea-ethoxy, tert-butoxy groups), alkoxy groups with about 1 to 4 carbon atoms/L/S ( Examples, formyl, acetyl μ1. propioni μ, n-butyly/L/
, 18o-butyryz+z7. %), γμ group having about 1 to 4 carbon atoms (e.g., formyloxy, acetyloxy, probionino 1/oxy, n-butyryloxy, 1so-butyrino!/oxy group), 6μ boxy group, carbon number About 2 to 4 alkoxycarbonyl groups (eg, methoxycarbonyl).

ethoxycarbon, yl-proboxycarbon, 180-proboxycarbonyl group), halogen atom (eg, fluorine, chlorine, bromine, iodine), hydroxyl group.

Nitro group, cyano group, trifluoromethyl group, amino group, heptanoalkylamino group (e.g. ethylamino, ethylamino, propylamino; isoglopymino, butylamino group), dialkylamino group (e.g. diethylamino,
Diethylamino, dibu, ropylamino, diisopropyμ
amino, diethylamino group), alkanoylamide group (
Examples, formamide, acetamide, propionylamide,
butyrylamide, isobutyrylamide group), etc.

In the above general formulas (m) and (I), the alkoxy in the hydroxyalkoxyalkyl group represented by R6 is preferably one having a scale number of 1 to 4, such as methoxy, ethoxy, n
-Propoxy.

Examples include 180-propoxy, n-butoxy, 160-butoxy, 1540-butoxy, tert-butoxy, etc., and alkyl/l/ preferably has 1 to 6 carbon atoms, such as methyl, ethyl/I /
, n-propy71z, 1so-propy/l/, n-butyl.

Examples include 1so-buty/L', tert-buty, 1-benchi/V, and H-hexVfi/.

The alkyl p in the force μboxyalk/L' group represented by R6 is preferably one having 1 to 6 carbon atoms, such as methyl, ethyl IV, 11-propyl, 18o-propyl, n-butyl, 180- Spot μ,
Examples include tert-butyl, n-pentyl, n-hegishi p group, and the like.

Ari-IV optionally having a substituent represented by R6
The aryl in the (aryl) group has 6 carbon atoms.
It is preferable that the value is about 10 to 10, and examples thereof include Fenniμ, a-Nafti/+7. Examples include β-nafti μ. Substitution methods include, for example, halogen atoms (e.g., fluorine, Q, bromine, iodine), alkyl/L/ groups of about 1 & 1 to 4 iodine (e.g., methyl, ethyl, propyl, isopropyl, butyμ, isobutyl, 5eo- Buchi/l/
, tert-butoxy/I/), carbon vf, 1 to 4 alkoxy groups (e.g., methoxy, ethoxy, propoxy, 1so-propoxy, n-butoxy, 1so-butoxy, 5ea-butoxy, tert-butoxy)
, Narcanoi μ group having about 1 to 4 carbon atoms (e.g., formi p,
acetiμ, fropioni/l/, n-butyryl, 18o-
butyryl), a hydroxyl group, a nitro group, a cyano group, a carboxino group, a trifluoromethyl/l' group, an amino group, and the like.

In the Vrt conversion reaction of the present invention, for example, compound (II) or a salt thereof and compound (l[) or a salt thereof are combined into (II)/
(I[)-1 to 20 (molar ratio) by themselves or with a suitable reaction solvent at a reaction temperature ranging from about oh to the boiling point of the reaction solvent, preferably about 20 to 10 (l). This can be carried out by reacting the compound (') for about 5 days to 5 days.
When salts such as methyl iodide, methanesulfonic acid methyl ester, benzenesulfonic acid methyl ρ ester/L/, p-) to enesulfonic acid meth ester are used, the reaction can proceed under even milder conditions. At this time, the resulting quaternary salt of compound (IF) may be isolated or may be hydrated by a method known per se. Examples of the reaction solvent in the substitution reaction between compound ('H) and compound (Iff) include water, methanol, ethanol, propatool, butano-p, pentano-p, and tetrahydrofuran.

Dioxane, acetonitrile, pyridine, dimethylphoμ
Muamide, dimethylnulfoside, fluorone, or an appropriate mixed solvent thereof is used.

When compound (I) or compound (Ill,) is used in the form of a base, such as a base (eg, sodium hydroxide).

Potassium hydroxide, lithium hydroxide, barium hydroxide, triethylamine, H-methylmorpholine) or salt (
Examples, sodium chloride, potassium chloride.

(μsium chloride, sodium PA, potassium carbonate, sodium hydrogen carbonate) at the optimum pH (usually pH approximately 5 to 13).
), the object CI) can advantageously be produced.

These positions # of the hydrocarbon residues represented by R4, R,
! For example, in the case of a poxy group, a hydroxyl group, an amino group or an apjinoamino group, methods known per se (J, F, W) may be used, if necessary.

McOmie, Protective Groups
in OryanicChemistry, Ple
num Press, London and New
York (1973), ) to substitutions protected or already reserved (e.g., alkanoyloxy groups, aρoxycarboniμ groups, alkanoylamide groups)
Using a starting compound (IN) having the following, a substitution reaction may be performed with the other starting material compound (II) to obtain compound (I), and then a protecting group elimination reaction may be performed.

The protecting group elimination reaction ti is carried out by subjecting the protective group to a commonly performed protecting group elimination reaction. For example, acids (e.g., hydrochloric acid,
Bromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid.

Trifluoroacetic acid, boron trifluoride, boron tribromide, hydrogen bromide-acetic acid)'! : Bamboo base (e.g., lithium hydroxide,
Sodium hydroxide, potassium hydroxide, barium hydroxide,
Potassium carbonate, sodium carbonate.

Aqueous ammonia, methylamine, dimethylamine.

ethylamine, dimethylamine, trimethylamine, triethylamine) and IJ! & (e.g., water, methanol, ethano-/I/l propanol μ, butanol, dioxane, tetrahydrofuran, methi p ether, nitrogen ether, dichloromethane, chloroform, carbon tetrachloride, benzene.

toluene, xylene or a suitable mixed solvent thereof) at a temperature of about -50 to 100°C, preferably -10 to 50°C, for about 30 minutes to 100 hours, preferably about 1 to 2
React for 0 hours, or use an appropriate catalytic reduction catalyst [(
Examples, palladium, platinum.

rhodium, thenium, nickel/L/) and a suitable solvent (eg, water, methanol, ethanol).

Propano-/L/, butano-ρ, dioxane, tetrahydrofone, methyl p-ether μ, ethyl μ-ether, benzene, toluene, xylene, 69 ethyl/l/.

Methyl acetate, acetic acid or an appropriate mixed solvent thereof),
It is carried out by catalytic reduction at a temperature of about lθ to 50° C. for about 1 to 100 hours = according to the method of the invention 11! The prepared 7-deazapurine derivative (I), conventional minute purification means, e.g. concentration,
It can be isolated from the reaction mixture by solvent extraction, chromatography, recrystallization, etc.

Furthermore, when Compound (I) is obtained in the retired form, it may be converted into a pharmaceutically acceptable salt form by a conventional method.

Examples of the salt of compound (1) include mineral acid salts with hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, etc., oxalic acid, tartaric acid,
Acetic acid, trifluoroacetic acid, methane p-phonic acid, benzenesulfonic acid, p-)μenesulfonic acid, camphoruth μ
Honic sea lion organic acid salts, specific methiμ, iodide methiμ,
Quaternary salts with methane μphonic acid methyl ester, benzene/l/indicating acid methyl ester A/, P-toluenesulfonic acid ester, etc. are included.

When compound (I) is obtained in the form of a salt other than a quaternary salt, it can also be in free form if desired. In this case, the salt of compound (1) can be prepared by a commonly used method, for example,
This can be easily carried out by subjecting it to neutralization reaction or anion exchange chromatography.

The compound (I) or its salt obtained in this way is
Growth of L517BY cultured cells in vitro and Meth^ in vivo.

8arooma 180, etc., and therefore has an antitumor effect. Further, even when compound (I) or a salt thereof is intraperitoneally administered to mice at R of 200 strokes/kV, no mortality is observed. Therefore, the compound (
I) It is also used by warm-blooded animals and mammals (e.g. mice, paws, cats, dogs).

rabbit? It can be used as an anti-A tumor agent for the purpose of treating tumors of Y'').

2. When used as an anti-tumor agent, it can be prepared as such or by using pharmaceutically acceptable carriers, excipients, diluents, etc., using commonly used methods, such as powder, granules, 2 tablets, or μ agent, fully open.

It can be administered orally or parenterally in the form of an injection. The dosage varies depending on the target animal, disease, symptoms, type of compound, route of administration, etc., but in the case of oral administration,
I) about 10 to 200 Q/At body weight per day, or about 10 to 100 Q/K for parenteral administration.
y is the weight.

Furthermore, compound (I) or a salt thereof has antiviral and antibacterial effects against various viruses and microorganisms, and has low toxicity as mentioned above, so it is effective against warm-blooded animals and mammals (e.g. mice, rats, cats, dogs, rabbits, humans)
An antiviral agent for the prevention and treatment of viral and bacterial infections.

It can be used as an antibacterial agent and disinfectant.

When compound (I) or a salt thereof is used as a bactericidal agent or disinfectant, for example, compound (I) or a salt thereof may be added to water at a concentration of about 0.5 to 500 q/+w/.

Isotonic glucose solutions, aqueous solutions such as Ringer's solution, or vegetable sources (e.g., cotton seeds, peanuts, corn).

and t) by making a liquid preparation contained in a non-aqueous solution such as fatty oil and applying it to the hands, feet, ears, etc. of a mammal.
It can be used to sterilize and disinfect the administration site.

Compound (I) or a salt thereof may be administered orally in the form of tablets containing excipients such as lactose, acid powder, and talc to prevent viral or bacterial infections in mammals. prevention,
It can be used for treatment.

The dosage in this case is as compound (I) - about 10 to
It is a kite that weighs 4 in 20 ON/.

The compound (I[
) can be produced, for example, by the reaction steps shown below.

(In the above formula, %R1112 and R3 have the same meaning as above.) In step A, compound (IV) and the general formula (in the formula,
R2 and R3 have the same meanings as above.

) in the presence of formaldehydes (Mannich reaction (Organi)).

Reaotrons 1 + 303 (1942) +
AngewandteChemie 6B, 265 (
1956)).

Compound (IV) and compound (■) may be used in the form of salts, such as mineral acid salts with hydrochloric acid, sulfuric acid, nitric acid) phosphoric acid, boric acid, etc., hydrochloric acid, oxalic acid, Examples include organic acid salts of tartaric acid-acetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and camphorsulfate.

As formaldehyde, Manni
oh) Reagents having an action equivalent to that of formal μdehyde during the reaction, such as formalin, formalin, methi2/L/.

Examples include ethioμ, piperidinomethylphthalimide, and hexamethylenetetramine.

The present May-Tschich (Mannich) reaction is carried out for the compound (i
v) and compound (■) at a molar ratio of (■)/(IV)-1 to 50, the mixture itself or the compound (■) may be reacted with a suitable reaction solvent using a suitable reaction solvent.
From C to the boiling point of the reaction solvent, about 20 to 100
The desired compound (
1q of IIHx-o) can be obtained.

In addition, as a reaction solvent, water, methanol, ethanol, propatool, getanol, pentano-μ, tetrahydrofuran, dioxane, aceF nitriμ, pyridine,
dimethy, /I/formamide, dimethyμsphoki Vdo,
Spophons or suitable mixtures thereof are used. Adjust the pH of the reaction solution with an acid (e.g., hydrochloric acid, sulfuric acid, phosphoric acid, boric acid,
Acetic acid, Shu-e, R-tarmic acid, triple oro αt'ti'!
, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, camphoric acid), bases (e.g.
Sodium hydroxide, potassium hydroxide, lithium hydroxide,
Barium hydroxide, ammonia, triethyl amine) or salts (e.g., sodium chloride, chloride, sodium acetate, potassium carbonate 911 sodium hydrogen chloride, ammonium chloride) at an optimum pH (usually pH approximately 2 to 10). ) to W4
When adjusted, the reaction rate and yield can be improved. The acid used in the final acid treatment is, for example, hydrochloric acid.

Sulfuric acid, nitric acid, phosphoric acid, boric acid, acetic acid, oxalic acid.

M stone M,) lifluoroacetic acid, methane μphonic acid.

Examples include benzenesulfonic acid and p-)luens μphonic acid. Compound (U;
-0) from the reaction mixture using conventional purification procedures such as concentration, solvent extraction, recrystallization.

It can be isolated using chromatography as appropriate.

In step B, compound (IV) and chlorinating agent (fIJ
The compound (
■) / Chlorine inhibitor - about 1 to 1/100 (molar ratio), by themselves or using a suitable reaction solvent, about 50 to 150
Reactant (V) can be obtained by reacting n11 for about 30 minutes to 10 minutes at t3.

Solvents used in the above reaction include toehabenzene, toluene, xylene, methylene chloride, chloroform, IQ'' tetrachloride, f+, l = 2-dichloroethane, 1,1.2-)dichloroethane, 1,1,
2.2-Tetrachloroethane. Examples include acetonitrile.

During the above reaction, dimethipuniline, diethylaniline,
Addition of triethyamine, dimethylformamide, etc. allows the reaction to proceed under mild conditions.

In the sulfurization reaction in step C, compound (V) and a sulfurizing agent (e.g., hydrogen sulfide, strium μ phyto, thiourea) are
Compound (V)/sulfurizing agent = about 1 to 20 (molar ratio), using a solvent that does not participate in the reaction, usually at 20 to 150°C.
This can be carried out by reacting for about 30 minutes to 1 day. Reaction solvents include water, alcohols (e.g., methanol/L/, ethanol, propatool, butanol,
5ea-butano-μ, t-butano-μ, ethylene glyco-μ.

Methoxyethanol, ethoxyethanol-A/), ether/! / (dimethyl ether, diethyl ether, tetrahydrofuran, dioxane, monogfime, diglyme), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), a.

Set Nitori! , dimethylformamide, or an appropriate mixed solvent thereof.

Compound (IIiX=8) is a combination of compound (VI) and compound (
(1)) in the presence of formaldehydes (Step D).

Compound (Vl) and compound (■) may be used in the form of a salt, and such salts include those similar to the salts of compound (■) and compound (■) described above.

Formaldehyde and Mannich
ch) A reagent that has an effect equivalent to *lumaldehyde during the reaction, such as formaldehyde.

Paraformaldehyde, formalin, methitool, ethylarμ, piperidinomethyμphthalimide.

Examples include hexamethylenetetramine.

In the reaction of this step, the compound (Vl, 0℃
to the boiling point of the reaction solvent, preferably about 20-100°C
The compound (niX-8
) can be obtained.

In addition, as a reaction solvent, water, methanol/l/, ethanol/L', globanol μ, butanol, pentanol,
Tetrahydrofuran, diyoxane, acetonitrile/l
/, pyridine, dimethymu-formamide, dimethyme-phosphoxide, sulfolane or 1:1: suitable mixtures thereof are used. Adjust the pI of the reaction solution to an acid (e.g., hydrochloric acid, sulfuric acid,
Phosphoric acid, boric acid, touge acid, cilic acid, tartaric acid, trifluoroacetic acid, methanulphonate, benzenesulfone lit,
p-) Luens rhophonic acid, camphorsulfone fermentation),
Bases (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, ammonia, triethylamine) or salts (e.g., sodium chloride, calcium chloride, sodium carbonate, potassium carbonate, sodium bicarbonate, ammonium chloride) The reaction rate and yield can be improved by adjusting the pH to the optimum pH (usually about 2 to 10).Furthermore, as the filtrate acid used in the final acid treatment, for example, Hydrochloric acid, sulfuric acid, nitric acid-phosphoric acid, boric acid, acetic acid, V-hydric acid, tartaric acid, trifluoroacetic acid, methanesulfone, benzenesulfone,
Examples include p-)μenesulfonic acid. The compound (IiX=8) produced by the above method can be isolated from the reaction mixture using conventional separation methods such as concentration, solvent extraction, recrystallization, chromatography, etc. as appropriate.

When compound (II) is obtained in free form in this way, it may be converted into a salt form by a conventional method and used as a raw material compound in the method of the present invention.

Examples of the salt of compound (II) include the same salts as the salts of compound (I) described above.

The compound (m) used in the method of the present invention may be in the form of a salt. Examples of the salt of compound (I[[) include the same salts as the above-mentioned salts of compound (IT) and compound (■).

The method of the present invention uses inexpensive and industrially easily available raw materials,
The number of reaction steps is short, the target product can be obtained with a high reaction yield, the reaction operation is simple and easy, and the equipment is advantageous.Therefore, 7-deazapurine derivatives are industrially advantageous. It is a manufacturing method.

The present invention will be explained in more detail with reference to Reference Examples and Examples below. In addition, the Rf value in the reference example is a thin layer of silica gel (manufactured by Merck & Co., Silicage/
The values are shown by L/HPTLC).

Reference Example 1 Production of 2-n-octanoylaminopyrroloC2,3-d]pyrimidin-4-one: Preparation of 2-aminopyrrolo(2,3-d)pyrimidin-4-one (6,(1)) in pyridine (80 n-octanoyl chloride (22,81F) with stirring on an ice bath.
) was added. After heating the reaction mixture at 85t3 for 30 minutes, the solvent was distilled off under reduced pressure, diluted hydrochloric acid was added to the residue, and the mixture was extracted with chloroform. The extracts were combined and evaporated to dryness,
The resulting residue was dissolved in 8% alcoholic ammonia (5011
When heated to temperature I/) and left at temperature m, the target object (8, 11)
precipitated as crystals.

NMR (DMSO-d6/D20,60MH2) δ 0
．． 87 (it, 3K), 1.30 (s, 10H), 2.
47 (t, 2m), 6.47 (a, IH), 6.80 (
d, IB).

IR (KBr) ν 1640cm ”Reference example 2 5-N,N-dibenzylaminomethy/l/-2-n-octanoylaminopyrroloC2,3-1pyrimidine-4-
2-n-octanoylaminopyrrolo(2,3-d)pyrimidin-4-one (1,e7g) obtained in Reference Example 1,
dibenzylamine (3,69) and 30% homolin (
1.72 g) was dissolved and suspended in 80% aqueous RIII4 acid (60 y/) and reacted at 60° C. for 20 hours, and then the solvent and excess reagents were distilled off under reduced pressure. The resulting residue was mixed with methanol/I/
(60 r/) and N-hydrochloric acid (60+wl) were added and dissolved, and after treatment at 80°C for 1 hour, ammoniacal potassium was obtained and concentrated to dryness. Water was added to the residue, extracted with chloroform, and the extracts were combined and evaporated to obtain a crude product.

This product was recrystallized from diethyl ether to obtain the pure target product (2,431F).

NMR(CD(!13/D20/DM80-d6
, 601JH2) δ0.90(It, 3B), 1.30
(bs, l0H), 2.47 (t, 2H), 3.80 (
s, 4H), 4.00(s, 2T(), 6.93(8,
IH), 7.33 (BS, 10! Ri.

I R (KBr) 1645, 1615cm 'Rt
-0,17 (extended Ff1m medium, chloroform:methanol sphere 7:1).

Reference Example 3 Preparation of 2-amino-5-M, N-dibenziμaminomethyρpyrroloC2,3-(1)pyrimidin-4-one: 5-M, II-dibenzene obtained in flJ, 2 Benzylaminomethyl l-2-n-octanoylaminopyrrolo (
2,3-d) Pyrimidin-4-one (971/l'!
7) in methanol/I//tetrahydrofuran (1:1.
60ml), 5N-KOH (2,5*t) was added thereto, and the mixture was left stirring at room temperature for 60 hours. The solvent was distilled off under reduced pressure, and the resulting residual carbon was subjected to column chromatography using silica gel and ion exchange resin. Then, the target object (601 Misaki) was obtained.

NMR(CDC13/DMSO(16, 60MHz
) δ 3.63 (R, 4H), 3.83 (F3.2H
), 5.87 (bs, 2H).

6.60 (bs, IH), 7.20 (m, 10H).

IR (KBr) 1665, 1625, 1600
c+++-1Rf-0,35 (developing solvent, chloroform:methanol-/L/-4:1).

Reference Example: Production of 5-H,N-dimethylaminomethyl l-2-n-octanoylaminopyrrolo(2,3-d)pyrimidin-4-one: In the same manner as Reference Example λ, 2-octanoyl The desired product was obtained from aminopyrroloC2,3-d) pyrimidin-4-one and dimethylamine.

Rr-o, x3 (developing solvent, chloroform: 58% WF
I3/ethanol = 4:1) Reference example (1) 2-amino-4-chloropyrrolo(2,:3-a)
Production of pyrimidine: 2-AminopyrroloC2,3-d]pyrimidin-4-one (459) was suspended in phosphorus oxychloride (150F7/) and reacted with stirring at 110°C for 3 hours. Excess phosphorus oxychloride was distilled off under reduced pressure, and 9-(Q In was mixed with ice water (600 Mt
) and completely dissolved, then cool +c'! ! The pH was adjusted to 9 with half a cup of aqueous ammonia. The resulting precipitate was separated, washed with water, and then recrystallized from hot methanol (4J) to obtain the desired product (34,69).NM!
t(DMSOd6.60MIIz): δ 6.23(
d, IH), 6.40 (bs, 3H), 7.05 (d,
, IH) IR (KBr): y 3420, 3330.
3170°2970,2820.1680.1640.
1620.1570cm "UV λ':j,:'i": 232.258,31
9 nm (2) P of 4-chloro-2-n-octanoylaminopyrrolo(2,3-L)pyrimidine! Construction: Above (1)
2-amino-4-tritetrapyrroloC2,3-(
1) Convert pyrimidine (16,99) to dry pyridine (200
rt) to lI! ! After the mixture became cloudy and dissolved, n-octanoyl tetralide (21,29) was added under stirring while cooling with water, and the mixture was returned to room temperature and reacted for 1 hour. 9.9% ethanol/
After adding l'-type aphanmonia/ma) and further stirring at room temperature for 2 hours, the solvent was distilled off under reduced pressure. Add water to the residue (
After stirring at room temperature for 1 hour, the resulting insoluble matter was removed, washed with 9 parts of sodium bicarbonate solution and then with water, and dried to give yellow powder crystals (23, 39). This one is 1.2
- When recrystallized from dimethoxyethane, the desired product (20,9
1F) was obtained.

MMR(CDCl3/DMSO(16,60MH
z) ” δ 0.87 (t, 3H), 1.30 (b
e, 10H), 2.5o(t, 2H).

6.43 (d, 11), 7.30 (d, IH), 10.
37 (R, IH), 12. ．． 10 (bs, IH) IR (KBr): ν 3430.3220,2920
゜1645.1610.1585,1375c+n-”
Reference Example 6 Production of 2-n-octanoylaminopyrrolo(2,3-d)pyrimidine-4-thousandone: The 4-chloro-2-n-octanoylaminopyrrolo(2,3-d)pyrimidine obtained up to Reference Example -d) Pyrimidine (xc+, c+
9) and thiourea (389) in 2-methoxyethanol/
1/(240 de/), and the mixture was stirred and reacted at 100C for 25 hours. After distilling off the solvent under reduced pressure, 1.
8% + 7) i Sodium water (300 F/liter) was added and stirred well at room temperature. The resulting precipitate was taken in 1 volume and recrystallized from ethanol to obtain 1 product (15.7 g).

NMR(CI)C13/DMSO-d6.60hoz
): δ0.87 (t, 3H), 133 (bs, l0H)
, 1.47 (t, 211).

6.63 (q, IH), 6.90 (q, IH), 11.
27 (b.s.

21), 13.20 (be, 11) I R (KBr): v 3220, 1680.163
5゜1600.1310cm' Reference Example Z 5-N,N-dipendiμaminomethy/L'-2-octanoyμaminopyrrolo(2,3-'d)pyrimidine-4
-Production of thione: Reference example 6. 2-octanoy obtained with! Aminopyrrolo (
2,3-d) Pyrimidine-4-thione (3,59) and dipendiμamine (9,59) were mixed in water/lh# (1:
4, 120*t) and 35% formalin (4, 120*t).
24F) and reacted at 60t3 for 14 hours. The solvent was distilled off under reduced pressure, water (30srt) was added and distilled off again, and the residue contained B-acl (64 stomachs/l) and methanol/l.
/ (100 l) was added and stirred at 60'C for 1.5 hours. Most of the methanol was distilled off under reduced pressure, the aqueous layer was converted into ammonia alkali, and acidic sodium sulfite (5,71F) was added.
was added, and then extracted with chloroform. The 111 km of chloroform layer was dried to obtain the crude target product (3,959). This product can be used directly in the next reaction without further MW.

NMR(CDC13,6()MFIg): δ 0.
83(t, 3B).

L20(bll, 101)C2,70(t, 21)-4
,07(be.

4H), 4.40 (bs, 21), 7.20 (m, 11
H) Reference example and production of 5-N,N-diaryμ aminomethyl l-2-n-octanoyμ aminopyrrolo(2,3-d)pyrimidin-4-one: In the same manner as Reference example λ, 2-octa Noylaminopyrroa(2,3-d)pyrimidin-4-one and diallylamine were obtained.

Rr -0,12 (exttu[, chloroform:methanol-/L' zero 7:1) Reference example 2-octanoylamino 15-(1-pyridine=Iv)
Production of methylpyrrolo(2,3-d)pyrimidin-4-one: In the same manner as in Reference Example λ, the desired product was prepared from 2-octanoylaminopyrrolo(2,3-tl)t'rimidin-4-one and pyrrolidine. Obtained.

n t = 0.24 (developing solvent, chloroform di6
．． 5% NH3/ethanol/l/-4:1) Reference flj10゜(1) Production of 2-bensylaminopyrroloC2,3-(D-pyrimidin-4-one: In the same manner as in the previous example, 2 -aminopyrrolo[2,3-
d) The desired product was obtained from pyrimidin-4-one and penceyl chloride.

Engineering R (KBr) 1635cm-1 (2) 5-N,yt-dibenzylaminomethy1v-2-
Bency μ aminopyrrolo (2,3-(1)pyrimidine-
Production of 4-one: 2-pencil y aminobi p
Mouth C2,3-d) Pyrimidin-4-one and benzy/l/
The desired product was obtained from the amine.

n t -0,35 (ex. F11m, chloroform:methano-1v-4: 1).

Example/2-amino-5-C (3B+41+58) 4.5-s
7-Hydroxycyclobento-1-en-3-y-aminomethy-]pyro(2,3-a)pyrimidin-4-one (q base) 1! ! -, reed 1: 2- obtained in Reference Example 3
Amino-5-11,N-dibenzylaminomethylpyrroloC2,3-d]pyrimidin-4-one (359'i7)
and (3S,4R,58)-4,5-0-isopropylidene-4°5-dihydroxycyclobent-1-ene-3
-ylamine (310r4) was dissolved in methanol/I/ and reacted with 6(l) for 24 hours in a sealed tube.
After adding N-hydrochloric acid and heating again at 70°C for 1 hour, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography using cellulose powder and ion exchange resin to obtain the desired product (65). Ta. Physical and chemical data line 5%vt /
Measured after conversion to hydrochloride with methanolic hydrochloric acid.

NMR (D20160MHz) δ 4.2 R-
4,60 (m, 2H), 4.50 (b8.2H),
6.13 (da, 11), 6.35 (m, IH), 7.
12 (1!, IH).

fll, p, 230-235 (decomp, )I
R (KBr) 3300.3100, 2950.277
0゜1675.1610cw+-" Example 2-Amino-5-aminomethylpyrrolo[2,3-d) Production of pyrimidin-4-one (Preq1 base): Reference 2-amino- obtained in t13. 5-N,H-dibenzylaminomethylpyrrolo(2,3-a)pyrimidin-4-one (320~) with 5% ammonia (tsm/) and ammonia water (15-) The solution was dissolved in a mixed solution of 45°C for 17 hours in a sealed tube.Then, the solvent was distilled off under reduced pressure and the 'f3 residue was purified by column chromatography using cellulose powder and ion exchange resin to obtain the desired product (120 ~)was gotten.

Physical and chemical data were measured after converting to the hydrochloride with methanolic hydrochloric acid.

NMR(eD301)/D20,60MH2)δ
4.32 (8,21), 7.12 (8,111) IR (KBr) ν 3100.1670.1605.1
050cm"-" IILP-220~225b (decamp, )
υV λmax 217, 260.281 nm Example 3 Production of 2-amino-5-aminomethymu pyrrolo[2,3-a) pyrimidin-4-one (PreQ1 filler thread); 5-N obtained in Reference Example disease , N-dimethylaminomethylμ
m2-n-octanoylaminopyrrolo[2,3-(1)
Pyrimidin-4-one (157F!/) in alcohol/L
/(25r/) and 25℃M ammonia water (8*υ) and reacted by heating at 75℃ for 15 hours in a sealed tube.From now on, a small amount of insoluble matter will be removed and the furnace liquid will be concentrated. After drying, a crude product was obtained.
The desired product (56Ff) was obtained by applying 1Rrs using column chromatography (Rohm & Hahne, Inc., USA).

The physical and chemical data were completely consistent with those obtained in Example λ.

Practical hilx example g 2-amino-5-((as, 4R, 5B)-4,
11 of 5-dihydroxycyclobent-1-en-3-ylaminomethyl)pyrrolo(2,3-d)pyrimidine-4-thione (6-thioQ base)! ! ! Preparation: β Crude 5-N,N-dibenzylaminomethyto-2-octanoylaminopyrrolo(2,3-d)pyrimidine-4 obtained in Example Z
-thione (3,ag) and (38,4R,5S)-4,5
-0-isopropylidene-4,5-dihydroxycyclobent-1-en-3-ylamine (1°55 g) was dissolved in ethanol/I/ (150 wt), and 751
The reaction was carried out at E for 200 hours. From now on, tetrahydrofufun (75*/) and 40! v Potassium hydroxide aqueous solution (
i1 Ashi υ was added and left at 5C for 3 days. 3 for this thing
A 0% aqueous ammonium chloride solution (IIFIt) was added, concentrated to dryness, and the residue was purified by silica gel column chromatography to 7L! %MH3-containing ethanol/1//chloroform (1:4) was used as the effluent solvent to separate and purify 2-amino-5-((38,4R,58)-4,5-0-isopropylidene-4,5-dihydroxy cyclobent-1-en-3-ylaminomethyl)pyrroloC2,3-d) pyrimidine-4-1,000 was obtained. The entire amount of this product was dissolved in methanol (100y/) and 2N-HCI (16P/)K, and after being left at room temperature overnight, the solvent was removed. After drying for 1 Tht, the target dihydrochloride (1,071F) was obtained.

MMR (D20, 60MHz): δ 4.20~
4.60 (m, 2H), 4.47 (ba, 2H)
, 6.13 (m, 2), γo3 (8, lH) Engineering R (KBr): v 2930 , 2780 , 16
911.

1590.1200 cm-1 Example: Production of 2-amino-5-aminomethylpyrrolo[2,3-d)pyrimidine-4-thione (6-thiAPreQ1 base): ? Crude 5-N obtained in Example 1, ↑l-dibenzylaminomethy/l/-2-octanoylaminopyrrolo[2,3-
d) Pyrimidine-4-thione (1-, Og) in ethanol
/' (50yl) *Tetra upper 1゛lofuran (30
Dissolved in a mixture of Fυ and concentrated ammonia water (20*/),
The reaction was carried out in a sealed tube at 80°C for 1.5 hours.

After distilling off the solvent under reduced pressure, the residue was washed with diethyl ether, and the remaining 18 minutes was washed with concentrated ammonia-saturated n-butano-
If μ is used as the effluent solvent and 1F of Shichibuyo is prepared, the target product (215
fff) was obtained. It was measured after converting it to the hydrochloride with methanolic hydrochloric acid.

PIMR (D20/CD30D, 60MHz)
: δ 4.13 (bs, 21), 6.90 (bs, I
H) IR (KBr) Niji 2920, 1690, 1595° 1195c prefecture-1 4th example.

Production of 2-amino-5-carboxymethylaminomethylpyrrolo(2,3-(1)pyrimidin-4-one: Crude 5-H,N-dibenzylaminomethyl-2-octanoyl obtained in Reference Example 2) Aminopyrrolo[2,3-d)pyrimidin-4-one (7,59) and glycine t-butyl ester Iv (9,84q) to t-ethano-#C225n
The suspension was suspended in a mixture of 1) and tetrahydrofuran (150*/), and reacted at 70°C with stirring for 24 hours. The reaction solvent was distilled off under reduced pressure, and the remaining In was solidified by adding diethyl ether to obtain a pale colored powder (5,59). this thing 8
．． 9% Ammoniacal x-fN1yv Co-Ivc 900
*/) to 197i:! After stirring at room temperature for 6 days and distilling off the solvent, purification by silica gel column chromatography yielded 2-amino-5-t-buto-V-bonylmethylaminopyrrolo(2,3-d)pyrimidin-4-one. (2
, 83g) was obtained. This (i, 6zl with methanol/L/(55 resistant) and tetrahydrofufun (55rl)
Suspend in a mixture of
) and then stirred at room temperature for 17 hours.
The pH was adjusted to 3.5 with 1N hydrochloric acid under ice cooling, and the desired product (1,319) was obtained as crystals.

NMR (D20+DC1, 60MHz): δ 4
．． 1B(a, 2H), 4. po(s, zu), Lz3(
s, tn) Engineering R (KBr) Niji 3450.3120,
1680°1655.1630,1590,1410.
13B0.1340°1320.835cm-” Example Z 2-amino-5-(N-(2,3-dihydroxyprohy/I/)aminomethyμ)pyrrolo(2,3-d]pyrimidin-4-one( Preparation of 2-carboxylic acid #&)'' Obtained by 5-II, ?f-dibendiμaminomethyl/l
/-2-octanoylaminopyrrolo[2,3-d)pyrimidin-4-one (7,289) and 3-amino-1,2
-Propanedio-/L/(6,83g) to ethanol-/L
/(2251+1/) and tetrahydrofuran (150*
i? ) and subjected to a two-press reaction at 70°C for 2 days. The reaction solution was concentrated to dryness, and the residue was mixed with methanol/L//tethohydrofone/diethyl ether/L/(50 solution t150
When solidified by adding a lamp (l/250 gt), a white powder (3,
54 g) was obtained. Add the remaining pieces of this to methanol/L/(
100xf? ) and tetrahydrofuran (100*e), and 25 m W/W ammonia water (20
After adding 0 lights/), it was left at room temperature for - night. The solvent was distilled off, 0.5N hydrochloric acid (50*/) was added to the residue, and the mixture was concentrated to dryness again. The residue was recrystallized from methanol-N/diethyl ether to obtain the desired product (4.3 tg).

HMR (D20, 60MHz) δ: 3.2B(
bd, 2H).

3.68 (bd, 2H), 4.43 (bs, 2H), 5
．． 30 (m.

IH), 7.12 (M, IH) Example 2-amino-5-(N-2-(2-hydroxyethoxy)ethylaminomethyl)pyrrolo[2,3-d)pyrimidin-4-one (2 Subsako of hydrochloric acid H4): In the same manner as in Example 7, 5-IT, IK-dibendiμ aminomethyl fi/
The desired product (4,83 g) was obtained from -2-octanoylaminopyrrolo(2,3-d)pyrimidine-4-,4-(7,289) and 2-(2-aminoethoxy)ethanol.

NMR (D20.60MHz) δ: -3,23(
bt, 3■0°3.50-3.77 (tn, 6H), 4
．． 32(e, 2H), 6.83(ba, iH) Example Z Production of 5-allylaminomethy/L'-2-octanoylaminopyrrolo(2,3-d)pyrimidin-4-one: Reference example 5-N,H-dibenzylaminomethy A/-2-octanoylaminopyrrolo [2,3-cl] obtained in
Pyrimidin-4-one (7,2 sq) and allylamine (4,2 gg) were dissolved in a mixture of ethanol/l/(225 pl/liter) and tetrahydrofuran (150 al),
The reaction was carried out for 3 days at 6 liters under nitrogen substitution.

When the reaction solution was cooled to 01+, the desired product (3.43 g) was obtained as a white precipitate.

IR(KBr)v 3230,2930.2850,1
635°1590.1540,1430,1250,1
180,920°780c River-1 Collection) m plate side 70 Production of 5-phenylaminomethyl-2-octanoylaminopyrrolo(2,3-d)pyrimidin-4-one: 5-obtained in Reference Example N, N-dibenzylaminomethy/l'-2-octanoylaminopyrrolo[2,3.
-d] Pyrimidin-4-one (7, iq) and aniline (14 g) were added to a 24.5 liter bath in a solvent (40 (ly/)) with a solubility ratio of ethanol to tetrahydrofuran of 7:1. The mixture was stirred for an hour. The desired product (5 g) was obtained by cooling and collecting the precipitated crystals in a furnace.

IR(KBr)v 3400.3220,2925.1
63511-1 Example/1 5-(p-chlorophenylv)aminomethyfi/-2-
Octanoylaminopyrrolo(2,3-d)pyrimidine-
Preparation of 4-one: 5-N,N-dibendiμaminomethy/L'-2-octanoylaminopyrrolo(2,
3-d) The target product is damaged by pyrimidin-4-one and p-chloroaniline.

IR (KBr) 3410, 3220, 2925, 1
635cat” Example/2 5-(tn-chloropheni/l/)amitunotyl-2-
octanoylaminopyrroloC2,3-d)pyrimidine-
Production of 4-one: In the same manner as in Example 10, 5-M,N-dibenzylaminomethy/l/-2-octanoyl p-aminopyrrolo[2,
3-d] The desired product was obtained from pyrimidin-4-one and m-chloropaniline.

IR(KBr)y 3400,3220.2925.1
635ffl-1 Example/3゜Production of 2-amino-5-(2-hydroxyphenylaminomethy/!/)pyrrolo(:2.3-4)pyrimidin-4-one: Reference example. 5-N,H-dibendiμaminomethy/L/-2-octanoylaminopyrrolo[2,3-d
) Pyrimidin-4-one (7,49) and ordoaminopheno-/+7 (16,3 g) were mixed in a solvent (400*i?
) The mixture was stirred for 65 hours at a bath temperature of 80°C.

The solvent was distilled off under reduced pressure and ethyl acetate/l/1000 was added to the IA residue.
1 Wf was added and stirred well, and the insoluble matter was removed by furnace. This was added to a solvent (200*i?) with a volume ratio of methanol to tethohydrofluorone of 1:1 at 25f% w/w aymo=7 water (
The mixture was stirred at room temperature for 40 hours in a solution to which 150*/) was added. The solvent was distilled off under reduced pressure, and the remaining L was purified by silica gel μ column chromatography to obtain the desired product (2,tg).

NMR(CF3COOH-D20,60M11z)
δ: 437 (be, 2H), 6.37-7.10 (m,
511)XR(KBr)y 3460.3160.16
75.1655°1610cm-1 Example/2-amino-5-benzylaminomethylpyrrolo(2,3
-d) To produce pyrimidin-4-one 5-N,N-dibenzylaminomethy/L'-
The desired product was obtained from 2-octanoylaminopyrrolo(2,3-a)pyrimidin-4-one and benziμ amine.

NMR(Duso-a6,6ouuz)'δ: 4
．． 20 (be, 4H), 6.70 (bs, 21),
6.73 (BS, IH), 7.40 (BA, 5H), 8
．． 43 (ba, 2H), 11.33 (bs, IH) Engineering R (KBr) v 3130.16G0, 1645.1
605゜1395cm ” Example 15 !l!II formation of 5-(2-adamantylaminomethy/I/)-2-aminopyrrolo(2,3-d)pyrimidin-4-one (disulfate): Reference example 5-H,N-'dibenzylamitume flV-2-octanoy~aminopyrrolo[2,3-d] obtained in
Pyrimidin-4-one (7,49), 2-adamantanamine mr & salt (10,5y), 28% w/w
Sodium methifutmethano-/L/solution (5,8f)
and potassium acetate (2,zsp) in ethanol-/I/(
500ff? ) The mixture was stirred for 40 hours at a bath temperature of 8 (l).

The solvent was distilled off under reduced pressure, and a solvent with a solubility ratio of diethyl ether μ to tetrahydrofuran of 1:1 (40OFF/) was added to the residue.
was added, and the insoluble matter was removed in a furnace and washed with water (150 ml). This was dissolved in a mixture of 2N hydrochloric acid (aO*/) and 2N hydrochloric acid (aO*/), and the newly precipitated crystals were collected to obtain the desired product (3,51F).

NMR(CF3COOH-D20.60MHz)δ
:2.00-2.23(bm, 14H), 3.60(b
s, l11), 4.43(bsT2H) -7,0
7(s, IH) Engineering R(KBr)y 3200,29
25.1705.1690m-1 Example/4゜2-amino-5-cyclopentylaminomethylpyrrolo(
2,3-d) Production of pyrimidin-4-one (dihydrochloride): 5-N,11-dibenzylaminomethy/l'-2-octanoyμ aminopyrrolo[2,3- d
) Pyrimidin-4-one (2,9+F) and cyclopentylamine (5,19) were dissolved in ethanol/lJJ tetrahydrofuran in a ratio of 1:1.

(200 L) The bath was kept at a bath temperature of 90 C for 22 hours (°τ V).

The solvent was distilled off under reduced pressure, and the residue was purified by rJl'% (120 t
It was dissolved in 5NKOH (8,4*/) and left to stand for 6 days. Ammonium chloride (
2,49) was added and distilled off, and tetrahydrofuran was added to the residue, stirred well, and the insoluble matter was taken out in a furnace.The mixture was mixed with water (100*/ml), stirred, and taken out again in the furnace. Add this to 1N hydrochloric acid (20
v/) and dried under reduced pressure to obtain the target product (1.6 g)
was gotten.

NMR<D201GOMH2)δ: 1.67~2
．． 40 (m, 8H), 3.67 (m, IF (), 4.3
0 (s, 2H), 7.00 (s, 1) 1) IR (KBr) sr 3200.3100~2400°1680.1600cm ” ヲ3 Examples/Z 2-amino-5-n-hexy μ aminomethyl μ Pirolo (2
, 3-4) Production of pyrimidin-4-one (dihydrochloride)? 0
: In the same manner as in Example/1, 5-N,N-dipendi p aminomethy/L/-2-octanoyl p aminopyrrolo(2,
3-d) The desired product was obtained from pyrimidin-4-one and n-hexylamine.

NMR(D20,60MIIz)δ: 0.87(
t, 3H).

1.07-2.03 (bm, 8H), 3.12 (t, 2
) I), 4.32 (e, 2H), γ00 (Q, IH) I R (KBr) v 3300 , 2960 , 29
30, 2770°2720.2430.1700,1
675.1620.1580゜1440.1380.1
245.1100.1050.810cm”-1 Example/2-amino-5-isoamylaminomethylpyro0[:2
．． 3-d,]] Production of pyrimidine y-4-,4-one 2ja acid salt): In the same manner as in Example/E, 5-N, If-dibendi
aminomethy/L'-2-octanoyl p aminobio a
(293-d) The desired product was obtained from pyrimidin-4-one and isoamylamine.

NMR (D20, 60MHz) δ: 0.96 (d
, 3M).

1.00 (d, 3H), 1.20-2.16 (m, 31
1), 2.93-3.18 (tn, 2111), 4.3
6 (e, 2H), 7.06 (8, 1II) Engineering R (KBr
) v 32B0, 318 (1, 2970, 272!
, 1゜1695.1680.1620.1ff80,1
450,1420゜13B0,1240.1130,1
100,1050.820cm' Example/9 2-amino-5-piberidinonotylvirolo(2,3-d
) Production of pyrimidin-4-one (dihydrochloride): 5-N,N-dibenzylaminomethy/I/-2-octanoyρaminopyro rJ(
213-d) The desired product was obtained from pyrimidin-4-one and piperidine.

tJ M'< (L D 30 D/D 20.60
MHZ) δ: 1.80 (m.

6H), 2.81) to 3.67 (fl+, 4H), 4.
30 (q, 2H).

7, (+2(s, IH) Engineering R(KBr)v 3:370,3175-2500.
1 (i80°, "1 Example 20 2-7 Minnow 5-C (38,4R,5B)-4,5-
Preparation of dihydroxycyclobent-1-en-3-y-aminomethymu]pyrrolo(2,3-d)pyrimidin-4-one (QjJ4 group): In the same manner as in Example/Reference Example The obtained 5-H,N-diallylaminomethy/l/-2-n-octanoylaminopyrrolo(2,3-
a) Pyrimidin-4-one and (3S,4R,58)-4
,5-0-isopropylidene-4,5-dihydroxyclobent-1-en-3-ylamine i uJ El
I got a deal.

The physical and chemical data were completely consistent with those obtained in Example 1.

Example 2/ Production of 2-amino-5-aminomethylpyrrolo[2,3-d)pyrimidin-4-one (PreqIJ-m group): In the same manner as in Example 3, the reference (obtained with Al Ta2-
The desired product was obtained from octanoylamino-5-(1-pyrrolidini/I/)methylpyrrolo(2,3-d)pyrimidin-4-one and aqueous ammonia.

The physical and chemical data were completely consistent with those obtained in the dormitory experiment.

Example 2 Production of 2-amino-5-aminomethylpyrrolo(2,3-d]pyrimidin-4-one (Pre Qt kl, Samurai): In the same manner as in Example 3, iL in Reference Example 10 ) was given 5
-N,H-dibenzylaminomethy/L'-2-benzoylaminopyrrolo(2,3-d)pyrimidin-4-one and aqueous ammonia were obtained.

The physical and chemical data were completely consistent with those obtained in Example 2.

Claims (2)

[Claims] (1) General formula [wherein,
3 represents an alkyl group having a methylene group at the 0-position, a μ-μ group, or a μ-μ group, respectively, and R2 and R3t may form a cyclic amino group together with the adjacent nitrogen atom. A 7-deazapurine derivative represented by the general formula It may form a group. ] wherein X, R1, R4 and R5 have the same meanings as above. ] A method for producing a 7-deazapurine derivative. (2) General formula [wherein R'1 has a hydrogen atom or an alkanoyl/l/co-to R6 hydroxyaμkoxyaμyl, a carboxyalkylμ group, an adamantylμ group, or a substituent power] Each shows a suitable aryl group. However, when R'1 is a hydrogen atom, R6 is an aryl group which may have a substituent. ] A deazapurine derivative or a salt thereof.