JPH01319496A - Uracil derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R1 is H, OH or formula II). EXAMPLE:1-(2-Deoxy-3,5-O-isopropylidene-beta-D-xylofuranosyl)-5-ethylu racil. USE:An intermediate of a remedy for AIDS. PREPARATION:Tetraacetyl xylofuranose of formula III (Ac is acetyl) is, e.g., reacted with 5-ethylbis(trimethylsilyl)uracil of formula IV (Me is methyl) in the presence of anhydrous tin chloride in an organic solvent to prepare 1-(2,3,5-tri-O-acetyl xylofuranosyl)-5-ethyluracil of formula V. The compound of the formula V is then hydrolyzed in the presence of a base to synthesize 1-beta-D-xylofuranosyl-5-ethyluracil of formula VI and this resultant compound is reacted with acetone in the presence of an acid to provide a compound with OH as the group R1 of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to 1-(
2-deoxy-3-azido-β-D-ribofuranosyl)
The present invention relates to a novel compound not described in conventional literature useful as a synthetic intermediate for -5-ethyluracil (hereinafter referred to as C8-85) and a novel method for producing the compound.

More specifically, the present invention provides a novel compound of the following formula (1) which is useful as an intermediate in the synthesis of C5-85 represented by the following formula (A) α which is used as a therapeutic agent for AIDS. R1 relates to a hydrogen atom, a hydroxyl group, or a uracil derivative represented by.

(Prior art) Conventionally, as a method for synthesizing C5-85 of the above formula (A), for example, 5-ethyluracil is used as a raw material, and the compound is reacted with acetic anhydride to produce N-1-acetyl-5-ethyluracil. was synthesized and the compound was treated with mercuric acetate to obtain N-
A monomercury salt of 1-acetyl-5-ethyluracil is prepared, and then the mercury salt is reacted with 3,5-di0-(p-chlorobenzoyl)-2-deoxy-α,β-D-ribofuranosyl chloride. to form 1-[3,5-di-0-(p-chlorobenzoyl)-2-deoxy-α,β-D-ribofuranosyl]-6-ethyluracil, which was then subjected to basic column chromatography. to form 2-deoxy-α,β-D-ribofuranosyl-5-ethyluracil, and the uracil is further reacted with benzoyl chloride to form 5-0-benzoyl-5-ethyl-2-deoxyuridine. A method is known in which the compound of the linear formula (A) is obtained by treating the uridine with mesyl chloride, reacting it with sodium azide, and then hydrolyzing it with acetic acid (J, Med, Che.
m,] 969, 12, 533-534 and J, Med.
, Chem, 19B7°30.1270-1278).

However, the above method has the disadvantages of long reaction steps and low yield, and cannot be called a practical method. Therefore, the formula (A
) is strongly desired.

(Problems to be Solved by the Invention) The object of the present invention is to solve the above-mentioned formula (
When synthesizing the compound of formula (A), unlike the above conventional proposals, the novel intermediate of the above formula (1) and its useful for synthesizing the compound of the above formula (A) in a short production process and in good yield. The purpose is to provide a manufacturing method.

(Means for Solving the i! Problem) The present inventors have conducted intensive research on the synthesis of C5-85 in order to eliminate the disadvantages and shortcomings of the above-mentioned conventional methods. As a result, tetraacetyl xylofuranose, which can be easily synthesized from xylose that is inexpensive and easily available on the market, or can be prepared manually [formula (5) below], which can be synthesized from the formula (1) of the present invention, has not been found in any prior literature. The present invention has been completed based on the discovery that the compound of formula (A) can be advantageously synthesized with good purity and yield by using a compound of formula (A) with industrially simple operations.

Therefore, according to the present invention, (a) tetraacetyl xylofuranose represented by the following formula (5), where Ac represents an acetyl group (the same applies hereinafter), for example, in the presence of anhydrous tin chloride. is reacted with 6-ethylbis(trimethylsilyl)uracil represented by the following formula (4) in an organic solvent, where Me represents a methyl group (the same applies hereinafter), to form a compound of the following formula (1 represented by 3). -(2,3,5-tri〇-acetylxylofuranosyl)-5-ethyluracil is formed, and (b) the compound of formula (3) is hydrolyzed in the presence of a base to form the following formula (2). By synthesizing l-β-D-xylofuranosyl-5-ethyluracil represented by the formula (C) and reacting the compound of formula (2) with acetone in the presence of an acid, the compound of formula (A) is synthesized. 1-(3,5-0-isopropylidene-β-
D-xylofuranosyl)-5-ethyluracil was synthesized, and (d) the compound of formula (1)-3 was reacted with phenyl chlorothionocarbonate and 4-dimethylaminocarbonate in acetonitrile in the presence of lysine to synthesize the above formula ( 1-(2-0-phenoxythiocarbonyl-3,5-0- Synthesize isopropylidene-β-D-xy-furanosyl)-5-ethyluracil, (e) synthesize the compound of formula (1)-2 above in a solvent containing n-
) By reacting in the presence of butyltin hydride and azobisisobutyronitrile, the following formula (1) included in the formula (1) of the present invention is useful as a synthetic intermediate for the compound of the above formula (A). ) 1-2-deoxy-3,5-0-isopropylidene-β-D-xylofuranosyl)-5-ethyluracil represented by -1 is synthesized, (f) then, the above formula (1)-1 1-(2-deoxy-β-D-xylofuranosyl)-5-ethyluracil represented by the following formula (D) is synthesized by hydrolyzing the compound in a solvent in the presence of an acid, and (g) The above formula (
By reacting the compound of D) with a benzoyl halide in an organic solvent, the following formula (C) is useful as a synthetic intermediate for the compound of the above formula (A). In the formula, Bz represents a benzoyl group (the same applies hereinafter). 1-(2-deoxy-5-benzoyl-β,D-xylofuranosyl)-5-ethyluracil is synthesized, and (h) the compound of the above formula (C) is mixed with mesityl halide in an organic solvent. 1-(2-deoxy-3-azido-5- Benzoyl-β,D-ribofuranosyl)-5-ethyluracil can be synthesized.

Furthermore, the compound of formula (A) can be easily synthesized by reacting the compound of formula (B) with a base such as sodium methylate in an organic solvent such as methanol.

The compound of formula (5) of the present invention is produced from the compound of formula (5), including the step of producing the compound of formula (A) from the compound of formula (D).
The reaction formula for producing the compound 1) is, for example, as follows.

Reaction formula summer +21
(1 no 3 (1) - 2 (1 + - 1 (DJ [CI (BJ
(A.

Note: AION=(Me)2C(CN)NSC(CN
)(Me)2 The method for producing the compound of formula (1) of the present invention, which is useful as a synthetic intermediate for C5-85 of formula (A), will be explained in more detail below according to the reaction formula (2) above.

First, the reaction of synthesizing the compound of formula (3) from the compound of formula (5) in step (a) is carried out by adding the compound of formula (5) to the compound of formula (5) in an organic solvent in the presence of anhydrous tin chloride. 4)
This can be easily carried out by reacting with 5-ethylbis(trimethylsilyl)uracil.

The above reaction varies depending on the type of organic solvent employed, but generally it is carried out at a temperature range of about 10°C to 50°C, and about 1
This can be done in about 10 hours.

There is no particular restriction on the amount of 5-ethylbis(trimethylsilyl)uracil of the above formula (4) used in the above reaction, but it is usually about 1 to about 1 mole of the compound of the above formula (5). It is used in a range of about 1.6 mol. Further, the amount of anhydrous tin chloride used as a catalyst can be varied within a wide range, but generally, for example, about 1 to about 1.5 A range on the order of moles is appropriate. Furthermore, the organic solvent used is not particularly limited and may be any solvent as long as it is inert to the reaction, but it is usually benzene, toluene,
, 2-dichloroethane, dichloromethane, carbon tetrachloride, etc. are often used.

The amount of these solvents to be used can be selected as appropriate, and for example, the amount used is preferably about 5 to about 50 times the weight of the compound of formula (5). After the reaction is completed, the product is neutralized and washed according to a conventional method, and if desired, purified by means such as column chromatography to obtain the compound of formula (3).

Next, in step (b), in order to synthesize the compound of the above formula (2) from the compound of the above formula (3), for example, the compound of the formula (3)
This can be easily carried out by reacting a compound with a base such as sodium ethylate or sodium methylate. The amount of base used in this reaction is sufficient to be a catalytic amount, but the preferred amount is, for example, about 1/100 to about 1/1 mole of the compound of formula (3). It is in the range of about 10 moles. When using a base as described above, it may be prepared from the corresponding alkaline earth metal sodium in the reaction system.The reaction is carried out at a temperature that allows the alcohol used to reflux.The reaction time is usually It is sufficient to carry out the reaction for about 2 hours. After the reaction is completed, the compound of formula (2) is neutralized with an acid such as an acidic ion exchange resin and purified by means such as recrystallization to obtain a compound of formula (2) with good purity and good yield. obtained at a rate.

Next, in step (c), the compound of the above formula (2) is reacted with acetone in the presence of an acid, and 1-( of the above formula (1)-3 included in the above formula (1) of the present invention It is sufficient to carry out the reaction capable of synthesizing 3,5-0-isopropylidene-β-D-xylofuranosyl-5-ethyluracil at a temperature of about room temperature for about 3 hours. Examples of acids that can be used in this reaction include p-)luenesulfonic acid, hydrochloric acid, and sulfuric acid. The amount of these acids used is sufficient in a catalytic amount, for example, it is sufficient to use about 1/10 (ljl 1%) of the compound of formula (2) above. For example, it is preferable to use about 1 to about 100 moles per 1 mole of the compound of formula (2). The compound of formula (1)-3 can be obtained in good purity and yield by further purifying the product by means such as recrystallization.

Next, in step (d), the compound of the above formula (1)-3 is converted to the above formula (1)-2 included in the above formula (1) of the present invention.
1-(2-0-phenoxythiocarbonyl-3,5-
0-isopropylidene-β-D-xylofuranosyl)5
- Ethyluracil is synthesized by reacting the compound of formula (1)-3 in acetonitrile in the presence of phenyl chlorothionocarbonate and 4-dimethylaminopyridine. ~about 4
It takes about an hour. The amount of phenyl chlorothionocarbonate used in this reaction is, for example, formula (1)-3
An example of the range is about 1 to about 1.5 mol per mol of the compound. Moreover, it is more advantageous to use 4-dimethylaminopyridine in excess, for example, formula (1)-3
It is generally used in an amount of about 1.5 to about 3 mol per mol of the compound. There are no particular restrictions on the amount of acetonitrile used, and it can be selected as appropriate.
Usually, for example, a range of about 5 to about 100 times the weight of the compound of formula (1)-3 is appropriate.

After completion of the reaction, partition extraction is carried out with a solvent such as ethyl acetate, the organic layer is washed with an aqueous solution of an acid such as hydrochloric acid, and if desired, the product is purified by means such as recrystallization to obtain the above formula (1) of the present invention. -2 is obtained with good purity and good yield.

Next, in step (e), from the compound of the above formula (1)-2, the compound of the above formula (1) included in the above formula (1) of the present invention is
To synthesize 1-(2-deoxy-3,6-〇-isopropylidene-β-D-xylofuranosyl)-6-ethyluracil of -1, for example, the compound of formula (1)-2 is ′? It is synthesized by treatment in # medium in the presence of n-tributyltin hydride and azobisisobutyronitrile.

Advantageously, the reaction is carried out under an inert atmosphere, such as nitrogen gas. Although the treatment temperature depends on the organic solvent used, a range of about 0°C to about 150°C is adopted for boat fishing. Although the treatment time can be selected as appropriate, it is usually in the range of about 2 to about 3 hours. The amount of n-tributyltin hydride used in this reaction is preferably in the range of about 2 to about 5 moles per mole of the compound of formula (1)-2.

Further, the preferable amount of azobisisobutyronitrile to be used is, for example, in the range of about 115 to about 1750 mol per 1 mol of the compound of formula (1)-2. Various organic solvents can be used, but preferred examples include toluene and xylene. There is no particular restriction on the amount of these solvents to be used, and an appropriate range can be selected.For example, formula (1)-
After the completion of the reaction, the reaction product is purified by means such as column chromatography or by means such as recrystallization. The compound of formula (1)-1 of the present invention is obtained in good purity and yield.

Next, in step (f), the compound of the above formula (1)-1 is reacted with an acid to create a 1-(2-deoxy-
For the reaction capable of synthesizing β,D-xylofuranosyl)-6-ethyluracil, a time of about 1 to about 5 hours at a temperature of about 0 to about 80°C is sufficient. Examples of acids that can be used in this reaction include p-)luenesulfonic acid, acetic acid, hydrochloric acid, sulfuric acid, and the like. The amount of these acids to be used is, for example, for compound 1 of formula (1)-1 above.
The range of about 0.1 to about 200 moles is preferable. The compound is obtained in good purity and yield.

Next, in step (g), the compound of formula (D) is converted to 1-(2-deoxy-5-benzoyl-β of formula (C)).
, D-xylofuranosyl)-5-ethyluracil, the reaction is carried out by reacting the compound of formula (D) with benzoyl chloride in an organic solvent at a temperature of about 50°C to about 50°C. It can be carried out for about 0.5 hours to about 5 hours. The amount of benzoyl chloride used in this reaction is, for example, in the range of about 1.0 to about 1.5 mol per 1 mol of the compound of formula (D). Further, examples of the 8N solvent used in the above reaction include pyridine, dichloromethane, etc., and the amount used is, for example, about 5 to about 20% by weight based on the compound of formula (D) above. After completion of the reaction, the compound of the above formula (C) can be obtained in good purity and yield using purification means such as extraction, vacuum distillation, and silica gel column chromatography. can.

Next, in step (h), 1-(2-deoxy-3-azito-5-benzoyl-β,D-ribofuranosyl)-6-ethyluracil of the above formula (B) is synthesized from the compound of the above formula (C). The mesylated product 1-(2-deoxy-3-mesyl-5-benzoyl-β) is prepared by reacting the compound of formula (C) with mesyl chloride in an organic solvent.

It is easily carried out by synthesizing D-xylofuranosyl)-5-ethyluracil and then reacting the mesylated product with sodium azide in a solvent to form an azidation. The mesylation reaction can be carried out at a temperature of about 0 to about 80°C for a period of about 6 hours. The amount of mesyl chloride used in this reaction may range from about 1 to about 5 moles based on the compound of formula (C).

In addition, the organic solvent used in the above reaction is usually pyridine,
Examples include dichloromethane. The amount of these solvents to be used may be appropriately selected, and for example, the amount to be used is preferably about 1 to about 30 times the weight of the compound of formula (C).

After the reaction is completed, the solvent can be removed and the product can be directly proceeded to the next azidation reaction without purification and isolation. The azidation reaction is carried out at a temperature of about 25 to about 100°C and a reaction rate of about 0.6 to
This can be done for about 5 hours. The amount of sodium azide used in the above reaction is, for example, given by the above formula (C).
The amount can be about 1 to about 5 mol per mol of the compound.

Further, various solvents can be used in the above reaction, and examples thereof include dimethylformamide and dimethyl sulfoxide. The usage of these solvents includes:
There is no particular restriction, and for example, the amount may range from about 1 to about 501 times the amount of the compound of formula (C). After the reaction is completed, the compound of formula (B) can be obtained with good purity and yield using purification means such as extraction, distillation, and silica gel column chromatography.

The compound of formula (B) produced as described above can be converted into C5-85, which can be used as a therapeutic agent for AIDS, for example, as shown in the reaction formula above.

C5-85 can be easily synthesized from the compound of formula (B) of the present invention by, for example, reacting the compound of formula (B) with a base such as sodium methylate in a solvent such as methanol. can be done.

(Examples and Reference Examples) The method for producing the compounds of formula (1) and C5-85 of the present invention will be further explained below with reference to Examples and Reference Examples.

Example 1 % formula % () of 1-(2,3,5-)-(2,3,5-)-5-ethyluracil [formula (3)]
] 16.3 g of tetraacetyl xylofuranose in the flask
(51.1 mmol), 16 g (56.2 mmol) of 5-ethylbis(trimethylsilyl)uracil, and 500 ml of 1,2-dichloroethane were charged and dissolved with stirring at room temperature. A solution containing 14.2 g (54.4 mmol) of anhydrous tin chloride was added dropwise over 30 minutes, and after the addition was complete, the reaction was continued at the same temperature for about 10 hours.

After the reaction was completed, 200ml of chloroform was added to the reaction solution.
After washing with a saturated aqueous sodium carbonate solution and drying the filtrate over sodium sulfate, it was concentrated under reduced pressure and subjected to silica gel column chromatography (chloroform:methanol = 9:l).
Purification was performed to obtain 19.7 g of the title compound.

Yield: 99.6% 1H-NMR (CDCI3) δppm: 1.16 (3H, t, J = 7.5Hz)
, 2.11 (3H, S), 2.14 (6H, S),
2.40 (2H, q, J=7.5Hz), 4.32~
4.6 (2H, m), 5.15-5.17 (IH,
m), 5.21-5.40 (IH, m), 8.09 (
IH, d, J = 2°9Hz), 7.26 (IH, br
, S), 9°46 (IH, brS) Example 2 1-β-D-xylofuranosyl-5-ethyluracil [
Synthesis of formula (2) [Step (b)] 18 g (46.6 mmol) of 1-(2,3,5-)-acetylxylofuranosyl)-δ-ethyluracil of formula (3) is added to the flask. After charging and dissolving 500 ml of anhydrous methanol, a catalytic amount of metallic sodium pieces was added at room temperature.
Refluxed for an hour. After the reaction is completed, ion exchange resin (Ambe
The filtrate was concentrated, and ethyl alcohol:ether (1:1) was added to the concentrated solution for recrystallization to obtain 11.95 g of the title compound.

Yield: 94.2% Melting point: 128°C Example 3 1-(3,5-0-isopropylidene-β-D-xylofuranosyl)-5-ethyluracil [Formula (1)-3]
Synthesis [Step (c) 11.95 g (43°9 mmol) of 1-β-D-xylofuranosyl-5-ethyluracil of formula (2), 300 ml of acetone and 1 p-)luenesulfone were placed in a coffin flask.
%t1. After the completion of the reaction, which was charged with Og and stirred at room temperature for 2 hours, the mixture was neutralized with 3 g of barium hydroxide, filtered, and concentrated. Column chromatography packed with 500 g of silica gel (chloroform:methanol = 9:l)
Purification was performed to obtain 10.69 g of the title compound.

Yield near 3.5% 1H-NMR (CDC13) δppm: 1.15 (3H, t, J = 7- δHz
), 1.27 (3H, S), 1.40 (2H, q,
J=7.5Hz), 1.48 (3H,S), 4.07
~4.61 (5H, m), 6.0 (IH, m), 7.
9E3 (IH, br, S) +10.70 (IH, b
rS) Example 4 l-(2-0-phenoxythiocarbonyl-3°5-0
-isopropylidene-β-D-xylofuranosyl)-5
-Ethyluracil [Synthesis of formula (1)-2] [Step (d)
] 4.15 g (13.3 mmol) of 1-(3,5-0-isopropylidene-β-D-xylofuranosyl)-5-ethyluracil of formula (1) -3 was added to 500 ml of anhydrous acetonitrile with stirring. In addition, 2.5 g (14.6 mmol) of phenyl chlorothionocarbonate and 4-
After adding 3.3 g (26.8 mmol) of dimethylaminopyridine and stirring at room temperature for 2 hours, the reaction was completed.
Partition extraction was carried out with 250 ml of ethyl acetate + 50 ml of ice water, and the organic layer was sufficiently cooled before INIHC1/H2.
0. Washing was performed successively with a saturated aqueous sodium carbonate solution and a saturated aqueous sodium chloride solution. Sodium sulfate was added, and the mixture was allowed to stand overnight, filtered, and concentrated to obtain 5.42 g of the title compound.

Yield 290.9% 'H-NMR (CDC13) δppm: 1.17 (3H, t, J=7.5Hz)
, 1.42 (3H,S), 1.49 (3H,S),
2.31 (2H, q, J=7.5Hz), 4.12~
4.20 (3H, m), 4.59 (IH, d, J=
7.5Hz), 5.56 (IH, br, S), 6.2
2 (IH, brS), 7°10~7.49 (5H,
m), 7.82 (IH, brS), 10.03 (I
H,brS)・Example 5 1-2-deoxy-3,5-0-isopropylidene-β-D-xylofuranosyl)-5-ethyluracil [
Synthesis of formula (1)-11 [Step (e) 1-(2-0-phenoxythiocarbonyl-3,5-〇-isopropylidene-β- of formula (1)-2 dried under reduced pressure in a codesicator)
D-xylofuranosyl)-5-ethyluracil 4.42
g (10°8 mmol) of distilled toluene 580 m
Add and dissolve azobisisobutyronitrile 321
mg (2.0 mmol) and 8.6 g (29.2 mmol) of n-)butyltin hydride were added. The mixture was heated to 75° C. and refluxed under a nitrogen gas stream for 5 hours.

After the reaction was completed, it was concentrated, and the residue was purified by silica gel column chromatography (chloroform:ethyl acetate=1:1) to obtain 2.83 g of the title compound.

Yield: 8B, 4% IH-NMR (CDC13) δppm: 1.16 (3H, t, J = 7.5H
z), 1.38 (3H,S), 1.48 (
3H.

S), 2.09-2.80 (H, m), 3.84
(I H, m), 4. 1 to 4.3 (2H, m)
+4.3 to 4.5 (IH, m), 6. 17 (
IH.

dd, J=5.9Hz), 7.93 (IH, brS
), 9.6 (IH, brS).

Reference example 1 l-(2-deoxy-β, D-xylofuranosyl)-5
-Synthesis of ethyluracil [formula (D)] [step (f)] 1-(2-deoxy-3,5 of formula (1)-1 is added to the flask.
-0-isopropylidene-β-D-xylofuranosyl)
2.0 g (6.7 mmol) of -5-ethyluracil and 67 ml of 70% acetic acid aqueous solution were charged, and the reaction was carried out for 2.5 hours with stirring at a temperature of 50°C. After completion of the reaction,
The residue was purified by silica gel column chromatography (chloroform:methanol=4:1) to obtain 1.21 g of the title compound.

Yield near 0.0% 1H-NMR (d5-DMSO) δppm: 1.05 (3H, t, J=7..5Hz
), 2.04 (IH, dd, J=14.7Hz, 2.
9Hz) + 2.14 (2H2Q, J = 7.5Hz
), 2.4-2.7 (I H, m).

3.5-3.9 (3H, m), 4.28 (IH, m
), 4.63 (IH, m), 5.22 (IH, d,
J=2.9Hz), 6.11 (IH.

dd, J=8.2Hz, 2.3Hz), 7.81 (I
H, S), 11.12 (IH, brS).

Reference Example 2 Synthesis of l-(2-deoxy-5-benzoyl-β,D-xylofuranosyl)-6-ethyluracil [formula (C)] [step (g)].

1-(2-deoxy-β of formula (D)) in the flask.

D-xylofuranosyl)-5-ethyluracil 1°0g
(3.9 mmol) and 20 ml of pyridine were charged and cooled with ice water. 0.66 g (4.7 mmol) of benzoyl chloride is added dropwise to the mixture while stirring. After completion of the dropwise addition, the reaction is further carried out at a temperature of 0° C. for 2 hours. After the reaction was completed, it was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (chloroform:methanol = 95:5).
Purification was performed to obtain 1.39 g of the title compound.

Yield: 99.3% 'H-NMR (CDCI3) δppm: 1. l 1 (3H, t, J=7.5Hz
), 2.31 (2H, q, J=7.5Hz).

2.1~2.8 (2H, m), 4.2~4.9 (4
H, m), 5.18 (IH, brS), 6.22 (
IH, dd, J = 8.2Hz, 2.3Hz).

7.23-8.01 (5) (, m), 8.58 (I
H, d, J = 3.7 Hz), 11.0 (LH, brS
).

Reference example 3 l-(2-deoxy-3-azido-5-benzoyl-β
-D-ribofuranosyl)-5-ethyluracil [formula (B
)] synthesis [step (h)].

In a flask, 1.3 g (3.6 mmol) of 1-(2-deoxy-5-benzoyl-β-D-xylofuranosyl)-5-ethyluracil of formula (C) and 30 lysine were added.
ml and cool with ice water.

Add 1.24 g of mesyl chloride to this while stirring.
(10.8 mmol) was added dropwise, and the reaction was further carried out at 0° C. for 3 hours. After the mesylation reaction was completed, treatments such as distillation and extraction were performed to obtain 1.98 g of 1-(2-deoxy-3-mesyl-6-penzoyl-β-D-xylofuranosyl)-6-ethyluracil.

1-(2-deoxy-3-mesyl-
1.9 g (4.4 mmol) of 5-benzoyl-β-D-xylofuranosyl)-5-ethyluracil, 50 ml of dimethylformamide, 470 ml of sodium azide
g (7.2 mmol) and 6 ml of water, and 10
After the reaction was completed at 0°C for 3 hours, it was distilled under reduced pressure and the residue was purified by silica gel chromatography (chloroform:methanol = 95:5) to obtain 1.27g of the title compound.

Yield: 87.3% 1H-NMR (CDC13) δppm: 0.95 (3H, t, J = 7.7Hz)
, 2.04-2.29 (2H, m), 2°48
(2H,q,,J"-7,7Hz), 4.08~4.7
9 (4H, m), 6. 15 (IH, t, J=
6.6Hz), 7. 13 (IH, S).

7.40-8.08 (5H, m), 9.31 (
IH, brS).

Reference Example 4 l-(2-deoxy-3-azido-β-D-ribofuranosyl-5-ethyluracil (C5-85) -azito-5-benzoyl-β-D-ribofuranosyl)-5-ethyluracil 830 mg, methanol 20 m [and I
2.2 ml of methanol solution of N-sodium methylate
(2.2 mmol) and stirred at room temperature.
．． The reaction is carried out for 5 hours. After the reaction is completed, ion exchange resin (A
The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (chloroform:methanol=95:5) to obtain 560 mg of the title compound. Yield: 9
2.4% 1H-NMR (d5-DMSO) δppm: 1.06 (3H, t, J = 7.δHz)
, 2.09-2.55 (4H, m), 3.67-3.
89 (3H2m), 4.41 (IH2q.

J=6.2Hz), 5.18 (IH, t, J=4°8
Hz), 6.13 ('IH,t,J:6.4Hz),
7.67 (IH,S), 11.19 (IH,S) 1 person

Claims (1)

[Claims] 1. The following formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) In the formula, R_1 is a hydrogen atom, a hydroxyl group, or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Uracil derivative represented by.