JPS6221348B2 - - Google Patents
Info
- Publication number
- JPS6221348B2 JPS6221348B2 JP56006479A JP647981A JPS6221348B2 JP S6221348 B2 JPS6221348 B2 JP S6221348B2 JP 56006479 A JP56006479 A JP 56006479A JP 647981 A JP647981 A JP 647981A JP S6221348 B2 JPS6221348 B2 JP S6221348B2
- Authority
- JP
- Japan
- Prior art keywords
- fluorouracil
- carbamoyl
- reaction solution
- formula
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 229960002949 fluorouracil Drugs 0.000 claims description 16
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 14
- FHLNOFIKNZLHOS-UHFFFAOYSA-N 5-fluoro-2,4-dioxopyrimidine-1-carboxamide Chemical compound NC(=O)N1C=C(F)C(=O)NC1=O FHLNOFIKNZLHOS-UHFFFAOYSA-N 0.000 claims description 13
- 239000012948 isocyanate Substances 0.000 claims description 9
- 150000002513 isocyanates Chemical class 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- -1 alicyclic hydrocarbon compound Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- 239000012535 impurity Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- ANJPRQPHZGHVQB-UHFFFAOYSA-N hexyl isocyanate Chemical compound CCCCCCN=C=O ANJPRQPHZGHVQB-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- QSTQPLFBYDUDHN-UHFFFAOYSA-N 1,3-dihexylurea Chemical compound CCCCCCNC(=O)NCCCCCC QSTQPLFBYDUDHN-UHFFFAOYSA-N 0.000 description 1
- SNKDCTFPQUHAPR-UHFFFAOYSA-N 1-fluoropyrimidine-2,4-dione Chemical compound FN1C=CC(=O)NC1=O SNKDCTFPQUHAPR-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- XORCSHBIHQYYJL-UHFFFAOYSA-N 5-fluoro-1-hexylpyrimidine-2,4-dione Chemical compound CCCCCCN1C=C(F)C(=O)NC1=O XORCSHBIHQYYJL-UHFFFAOYSA-N 0.000 description 1
- AVSGWXRHDLBYLK-UHFFFAOYSA-N 5-fluoro-2,4-dioxo-n-propan-2-ylpyrimidine-1-carboxamide Chemical compound CC(C)NC(=O)N1C=C(F)C(=O)NC1=O AVSGWXRHDLBYLK-UHFFFAOYSA-N 0.000 description 1
- PIUCHDXNDBQRTH-UHFFFAOYSA-N 5-fluoro-2,4-dioxo-n-propylpyrimidine-1-carboxamide Chemical compound CCCNC(=O)N1C=C(F)C(=O)NC1=O PIUCHDXNDBQRTH-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 230000021235 carbamoylation Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- PVSNDBKXSKXPHM-UHFFFAOYSA-N n-butyl-5-fluoro-2,4-dioxopyrimidine-1-carboxamide Chemical compound CCCCNC(=O)N1C=C(F)C(=O)NC1=O PVSNDBKXSKXPHM-UHFFFAOYSA-N 0.000 description 1
- GDSVEJKZPZSFPE-UHFFFAOYSA-N n-tert-butyl-5-fluoro-2,4-dioxopyrimidine-1-carboxamide Chemical compound CC(C)(C)NC(=O)N1C=C(F)C(=O)NC1=O GDSVEJKZPZSFPE-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
【発明の詳細な説明】
本発明は式(1)で示される１−カルバモイル−５
−フルオロウラシル類の分離方法に関する。Detailed Description of the Invention The present invention provides 1-carbamoyl-5 represented by formula (1)
-Regarding a method for separating fluorouracils.
（式中、Ｒは炭素数３〜８のアルキル基を表わ
す）１−カルバモイル−５−フルオロウラシル類
は制ガン剤として有用な医薬であり、特に１−ｎ
−ヘキシル−５−フルオロウラシルは卓越した薬
効があり、特開昭50−148365、特開昭52−77073
などで公知である。式(1)の１−カルバモイル−５
−フルオロウラシル類の製造方法は、５−フルオ
ロウラシルを式(2)
Ｒ−NCO (2)
（式中、Ｒは式(1)で定義した基を表わす。）
で表わされるイソシアナートまたは式(3)
（式中、Ｒは式(1)で定義した基を表わし、Ｘはハ
ロゲン原子を表わす。）
で表わされるカルバミルハライドでカルバモイル
化することによつて製造することができる。 (In the formula, R represents an alkyl group having 3 to 8 carbon atoms) 1-carbamoyl-5-fluorouracils are useful medicines as anticancer agents, especially 1-n
-Hexyl-5-fluorouracil has outstanding medicinal efficacy, JP 50-148365, JP 52-77073
It is publicly known as. 1-carbamoyl-5 of formula (1)
- The method for producing fluorouracils includes converting 5-fluorouracil into an isocyanate represented by formula (2) R-NCO (2) (wherein R represents a group defined in formula (1)) or formula (3) (In the formula, R represents a group defined in formula (1), and X represents a halogen atom.) It can be produced by carbamoylation with a carbamyl halide represented by the following formula.
この反応は、通常、有機溶媒中で行なわれ、溶
媒としては、例えば、ジメチルスルホキシド、ジ
メチルホルムアミド、ジメチルアセトアミド、ア
セトニトリル、ピリジン、ピコリンなどに５−フ
ルオロウラシルを溶媒に溶かし、これに一般式(2)
で表わされるイソシアナートまたは一般式(3)で表
わされるカルバミルハライドを加え、室温ないし
反応液の沸点で反応を行なう。 This reaction is usually carried out in an organic solvent, such as dimethylsulfoxide, dimethylformamide, dimethylacetamide, acetonitrile, pyridine, picoline, etc., in which 5-fluorouracil is dissolved and the general formula (2)
An isocyanate represented by the formula (3) or a carbamyl halide represented by the general formula (3) is added, and the reaction is carried out at room temperature to the boiling point of the reaction solution.
このようにして得られた反応液から１−カルバ
モイル−５−フルオロウラシルを単離する場合、
公知の方法は、反応液からイソシアナートなど未
反応物及び溶媒を減圧下に留去した反応濃縮液を
冷水中に注入して、１−カルバモイル−５−フル
オロウラシルの結晶を析出させるか、またはクロ
ロホルム等の溶媒で１−カルバモイル−５−フル
オロウラシルを抽入し、抽出溶媒を留去後残留物
から精製して目的物を得ている。 When isolating 1-carbamoyl-5-fluorouracil from the reaction solution obtained in this way,
In a known method, unreacted substances such as isocyanate and the solvent are distilled off from the reaction solution under reduced pressure, and the reaction concentrate is injected into cold water to precipitate crystals of 1-carbamoyl-5-fluorouracil, or chloroform 1-carbamoyl-5-fluorouracil is extracted with a solvent such as, and the target product is obtained by distilling off the extraction solvent and purifying the residue.
しかしながら、冷水中に注入して結晶を析出さ
せる場合は、生成した１−カルバモイル−５−フ
ルオロウラシルを水が分解するばかりでなく、反
応濃縮液中になお残存している未反応イソシアナ
ート類と反応してウレア化合物を生成するので好
ましくない。また、クロロホルム等による抽出で
は水洗、脱水、濃縮乾固などの多工程の精製操作
を必要とするので有利な方法ではない。水の代り
にアルコール類の使用も未反応イソシアナート類
とカーバメイトを造り、目的生成物に不純物とし
て混入されることがわかつた。１−カルバモイル
−５−フルオロウラシルは医薬として使用される
ので、極力不純物の混入を減らす必要があり、析
出時の不純物混入は再結晶精製工程で多大の不利
益をもたらす。 However, when injecting into cold water to precipitate crystals, the water not only decomposes the generated 1-carbamoyl-5-fluorouracil, but also reacts with unreacted isocyanates still remaining in the reaction concentrate. This is not preferable because it generates urea compounds. Furthermore, extraction with chloroform or the like requires multiple purification steps such as washing with water, dehydration, and concentration to dryness, so it is not an advantageous method. It has been found that the use of alcohols in place of water also creates unreacted isocyanates and carbamates that are incorporated into the desired product as impurities. Since 1-carbamoyl-5-fluorouracil is used as a medicine, it is necessary to reduce the contamination of impurities as much as possible, and contamination of impurities during precipitation brings about a great disadvantage in the recrystallization purification process.
本発明者らは１−カルバモイル−５−フルオロ
ウラシルの析出法を鋭意検討した結果、反応濃縮
液を、室温以下で液状である脂肪族炭化水素また
は脂環族炭化水素化合物で希釈して１−カルバモ
イル−５−フルオロウラシルを析出分離すること
により、不純物含有量を極力少くして高収率で１
−カルバモイル−５−フルオロウラシルを取得で
きる分離方法を完成させたものである。 As a result of intensive studies on the method for precipitating 1-carbamoyl-5-fluorouracil, the present inventors found that the reaction concentrate was diluted with an aliphatic hydrocarbon or alicyclic hydrocarbon compound that is liquid at room temperature or below to produce 1-carbamoyl-5-fluorouracil. By precipitating and separating -5-fluorouracil, the impurity content is minimized and 1-fluorouracil is produced in high yield.
-A separation method capable of obtaining carbamoyl-5-fluorouracil has been completed.
上記、反応濃縮液から１−カルバモイル−５−
フルオロウラシルを析出させるための析出溶媒と
しては、室温、即ち30℃付近以下で液状を保有す
る脂肪族炭化水素または脂環族炭化水素であれば
いずれでもよく、C5〜C8の炭化水素が適当な析
出溶媒であり、これらを単独もしくは混合物とし
て使用する。特に脂肪族飽和炭化水素が好まし
く、ｎ−ヘキサン、リグロインなどが挙げられ
る。芳香族炭化水素類も使用出来るが、１−カル
バモイル−５−フルオロウラシルを少々溶解する
ので、好しいものではない。また、式(1)で示した
１−カルバモイル−５−フルオロウラシル類とし
ては、１−ｎ−プロピルカルバモイル−５−フル
オロウラシル、１−iso−プロピルカルバモイル
−５−フルオロウラシル、１−ｎ−ブチルカルバ
モイル−５−フルオロウラシル、１−ｔ−ブチル
カルバモイル−５−フルオロウラシル、１−ｎ−
ヘキシルカルバモイル−５−フルオロウラシル、
１−ｎ−シクロヘキシルカルバモイル−５−フル
オロウラシルなどが挙げられる。 From the above reaction concentrate, 1-carbamoyl-5-
As a precipitation solvent for precipitating fluorouracil, any aliphatic hydrocarbon or alicyclic hydrocarbon that remains liquid at room temperature, that is, around 30°C or lower, may be used, and C 5 to C 8 hydrocarbons are suitable. These solvents can be used alone or as a mixture. Particularly preferred are aliphatic saturated hydrocarbons, such as n-hexane and ligroin. Aromatic hydrocarbons can also be used, but are not preferred because they slightly dissolve 1-carbamoyl-5-fluorouracil. Further, as the 1-carbamoyl-5-fluorouracil shown by formula (1), 1-n-propylcarbamoyl-5-fluorouracil, 1-iso-propylcarbamoyl-5-fluorouracil, 1-n-butylcarbamoyl-5 -Fluorouracil, 1-t-butylcarbamoyl-5-fluorouracil, 1-n-
hexylcarbamoyl-5-fluorouracil,
Examples include 1-n-cyclohexylcarbamoyl-5-fluorouracil.
５−フルオロウラシルと相応するイソシアナー
ト類を溶媒の存在下に反応して得られた上記１−
カルバモイル−５−フルオロウラシル類の反応液
からの析出分離は、通常以下のようにして実施す
る。 The above 1- obtained by reacting 5-fluorouracil and the corresponding isocyanate in the presence of a solvent.
Precipitation separation of carbamoyl-5-fluorouracil from the reaction solution is usually carried out as follows.
反応液を５〜50mmHg好ましくは20〜30mmHgの
減圧下20〜60℃の温度範囲で濃縮して、反応溶媒
を反応時に使用した量の10〜80％迄蒸発留去す
る。この際溶存している未反応イソシアナートも
一部留去される。濃縮された反応液を−10〜30℃
に維持された脂肪族炭化水素または脂環族炭化水
素の析出溶媒中に注入して0.5〜24時間保持すれ
ばイソシアナート反応物などの不純物を殆んど含
有しない１−カルバモイル−５−フルオロウラシ
ルの結晶が得られる。この粗結晶を過分離、水
洗乾燥し、さらにエタノールなどの溶媒で再結晶
すれば、純度99.95％以上のものが得られる。 The reaction solution is concentrated under a reduced pressure of 5 to 50 mmHg, preferably 20 to 30 mmHg, at a temperature in the range of 20 to 60°C, and the reaction solvent is evaporated to 10 to 80% of the amount used during the reaction. At this time, a portion of dissolved unreacted isocyanate is also distilled off. Store the concentrated reaction solution at −10 to 30℃.
1-carbamoyl-5-fluorouracil, which contains almost no impurities such as isocyanate reactants, can be obtained by injecting it into a precipitation solvent for aliphatic or alicyclic hydrocarbons maintained at Crystals are obtained. If this crude crystal is subjected to excessive separation, washed with water, dried, and further recrystallized with a solvent such as ethanol, a product with a purity of 99.95% or higher can be obtained.
以上のように本発明によれば不純物の生成が抑
制され、純度の高い１−カルバモイル−５−フル
オロウラシル類が高収率で得られ、しかも取り扱
い操作も簡単になり工業化に非常に有利となる。 As described above, according to the present invention, the production of impurities is suppressed, highly pure 1-carbamoyl-5-fluorouracils can be obtained in high yield, and handling operations are also simple, which is very advantageous for industrialization.
以下に本発明の方法を実施例を挙げて説明す
る。 The method of the present invention will be explained below by giving examples.
実施例 １
５−フルオロウラシル13.0ｇ（0.1モル）、ｎ−
ヘキシルイソシアナート19.1ｇおよびピリジン
40.0ｇを混合し90℃に1.5時間反応を行つた。反
応液を室温まで徐冷後減圧下に反応液を濃縮し
た。濃縮液を０℃に維持したｎ−ヘキサン100ｇ
に加え析出した結晶を過後ｎ−ヘキサンで洗浄
し乾燥して１−（ｎ−ヘキシルカルバモイル）−５
−フルオロウラシル24.7gを得た。収率96％で、
液体クロマト分析より純度99％で、残りは殆んど
が５−フルオロウラシルであつた。Example 1 5-fluorouracil 13.0 g (0.1 mol), n-
19.1g hexyl isocyanate and pyridine
40.0g were mixed and reacted at 90°C for 1.5 hours. After slowly cooling the reaction solution to room temperature, the reaction solution was concentrated under reduced pressure. 100g of n-hexane with concentrated liquid maintained at 0℃
After filtration, the precipitated crystals were washed with n-hexane and dried to give 1-(n-hexylcarbamoyl)-5.
-24.7 g of fluorouracil was obtained. With a yield of 96%,
Liquid chromatography analysis showed that the purity was 99%, with the remainder being mostly 5-fluorouracil.
実施例 ２
５−フルオロウラシル13.0ｇ（0.10モル）をジ
メチルアセトアミド60mlに混合させ、これにｎ−
ヘキシルイソシアナート14.0ｇを室温で添加し、
50℃で８時間反応を行つた。反応液を室温まで徐
冷後、減圧下に反応液を濃縮した。濃縮液を０℃
に維持したりグロイン100ｇ中に注入して析出し
た結晶を過、洗浄乾燥して１−ｎ−ヘキシルカ
ルバモイル−５−フルオロウラシル21.9ｇを得
た。収率85％で、純度99％以上であり、残りは殆
んどが５−フルオロウラシルであつた。Example 2 13.0 g (0.10 mol) of 5-fluorouracil was mixed with 60 ml of dimethylacetamide, and n-
Add 14.0 g of hexyl isocyanate at room temperature,
The reaction was carried out at 50°C for 8 hours. After slowly cooling the reaction solution to room temperature, the reaction solution was concentrated under reduced pressure. Heat the concentrate to 0℃
The precipitated crystals were filtered, washed and dried to obtain 21.9 g of 1-n-hexylcarbamoyl-5-fluorouracil. The yield was 85%, the purity was 99% or more, and the remainder was mostly 5-fluorouracil.
実施例 ３
実施例１と同様にして得られた濃縮液を０℃に
維持したシクロヘキサン100ｇ中に注入し析出し
た結晶を過、洗浄、乾燥して１−（ｎ−ヘキシ
ルカルバモイル）−５−フルオロウラシル23.4ｇ
を得た。収率91％、純度99％で残り不純物は殆ん
どが５−フルオロウラシルであつた。Example 3 A concentrated solution obtained in the same manner as in Example 1 was poured into 100 g of cyclohexane maintained at 0°C, and the precipitated crystals were filtered, washed, and dried to obtain 1-(n-hexylcarbamoyl)-5-fluorouracil. 23.4g
I got it. The yield was 91%, the purity was 99%, and most of the remaining impurities were 5-fluorouracil.
実施例 ４
５−フルオロウラシル13.0ｇ、シクロヘキシル
イソシアナート19.1ｇ及びピリジン40.0ｇを混合
し、90℃に1.5時間反応を行つた。反応液を室温
まで徐冷後減圧下に反応液を濃縮し、濃縮液を０
℃のｎ−ヘキサン100ｇ中に注入し析出した結晶
を過後ｎ−ヘキサンで洗浄し乾燥して１−ｎ−
シクロヘキシル−５−フルオロウラシル23.1ｇを
得た。収率90％、純度99％以上で残り不純物は殆
んどが５−フルオロウラシルであつた。Example 4 13.0 g of 5-fluorouracil, 19.1 g of cyclohexyl isocyanate and 40.0 g of pyridine were mixed and reacted at 90°C for 1.5 hours. After slowly cooling the reaction solution to room temperature, the reaction solution was concentrated under reduced pressure, and the concentrated solution was reduced to 0.
The precipitated crystals were poured into 100 g of n-hexane at ℃, washed with n-hexane and dried to give 1-n-
23.1 g of cyclohexyl-5-fluorouracil was obtained. The yield was 90%, the purity was 99% or more, and most of the remaining impurities were 5-fluorouracil.
比較例
実施例２と同様にして得られた濃縮液を水400
ml中に注入し、析出した結晶を過、水洗、乾燥
して、１−ｎ−ヘキシルカルバモイル−５−フル
オロウラシル19.3ｇを得た。収率75.0％で、純度
97.5％であり、不純物はジ−ｎ−ヘキシルウレア
と、５−フルオロウラシル未反応物であつた。Comparative example A concentrated solution obtained in the same manner as in Example 2 was mixed with 400% water.
ml, and the precipitated crystals were filtered, washed with water, and dried to obtain 19.3 g of 1-n-hexylcarbamoyl-5-fluorouracil. Yield 75.0%, purity
The impurities were di-n-hexylurea and unreacted 5-fluorouracil.
Claims (1)
溶媒の存在下反応して得られた反応液から１−カ
ルバモイル−５−フルオロウラシルを分離する方
法において、反応液を濃縮後、室温以下で液状を
保有する脂肪族炭化水素または脂環族炭化水素化
合物で希釈して１−カルバモイル−５−フルオロ
ウラシル類を析出させて分離することを特徴とす
る１−カルバモイル−５−フルオロウラシル類の
分離方法。 ２ １−カルバモイル−５−フルオロウラシル類
が１−ｎ−ヘキシルカルバモイル−５−フルオロ
ウラシルである。特許請求の範囲第１項記載の方
法。[Claims] 1. In a method for separating 1-carbamoyl-5-fluorouracil from a reaction solution obtained by reacting 5-fluorouracil and isocyanates in the presence of a solvent, the reaction solution is concentrated and then heated at room temperature or below. 1. A method for separating 1-carbamoyl-5-fluorouracils, which comprises diluting with a liquid aliphatic hydrocarbon or alicyclic hydrocarbon compound to precipitate and separate 1-carbamoyl-5-fluorouracils. 2 The 1-carbamoyl-5-fluorouracil is 1-n-hexylcarbamoyl-5-fluorouracil. A method according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56006479A JPS57120578A (en) | 1981-01-21 | 1981-01-21 | Separation of 1-carbamoyl-5-fluorouracils |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56006479A JPS57120578A (en) | 1981-01-21 | 1981-01-21 | Separation of 1-carbamoyl-5-fluorouracils |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57120578A JPS57120578A (en) | 1982-07-27 |
| JPS6221348B2 true JPS6221348B2 (en) | 1987-05-12 |
Family
ID=11639604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56006479A Granted JPS57120578A (en) | 1981-01-21 | 1981-01-21 | Separation of 1-carbamoyl-5-fluorouracils |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57120578A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0310338B2 (en) * | 1987-02-16 | 1991-02-13 | Kaneki Nenryo Jugengaisha |
-
1981
- 1981-01-21 JP JP56006479A patent/JPS57120578A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0310338B2 (en) * | 1987-02-16 | 1991-02-13 | Kaneki Nenryo Jugengaisha |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57120578A (en) | 1982-07-27 |
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