JPS636079B2 - - Google Patents

Info

Publication number: JPS636079B2
Authority: JP; Japan
Prior art keywords: phosphorylcholine; general formula; choline; reaction; cdp
Prior art date: 1979-06-15
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

Application number

JP7454979A

Other languages

English (en)

Japanese (ja)

Other versions

JPS55167298A (en

Inventor

Takeshi Kawashima

Osamu Maruyama

Sada Kanai

Makoto Yokoyama

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Kojin Co Ltd

Original Assignee

Kojin Co Ltd

Priority date (The priority date 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 date listed.)

1979-06-15

Filing date

1979-06-15

Publication date

1988-02-08

1979-06-15 Application filed by Kojin Co Ltd filed Critical Kojin Co Ltd

1979-06-15 Priority to JP7454979A priority Critical patent/JPS55167298A/ja

1980-12-26 Publication of JPS55167298A publication Critical patent/JPS55167298A/ja

1988-02-08 Publication of JPS636079B2 publication Critical patent/JPS636079B2/ja

Status Granted legal-status Critical Current

Links

229950004354 phosphorylcholine Drugs 0.000 claims description 31
RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 claims description 30
IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 claims description 18
238000000034 method Methods 0.000 claims description 17
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 11
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 10
229960001284 citicoline Drugs 0.000 claims description 8
125000004663 dialkyl amino group Chemical group 0.000 claims description 8
239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims description 3
235000019743 Choline chloride Nutrition 0.000 claims description 3
SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims description 3
229960003178 choline chloride Drugs 0.000 claims description 3
125000005265 dialkylamine group Chemical group 0.000 claims description 2
YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims 5
238000006243 chemical reaction Methods 0.000 description 25
PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
-1 monosubstituted amides Chemical class 0.000 description 15
239000002904 solvent Substances 0.000 description 14
IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000013078 crystal Substances 0.000 description 12
150000001875 compounds Chemical class 0.000 description 11
239000000706 filtrate Substances 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
238000003756 stirring Methods 0.000 description 9
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
238000001914 filtration Methods 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
238000000862 absorption spectrum Methods 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
239000000203 mixture Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
230000035484 reaction time Effects 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
238000004816 paper chromatography Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
239000002253 acid Substances 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000007810 chemical reaction solvent Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
LOUZURPQCYZSJH-UHFFFAOYSA-N 1-chloro-2-dichlorophosphorylethane Chemical compound ClCCP(Cl)(Cl)=O LOUZURPQCYZSJH-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
239000003456 ion exchange resin Substances 0.000 description 2
229920003303 ion-exchange polymer Polymers 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical class OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
ZWIADYZPOWUWEW-XVFCMESISA-N CDP Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-XVFCMESISA-N 0.000 description 1
ZWIADYZPOWUWEW-UHFFFAOYSA-N Cytidine 5'-diphosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-UHFFFAOYSA-N 0.000 description 1
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
208000030886 Traumatic Brain injury Diseases 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000007806 chemical reaction intermediate Substances 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
150000001470 diamides Chemical class 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
230000009760 functional impairment Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000003317 industrial substance Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
238000011084 recovery Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1

Landscapes

Saccharide Compounds (AREA)

JP7454979A 1979-06-15 1979-06-15 Preparation of cytidine diphosphate choline Granted JPS55167298A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP7454979A JPS55167298A (en)	1979-06-15	1979-06-15	Preparation of cytidine diphosphate choline

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP7454979A JPS55167298A (en)	1979-06-15	1979-06-15	Preparation of cytidine diphosphate choline

Publications (2)

Publication Number	Publication Date
JPS55167298A JPS55167298A (en)	1980-12-26
JPS636079B2 true JPS636079B2 (fr)	1988-02-08

Family

ID=13550434

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP7454979A Granted JPS55167298A (en)	1979-06-15	1979-06-15	Preparation of cytidine diphosphate choline

Country Status (1)

Country	Link
JP (1)	JPS55167298A (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0282215U (fr) *	1988-12-16	1990-06-26

1979
- 1979-06-15 JP JP7454979A patent/JPS55167298A/ja active Granted

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0282215U (fr) *	1988-12-16	1990-06-26

Also Published As

Publication number	Publication date
JPS55167298A (en)	1980-12-26

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EP0521923B1 (fr)	1995-03-08	Procede de production de nucleosides et analogues
US4567254A (en)	1986-01-28	Method for preparing N6,8-disubstituted 3',5'-cyclic adenosine monophosphate and salt thereof
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US4751293A (en)	1988-06-14	Process for preparation of N6 -substituted 3',5'-cyclic adenosine monophosphate and salt thereof
JPS636079B2 (fr)	1988-02-08
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US4371472A (en)	1983-02-01	Process for preparing cysteamine-S-substituted compounds and derivatives thereof
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CA1297878C (fr)	1992-03-24	Procede de production de l'ester ethylique de l'acide apovincaminique
US5215973A (en)	1993-06-01	Optically active and racemic hydrated diacetylesters of α-glycero-phosphoryl-choline
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JPH10287657A (ja)	1998-10-27	放射線増感剤の製造方法
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JPH03135995A (ja)	1991-06-10	８―アルコキシアデノシン―３′，５′―環状リン酸の分離精製法
JPS601199A (ja)	1985-01-07	シチジン−５′−ジリン酸コリンの製造方法
EP0690848B1 (fr)	1998-01-21	Clathrates aqueux de piperazinylpyridinyle
US5164500A (en)	1992-11-17	Oxetanocin G
KR0164947B1 (ko)	1999-01-15	7-아미노-3-메톡시메틸-3-세펨-4-카르복실산의 신규 제조방법
CA1055925A (fr)	1979-06-05	N-formylcephalosporine a et c et procede de production
CN121591669A (zh)	2026-03-03	一种西诺氨酯中间体的制备方法
KR930007816B1 (ko)	1993-08-20	세펨 화합물의 새로운 제조방법
JPS633877B2 (fr)	1988-01-26
SU802285A1 (ru)	1981-02-07	Способ получени 1- - - АРАбиНОфуРАНОзил-5-фТОРциТОзиНА
JPH07116213B2 (ja)	1995-12-13	新規なｎ▲上６▼，２′―ｏ―ジ置換―アデノシン―３′，５′―環状リン酸及びその製法

JPS636079B2 - - Google Patents

Info

Links

Landscapes

Priority Applications (1)

Applications Claiming Priority (1)

Publications (2)

Family

ID=13550434

Family Applications (1)

Country Status (1)

Cited By (1)

Cited By (1)

Also Published As

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