CA2012094C - Procede de production de la cytarabine et de ses analogues - Google Patents

Procede de production de la cytarabine et de ses analogues

Info

Publication number: CA2012094C
Authority: CA; Canada
Prior art keywords: group; cytarabine; hydrogen; process defined; amine
Prior art date: 1990-03-13
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 - Fee Related

Application number

CA 2012094

Other languages

English (en)

Other versions

CA2012094A1 (fr

Inventor

Khashayar Karimian

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.)

Apotex Pharmachem Inc

Original Assignee

Acic Canada Inc

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.)

1990-03-13

Filing date

1990-03-13

Publication date

1996-07-23

1990-03-13 Priority to CA 2012094 priority Critical patent/CA2012094C/fr

1990-03-13 Application filed by Acic Canada Inc filed Critical Acic Canada Inc

1991-03-13 Priority to DE69108014T priority patent/DE69108014T2/de

1991-03-13 Priority to AU74737/91A priority patent/AU7473791A/en

1991-03-13 Priority to EP91906244A priority patent/EP0521923B1/fr

1991-03-13 Priority to PCT/CA1991/000077 priority patent/WO1991013900A1/fr

1991-03-13 Priority to BR919106158A priority patent/BR9106158A/pt

1991-03-13 Priority to AT91906244T priority patent/ATE119541T1/de

1991-03-13 Priority to HU9202906A priority patent/HUT61566A/hu

1991-09-13 Publication of CA2012094A1 publication Critical patent/CA2012094A1/fr

1994-09-27 Priority to US08/313,579 priority patent/US5610292A/en

1996-07-23 Application granted granted Critical

1996-07-23 Publication of CA2012094C publication Critical patent/CA2012094C/fr

2010-03-13 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 25
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 title abstract description 29
229960000684 cytarabine Drugs 0.000 title abstract description 24
150000001412 amines Chemical class 0.000 claims abstract description 12
239000003125 aqueous solvent Substances 0.000 claims abstract description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
-1 methoxytrityl Chemical group 0.000 claims description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 5
239000000203 mixture Substances 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
150000001875 compounds Chemical class 0.000 claims description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000005257 alkyl acyl group Chemical group 0.000 claims description 3
125000005251 aryl acyl group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
229910019142 PO4 Inorganic materials 0.000 claims description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
235000021317 phosphate Nutrition 0.000 claims description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 2
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
BBDAGFIXKZCXAH-CCXZUQQUSA-N ancitabine Chemical compound N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 BBDAGFIXKZCXAH-CCXZUQQUSA-N 0.000 abstract description 5
230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
239000002246 antineoplastic agent Substances 0.000 abstract description 2
239000003443 antiviral agent Substances 0.000 abstract description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
238000004519 manufacturing process Methods 0.000 description 8
UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 7
UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 7
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000000243 solution Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
KZOWNALBTMILAP-JBMRGDGGSA-N ancitabine hydrochloride Chemical compound Cl.N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 KZOWNALBTMILAP-JBMRGDGGSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical compound C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 description 2
239000001177 diphosphate Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
239000012264 purified product Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
244000233967 Anethum sowa Species 0.000 description 1
238000013019 agitation Methods 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
244000309464 bull Species 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000002950 deficient Effects 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229910001887 tin oxide Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA 2012094 1990-03-13 1990-03-13 Procede de production de la cytarabine et de ses analogues Expired - Fee Related CA2012094C (fr)

Priority Applications (9)

Application Number	Priority Date	Filing Date	Title
CA 2012094 CA2012094C (fr)	1990-03-13	1990-03-13	Procede de production de la cytarabine et de ses analogues
AU74737/91A AU7473791A (en)	1990-03-13	1991-03-13	Process for producing 2,2'-o-cyclonucleosides, nucleosides, and analogs thereof
EP91906244A EP0521923B1 (fr)	1990-03-13	1991-03-13	Procede de production de nucleosides et analogues
PCT/CA1991/000077 WO1991013900A1 (fr)	1990-03-13	1991-03-13	Procede de production de 2-2'-o-cyclonucleosides, nucleosides et analogues
DE69108014T DE69108014T2 (de)	1990-03-13	1991-03-13	Verfahren zur herstellung von nucleosiden und ihre analogen.
BR919106158A BR9106158A (pt)	1990-03-13	1991-03-13	Processo para produzir 2,2'-o-ciclonucleosideos,nucleosideos e seus analogos
AT91906244T ATE119541T1 (de)	1990-03-13	1991-03-13	Verfahren zur herstellung von nucleosiden und ihre analogen.
HU9202906A HUT61566A (en)	1990-03-13	1991-03-13	Process for producing 2,2'-o-cyclonucleosides, nucleosides and their analogous compounds
US08/313,579 US5610292A (en)	1990-03-13	1994-09-27	Process for producing 2,2'-o-cyclonucleosides nucleosides, and analogs thereof

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA 2012094 CA2012094C (fr)	1990-03-13	1990-03-13	Procede de production de la cytarabine et de ses analogues

Publications (2)

Publication Number	Publication Date
CA2012094A1 CA2012094A1 (fr)	1991-09-13
CA2012094C true CA2012094C (fr)	1996-07-23

Family

ID=4144516

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2012094 Expired - Fee Related CA2012094C (fr)	1990-03-13	1990-03-13	Procede de production de la cytarabine et de ses analogues

Country Status (1)

Country	Link
CA (1)	CA2012094C (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN115925755A (zh) *	2022-12-14	2023-04-07	北京斯利安药业有限公司	盐酸阿糖胞苷的制备方法

1990
- 1990-03-13 CA CA 2012094 patent/CA2012094C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2012094A1 (fr)	1991-09-13

Legal Events

Date	Code	Title	Description
1990-07-13	EEER	Examination request
2001-03-13	MKLA	Lapsed

Publication	Publication Date	Title
EP0521923B1 (fr)	1995-03-08	Procede de production de nucleosides et analogues
EP0719788B1 (fr)	1999-05-12	Procédé pour la préparation de l'hydrochlorure de 1-(2'-deoxy-2',2'-difluoro-D-ribofuranosyl)-4-amino-pyrimidine-2-one
US4182859A (en)	1980-01-08	Process for the preparation of 2'-deoxyribofuranosyl nucleosides
CA2012094C (fr)	1996-07-23	Procede de production de la cytarabine et de ses analogues
JP2744454B2 (ja)	1998-04-28	ベータ―２’，２’―ジフルオロヌクレオシド類の製造方法
US4751293A (en)	1988-06-14	Process for preparation of N6 -substituted 3',5'-cyclic adenosine monophosphate and salt thereof
EP0635517B1 (fr)	2000-05-17	Procédé pour la production des dérivés de 1-(2'-déoxy-bêta-D-érythropentofuranosyl)-5-trifluorométhyluracil
EP0523080B1 (fr)	1995-07-19	Composes de 2,3'-o-cyclocytidine, et leur procede de production
CA2012096C (fr)	1997-10-28	Composes de cytosine et procede de production
JP2666160B2 (ja)	1997-10-22	５−ｏ−ピリミジル−２，３−ジデオキシ−１−チオフラノシド誘導体，その製造方法及び用途
CA2012093C (fr)	1995-12-26	Procede de production de 2,2'-cyclocitidine et de leurs analogues
US20030236397A1 (en)	2003-12-25	Process for preparing beta-L-2'deoxy-thymidine
HU198179B (en)	1989-08-28	Process for producing n-methyl-1-alkylthio-2-nitroethenamine derivatives
JP3005422B2 (ja)	2000-01-31	２’−デオキシ−５−トリフルオロメチル−β−ウリジン誘導体の製造法
JP2002293792A (ja)	2002-10-09	ヌクレオシド又は糖のフッ素化誘導体の製造方法
KR100317615B1 (ko)	2001-12-22	8-클로로아데노신 3',5'-사이클릭 모노포스페이트 또는 그 염의 제조방법
JPH0665281A (ja)	1994-03-08	２−アミノ（２，３，５−トリ−０−ベンジル−β−Ｄ−アラビノフラノシル）アデニンの調製の改良方法
EP1654270B1 (fr)	2007-12-26	Procede de preparation de 2',3'-didehydro-2',3'-dideoxynucleosides et de 2',3'-dideoxynucleosides
JPWO1995012593A1 (ja)	1995-10-05	５−ｏ−ピリミジル−２，３−ジデオキシ−１−チオフラノシド誘導体，その製造方法及び用途
CA2207617C (fr)	2007-06-26	Procede de preparation de chlorhydrate de 1-(2'-desoxy-2',2'-difluoro-d-ribofuranosyl)-4-aminopyrimidine-2-one
JPH09301992A (ja)	1997-11-25	２−チオシトシンアラビノシド誘導体ならびに同誘導体または２−チオシトシンアラビノシドの製造方法
JPH0529369B2 (fr)	1993-04-30
JPS633877B2 (fr)	1988-01-26
JP2001031691A (ja)	2001-02-06	９−（２−ホスホニルメトキシアルキル）アデニンの製造法
JPWO2000039144A1 (ja)	2002-04-16	ヌクレオシド又は糖のフッ素化誘導体の製造方法