CA2012095C - Composes de 3'-tosylcytidine et procede de production - Google Patents

Composes de 3'-tosylcytidine et procede de production

Info

Publication number: CA2012095C
Authority: CA; Canada
Prior art keywords: group; compound; formula; compounds; tosylcytidine
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 2012095

Other languages

English (en)

Other versions

CA2012095A1 (fr

Inventor

Khashayar Karimian

Bruno Konrad Radatus

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 2012095 priority Critical patent/CA2012095C/fr

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

1991-03-13 Priority to AU74801/91A priority patent/AU7480191A/en

1991-03-13 Priority to US07/930,605 priority patent/US5399682A/en

1991-03-13 Priority to PCT/CA1991/000078 priority patent/WO1991013901A1/fr

1991-03-13 Priority to EP91906308A priority patent/EP0523080B1/fr

1991-03-13 Priority to DE69111438T priority patent/DE69111438T2/de

1991-03-13 Priority to BR919106157A priority patent/BR9106157A/pt

1991-03-13 Priority to AT91906308T priority patent/ATE125265T1/de

1991-03-13 Priority to HU9202905A priority patent/HUT61565A/hu

1991-09-13 Publication of CA2012095A1 publication Critical patent/CA2012095A1/fr

1994-02-02 Priority to US08/191,192 priority patent/US5527782A/en

1994-12-15 Priority to US08/356,498 priority patent/US5536824A/en

1995-06-06 Priority to US08/469,506 priority patent/US5596093A/en

1996-07-23 Application granted granted Critical

1996-07-23 Publication of CA2012095C publication Critical patent/CA2012095C/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 17
238000004519 manufacturing process Methods 0.000 title abstract description 7
VLIXZEKAVFLJRY-UJDVCPFMSA-N 4-amino-1-[(2r,3s,4r,5r)-3,4-dihydroxy-5-(hydroxymethyl)-4-(4-methylphenyl)sulfonyloxolan-2-yl]pyrimidin-2-one Chemical class C1=CC(C)=CC=C1S(=O)(=O)[C@]1(O)[C@@H](O)[C@H](N2C(N=C(N)C=C2)=O)O[C@@H]1CO VLIXZEKAVFLJRY-UJDVCPFMSA-N 0.000 title description 8
-1 p-toluenesulfonyl Chemical group 0.000 claims abstract description 20
150000001875 compounds Chemical class 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 10
150000001412 amines Chemical class 0.000 claims abstract description 9
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
239000001257 hydrogen Substances 0.000 claims abstract description 7
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims abstract description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 5
125000005257 alkyl acyl group Chemical group 0.000 claims abstract description 5
125000005251 aryl acyl group Chemical group 0.000 claims abstract description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 4
229910019142 PO4 Inorganic materials 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 4
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 4
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 abstract description 4
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims abstract description 3
235000021317 phosphate Nutrition 0.000 claims abstract 2
150000003013 phosphoric acid derivatives Chemical class 0.000 claims abstract 2
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
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 4
150000002431 hydrogen Chemical class 0.000 claims description 3
239000012359 Methanesulfonyl chloride Substances 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 2
150000001805 chlorine compounds Chemical group 0.000 claims 1
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 abstract description 6
230000006819 RNA synthesis Effects 0.000 abstract 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 5
239000000203 mixture Substances 0.000 description 5
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 4
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 4
239000002244 precipitate Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
240000001414 Eucalyptus viminalis Species 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
HNNLWPATHYVXMO-NMFUWQPSSA-N [(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 4-methylbenzenesulfonate Chemical class C1=CC(C)=CC=C1S(=O)(=O)O[C@H]1[C@@H](O)[C@H](N2C(N=C(N)C=C2)=O)O[C@@H]1CO HNNLWPATHYVXMO-NMFUWQPSSA-N 0.000 description 2
VAUJJKNQYHUZFJ-ZOQUXTDFSA-N [(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] methanesulfonate Chemical compound O[C@@H]1[C@H](OS(=O)(=O)C)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 VAUJJKNQYHUZFJ-ZOQUXTDFSA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
239000012043 crude product Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
WCXOOVODAUHPMZ-VDSQZSGCSA-N 4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-4-(4-methylphenyl)sulfonyloxolan-2-yl]pyrimidin-2-one ethanol Chemical compound C(C)O.S(=O)(=O)(C1=CC=C(C)C=C1)[C@@]1([C@H]([C@@H](O[C@@H]1CO)N1C(=O)N=C(N)C=C1)O)O WCXOOVODAUHPMZ-VDSQZSGCSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
NIDVTARKFBZMOT-PEBGCTIMSA-N N(4)-acetylcytidine Chemical compound O=C1N=C(NC(=O)C)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NIDVTARKFBZMOT-PEBGCTIMSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
238000013019 agitation Methods 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
238000009835 boiling Methods 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
229910001887 tin oxide Inorganic materials 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 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 2012095 1990-03-13 1990-03-13 Composes de 3'-tosylcytidine et procede de production Expired - Fee Related CA2012095C (fr)

Priority Applications (12)

Application Number	Priority Date	Filing Date	Title
CA 2012095 CA2012095C (fr)	1990-03-13	1990-03-13	Composes de 3'-tosylcytidine et procede de production
HU9202905A HUT61565A (en)	1990-03-13	1991-03-13	Process for producing 2,3'-0-cyclocytidine and 1-(beta-d-xylopento-furanosyl)-cytosine derivatives and their analogous compounds, as well as 3'-0-(p-toluenesulfonyl)-cytidine derivatives
PCT/CA1991/000078 WO1991013901A1 (fr)	1990-03-13	1991-03-13	Composes de tosylcytidine-3'-0 et de cytosine, et leur procede de production
EP91906308A EP0523080B1 (fr)	1990-03-13	1991-03-13	Composes de 2,3'-o-cyclocytidine, et leur procede de production
DE69111438T DE69111438T2 (de)	1990-03-13	1991-03-13	2,3'-o-cyclocytidine und verfahren zu deren herstellung.
BR919106157A BR9106157A (pt)	1990-03-13	1991-03-13	Compostos e processo 3'-o-tosil citidina e citosina e processo para producao dos mesmos
AU74801/91A AU7480191A (en)	1990-03-13	1991-03-13	3'-o-tosylcytidine and cytosine compounds, and process for production thereof
US07/930,605 US5399682A (en)	1990-03-13	1991-03-13	Process for preparing 2,3'-O-cyclocytidine
AT91906308T ATE125265T1 (de)	1990-03-13	1991-03-13	2,3'-o-cyclocytidine und verfahren zu deren herstellung.
US08/191,192 US5527782A (en)	1990-03-13	1994-02-02	5-halo-2,3'-O-cyclocytidines
US08/356,498 US5536824A (en)	1990-03-13	1994-12-15	Organosulfonyl salts of 2,3'-O-cyclocytidine
US08/469,506 US5596093A (en)	1990-03-13	1995-06-06	Process for preparing halogenated 2,3-O-cyclocytidine derivatives

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA 2012095 CA2012095C (fr)	1990-03-13	1990-03-13	Composes de 3'-tosylcytidine et procede de production

Publications (2)

Publication Number	Publication Date
CA2012095A1 CA2012095A1 (fr)	1991-09-13
CA2012095C true CA2012095C (fr)	1996-07-23

Family

ID=4144517

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2012095 Expired - Fee Related CA2012095C (fr)	1990-03-13	1990-03-13	Composes de 3'-tosylcytidine et procede de production

Country Status (1)

Country	Link
CA (1)	CA2012095C (fr)

1990
- 1990-03-13 CA CA 2012095 patent/CA2012095C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2012095A1 (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
JPH0959292A (ja)	1997-03-04	４−アミノピリミジンヌクレオシドの製造法
US5399682A (en)	1995-03-21	Process for preparing 2,3'-O-cyclocytidine
US5124442A (en)	1992-06-23	Process for preparing azt (3'-azido-3'-deoxy-thymidine) and related compounds
CA2012096C (fr)	1997-10-28	Composes de cytosine et procede de production
JPS59206350A (ja)	1984-11-22	１−置換アゼチジン−３−オ−ル誘導体の製造
EP0473435B1 (fr)	1995-07-19	Mono-N,N-diméthyl-4-aminopyridinium sn glycérol-3-phosphate, sa préparation et utilisation pour la préparation d'acides phosphatidiques
CA2012093C (fr)	1995-12-26	Procede de production de 2,2'-cyclocitidine et de leurs analogues
CA2012094C (fr)	1996-07-23	Procede de production de la cytarabine et de ses analogues
US5206351A (en)	1993-04-27	Process for the preparation of 2-amino (2,3,5-tri-o-benzyl-beta-d-arabinofuranosyl)adenine
JP3499896B2 (ja)	2004-02-23	２’−デオキシヌクレオシド類の製造方法
US5162535A (en)	1992-11-10	Mono-N,N-dimethyl-4 aminopyridinium sn-glycerol-3-phosphate, its production and use in preparation of phosphatidic acids
KR100317615B1 (ko)	2001-12-22	8-클로로아데노신 3',5'-사이클릭 모노포스페이트 또는 그 염의 제조방법
JP4004082B2 (ja)	2007-11-07	環状ニトログアニジン誘導体の製造法
JPS63250396A (ja)	1988-10-18	３′−アジド−３′−デオキシチミジン誘導体
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
US4324895A (en)	1982-04-13	Novel process for producing pyrimidine nucleosides and novel pyrimidine nucleosides obtained thereby
HU198949B (en)	1989-12-28	Process for producing 5-substituted-3'azido-2',3'-dideoxyribonucleosides
JPH0134234B2 (fr)	1989-07-18
JPH0535157B2 (fr)	1993-05-25
JPH06135962A (ja)	1994-05-17	２’，３’−ジデオキシヌクレオシド誘導体の製造方法
JPH05339264A (ja)	1993-12-21	１−（２，３−ジデオキシ−ｄ−グリセロ−ペントフラノシル）チミン誘導体の製造方法
JPH10259192A (ja)	1998-09-29	ホスホロチオエートジエステル化合物の製造法
JPH029859A (ja)	1990-01-12	スルホニウム化合物の製造方法
JPH03264582A (ja)	1991-11-25	２’，３’―ジデオキシ―２’，３’―ジ置換―ヌクレオシド類とその製造方法