EP1032573A1 - Procede de preparation d'un analogue de nucleoside chiral - Google Patents

Procede de preparation d'un analogue de nucleoside chiral

Info

Publication number
EP1032573A1
EP1032573A1 EP97952769A EP97952769A EP1032573A1 EP 1032573 A1 EP1032573 A1 EP 1032573A1 EP 97952769 A EP97952769 A EP 97952769A EP 97952769 A EP97952769 A EP 97952769A EP 1032573 A1 EP1032573 A1 EP 1032573A1
Authority
EP
European Patent Office
Prior art keywords
compound
formula
amino
methanol
cyclopropylamino
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.)
Withdrawn
Application number
EP97952769A
Other languages
German (de)
English (en)
Inventor
Christopher John Wallis
Martin Francis Jones
Shiping Xie
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.)
Glaxo Group Ltd
Original Assignee
Glaxo Group 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.)
Filing date
Publication date
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Publication of EP1032573A1 publication Critical patent/EP1032573A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems

Definitions

  • the present invention relates to a new process for the preparation of the chiral nucleoside analogue (1S, 4R)-4-[2-amino-6-(cyclopropylamino)-9H purin-9-yl]-2- cyclopentene-1-methanol (compound of Formula (I)).
  • WO91/15490 discloses a single step process for the formation of the (1S, 4R)- 4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1- methanol intermediate by reacting (1S, 4R)-4-hydroxy-2-cyclopentene-1 -methanol, in which the allylic hydroxyl group has been activated as an ester or carbonate and the other hydroxyl group has a blocking group attached (for example 1 ,4- bis- methylcarbonate) with 2-amino-6-chloropurine.
  • This process offers significant cost savings compared to previous processes described and represents the first aspect of the present invention.
  • the major commercial advantages are the length of time to manufacture the compound of formula (I) is significantly reduced using the process of the invention compared to earlier processes described, and wastage is significantly reduced.
  • X is H or a blocking group and Y is H or an activating group, with 2- amino-6-(cyclopropylamino) purine in the presence of a catalyst.
  • 2-Amino-6-cyclopropylamino-9H-purine can be prepared by treating 2-amino-6- chloropurine with cyclopropylamine, or in accordance with the methods described in US5420115.
  • (1S, 4R)- 4-Hydroxy-2-cyclopentene-1 -methanol and the activated and/or blocked version of (1S, 4R)-4-hydroxy-2-cyclopentene-1-methanol may be prepared in accordance with reactions described in WO91/15490 or Hodgson et al. in J.Chem. Soc. Perkin Trans. 1 1994; 3373-3378..
  • the preferred catalyst is a transition metal catalyst, preferably a palladium compound but may also be a derivative of other transition metals (such as nickel, molybdenum, tungsten), preferably in the presence of a ligand such as a phosphine.
  • a transition metal catalyst preferably a palladium compound but may also be a derivative of other transition metals (such as nickel, molybdenum, tungsten), preferably in the presence of a ligand such as a phosphine.
  • Preferred transition metal catalyst are tetrakis (triphenylphosphine) palladium, or tris(dibenzylideneacetone) dipalladium, in the presence of triphenylphosphine
  • Suitable activated derivatives of the allylic alcohol group of the compound of formula (II) or (III) include esters (such as acetate); carbonates (such as methylcarbonate); carbamates, preferably RR 'NOC wherein R and R 1 independently selected from C1-6alkyl, aryl or heteroaryl; or phosphates, preferably (RO) 2 OP wherein each R is independently selected from C1-6alkyl, aryl and heteroaryl.
  • a preferred activng blocking groups are cylic carbonates (such as used for the compound of formula (IV).
  • Suitable blocking groups may be any such groups recognised in the art of organic chemistry as suitable for protecting primary hydroxymethyl groups, suitable blocking groups include those reported by T W Green in Protecting Groups in Organic Synthesis, Chapter 7, page 10. J. Wiley and sons, New York, 1981 , and include esters, ethers and carbonates (such as methyl carbonate).
  • Suitable solvents include, for example, dimethylsulphoxide, N.N- dimethylformamide, N.N-dimethylacetamide or tetrahydrofuran preferably at temperatures between 0° and 150°C.
  • Triphenylphosphine 14mg was added, under nitrogen, to a mixture of (1S.4R)- 4-hydroxy-2-cyclopentene -1 -methanol bis(methylcarbonate) (91 mg), 2-amino-6- (cyclopropylamino) purine (90mg), tris(dibenzylideneacetone)dipalladium (12mg) and dry DMF (2ml) and the resulting solution stirred at room temperature for 40 min.
  • the DMF was removed at 60° in vacuo and the residue partitioned between ethyl acetate (25ml.) and 20% sodium chloride solution (10ml.).
  • the ethyl acetate solution was washed with 20% sodium chloride (2x12ml.) and with saturated sodium chloride solution, then dried (MgSO ) and the solvent removed in vacuo.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un nouveau procédé permettant de préparer l'analogue de nucléoside chiral (1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H purin-9-yl]-2-cyclopentène-1-méthanol, consistant à faire réagir un composé représenté par la formule (II) ou (III), dans lesquelles X est H ou un groupe bloquant et Y est H ou un groupe activateur, avec la 2-amino-6-(cyclopropylamino)purine en présence d'un catalyseur.
EP97952769A 1997-11-12 1997-11-12 Procede de preparation d'un analogue de nucleoside chiral Withdrawn EP1032573A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP1997/006379 WO1999024431A1 (fr) 1997-11-12 1997-11-12 Procede de preparation d'un analogue de nucleoside chiral

Publications (1)

Publication Number Publication Date
EP1032573A1 true EP1032573A1 (fr) 2000-09-06

Family

ID=8166798

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97952769A Withdrawn EP1032573A1 (fr) 1997-11-12 1997-11-12 Procede de preparation d'un analogue de nucleoside chiral

Country Status (4)

Country Link
EP (1) EP1032573A1 (fr)
JP (1) JP2001522850A (fr)
AU (1) AU5653498A (fr)
WO (1) WO1999024431A1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT95516A (pt) * 1989-10-06 1991-08-14 Wellcome Found Processo para a preparacao de derivados de 2',3'-didesoxi nucleosidos 6-substituidos
MY104575A (en) * 1989-12-22 1994-04-30 The Wellcome Foundation Ltd Therapeutic nucleosides.
US5126452A (en) * 1990-04-06 1992-06-30 Glaxo Inc. Synthesis of purine substituted cyclopentene derivatives
GB9402161D0 (en) * 1994-02-04 1994-03-30 Wellcome Found Chloropyrimidine intermediates

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9924431A1 *

Also Published As

Publication number Publication date
WO1999024431A1 (fr) 1999-05-20
AU5653498A (en) 1999-05-31
JP2001522850A (ja) 2001-11-20

Similar Documents

Publication Publication Date Title
CA2167345A1 (fr) Derives de disubstitution en 2,8 de quinazolinones
CA2307951A1 (fr) Procede de synthese d'analogues de nucleosides
Siddiqi et al. Enantiospecific synthesis of 5′-noraristeromycin and its 7-deaza derivative and a formal synthesis of (-)-5′-homoaristeromycin
US5126452A (en) Synthesis of purine substituted cyclopentene derivatives
KR100701114B1 (ko) 푸린 유도체 및 이를 위한 중간체를 제조하는 방법
Mekonnen et al. Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin
WO1999021861A1 (fr) Procede de preparation d'un analogue de nucleoside chiral
AU3760793A (en) Antiviral phosphonic acid derivatives of purine analogues
EP1032573A1 (fr) Procede de preparation d'un analogue de nucleoside chiral
CN102532199A (zh) 核苷类化合物之新型苄基胺基磷酸酯前药的结构与合成
Szakonyi et al. Carbocyclic nucleosides from enantiomeric, α-pinane-based aminodiols
US5057630A (en) Synthesis of cyclopentene derivatives
Huang et al. Synthesis of the minor acrolein adducts of 2′-deoxyguanosine and their generation in oligomeric DNA
Boryski A facile synthesis of 9-(1, 3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) from guanosine
US6437125B1 (en) Process for the production of purine derivatives
EP1456211A1 (fr) Indolocarbazoles monosubstitues a n-carbacycles utilises comme inhibiteurs de proteine-kinase
EP0564006A2 (fr) Dérivés de purine et procédé pour leur préparation
Sagi et al. Synthesis and enzymic activity of some new purine ring system analogs of adenosine 3'5'-cyclic monophosphate
US5079364A (en) T-alkyl ergoline derivatives
Vince et al. 6-Deoxycarbovir: a xanthine oxidase activated prodrug of carbovir
KR20190002779A (ko) 알콕시알렌 화합물로부터 금속 촉매를 사용하여 n-글리코사이드 화합물을 위치선택적 및 입체선택적으로 제조하는 방법
US5241069A (en) Carbonate intermediates for the synthesis of purine substituted cyclopentene derivatives
US4690917A (en) Imidazopyridayine derivatives having antiviral activity
Moreno‐Mañas et al. 2, 4, 6‐Triphenylpyridine as a neutral leaving group in the palladium (0)‐catalyzed allylation of nucleophiles
Curran An Unanticipated Result in the Pd (0) Catalyzed Coupling of Sodium Adenate with cis-4-Acetyloxy-and cis-4-t-Butyldimethylsilyloxy-2-Cyclopentenyl Diethylphosphate

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20000511

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL PAYMENT 20000511;LT PAYMENT 20000511;LV PAYMENT 20000511;MK PAYMENT 20000511;RO PAYMENT 20000511;SI PAYMENT 20000511

17Q First examination report despatched

Effective date: 20001229

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20021026