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1. WO2002004417 - PROCESS FOR THE PREPARATION OF DERIVATIVES OF 4-AMINO-3-HYDROXYPYRROLE-2-CARBOXYLIC ACID

Publication Number WO/2002/004417
Publication Date 17.01.2002
International Application No. PCT/US2001/021274
International Filing Date 05.07.2001
Chapter 2 Demand Filed 06.02.2002
IPC
C07C 229/30 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
CACYCLIC OR CARBOCYCLIC COMPOUNDS
229Compounds containing amino and carboxyl groups bound to the same carbon skeleton
02having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
30the carbon skeleton being acyclic and unsaturated
C07D 207/36 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
207Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
30having two double bonds between ring members or between ring members and non-ring members
34with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
36Oxygen or sulfur atoms
C07D 207/42 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
207Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
30having two double bonds between ring members or between ring members and non-ring members
34with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
42Nitro radicals
CPC
C07C 229/30
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
CACYCLIC OR CARBOCYCLIC COMPOUNDS
229Compounds containing amino and carboxyl groups bound to the same carbon skeleton
02having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
30the carbon skeleton being acyclic and unsaturated
C07D 207/36
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
207Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
30having two double bonds between ring members or between ring members and non-ring members
34with heteroatoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
36Oxygen or sulfur atoms
C07D 207/42
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
207Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
30having two double bonds between ring members or between ring members and non-ring members
34with heteroatoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
42Nitro radicals
Applicants
  • PHARMACIA CORPORAION [US]/[US] (AllExceptUS)
  • PHILLION, Dennis, P. [US]/[US] (UsOnly)
  • SINGH, Megh [US]/[US] (UsOnly)
Inventors
  • PHILLION, Dennis, P.
  • SINGH, Megh
Agents
  • ROEDEL, John K Jr.
  • BOSCH, Henry A.
Priority Data
60/216,10106.07.2000US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) PROCESS FOR THE PREPARATION OF DERIVATIVES OF 4-AMINO-3-HYDROXYPYRROLE-2-CARBOXYLIC ACID
(FR) PROCEDE RELATIF A L'ELABORATION DE DERIVES D'ACIDE 4-AMINO-3-HYDROXYPYRROLE-2-CARBOXYLIQUE
Abstract
(EN) Novel processes and intermediates are provided for the synthesis of derivatives of 4-amino-3-hydroxypyrrole-2-carboxylic acids that are useful as monomers for polyamides capable of binding dsDNA. According to one preferred reaction scheme, an alkyl alkoxymethylene nitroacetate (Formula VIII) is prepared by reaction of a trialkyl orthoformate or orthoacetate with a nitroacetate ester in the presence of a carboxylic anhydride. The compound of Formula VIII is condensed with an N-substituted glycine to yield an N-substituted(2-nitro-2-alkoxycarbonyl)vinyl glycinate ester (Formula VII). Ring closure in the presence of an alkali metal alkoxide yields a 4-nitro-3-hydroxypyrrole-2-carboxylic ester (Formula V). After blocking of the 3-hydroxy group to produce a further intermediate (Formula IV), the 4-nitro group is reduced to a 4-amino group (Formula III), and the 4-amino group is then blocked by reaction with a dicarbonate diester to produce the fully blocked intermediate (Formula II). Saponification of the 2-carboxylic acid ester yields a monomer having a free 2-carboxylic ester moiety (Formula I).
(FR) L'invention concerne des procédés et des intermédiaires pour la synthèse de dérivés d'acides 4-amino-3-hydroxypyrrole-2-carboxyliques utiles comme monomères pour des polyamides capables de liaison avec de l'ADN double brin. Selon un mode de réalisation préféré, on élabore un nitroacétate d'alkyle et d'alcoxyméthylène (formule VIII) par réaction entre un orthoformate ou un orthoacétate de trialkyle et un ester de nitroacétate, en présence d'anhydride carboxylique. Le composé de formule VIII est condensé avec une glycine à substitution en N, donnant un ester de glycinate de vinyle (2-nitro-2-alcoxycarbonyle) à substitution en N (formule VII). La cyclisation en présence d'alcoxyde de métal alcalin donne un ester 4-nitro-3-hydroxypyrrole-2-carboxylique (formule V). Après le blocage du groupe 3-hydroxy visant à produire un intermédiaire supplémentaire (formule IV), on réduit le groupe 4-nitro en groupe 4-amino (formule III), lequel est ensuite bloqué par réaction avec un diester de dicarbonate pour donner un intermédiaire entièrement bloqué (formule II). La saponification de l'ester d'acide 2-carboxylique donne un monomère à fraction ester 2-carboxylique libre (formule I).
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