EP1107943A4 - Procede de preparation de 2-amino-5-cyanophenol - Google Patents

Procede de preparation de 2-amino-5-cyanophenol

Info

Publication number
EP1107943A4
EP1107943A4 EP99943937A EP99943937A EP1107943A4 EP 1107943 A4 EP1107943 A4 EP 1107943A4 EP 99943937 A EP99943937 A EP 99943937A EP 99943937 A EP99943937 A EP 99943937A EP 1107943 A4 EP1107943 A4 EP 1107943A4
Authority
EP
European Patent Office
Prior art keywords
formula
compound
iii
aprotic solvent
cyanide
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Withdrawn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
EP99943937A
Other languages
German (de)
English (en)
Other versions
EP1107943A1 (fr
Inventor
Clifford S Labaw
Susan C Shilcrat
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.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
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 SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Publication of EP1107943A1 publication Critical patent/EP1107943A1/fr
Publication of EP1107943A4 publication Critical patent/EP1107943A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups

Definitions

  • PROCESS FOR MAKING 2-AMINO-5-CYANOPHENOL Scope of the Invention This invention relates to a process for making intermediates useful for making certain phenyl urea compounds.
  • the end-product phenyl urea compounds are useful in treating IL-8, GRO ⁇ , GRO ⁇ , GRO ⁇ and NAP-2 mediated diseases. They are disclosed in PCT application serial number PCT/US96/13632, published 21 August 1997 as WIPO No. WO97/29743 and co-pending U.S. application 08/894291.
  • Interleukin-8 is a chemoattractant for neutrophils, basophils, and a subset of
  • T-cells The T-cells. It is produced by a majority of nucleated cells including macrophages, fibroblasts, endothelial and epithelial cells exposed to TNF, IL-la, IL-lb or LPS, and by neutrophils themselves when exposed to LPS or chemotactic factors such as FMLP.
  • This invention provides a method for making 2-amino-5-cyano-phenol which is a useful intermediate for synthesising N-[2-hydroxy-4-cyanophenyl]-N'-[2-bromophenyl]urea, a compound disclosed in the aforementioned PCT application.
  • This invention relates to a process for making 2-amino-5-cyanophenol.
  • this process comprises preparing the phenol of Formula (I)
  • this invention comprises a process for preparing a compound of Formula (I) from o-anisidine, which process comprises treating o-anisidine with a halogenating agent to obtain Formula (III)
  • Scheme 1 outlines the chemistry for preparing to 2-amino-5-cyanophenol, a third stage intermediate in a synthesis of N-[2-hydroxy-4-cyanophenyl]-N'-[2- bromophenyljurea.
  • stage A The p ⁇ r ⁇ bromination of o-anisidine (stage A) has been described in the literature, using several different reagents (Choudary, B. M.; Sudha, Y., and Reddy, P. N. Synlett., 1994, 450; Reeves, W. P.; and King, R. M. Synth. Comm. 1993, 23, 855; Fox, G. J.; Hallas, G.; Hepworth, J. D.; and Paskins, K. N. Org. Synth., Coll. Vol. 6, 181).
  • the crude reaction product is typically a mixture of the starting material, Formula (III), the ortho isomer 2-bromo-6-methoxy-aniline (1) and the product of over bromination, 2,4-dibromo-6-methoxy-aniline (2) below.
  • a typical crude GC product ratio for 2,4,4,6-tetrabromo-2,5-cyclohexadien-l-one was 15% o- anisidine/6% formula 1/61% o-anisidine/17% formula 2; for HBr-DMSO it was 13% o-anisidine/13% formula 1/53% Formula (II)/22% formula 2.
  • stage b was effected by treating Formula (III) with copper (I) cyanide in either refluxing NN-dimethylformamide or l-methyl-2-pyrrolidinone for 3-5 hours. While the reaction proceeded faster in l-methyl-2-pyrrolidinone, workup was difficult and it was easiest to carry the crude reaction mixture through stage c, then purify by crystallization Stage c provided a crude recovery of 75%.
  • stage c Demethylation of crude Formula (II) (stage c) was effected by several reagents: boron tribromide, sodium ethyl thiolate, and sodium cyanide in refluxing dimethyl sulfoxide.
  • boron tribromide the reaction is carried out in an aprotic solvent such as methylene chloride.
  • the reaction is carried out under an inert gas such as nitrogen. This reaction goes to completion at a reduced temperature, i.e., about -10 to +10 °C in about 1-3 hours.
  • the sodium cyanide reaction proceeds best in dimethyl sulfoxide.
  • the reaction is run under an inert gas such as nitrogen. Refluxing for 3-7 hours is needed to effect the reaction.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé de préparation de 2-amino-5-cyanophénol.
EP99943937A 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol Withdrawn EP1107943A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9833598P 1998-08-28 1998-08-28
US98335P 1998-08-28
PCT/US1999/019494 WO2000012461A1 (fr) 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol

Publications (2)

Publication Number Publication Date
EP1107943A1 EP1107943A1 (fr) 2001-06-20
EP1107943A4 true EP1107943A4 (fr) 2002-07-24

Family

ID=22268831

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99943937A Withdrawn EP1107943A4 (fr) 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol

Country Status (4)

Country Link
EP (1) EP1107943A4 (fr)
JP (1) JP2003525856A (fr)
CA (1) CA2341711A1 (fr)
WO (1) WO2000012461A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY143477A (en) 2002-10-29 2011-05-31 Smithkline Beecham Corp Il-8 receptor antagonists
PT2009992E (pt) 2006-04-21 2012-09-06 Glaxosmithkline Llc Antagonistas de receptores da il-8
RU2008145871A (ru) 2006-04-21 2010-05-27 Смитклайн Бичам Корпорейшн (US) Антагонисты рецептора il-8

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1792156A (en) * 1928-01-17 1931-02-10 Gen Aniline Works Inc 5-halogen-2-amino-1-alkyloxy and 1-aralkyloxy-benzenes and intermediate products thereof and process of preparing them
EP0100172A1 (fr) * 1982-07-23 1984-02-08 Imperial Chemical Industries Plc Dérivés d'amides
US5508464A (en) * 1986-11-07 1996-04-16 L'oreal Process for the preparation of 5,6-dihydroxyindole and intermediate compounds
WO1998033763A1 (fr) * 1997-01-30 1998-08-06 American Home Products Corporation Derives hydroxy-anilino-substitues de cyclobutene-3,4-diones

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1792156A (en) * 1928-01-17 1931-02-10 Gen Aniline Works Inc 5-halogen-2-amino-1-alkyloxy and 1-aralkyloxy-benzenes and intermediate products thereof and process of preparing them
EP0100172A1 (fr) * 1982-07-23 1984-02-08 Imperial Chemical Industries Plc Dérivés d'amides
US5508464A (en) * 1986-11-07 1996-04-16 L'oreal Process for the preparation of 5,6-dihydroxyindole and intermediate compounds
WO1998033763A1 (fr) * 1997-01-30 1998-08-06 American Home Products Corporation Derives hydroxy-anilino-substitues de cyclobutene-3,4-diones

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO0012461A1 *

Also Published As

Publication number Publication date
WO2000012461A1 (fr) 2000-03-09
EP1107943A1 (fr) 2001-06-20
CA2341711A1 (fr) 2000-03-09
JP2003525856A (ja) 2003-09-02

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