WO2000012461A1 - Procede de preparation de 2-amino-5-cyanophenol - Google Patents

Procede de preparation de 2-amino-5-cyanophenol Download PDF

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Publication number
WO2000012461A1
WO2000012461A1 PCT/US1999/019494 US9919494W WO0012461A1 WO 2000012461 A1 WO2000012461 A1 WO 2000012461A1 US 9919494 W US9919494 W US 9919494W WO 0012461 A1 WO0012461 A1 WO 0012461A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
iii
aprotic solvent
cyanide
Prior art date
Application number
PCT/US1999/019494
Other languages
English (en)
Inventor
Clifford S. Labaw
Susan C. Shilcrat
Original Assignee
Smithkline Beecham Corporation
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 Corporation filed Critical Smithkline Beecham Corporation
Priority to EP99943937A priority Critical patent/EP1107943A4/fr
Priority to CA002341711A priority patent/CA2341711A1/fr
Priority to JP2000567496A priority patent/JP2003525856A/ja
Publication of WO2000012461A1 publication Critical patent/WO2000012461A1/fr

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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.
PCT/US1999/019494 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol WO2000012461A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP99943937A EP1107943A4 (fr) 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol
CA002341711A CA2341711A1 (fr) 1998-08-28 1999-08-26 Procede de preparation de 2-amino-5-cyanophenol
JP2000567496A JP2003525856A (ja) 1998-08-28 1999-08-26 ２−アミノ−５−シアノフェノールの製法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US9833598P 1998-08-28 1998-08-28
US60/098,335 1998-08-28

Publications (1)

Publication Number Publication Date
WO2000012461A1 true WO2000012461A1 (fr) 2000-03-09

Family

ID=22268831

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/019494 WO2000012461A1 (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)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7709485B2 (en) 2002-10-29 2010-05-04 Glaxosmithkline Llc IL-8 receptor antagonists
US7893089B2 (en) 2006-04-21 2011-02-22 GlaxoSmithKline, LLC IL-8 receptor antagonists
US8097626B2 (en) 2006-04-21 2012-01-17 Glaxosmithkline Llc IL-8 receptor antagonists

Family Cites Families (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
ATE28864T1 (de) * 1982-07-23 1987-08-15 Ici Plc Amide-derivate.
CH676845A5 (fr) * 1986-11-07 1991-03-15 Oreal
WO1998033763A1 (fr) * 1997-01-30 1998-08-06 American Home Products Corporation Derives hydroxy-anilino-substitues de cyclobutene-3,4-diones

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BENTON ET AL.: "The Cleavage of Ethers with Boron Bromide. I. Some Common Ethers", J. AMER. CHEM. SOC., vol. 64, May 1942 (1942-05-01), pages 1128 - 1129, XP002925614 *
CALLEN ET AL.: "9-CYANOPHENANTHRENE", ORGANIC SYNTHESES COLLECTIVE, vol. 3, 1955, pages 212 - 213, XP002925621 *
FRASER ET AL.: "Demethylation of Labile Aryl Ethers", J. ORG. CHEM., vol. 41, no. 1, 1976, pages 170 - 171, XP002925615 *
NEWMAN ET AL.: "Phenolic and Ketonic Tautomers in Polycyclic Aromatic Hydrocarbons", J. AMER. CHEM. SOC., vol. 98, no. 11, 26 May 1976 (1976-05-26), pages 3237 - 3242, XP002925616 *
NEWMAN M.S.: "alpha-Napthonitrile", ORG. SYN. COL., vol. 3, 1955, pages 631 - 633, XP002925617 *
See also references of EP1107943A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7709485B2 (en) 2002-10-29 2010-05-04 Glaxosmithkline Llc IL-8 receptor antagonists
US7893089B2 (en) 2006-04-21 2011-02-22 GlaxoSmithKline, LLC IL-8 receptor antagonists
US8097626B2 (en) 2006-04-21 2012-01-17 Glaxosmithkline Llc IL-8 receptor antagonists

Also Published As

Publication number Publication date
JP2003525856A (ja) 2003-09-02
CA2341711A1 (fr) 2000-03-09
EP1107943A1 (fr) 2001-06-20
EP1107943A4 (fr) 2002-07-24

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