PE20000429A1 - PROCESS TO PREPARE 4-SUBSTITUTED-1H-INDOL-3-GLIOXAMIDES - Google Patents

PROCESS TO PREPARE 4-SUBSTITUTED-1H-INDOL-3-GLIOXAMIDES

Info

Publication number
PE20000429A1
PE20000429A1 PE1999000311A PE00031199A PE20000429A1 PE 20000429 A1 PE20000429 A1 PE 20000429A1 PE 1999000311 A PE1999000311 A PE 1999000311A PE 00031199 A PE00031199 A PE 00031199A PE 20000429 A1 PE20000429 A1 PE 20000429A1
Authority
PE
Peru
Prior art keywords
alkyl
compound
alcoxy
halo
group
Prior art date
Application number
PE1999000311A
Other languages
Spanish (es)
Inventor
Benjamin Alan Anderson
Nancy Kay Harn
Richard Duane Miller
Edward Francis Plocharczyk
Original Assignee
Lilly Co Eli
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 Lilly Co Eli filed Critical Lilly Co Eli
Publication of PE20000429A1 publication Critical patent/PE20000429A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/22Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Indole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

SE REFIERE A UN PROCEDIMIENTO PARA PREPARAR 1H-INDOL-3-GLIOXAMIDAS DE FORMULA I, DONDE R1 ES ALQUILO C7-C20, GRUPO a, b, c; R10 ES HALO, ALQUILO C1-C10, ALCOXI C1-C10, ENTRE OTROS; t ES 0-5; R2 ES H, HALO, ALQUILO C1-C3, ENTRE OTROS; R4 ES -CO2H, -SO3H, PO(OH)2; R5 ES H, ALQUILO C1-C6, ALCOXI C1-C6, ENTRE OTROS; QUE COMPRENDE a)HALOGENAR R8-O-C(=O)-CH2-C(0O)-R2, R8 ES ALQUILO C1-C6, ARILO, HET CON SO2Cl2 Y FORMAR R8-O-C(=O)-CH(Cl)-C(=O)-R2; LUEGO HIDROLIZAR Y DESCARBOXILAR PARA FORMAR Cl-CH2-C(=O)-R2; LUEGO ALQUILAR UN COMPUESTO VII CON Cl-CH2-C(=O)-R2, PARA FORMAR UN COMPUESTO VI; LUEGO AMINAR Y DESHIDRATAR CON UNA AMINA R1NH2, EN UN SOLVENTE QUE FORMA UN AZEOTROPO CON AGUA PARA FORMAR UN COMPUESTO V; LUEGO OXIDAR CALENTANDO CON UNA BASE Y RSOX, R ES ALQUILO C1-C6, ARILO, X ES ALCOXI C1-C6, HALO, -OCO2(ALQUILO C1-C6) PARA FORMAR UN COMPUESTO IV; LUEGO ALQUILAR CON UN AGENTE ALQUILIZANTE XCH2R4a; X ES UN GRUPO SALIENTE; R4a ES -CO2R4b, -SO3R4b, -PO(OR4b)2, -PO(OR4b)H; R4b ES UN ACIDO PROTECTOR PARA FORMAR UN GRUPO III; LUEGO REACCIONAR CON CLORURO DE OXALILO Y AMONIACO PARA FORMAR UN COMPUESTO II; LUEGO HIDROLIZAR FORMAR COMPUESTO I Y OPCIONALMENTE SALIFICAR. EL COMPUESTO I PUEDE SER UTIL PARA INHIBIR LA LIBERACION DE ACIDOS GRASOS OCASIONADA POR sPLA2 Y TRATAR SHOCK SEPTICO, SINDROME DE DIFICULTAD RESPIRATORIA DEL ADULTOREFERS TO A PROCEDURE FOR PREPARING 1H-INDOL-3-GLYOXAMIDES OF FORMULA I, WHERE R1 IS C7-C20 ALKYL, GROUP a, b, c; R10 IS HALO, C1-C10 ALKYL, C1-C10 ALCOXY, AMONG OTHERS; t IS 0-5; R2 IS H, HALO, C1-C3 ALKYL, AMONG OTHERS; R4 IS -CO2H, -SO3H, PO (OH) 2; R5 IS H, C1-C6 ALKYL, C1-C6 ALCOXY, AMONG OTHERS; WHICH INCLUDES a) HALOGENATE R8-OC (= O) -CH2-C (0O) -R2, R8 IS C1-C6 ALKYL, ARYL, HET WITH SO2Cl2 AND FORM R8-OC (= O) -CH (Cl) -C (= O) -R2; THEN HYDROLIZE AND DECARBOXYLATE TO FORM Cl-CH2-C (= O) -R2; THEN RENT A COMPOUND VII WITH Cl-CH2-C (= O) -R2, TO FORM A COMPOUND VI; THEN AMINATE AND DEHYDRATE WITH AN AMINE R1NH2, IN A SOLVENT THAT FORMS AN AZEOTROPE WITH WATER TO FORM A COMPOUND V; THEN OXIDIZE BY HEATING WITH A BASE AND RSOX, R IS C1-C6 ALKYL, ARYL, X IS C1-C6 ALCOXY, HALO, -OCO2 (C1-C6 ALKYL) TO FORM A COMPOUND IV; THEN RENT WITH A RENTAL AGENT XCH2R4a; X IS AN OUTGOING GROUP; R4a IS -CO2R4b, -SO3R4b, -PO (OR4b) 2, -PO (OR4b) H; R4b IS A PROTECTIVE ACID TO FORM A GROUP III; THEN REACT WITH OXALYL AND AMMONIA CHLORIDE TO FORM A COMPOUND II; THEN HYDROLIZE FORM COMPOUND I AND OPTIONALLY SALIFY. COMPOUND I MAY BE USEFUL TO INHIBIT THE RELEASE OF FATTY ACIDS CAUSED BY sPLA2 AND TO TREAT SEPTIC SHOCK, RESPIRATORY DIFFICULTY SYNDROME, ADULT

PE1999000311A 1998-10-09 1999-04-15 PROCESS TO PREPARE 4-SUBSTITUTED-1H-INDOL-3-GLIOXAMIDES PE20000429A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US10360498P 1998-10-09 1998-10-09

Publications (1)

Publication Number Publication Date
PE20000429A1 true PE20000429A1 (en) 2000-05-23

Family

ID=22296053

Family Applications (1)

Application Number Title Priority Date Filing Date
PE1999000311A PE20000429A1 (en) 1998-10-09 1999-04-15 PROCESS TO PREPARE 4-SUBSTITUTED-1H-INDOL-3-GLIOXAMIDES

Country Status (11)

Country Link
EP (1) EP1119549A4 (en)
JP (1) JP2002527421A (en)
AR (1) AR015766A1 (en)
AU (1) AU3564499A (en)
CA (1) CA2347718A1 (en)
CO (1) CO5021230A1 (en)
DZ (1) DZ2771A1 (en)
PE (1) PE20000429A1 (en)
SV (1) SV1999000042A (en)
TW (1) TW472041B (en)
WO (1) WO2000021929A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPQ876400A0 (en) * 2000-07-14 2000-08-03 University Of Queensland, The Compositions and method of using them

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6032769A (en) * 1983-08-02 1985-02-19 Sagami Chem Res Center Preparation of 4-hydroxyindole derivative
HUT72048A (en) * 1994-04-01 1996-03-28 Lilly Co Eli 1h-indole-3-glyoxylamide spla2 inhibitors and pharmaceutical compositions containing these compounds
AU6229298A (en) * 1997-02-20 1998-09-09 Shionogi & Co., Ltd. Indole dicarboxylic acid derivatives

Also Published As

Publication number Publication date
EP1119549A4 (en) 2003-01-29
AU3564499A (en) 2000-05-01
JP2002527421A (en) 2002-08-27
TW472041B (en) 2002-01-11
EP1119549A1 (en) 2001-08-01
DZ2771A1 (en) 2003-12-01
WO2000021929A1 (en) 2000-04-20
CO5021230A1 (en) 2001-03-27
SV1999000042A (en) 2000-04-11
AR015766A1 (en) 2001-05-16
CA2347718A1 (en) 2000-04-20

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Legal Events

Date Code Title Description
FG Grant, registration
FD Application declared void or lapsed