AR032175A1 - PROCESS FOR THE MANUFACTURE OF N-ARIL-ANTRANILIC ACIDS AND THEIR DERIVATIVES - Google Patents

PROCESS FOR THE MANUFACTURE OF N-ARIL-ANTRANILIC ACIDS AND THEIR DERIVATIVES

Info

Publication number
AR032175A1
AR032175A1 ARP010104047A ARP010104047A AR032175A1 AR 032175 A1 AR032175 A1 AR 032175A1 AR P010104047 A ARP010104047 A AR P010104047A AR P010104047 A ARP010104047 A AR P010104047A AR 032175 A1 AR032175 A1 AR 032175A1
Authority
AR
Argentina
Prior art keywords
group
aryl
alkyl
hydrogen
metal cation
Prior art date
Application number
ARP010104047A
Other languages
Spanish (es)
Original Assignee
Warner Lambert Co
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 Warner Lambert Co filed Critical Warner Lambert Co
Publication of AR032175A1 publication Critical patent/AR032175A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
    • 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
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
    • C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Indole Compounds (AREA)

Abstract

Se propone un proceso para la preparacion de ácidos N-aril-antranílicos, que son agentes farmacéuticos utiles, por ejemplo, como agentes antiinflamatorios. Dichos ácidos pueden servir como intermedios en la preparacion de amidas N-aril antranílicas, ácidos hidroxámicos N-aril-antranílicos y ésteres de ácidos hidroxámicos N-aril-antranílicos. Dichos compuestos inhiben ciertas enzimas quinasa de especificidad doble involucradas en enfermedades proliferativas tales como cáncer y restenosis. Un proceso para sintetizar un compuesto de formula (1), o una sal farmacéuticamente aceptable de él, en donde R1 es hidrogeno, alquilo, alcoxi, o arilo; R2, R3, R4, R5, R6, R7, R8, R9 y R10 se seleccionan cada uno independientemente de: hidrogeno, halo, alquilo, arilo, un grupo heterocíclico, haloalquilo, alcoxi, nitro, CN, -(=)m-(CH2) n-R11, en donde m, n, y R11 son lo definido abajo, o dos sustituyentes cualquiera de R2, R3, R4, R5, R6, R7, R8, R9 y R10 que están unidos a átomos de carbono de anillos contiguos, se pueden tomar junto con los átomos de carbono de los anillos contiguos, para formar un grupo arilo, heteroarilo, heterocíclico, o cicloalquilo de 4 a 7 átomos totales en el anillo, o R1 y R6 se pueden tomar junto con el átomo de nitrogeno, al cual está unido R1, el átomo de carbono al cual está unido R6 y el átomo de carbono contiguo a dicho átomo de carbono al cual está unido R6 para formar un anillo aromático o dihidroaromático de 5 o 6 miembros que tiene átomos de carbono en 1 o 2 átomos de nitrogeno; R11 es hidrogeno, hidroxi,, -CO2H, o N(R12)R13, R12 y R13 son cada uno independientemente hidrogeno, alquilo o R12 y R13 se toman junto con el átomo de nitrogeno al cual están unidos para formar un grupo heterocíclico de 3 a 10 miembros que tiene átomos de carbono y uno, dos o tres heteroátomos seleccionados de O, S, y NR14, en donde R14 es hidrogeno o alquilo; m es un numero entero de 0 a 1; n es un numero entero seleccionado de 0, 1, 2, 3, 4; y -Z es COOH, COOM, COOR15, -C(O)R15, -C(O)N(R16)R17, -C(O)N(R18)OR19, NO2, o CN, en donde M es un cation de metal del GrupoI metal o un hemication de metal del Grupo II, R15 es alquilo, alquenilo, arilo o un grupo heterocíclico, y R16, R17, R18 y R19 se seleccionan cada uno independientemente de hidrogeno, alquilo, alquenilo, fenilo, y bencilo, o R16 y R17 se toman junto con el átomo de nitrogeno al cual están unidos para formar un grupo heterocíclico de 3 a 10 miembros que tiene átomos de carbono y uno, dos o tres heteroátomos seleccionados de O, S, y NR14, en donde R14 es hidrogeno o alquilo; que comprende hacer reaccionar un compuesto de formula (2), en donde R1, R6, R7, R8, R9, y R10 son lo definido anteriormente, con un compuesto de la formula (3), en donde Z, R2, R3, R4 y R5 son lo definido anteriormente, y X es halo o O-LG, en donde LG es SO2R20 o P(=O) (OR20)2, donde R20 es alquilo o arilo, optativamente en un solvente, y en la presencia de 1 equivalente en moles a 10 equivalentes en moles de una base, en donde la base se selecciona de: un hidruro de cation de metal del Grupo I o un hidruro de cation de metal del Grupo II, que incluyen hidruro de litio, hidruro de sodio, hidruro de potasio, e hidruro de calcio, una dialquilamida de cation de metal del Grupo II, que incluyen diisopropilamida de litio, una amida de cation de metal del Grupo I o una amida de cation de metal del Grupo II, que incluyen amida de litio, amida de sodio, amida de potasio, y un alcoxido de cation de metal del Grupo I o un alcoxido de cation de metal del Grupo II, que incluyen etoxido de sodio, ter-butoxido de potasio, y etoxido de magnesio, durante un tiempo, y a una temperatura suficiente para dar un compuesto de la formula (1).A process for the preparation of N-aryl-anthranilic acids is proposed, which are useful pharmaceutical agents, for example, as anti-inflammatory agents. Such acids can serve as intermediates in the preparation of N-aryl anthranilic amides, N-aryl-anthranilic hydroxamic acids and esters of N-aryl-anthranilic hydroxamic acids. Such compounds inhibit certain double specificity kinase enzymes involved in proliferative diseases such as cancer and restenosis. A process for synthesizing a compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, alkyl, alkoxy, or aryl; R2, R3, R4, R5, R6, R7, R8, R9 and R10 are each independently selected from: hydrogen, halo, alkyl, aryl, a heterocyclic group, haloalkyl, alkoxy, nitro, CN, - (=) m- (CH2) n-R11, where m, n, and R11 are as defined below, or two substituents of R2, R3, R4, R5, R6, R7, R8, R9 and R10 that are attached to carbon atoms of contiguous rings, can be taken together with the carbon atoms of the adjacent rings, to form an aryl, heteroaryl, heterocyclic, or cycloalkyl group of 4 to 7 total atoms in the ring, or R1 and R6 can be taken together with the atom of nitrogen, to which R1 is attached, the carbon atom to which R6 is attached and the carbon atom adjacent to said carbon atom to which R6 is attached to form a 5- or 6-membered aromatic or dihydroaromatic ring having atoms of carbon in 1 or 2 nitrogen atoms; R11 is hydrogen, hydroxy ,, -CO2H, or N (R12) R13, R12 and R13 are each independently hydrogen, alkyl or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic group of 3 to 10 members having carbon atoms and one, two or three heteroatoms selected from O, S, and NR14, wherein R14 is hydrogen or alkyl; m is an integer from 0 to 1; n is an integer selected from 0, 1, 2, 3, 4; and -Z is COOH, COOM, COOR15, -C (O) R15, -C (O) N (R16) R17, -C (O) N (R18) OR19, NO2, or CN, where M is a cation Group I metal or Group II metal hemication, R15 is alkyl, alkenyl, aryl or a heterocyclic group, and R16, R17, R18 and R19 are each independently selected from hydrogen, alkyl, alkenyl, phenyl, and benzyl , or R16 and R17 are taken together with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocyclic group having carbon atoms and one, two or three heteroatoms selected from O, S, and NR14, where R14 is hydrogen or alkyl; which comprises reacting a compound of formula (2), wherein R1, R6, R7, R8, R9, and R10 are as defined above, with a compound of formula (3), wherein Z, R2, R3, R4 and R5 are as defined above, and X is halo or O-LG, where LG is SO2R20 or P (= O) (OR20) 2, where R20 is alkyl or aryl, optionally in a solvent, and in the presence of 1 mole equivalent to 10 mole equivalents of a base, wherein the base is selected from: a Group I metal cation hydride or a Group II metal cation hydride, including lithium hydride, sodium hydride, potassium hydride, and calcium hydride, a Group II metal cation dialkylamide, which include lithium diisopropylamide, a Group I metal cation amide or a Group II metal cation amide, which include lithium amide , sodium amide, potassium amide, and a Group I metal cation alkoxide or a Group II metal cation alkoxide, including sodium ethoxide, potassium tert-butoxide, and magnesium ethoxide, for a time, and at a temperature sufficient to give a compound of the formula (1).

ARP010104047A 2000-08-25 2001-08-24 PROCESS FOR THE MANUFACTURE OF N-ARIL-ANTRANILIC ACIDS AND THEIR DERIVATIVES AR032175A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US22820600P 2000-08-25 2000-08-25

Publications (1)

Publication Number Publication Date
AR032175A1 true AR032175A1 (en) 2003-10-29

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ID=22856235

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Country Status (31)

Country Link
EP (1) EP1313694A1 (en)
JP (1) JP2004507518A (en)
KR (1) KR20030059115A (en)
CN (1) CN1458921A (en)
AP (1) AP2001002249A0 (en)
AR (1) AR032175A1 (en)
AU (1) AU2001277044A1 (en)
BG (1) BG107635A (en)
BR (1) BR0113520A (en)
CA (1) CA2420003A1 (en)
CZ (1) CZ2003477A3 (en)
DO (1) DOP2001000238A (en)
EA (1) EA200300187A1 (en)
GT (1) GT200100174A (en)
HN (1) HN2001000216A (en)
HU (1) HUP0300828A2 (en)
IL (1) IL154507A0 (en)
IS (1) IS6724A (en)
MA (1) MA26949A1 (en)
MX (1) MXPA03001654A (en)
NO (1) NO20030844L (en)
PA (1) PA8526501A1 (en)
PE (1) PE20020393A1 (en)
PL (1) PL360699A1 (en)
SK (1) SK2072003A3 (en)
SV (1) SV2002000601A (en)
TN (1) TNSN01127A1 (en)
UY (1) UY26908A1 (en)
WO (1) WO2002018319A1 (en)
YU (1) YU14303A (en)
ZA (1) ZA200301182B (en)

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US8329701B2 (en) 2006-07-06 2012-12-11 Array Biopharma Inc. Dihydrofuro pyrimidines as AKT protein kinase inhibitors
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WO2008044041A1 (en) 2006-10-12 2008-04-17 Astex Therapeutics Limited Pharmaceutical combinations
GB0620259D0 (en) 2006-10-12 2006-11-22 Astex Therapeutics Ltd Pharmaceutical compounds
EP2073807A1 (en) 2006-10-12 2009-07-01 Astex Therapeutics Limited Pharmaceutical combinations
EP2173723B3 (en) 2007-07-05 2014-11-19 Array Biopharma Inc. Pyrimidyl cyclopentanes as akt protein kinase inhibitors
US8846683B2 (en) 2007-07-05 2014-09-30 Array Biopharma, Inc. Pyrimidyl cyclopentanes as Akt protein kinase inhibitors
US9409886B2 (en) 2007-07-05 2016-08-09 Array Biopharma Inc. Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
RU2486181C2 (en) 2007-07-05 2013-06-27 Эррэй Биофарма Инк. Pyrimidyl cyclopentanes as akt/protein kinase inhibitors
ES2422733T3 (en) 2008-01-09 2013-09-13 Array Biopharma Inc Hydroxylated pyrimidylcyclopentanes as AKT protein kinase inhibitors
AU2009204019B2 (en) 2008-01-09 2014-02-20 Array Biopharma Inc. Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor
GB0806527D0 (en) 2008-04-11 2008-05-14 Astex Therapeutics Ltd Pharmaceutical compounds
CN101985428B (en) * 2009-07-29 2014-02-12 杭州民生药业有限公司 O-anilino benzoic acid derivatives or pharmaceutically acceptable salts thereof as well as preparation method and application thereof
JP2013519714A (en) * 2010-02-19 2013-05-30 センター ナショナル デ ラ リシェルシェ サイエンティフィック Process for the preparation of desired chemical compounds by aromatic nucleophilic substitution
JP2013519715A (en) * 2010-02-19 2013-05-30 センター ナショナル デ ラ リシェルシェ サイエンティフィック Process for the preparation of desired chemical compounds by aromatic nucleophilic substitution of aromatic carboxylic acid derivatives having at least one electron withdrawing group
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Also Published As

Publication number Publication date
JP2004507518A (en) 2004-03-11
SV2002000601A (en) 2002-04-03
WO2002018319A1 (en) 2002-03-07
IS6724A (en) 2003-02-20
NO20030844D0 (en) 2003-02-24
MXPA03001654A (en) 2004-09-10
AP2001002249A0 (en) 2001-09-30
YU14303A (en) 2006-08-17
CN1458921A (en) 2003-11-26
TNSN01127A1 (en) 2005-11-10
KR20030059115A (en) 2003-07-07
HUP0300828A2 (en) 2003-09-29
PE20020393A1 (en) 2002-05-09
DOP2001000238A (en) 2003-01-31
MA26949A1 (en) 2004-12-20
SK2072003A3 (en) 2004-01-08
EP1313694A1 (en) 2003-05-28
AU2001277044A1 (en) 2002-03-13
PA8526501A1 (en) 2002-07-30
NO20030844L (en) 2003-02-25
UY26908A1 (en) 2001-11-30
BR0113520A (en) 2003-06-24
BG107635A (en) 2004-09-30
IL154507A0 (en) 2003-09-17
CA2420003A1 (en) 2002-03-07
GT200100174A (en) 2002-07-18
ZA200301182B (en) 2004-05-12
CZ2003477A3 (en) 2003-10-15
EA200300187A1 (en) 2003-08-28
PL360699A1 (en) 2004-09-20
HN2001000216A (en) 2002-05-22

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