AR044510A1 - Procedimiento e intermedios para preparar acidos carboxilicos de pirrolidina - Google Patents

Procedimiento e intermedios para preparar acidos carboxilicos de pirrolidina

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Publication number
AR044510A1
AR044510A1 ARP040101164A ARP040101164A AR044510A1 AR 044510 A1 AR044510 A1 AR 044510A1 AR P040101164 A ARP040101164 A AR P040101164A AR P040101164 A ARP040101164 A AR P040101164A AR 044510 A1 AR044510 A1 AR 044510A1
Authority
AR
Argentina
Prior art keywords
alkyl
heteroaryl
structural formula
phenyl
defined above
Prior art date
Application number
ARP040101164A
Other languages
English (en)
Original Assignee
Merck & Co Inc
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 Merck & Co Inc filed Critical Merck & Co Inc
Publication of AR044510A1 publication Critical patent/AR044510A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with 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
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

Se proporciona un procedimiento para preparar ácidos carboxílicos de pirrolidina, y los intermedios útiles obtenidos de los mismos. Estos compuestos son intermedios para la síntesis del receptor de melanocortina-4 (MC-4R), que son útiles para el tratamiento de trastornos tales como obesidad, diabetes, disfunción sexual masculina y disfunción sexual femenina. Reivindicación 1: Un procedimiento para preparar compuestos de fórmula estructural (1) : en la que R1 se selecciona del grupo compuesto por (1) hidrógeno, (2) amidino, (3) alquiliminoilo C1-4, (4) alquilo C1-10, (5) -(CH2)n-cicloalquilo C3-7, (6) -(CH2)n-fenilo, (7) -(CH2)n-naftilo, y (8) -(CH2)n-heteroarilo, en los que el fenilo, naftilo, y heteroarilo están no substituidos o substituidos con uno a tres grupos seleccionados independientemente entre R3; y alquilo, cicloalquilo, y (CH2)n están no substituidos o substituidos con uno a tres grupos seleccionados independientemente entre R3 y oxo; R2 se selecciona del grupo compuesto por (1) alquilo C1-4, (2) -(CH2)n-cicloalquilo, (3) -(CH2)n-heterocicloalquilo, (4) -(CH2)n-fenilo, (5) -(CH2)n-naftilo, y (6) -(CH2)n-heteroarilo en el que heteroarilo se selecciona del grupo compuesto por (1) piridinilo, (2) furilo, (3) tienilo, (4) pirrolilo, (5) oxazolilo, (6) tiazolilo, (7) imidazolilo, (8) pirazolilo, (9) isoxazolilo, (10) isotiazolilo, (11) pirimidinilo, (12) pirazinilo, (13) piridazinilo, (14) quinolilo, (15) isoquinolilo, (16) benzimidazolilo, (17) benzofurilo,(18) benzotienilo, (19) indolilo, (20) benzotiazolilo, y (21) benzoxazolilo; en los que alquilo, fenilo, naftilo, heteroarilo, y (CH2)n están no substituidos o substituidos con uno a tres grupos seleccionados independientemente entre R3; cada R3 se selecciona independientemente del grupo compuesto por (1) alquilo C1-6,(2) -(CH2)n-fenilo, (3) -(CH2)n-naftilo, (4) -(CH2)n-heteroarilo, (5) -(CH2)n-heterocicloalquilo, (6) -(CH2)ncicloalquilo C3-7, (7) halógeno, (8) OR4, (9) -(CH2)nN(R4)2, (10) NO2, (11) -(CH2)nNR4SO2R4, (12) -(CH2)nSO2N(R4)2, (13) -(CH2)nS(O)pR4, (14) CF3, (15) CH2CF3, (16) OCF3, y (17) OCH2CF3; en los que heteroarilo es según se ha definido anteriormente; alquilo, fenilo, naftilo, heteroarilo, cicloalquilo, y heterocicloalquilo están no substituidos o substituidos con uno a tres substituyentes seleccionados independientemente entre halógeno, hidroxi, oxo, alquilo C1-4, trifluorometilo, y alcoxi C1-4; y cualquier átomo de carbono de metileno (CH2) de R3 no está substituido o está substituido con uno a dos grupos seleccionados independientemente entre halógeno, hidroxi, y alquilo C1-4; o dos substituyentes cuando en el mismo grupo metileno (CH2) se toman junto con el átomo de carbono al que están unidos, para formar un grupo ciclopropilo; cada R4 se selecciona independientemente del grupo compuesto por (1) hidrógeno, (2) alquilo C1-6,(3) -(CH2)n-fenilo, (4) -(CH2)n-heteroarilo, (5) -(CH2)n-naftilo, (6) -(CH2)n-heterocicloalquilo, (7) -(CH2)ncicloalquilo C3-7, y (8) -(CH2)nbicicloalquilo C3-7; en los que alquilo, fenilo, heteroarilo, heterocicloalquilo, y cicloalquilo están no substituidos o substituidos con uno a tres grupos seleccionados independientemente entre halógeno, alquilo C1-4, hidroxi, y alcoxi C1-4; o dos grupos R4 junto con el átomo al que están unidos forman un sistema de anillo mono- o bicíclico de 4 a 8 miembros, que contiene opcionalmente, un heteroátomo adicional seleccionado entre O, S, y Nalquilo C1-4; y n es 0, 1, 2, 3 o 4; que comprende las etapas de: (a) preparar un alcohol de fórmula estructural (2) en la que X es bromuro o cloruro, y R2 es según se ha definido anteriormente, tratando una cetona de fórmula estructural (3), en la que X es bromuro o cloruro, y R2 es según se ha definido anteriormente, con un agente reductor, y aislando el producto resultante; (b) formar un amino alcohol de fórmula estructural (4) en la que R1 y R2 son según se han definido anteriormente, tratando el alcohol de fórmula estructural (2) con una amina de fórmula general R1NH2 en la que R1 es según se ha definido anteriormente, y una base en un disolvente, y aislando el producto resultante; (c) formar un compuesto de fórmula estructural (5) en la que Y es -CN o -CO2R5 y R5 es alquilo C1-4, y en la que R1 y R2 son según se han definido anteriormente, tratando el amino alcohol de fórmula estructural (4) con un compuesto de fórmula general (6) en la que Y es -CN o -CO2R5, y R5 es alquilo C1-4, y aislando el producto resultante; (d) formar un compuesto de pirrolidina de fórmula estructural (7) en la que Y, R1 y R2 son según se han definido anteriormente, tratando el compuesto de fórmula estructural (5) con un reactivo activador de alcohol, seguido de una base; (e) formar un ácido de trans-pirrolidina de fórmula estructural (1) en la que R1 y R2 son según se han definido anteriormente, hidrolizando el compuesto de pirrolidina de fórmula estructural (7) con una base acuosa en un disolvente; y (f) aislar el producto resultante.
ARP040101164A 2003-04-14 2004-04-06 Procedimiento e intermedios para preparar acidos carboxilicos de pirrolidina AR044510A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US46279503P 2003-04-14 2003-04-14

Publications (1)

Publication Number Publication Date
AR044510A1 true AR044510A1 (es) 2005-09-14

Family

ID=33299992

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP040101164A AR044510A1 (es) 2003-04-14 2004-04-06 Procedimiento e intermedios para preparar acidos carboxilicos de pirrolidina

Country Status (8)

Country Link
US (1) US20060199958A1 (es)
EP (1) EP1615882A2 (es)
JP (1) JP2006523700A (es)
CN (1) CN1774419A (es)
AR (1) AR044510A1 (es)
CA (1) CA2521487A1 (es)
TW (1) TW200504011A (es)
WO (1) WO2004092126A2 (es)

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WO2006123762A1 (ja) * 2005-05-16 2006-11-23 Sumitomo Chemical Company, Limited ピロリジン化合物の製造方法
US8013189B2 (en) * 2007-09-21 2011-09-06 Basf Se Accelerated amide and ester reductions with amine boranes and additives
JPWO2010119848A1 (ja) 2009-04-14 2012-10-22 アステラス製薬株式会社 光学活性ピロリジン化合物の新規製造法
CN104695023B (zh) * 2015-02-14 2017-02-01 河北科技大学 一水合四氢吡咯‑2‑羧酸单晶及其制备方法
US10550126B2 (en) 2015-10-16 2020-02-04 Abbvie Inc. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
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AU2021370071B2 (en) 2020-10-29 2024-01-11 Lg Chem, Ltd. Amorphous melanocortin-4 receptor agonist
CA3195298A1 (en) 2020-10-29 2022-05-05 Lg Chem, Ltd. Crystalline form i of melanocortin receptor agonist compound and preparation method therefor
AU2021371829B2 (en) 2020-10-29 2024-01-18 Lg Chem, Ltd. Crystalline form ii of melanocortin receptor agonist compound and preparation method therefor
EP4249483A1 (en) 2020-12-22 2023-09-27 Lg Chem, Ltd. Crystalline form i of melanocortin receptor agonist compound and method for preparing same
CN116648249A (zh) 2020-12-22 2023-08-25 株式会社Lg化学 黑皮质素受体激动剂化合物的结晶形式ii及其制备方法
WO2022139446A1 (ko) 2020-12-22 2022-06-30 주식회사 엘지화학 멜라노코르틴 수용체 작용제 화합물의 결정형 ⅲ 및 이의 제조방법
KR20220090455A (ko) 2020-12-22 2022-06-29 주식회사 엘지화학 무정형의 멜라노코르틴 수용체 작용제 및 이의 제조방법
TWI826938B (zh) 2021-02-26 2023-12-21 南韓商Lg化學股份有限公司 黑皮質素-4受體促效劑
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WO2022235105A1 (ko) 2021-05-06 2022-11-10 주식회사 엘지화학 멜라노코르틴 수용체 작용제 화합물의 결정형 ⅶ 및 이의 제조방법
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Also Published As

Publication number Publication date
CN1774419A (zh) 2006-05-17
CA2521487A1 (en) 2004-10-28
WO2004092126A3 (en) 2005-01-20
TW200504011A (en) 2005-02-01
US20060199958A1 (en) 2006-09-07
EP1615882A2 (en) 2006-01-18
WO2004092126B1 (en) 2005-03-31
WO2004092126A2 (en) 2004-10-28
JP2006523700A (ja) 2006-10-19

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