AR072539A1 - Sintesis de derivados de 3,4-diaril -4,5-dihidro -(1h) - pirazol -1- carboxamida - Google Patents

Sintesis de derivados de 3,4-diaril -4,5-dihidro -(1h) - pirazol -1- carboxamida

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Publication number
AR072539A1
AR072539A1 ARP090102881A ARP090102881A AR072539A1 AR 072539 A1 AR072539 A1 AR 072539A1 AR P090102881 A ARP090102881 A AR P090102881A AR P090102881 A ARP090102881 A AR P090102881A AR 072539 A1 AR072539 A1 AR 072539A1
Authority
AR
Argentina
Prior art keywords
formula
alkyl
compound
group
trifluoromethyl
Prior art date
Application number
ARP090102881A
Other languages
English (en)
Inventor
Josephus H M Lange
Hans J Sanders
Rheenen Jeroen Van
Original Assignee
Solvay Pharm Bv
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 Solvay Pharm Bv filed Critical Solvay Pharm Bv
Publication of AR072539A1 publication Critical patent/AR072539A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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 linked by a chain containing hetero atoms as chain links

Abstract

Se refiere a una ruta química hacia derivados de 3,4-diaril-4,5-dihidro-(1H)-pirazol-1-carboxamidina, conocidos como potentes antagonistas de receptores cannabinoides CB1 y a intermediarios de estos compuestos. La ruta de síntesis produce rendimientos considerablemente mayores que los informados, sin el uso de reactivos corrosivos. Reivindicacion 1: Un proceso para la preparacion de un compuesto de formula (1) en donde R1 y R2 independientemente son elegidos de alquilo C1-3, alcoxi C1-3, hidroxi, halogeno, trifluorometilo, trifluorometoxi y ciano; m y n independientemente son 0, 1 o 2; R3 es alquilo C1-8 ramificado o lineal o cicloalquilo C3-8; R4 es elegido de fenilo, tienilo o piridilo, los cuales grupos están insustituidos o sustituidos con 1 o 2 sustituyentes, que pueden ser iguales o diferentes, elegidos de alquilo C1-3 o alcoxi C1-3, hidroxi, halogeno, trifluorometilo, trifluorometoxi y ciano, o R4 representa un grupo alquilo C5-10 o alquenilo C5-10 monocíclico o bicíclico o un grupo heteroalquilo C5-10 o heteroalquenilo C5-10 monocíclico o bicíclico que contiene uno o dos heteroátomos de anillo o grupos moleculares que contienen heteroátomos de anillo elegidos de N O, S o SO2, el cual grupo R4 está insustituido o sustituido con un sustituyente elegido de hidroxi o alquilo C1-3 o R4 representa un grupo 4,4-difluoropiperidin-1-ilo, 4-fluoropiperidin-1-ilo o 4-(trifluorometil)piperidin-1-ilo, que comprende las etapas de: (i) hacer reaccionar un 3,4-diaril-4,5-dihidro-(1H)-pirazol de la formula (2) en donde R1, R2, m y n tienen los significados dados precedentemente, con un isotiocianato de alquilo o un isotiocianato de cicloalquilo de la formula R3-N=c=S, en donde R3 tiene el significado dado precedentemente, en un alcohol C1-8 preferiblemente etanol absoluto, para brindar una 3,4-diaril-N-alquil-4,5-dihidro-(1H)-pirazol-1-carbotiamida o una 3,4-diaril-N-cicloalquil-4,5-dihidro-(1H)-pirazol-1-carbotiamida de la formula (3); (ii) hacer reaccionar -en un alcohol C1-8, preferiblemente metanol- el compuesto obtenido de la formula (3), con un reactivo alquilante de la formula general Rx-L, en donde Rx representa un grupo alquilo C1-8 y L representa un ôgrupo salienteö, preferiblemente elegido de Br, Cl o l para brindar un compuesto de le formula (4); (iii) hacer reaccionar -en un solvente orgánico inerte, preferiblemente acetonitrilo- el compuesto obtenido de la formula (4), con un derivado de sulfonamida de la formula R4SO2NH2, en donde R4 tiene el significado dado precedentemente, para brindar un compuesto de la formula (1); (iv) aislar el compuesto de la formula (1) de la mezcla de reaccion. Reivindicacion 8: Un compuesto de la formula (3) o (3a) en donde: R1 y R2 independientemente son elegidos de alquilo C1-3 o alcoxi C1-3, hidroxi, halogeno, trifluorometilo, trifluorometoxi y ciano; m y n independientemente son 0, 1 o 2; R3 es alquilo C1-8 ramificado o lineal; así como tautomeros, estereoisomeros, N-oxidos y sales de cualquiera de los anteriores, siendo tales compuestos utiles en la síntesis de los compuestos de la formula (1). Reivindicacion 9: Un compuesto de la formula (4) en donde: R1 y R2 independientemente son elegidos de alquilo alcoxi C1-3, hidroxi, halogeno, trifluorometilo, trifluorometoxi y ciano; m y n independientemente son 0, 1 o 2; R3 es alquilo C1-8 ramificado o lineal o cicloalquilo C3-8; Rx es un grupo alquilo C1-8 lineal; así como tautomeros, estereoisomeros, N-oxidos y sales de cualquiera de los anteriores, siendo tales compuestos utiles en la síntesis de los compuestos de la formula (1).
ARP090102881A 2008-08-01 2009-07-29 Sintesis de derivados de 3,4-diaril -4,5-dihidro -(1h) - pirazol -1- carboxamida AR072539A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP08161619 2008-08-01

Publications (1)

Publication Number Publication Date
AR072539A1 true AR072539A1 (es) 2010-09-01

Family

ID=40380031

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090102881A AR072539A1 (es) 2008-08-01 2009-07-29 Sintesis de derivados de 3,4-diaril -4,5-dihidro -(1h) - pirazol -1- carboxamida

Country Status (12)

Country Link
EP (1) EP2321280A2 (es)
JP (1) JP2011529868A (es)
KR (1) KR20110042095A (es)
CN (1) CN102089284A (es)
AR (1) AR072539A1 (es)
AU (1) AU2009275838A1 (es)
BR (1) BRPI0916692A2 (es)
CA (1) CA2729969A1 (es)
EA (1) EA201170284A1 (es)
MX (1) MX2011001211A (es)
TW (1) TW201010981A (es)
WO (1) WO2010012797A2 (es)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR079935A1 (es) * 2010-01-29 2012-02-29 Abbott Healthcare Products Bv Sintesis de derivados de pirazolin carboxamidina sustituida
US20220227714A1 (en) * 2019-05-17 2022-07-21 The United States Of America,As Represented By The Secretary,Department Of Health And Human Services A scalable synthesis of dual-target inhibitor of cannabinoid-1 receptor and inducible nitric oxide synthase
CN111686806B (zh) * 2020-05-29 2022-09-30 黑龙江大学 一种聚[2-(3-噻吩基)乙醇]/石墨相氮化碳复合可见光催化剂的制备方法及应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2074179A1 (en) * 1990-01-31 1991-08-01 Charles R. Harrison Arthropodicidal pyrazolines, pyrazolidines and hyrazines
DE4005114A1 (de) * 1990-02-17 1991-08-22 Bayer Ag Substituierte pyrazolinderivate
SK287074B6 (sk) * 2000-03-23 2009-11-05 Solvay Pharmaceuticals B. V. 4,5-Dihydro-1H-pyrazolové deriváty, spôsoby ich prípravy, medziprodukty a ich použitie
CN1529595A (zh) * 2001-09-21 2004-09-15 ������ҩ�����޹�˾ 具有效cb1-拮抗活性的4,5-2氢-1h-吡唑衍生物

Also Published As

Publication number Publication date
CN102089284A (zh) 2011-06-08
MX2011001211A (es) 2011-03-29
TW201010981A (en) 2010-03-16
JP2011529868A (ja) 2011-12-15
WO2010012797A3 (en) 2010-04-22
BRPI0916692A2 (pt) 2016-05-17
KR20110042095A (ko) 2011-04-22
EA201170284A1 (ru) 2011-06-30
CA2729969A1 (en) 2010-02-04
EP2321280A2 (en) 2011-05-18
AU2009275838A1 (en) 2010-02-04
WO2010012797A2 (en) 2010-02-04

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