AR046786A1 - PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS - Google Patents

PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS

Info

Publication number
AR046786A1
AR046786A1 ARP040104526A ARP040104526A AR046786A1 AR 046786 A1 AR046786 A1 AR 046786A1 AR P040104526 A ARP040104526 A AR P040104526A AR P040104526 A ARP040104526 A AR P040104526A AR 046786 A1 AR046786 A1 AR 046786A1
Authority
AR
Argentina
Prior art keywords
formula
compound
previously mentioned
solvent
alkyl
Prior art date
Application number
ARP040104526A
Other languages
Spanish (es)
Original Assignee
Vinas Lab
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 Vinas Lab filed Critical Vinas Lab
Publication of AR046786A1 publication Critical patent/AR046786A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C401/00Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Los compuestos de fórmula (1) son útiles para el tratamiento terapéutico y/o prevención de enfermedades del metabolismo óseo, enfermedades dermatológicas y oncológicas. Reivindicación 1: Un procedimiento para la obtención de un derivado de vitamina D de fórmula general (1) en donde A se selecciona entre los restos de fórmulas generales (2), (3), y (4); donde Z y Z´, independientemente entre sí, representan H, hidroxilo; o hidroxilo protegido con un grupo protector de hidroxilo; W representa un dienófilo, y R´1, R´2, y R´3, independientemente entre sí representan, halógeno, hidroxilo, hidroxilo protegido con un grupo protector de hidroxilo; alquilo C1-6 opcionalmente sustituido con halógeno, hidroxilo, ciano, o amino; alquenilo C2-6 opcionalmente sustituido con halógeno, hidroxilo, ciano o amino, dialquil(C1-5)éter; o alquil (C1-5)amino; R1, R2, R3 y R4, independientemente entre sí, representan H, alquilo C1-8, cicloalquilo C3-6 o arilo C6-14; D es H; -CR5R6Y, donde R5 y R6, independientemente entre sí, representan H, alquilo C1-8; cicloalquilo C3-6; arilo C6-14; o un grupo -OR7, donde R7 representa H; alquilo C1-8; cicloalquilo C3-6; o arilo C6-14; e Y representa H; hidroxilo; hidroxilo protegido con un grupo protector de hidroxilo; o un grupo -OR7, donde R7 tiene el significado indicado previamente; o -C(O)R5 en donde R5 tiene el significado previamente mencionado; m es un número entero seleccionado entre 0, 1 y 2; n es un número entero seleccionado entre 0 y 1; p es un número entero seleccionado entre 0, 1, 2, 3, 4, 5 y 6; con la condición de que al menos, uno de "m", "n" o "p" es cero, y la suma de "m", "n" y "p" es igual o mayor que 1 ("m" + "n" + "p" l 1); caracterizado porque comprende: (i) hacer reaccionar un alquenilmonohaloderivado de fórmula (5) en donde A tiene el significado indicado previamente; y X representa un átomo de halógeno seleccionado entre Cl, Br y I; con (A) un compuesto de fórmula M(NR8R9) donde M; es un metal alcalina, y R8 y R9, independientemente entre sí, representan H, alquilo C1-6; alquil(C1-6)sililo; o cicloalquilo C3-6; en un disolvente, para obtener el correspondiente alquiniluro metálico, y, a continuación, hacer reaccionar dicho alquiniluro metálico con un compuesto seleccionado entre: -un compuesto de fórmula R5CON(CH3)OCH3 donde R5 tiene el significado previamente mencionado, y -un compuesto de fórmula R5CHO donde R5 tiene el significado previamente mencionado; para obtener un compuesto de fórmula (1) en el que m=0, n=1 y p=0; o bien con (B) un alcóxido metálico de fórmula MOR10 donde M es un metal alcalino, y R10 es alquilo C1-6; en un disolvente, y, posteriormente, con un agente sililante, y, a continuación, con un compuesto alquillitio de fórmula LiR10 donde R10 tiene el significado previamente mencionado; para obtener el correspondiente alquiniluro de litio; y, a continuación, hacer reaccionar dicho alquiniluro de litio con un compuesto seleccionado entre: -un compuesto de fórmula R5CON(CH3)OCH3 donde R5 tiene el significado previamente mencionado, y -un compuesto de fórmula R5CHO donde R5 tiene el significado previamente mencionado; para obtener un compuesto de fórmula (1) en el que m=0, n=1 y p=0; o bien con (C) un compuesto de fórmula M(NR8R9) donde M, R8 y R9 tienen los significados previamente mencionados; en un primer disolvente y, posteriormente, con un epóxido de fórmula (6) donde R5 y R6 tienen los significados previamente mencionados, en un segundo disolvente, para obtener un compuesto de fórmula (I) en el que m = 0, n = 1 y p = 1; o bien con (D) un complejo de paladio o de níquel, en un disolvente, y con un compuesto organometálico de fórmula (T)oM´(CR3R4)pCHR5R6 donde M´ se selecciona entre Li, Mg, Zn, Al, Zr, B y Sn; T es halógeno o alquilo C1-5, "o" es 0 o 1, siendo 0 cuando M´ es un metal monovalente; y p, R3, R4, R5 y R6 tienen los significados previamente mencionados; para obtener un compuesto de fórmula (1) en el que m=1, n=0 y p=1-6; o bien con (E) un compuesto de fórmula M"(L)q donde M" se selecciona entre un metal alcalino, un metal alcalinotérreo, Zn, Cu y Ti; L es halógeno, alquilo C1-5, trifenilfosfina, cianuro, o sulfocianuro; y "q" es un número entero seleccionado entre 0, 1, 2, 3, 4, 5 y 6, en un disolvente, para obtener un compuesto de fórmula (E)vM"(L)q donde E es un resto de fórmula (7) en donde A tiene el significado previamente indicado; v es un entero comprendido entre 1 y la valencia del metal M"; y M", L´ y q tienen los significados previamente mencionados, con la condición que de "v" + "q" satisface la valencia de M" y/o el número de coordinación de M"; y posteriormente, hacer reaccionar dicho compuesto con un compuesto de fórmula R5COR6 donde R5 y R6 tienen los significados previamente mencionados; para obtener un compuesto de fórmula (1) en el que m=1, n=0 y p=0; o bien con (F) un compuesto de cromo, en presencia de una sal de níquel y/o de paladio, en un disolvente, y con un compuesto de fórmula R5COR6 donde R5 y R6 tienen los significados de fórmula (1) en el que m=1, n=0 y p=0;o bien con (G) un compuesto de paladio, en presencia de una base, en un disolvente, y con una cetona de fórmula CH3COR5 donde R5 tiene el significado previamente mencionado, excepto H; para obtener un compuesto de fórmula (1) en el que m=1, n=0 y p=1; o bien con (H) un compuesto de paladio, en presencia de una base y de una sal de cobre (i) opcionalmente complejada, en un disolvente, opcionalmente en presencia de un catalizador de transferencia de fase, y con un alcohol propargílico de fórmula CHsC-C(OH)R5R6 donde R5 y R6 tienen el significado previamente mencionado; para obtener un compuesto de fórmula (1) en el que m=1, n=1 y p=0; o bien con (I) un compuesto de paladio, en presencia de una base, en un disolvente, opcionalmente, en presencia de un catalizador de transferencia de fase, y con un compuesto de fórmula R1-CH=CH-COR5 donde R1 y R5 tienen los significados antes mencionados, para obtener un compuesto de fórmula (1) en el que m=2, n=0 y p=0; o bien con (J) un compuesto de paladio, en presencia de una base y de una sal de plata, en un disolvente, y con un compuesto de fórmula R1-CH=C(OH)R5R6 donde R1, R5 y R6 tienen los significados previamente mencionados; para obtener un compuesto de fórmula (I) en el que m=2, n=0 y p=0; y, si se desea, (ii) convertir dicho compuesto de fórmula (1) en otro compuesto de fórmula (1).The compounds of formula (1) are useful for the therapeutic treatment and / or prevention of bone metabolism diseases, dermatological and oncological diseases. Claim 1: A process for obtaining a vitamin D derivative of the general formula (1) wherein A is selected from the moieties of general formulas (2), (3), and (4); where Z and Z ', independently of each other, represent H, hydroxyl; or hydroxyl protected with a hydroxyl protecting group; W represents a dienophile, and R´1, R´2, and R´3, independently of each other represent, halogen, hydroxyl, hydroxyl protected with a hydroxyl protecting group; C1-6 alkyl optionally substituted with halogen, hydroxyl, cyano, or amino; C2-6 alkenyl optionally substituted with halogen, hydroxyl, cyano or amino, dialkyl (C1-5) ether; or (C1-5) alkyl amino; R1, R2, R3 and R4, independently of each other, represent H, C1-8 alkyl, C3-6 cycloalkyl or C6-14 aryl; D is H; -CR5R6Y, where R5 and R6, independently of each other, represent H, C1-8 alkyl; C3-6 cycloalkyl; C6-14 aryl; or a group -OR7, where R7 represents H; C1-8 alkyl; C3-6 cycloalkyl; or C6-14 aryl; and Y represents H; hydroxyl; hydroxyl protected with a hydroxyl protecting group; or a group -OR7, where R7 has the meaning indicated previously; or -C (O) R5 where R5 has the previously mentioned meaning; m is an integer selected from 0, 1 and 2; n is an integer selected from 0 to 1; p is an integer selected from 0, 1, 2, 3, 4, 5 and 6; with the proviso that at least one of "m", "n" or "p" is zero, and the sum of "m", "n" and "p" is equal to or greater than 1 ("m" + "n" + "p" l 1); characterized in that it comprises: (i) reacting an alkenylmonohalo derivative of formula (5) wherein A has the previously indicated meaning; and X represents a halogen atom selected from Cl, Br and I; with (A) a compound of formula M (NR8R9) where M; it is an alkali metal, and R8 and R9, independently of each other, represent H, C1-6 alkyl; (C1-6) alkyl silyl; or C3-6 cycloalkyl; in a solvent, to obtain the corresponding metal alkynylide, and then to react said metal alkynylide with a compound selected from: -a compound of formula R5CON (CH3) OCH3 where R5 has the previously mentioned meaning, and -a compound of formula R5CHO where R5 has the previously mentioned meaning; to obtain a compound of formula (1) in which m = 0, n = 1 and p = 0; or with (B) a metal alkoxide of formula MOR10 where M is an alkali metal, and R10 is C1-6 alkyl; in a solvent, and subsequently with a silylating agent, and then with an alkyl lithium compound of the formula LiR10 where R10 has the previously mentioned meaning; to obtain the corresponding lithium alkynylide; and then reacting said lithium alkynylide with a compound selected from: -a compound of formula R5CON (CH3) OCH3 where R5 has the previously mentioned meaning, and -a compound of formula R5CHO where R5 has the previously mentioned meaning; to obtain a compound of formula (1) in which m = 0, n = 1 and p = 0; or with (C) a compound of formula M (NR8R9) where M, R8 and R9 have the previously mentioned meanings; in a first solvent and, subsequently, with an epoxide of formula (6) where R5 and R6 have the previously mentioned meanings, in a second solvent, to obtain a compound of formula (I) in which m = 0, n = 1 and p = 1; or with (D) a palladium or nickel complex, in a solvent, and with an organometallic compound of formula (T) or M '(CR3R4) pCHR5R6 where M' is selected from Li, Mg, Zn, Al, Zr, B and Sn; T is halogen or C1-5 alkyl, "or" is 0 or 1, where 0 is when M 'is a monovalent metal; and p, R3, R4, R5 and R6 have the previously mentioned meanings; to obtain a compound of formula (1) in which m = 1, n = 0 and p = 1-6; or with (E) a compound of formula M "(L) q where M" is selected from an alkali metal, an alkaline earth metal, Zn, Cu and Ti; L is halogen, C1-5 alkyl, triphenylphosphine, cyanide, or sulfocyanide; and "q" is an integer selected from 0, 1, 2, 3, 4, 5 and 6, in a solvent, to obtain a compound of formula (E) vM "(L) q where E is a remainder of formula (7) where A has the previously indicated meaning; v is an integer between 1 and the valence of the metal M "; and M ", L´ and q have the previously mentioned meanings, with the condition that" v "+" q "satisfies the valence of M" and / or the coordination number of M "; and subsequently, reacting said compound with a compound of formula R5COR6 where R5 and R6 have the previously mentioned meanings; to obtain a compound of formula (1) in which m = 1, n = 0 and p = 0; or with (F) a chromium compound, in presence of a nickel and / or palladium salt, in a solvent, and with a compound of formula R5COR6 where R5 and R6 have the meanings of formula (1) in which m = 1, n = 0 and p = 0; or either with (G) a palladium compound, in the presence of a base, in a solvent, and with a ketone of formula CH3COR5 where R5 has the previously mentioned meaning, except H; to obtain a compound of formula (1) in which m = 1, n = 0 and p = 1; or with (H) a palladium compound, in the presence of a base and an optionally complexed copper salt (i), in a solvent, option occasionally in the presence of a phase transfer catalyst, and with a propargyl alcohol of formula CHsC-C (OH) R5R6 where R5 and R6 have the previously mentioned meaning; to obtain a compound of formula (1) in which m = 1, n = 1 and p = 0; or with (I) a palladium compound, in the presence of a base, in a solvent, optionally, in the presence of a phase transfer catalyst, and with a compound of formula R1-CH = CH-COR5 where R1 and R5 they have the aforementioned meanings, to obtain a compound of formula (1) in which m = 2, n = 0 and p = 0; or with (J) a palladium compound, in the presence of a base and a silver salt, in a solvent, and with a compound of formula R1-CH = C (OH) R5R6 where R1, R5 and R6 have the previously mentioned meanings; to obtain a compound of formula (I) in which m = 2, n = 0 and p = 0; and, if desired, (ii) converting said compound of formula (1) into another compound of formula (1).

ARP040104526A 2003-12-05 2004-12-03 PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS AR046786A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES200302875A ES2234423B1 (en) 2003-12-05 2003-12-05 PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS.

Publications (1)

Publication Number Publication Date
AR046786A1 true AR046786A1 (en) 2005-12-21

Family

ID=34707570

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP040104526A AR046786A1 (en) 2003-12-05 2004-12-03 PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS

Country Status (4)

Country Link
KR (1) KR101117246B1 (en)
AR (1) AR046786A1 (en)
ES (1) ES2234423B1 (en)
SI (1) SI21657A (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2411834B1 (en) * 2011-12-30 2014-03-18 Laboratorios Viñas S.A. Industrial process to obtain intermediates suitable for the synthesis of Vitamin D analogues
ES2620905B1 (en) * 2015-12-29 2018-04-09 Laboratorios Viñas S.A. Procedure to reduce ketones derived from vitamin D in continuous and procedure of manufacture of calcipotriol and corresponding use
CN114560753B (en) * 2020-11-27 2024-04-26 深圳千越生物科技有限公司 Process for preparing hydroxy epoxy analogues

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8915770D0 (en) * 1989-07-10 1989-08-31 Leo Pharm Prod Ltd Chemical compounds
GB9017890D0 (en) * 1990-08-15 1990-09-26 Leo Pharm Prod Ltd Chemical compounds i
GB9314400D0 (en) * 1993-07-12 1993-08-25 Leo Pharm Prod Ltd Produktionsaktieselskab) chemical compounds
WO2003087048A2 (en) * 2002-04-11 2003-10-23 Instytut Farmaceutyczny Preparation of 24 alkyl analogs of cholecalciferol and non-racemic compounds

Also Published As

Publication number Publication date
SI21657A (en) 2005-06-30
ES2234423B1 (en) 2006-03-01
ES2234423A1 (en) 2005-06-16
KR20050054857A (en) 2005-06-10
KR101117246B1 (en) 2012-04-12

Similar Documents

Publication Publication Date Title
RU2006144123A (en) NEW ENANTIOMEROUS-B-AGONISTS, METHOD FOR PRODUCING THEM AND THEIR APPLICATION AS MEDICINES
RU2002121493A (en) APPLICATION OF FUMARIC ACID DERIVATIVES FOR THE TREATMENT OF MITOCHONDRIAL DISEASES
AR055622A1 (en) METHODS OF PREPARATION OF SUBSTITUTED BENZIMIDAZOLS AND COMPOUNDS DERIVED FROM THEM.
JP2007511546A5 (en)
HRP20060361A2 (en) Novel c-crystalline form of perindopril tert-butylamine salt, preparation method, and pharmaceutical compositions containing same
JP2015500843A5 (en)
AR048316A1 (en) ARIL PIPERIDINES OR PIPERAZINAS REPLACED WITH FIVE MIXED INHIBITING MEMBERS OF THE MTP, METHODS FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THE MANUFACTURE OF MEDICINES FOR THE TREATMENT PROCESSING METRO.
AR067824A1 (en) BORONIC ACID COMPOUNDS AND BORONIC ESTER INHIBITORS OF PROTEASOMA, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND USES OF THE SAME FOR THE TREATMENT OF CANCER.
JP2013507423A5 (en)
AR034124A1 (en) ALFA CRYSTAL FORM OF PERINDOPRIL TERBUTILAMINE SALT, PROCEDURE FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING IT
BR9405988A (en) Dialotriazolpyrimidine derivatives as fungicides
GB2463981B (en) Process for the preparation of vitamin K2
BR9905788A (en) 2- (2-oxo-ethylidene) -imidazolidin-4-one derivatives and compositions and methods for inhibiting abnormal cell growth comprising said derivatives
AR080076A1 (en) ORAL CARE PRODUCT FOR SENSITIVE ENAMEL CARE
AR039936A1 (en) PHARMACEUTICAL FORMULATION OF MODIFIED LIBERATION
RU2013138372A (en) ASETIDINE DERIVATIVES USED FOR TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES
ES2187261A1 (en) Ether and amide compounds and preparation of thereof as antidiadetics.
AR046786A1 (en) PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS
ATE302579T1 (en) COSMETIC COMPOSITIONS CONTAINING VITAMIN B3
SG170620A1 (en) Novel compounds, pharmaceutical compositions containing same, and methods of use for same
JP2017514818A5 (en)
ATE239711T1 (en) NEW ALLYTHIOPYRIDAZINE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF
AR053560A1 (en) ANTIBACTERIAL COMPOUNDS OF 3,3 'DIALCOXI-2,2' -DIHIDROXI -1,1 '-BIFENILO 5,5' DISUSTITUTED AND RELATED METHODS
JP2006517932A5 (en)
NO20051028L (en) Substituted thiazines as protective agents

Legal Events

Date Code Title Description
FG Grant, registration