AR038450A1 - Un procedimiento para la preparacion de alfa-difluorometil ornitina (dfmo), un procedimiento para aislar diclorhidrato de 2-difluorometil ornitina, un compuesto intermediario y un procedimiento para la preparacion de un compuesto intermediario - Google Patents

Un procedimiento para la preparacion de alfa-difluorometil ornitina (dfmo), un procedimiento para aislar diclorhidrato de 2-difluorometil ornitina, un compuesto intermediario y un procedimiento para la preparacion de un compuesto intermediario

Info

Publication number
AR038450A1
AR038450A1 ARP020103242A ARP020103242A AR038450A1 AR 038450 A1 AR038450 A1 AR 038450A1 AR P020103242 A ARP020103242 A AR P020103242A AR P020103242 A ARP020103242 A AR P020103242A AR 038450 A1 AR038450 A1 AR 038450A1
Authority
AR
Argentina
Prior art keywords
compound
formula
preparation
procedure
give
Prior art date
Application number
ARP020103242A
Other languages
English (en)
Inventor
Jingyang Zhu
Scott T Chadwick
Benjamin A Price
Shannon X Zhao
Carrie A Costello
Purushotham Vemishetti
Original Assignee
Women First Healthcare 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 Women First Healthcare Inc filed Critical Women First Healthcare Inc
Publication of AR038450A1 publication Critical patent/AR038450A1/es

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Classifications

    • 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
    • C07C227/26—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing carboxyl groups by reaction with HCN, or a salt thereof, and amines, or from aminonitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the 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
    • C07C227/10—Formation of amino groups in compounds containing carboxyl groups with simultaneously increasing the number of carbon atoms in the 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
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • 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
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • 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
    • C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
    • 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
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • 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
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • C07C227/42—Crystallisation
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/28—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups, amino groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

Un procedimiento para la preparación de a-difluorometilornitina (DFMO) de la fórmula (1), comprendiendo el procedimiento: (a) reducir selectivamente una parte nitrilo de un compuesto de la fórmula (2), en donde R1 es un alquilo C1-4 lineal o ramificado y Z es (i) -NH2 o (ii) una parte seleccionada entre el grupo consistente en: un resto de fórmula (3), en donde R2 es hidrógeno, arilo o alquilo C1-4 lineal o ramificado, y un resto de fórmula (4), en donde R4 es alcoxi, arilo o alquilo C1-4 lineal o ramificado; (b) de estar presente, hidrolizar la parte de fórmula (3) produciendo, como resultado del paso (a), o del paso (a) y del paso (b) un compuesto de una de las siguientes fórmulas (5), (6) y (7); (c) hidrolizar las partes éster y amida (incluyendo la lactama) de las fórmulas (5), (6) y (7) para dar el compuesto de fórmula (1). Un procedimiento para la preparación del compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, comprendiendo el procedimiento: (a) hacer reaccionar un compuesto de la fórmula (8) con acrilonitrilo o 3-halopropionitrilo para dar un compuesto de fórmula (9); (b) alquilar el compuesto (9) con clorodifluorometano para dar el compuesto de fórmula (10); (c) hidrolizar el compuesto (10) para dar el compuesto de fórmula (11); (d) reducir selectivamente el compuesto de la fórmula (11) con un catalizador de un metal de transición heterogéneo seleccionado entre catalizadores de paladio y platino, en presencia de un ácido para dar un compuesto de fórmula (5) o una sal del mismo; y (e) hidrolizar la parte de éster del compuesto (5) con un ácido para proveer el compuesto (1). Procedimiento para la preparación del compuesto de fórmula (10), descripto anteriormente. Un procedimiento para aislar diclorhidrato de 2-difluorometilornitina que comprende: (a) tratar una solución de 2-difluorometilornitina y ácido clorhídrico en un alcohol con suficiente base de alquilamina terciaria para lograr un pH de aprox. 3,8 a 4,2 para formar una lechada; y (b) recuperar el diclorhidrato de 2-difluorometilornitina a partir de la lechada. Un compuesto intermediario de fórmula (12), en donde R5 tiene los valores de Z dados anteriormente. La DFMO tiene un gran número de aplicaciones dentro de los cuales se incluyen su uso como sustancia en una composición para inhibir el crecimiento de pelo no deseado, como terapia anti-cáncer y como anti-inflamatorio por su capacidad para interrumpir el metabolismo celular en un número de tipos de células.
ARP020103242A 2001-08-29 2002-08-29 Un procedimiento para la preparacion de alfa-difluorometil ornitina (dfmo), un procedimiento para aislar diclorhidrato de 2-difluorometil ornitina, un compuesto intermediario y un procedimiento para la preparacion de un compuesto intermediario AR038450A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US31583201P 2001-08-29 2001-08-29

Publications (1)

Publication Number Publication Date
AR038450A1 true AR038450A1 (es) 2005-01-19

Family

ID=23226251

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP020103242A AR038450A1 (es) 2001-08-29 2002-08-29 Un procedimiento para la preparacion de alfa-difluorometil ornitina (dfmo), un procedimiento para aislar diclorhidrato de 2-difluorometil ornitina, un compuesto intermediario y un procedimiento para la preparacion de un compuesto intermediario

Country Status (17)

Country Link
US (2) US6730809B2 (es)
EP (1) EP1421058B1 (es)
JP (1) JP2005501881A (es)
KR (1) KR100668473B1 (es)
CN (2) CN100478329C (es)
AR (1) AR038450A1 (es)
AT (1) ATE466836T1 (es)
AU (1) AU2002331714B2 (es)
BR (1) BR0212153A (es)
CA (1) CA2457854C (es)
DE (1) DE60236295D1 (es)
HK (1) HK1083213A1 (es)
IL (2) IL160314A0 (es)
MX (1) MXPA04001837A (es)
NZ (1) NZ531331A (es)
RU (1) RU2004108856A (es)
WO (1) WO2003020209A2 (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7261878B2 (en) 2001-08-10 2007-08-28 The Gillette Company Reduction of hair growth
US6730809B2 (en) * 2001-08-29 2004-05-04 Women First Healthcare, Inc. Processes for the production of α-difluoromethyl ornithine (DFMO)
US7015349B2 (en) 2003-03-26 2006-03-21 The Gillette Company Reduction of hair growth
US20100120727A1 (en) * 2008-11-12 2010-05-13 Kyphia Pharmaceuticals, Inc. Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
US20130197088A1 (en) * 2010-03-12 2013-08-01 Robert A. Casero, JR. Compositions and Methods for Combinations of Oligoamines with 2-Difluoromethylornithine (DFMO)
JP2012116776A (ja) * 2010-11-30 2012-06-21 Kyoto Univ ホスホン酸ジエステル誘導体の製造法
CN103724218B (zh) * 2014-01-22 2015-08-12 呼伦贝尔东北阜丰生物科技有限公司 一种赖氨酸盐酸盐结晶新工艺
CN105017244A (zh) * 2014-04-16 2015-11-04 上海药明康德新药开发有限公司 顺反叔丁基-4-氧六氢化-1H-吡咯[3,4-c]吡啶-2(3H)-羧酸叔丁酯的合成方法
WO2016130918A1 (en) * 2015-02-12 2016-08-18 The Arizona Board Of Regents On Behalf Of The University Of Arizona Methods for treating neuroblastoma
CN105660637B (zh) * 2016-01-07 2018-04-24 南京中医药大学 防治当归早薹的药物及其应用

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4201788A (en) 1976-10-20 1980-05-06 University Patents, Inc. Process for alleviating proliferative skin diseases
US4413141A (en) 1977-07-11 1983-11-01 Merrell Toraude Et Compagnie 2-(Difluoromethyl)-2,5-diaminopentanoic acid
US4309442A (en) 1977-07-11 1982-01-05 Merrell Toraude Et Compagnie Method for controlling fertility in mammals
US4421768A (en) 1982-08-11 1983-12-20 Merrell Toraude Et Compagnie Fluorinated diamino-heptene and-heptyne derivatives
US4720489A (en) 1984-10-15 1988-01-19 Douglas Shander Hair growth modification with ornithine decarboxylase inhibitors
CH672124A5 (en) 1987-07-03 1989-10-31 Lonza Ag 2-di:fluoromethyl-2-cyanoethyl malonic acid lower alkyl ester(s) - obtd. by reacting di:alkyl-malonate with acrylonitrile, then with chloro:fluoromethane in presence of alkali, etc
US5096911A (en) 1990-06-25 1992-03-17 Ahluwalia Gurpreet S Alteration of rate and character of hair growth
ATE159428T1 (de) 1990-08-14 1997-11-15 Joseph H Handelman Enzymatische änderung des haarwuchses
US5095007A (en) 1990-10-24 1992-03-10 Ahluwalia Gurpreet S Alteration of rate and character of hair growth
US5648394A (en) 1993-05-27 1997-07-15 Boxall; Brian Alfred Topical composition for inhibiting hair growth
US5851537A (en) 1996-02-02 1998-12-22 Cancer Technologies, Inc. Topical application of α-DFMO for preventing skin cancer
AU5526898A (en) 1996-12-13 1998-07-03 Ilex Oncology, Inc. Isomeric pharmaceutical formulation containing dfmo for the treatment of cancer
US6730809B2 (en) * 2001-08-29 2004-05-04 Women First Healthcare, Inc. Processes for the production of α-difluoromethyl ornithine (DFMO)

Also Published As

Publication number Publication date
HK1083213A1 (en) 2006-06-30
US7012158B2 (en) 2006-03-14
US20040171876A1 (en) 2004-09-02
US20030083384A1 (en) 2003-05-01
MXPA04001837A (es) 2005-04-19
KR20040064258A (ko) 2004-07-16
CN1564806A (zh) 2005-01-12
CN100478329C (zh) 2009-04-15
DE60236295D1 (de) 2010-06-17
US6730809B2 (en) 2004-05-04
EP1421058A2 (en) 2004-05-26
IL160314A0 (en) 2004-07-25
EP1421058B1 (en) 2010-05-05
IL160314A (en) 2009-11-18
ATE466836T1 (de) 2010-05-15
WO2003020209A3 (en) 2004-03-04
CA2457854C (en) 2006-10-31
CA2457854A1 (en) 2003-03-13
RU2004108856A (ru) 2005-09-20
AU2002331714B2 (en) 2007-11-01
JP2005501881A (ja) 2005-01-20
BR0212153A (pt) 2004-07-13
KR100668473B1 (ko) 2007-01-12
NZ531331A (en) 2004-06-25
EP1421058A4 (en) 2006-02-08
CN1680293A (zh) 2005-10-12
CN1279019C (zh) 2006-10-11
WO2003020209A2 (en) 2003-03-13

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