Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1998-10-15
2000-08-29
Bernhardt, Emily
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
548209, C07D41704, C07D29526, C07D27504
Patent
active
061111058
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to processes for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole or one of its pharmaceutically acceptable salts and to novel intermediates used in said processes. 3-(1-Piperazinyl)-1,2-benzisothiazole is a key intermediate useful for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydr o-2H-indol-2-one (ziprasidone). This compound has neuroleptic activity.
U.S. Pat. No. 4,831,031, issued May 16, 1989, which is hereby incorporated by reference in its entirety, discloses 5-(2-(4-(1,2-benzisothiazol-3-yl)-piperazinyl)ethyl)-6-chloro-1,3-dihydro- 2H-indol-2-one hydrochloride, which has the formula ##STR1## wherein Ar is benzisothiazol-3-yl, in the hemihydrate form (hereafter "the hemihydrate").
U.S. Pat. No. 5,312,925 issued May 17, 1994, which is hereby incorporated by reference in its entirety, refers to the monohydrates hydrochloride salt of ziprasidone, processes for its preparation, and pharmaceutical compositions and methods of treating psychotic disorders.
U.S. Pat. No. 5,359,068, issued Oct. 25, 1994, which is hereby incorporated by reference in its entirety, refers to processes and intermediates for the preparation of ziprasidone.
U.S. Pat. No. 5,206,366, issued Apr. 27, 1993, which is hereby incorporated by reference in its entirety, refers to an aqueous based process for preparing ziprasidone.
U.S. Pat. No. 4,590,196, issued May 20, 1986, refers to 1-(1,2-benzisothiazol-3-yl)piperazine, which is the penultimate intermediate made by the processes of the present invention.
Japanese Patent Publication 6,220,030 published Aug. 9, 1994 refers to the preparation of 3-amino-1,2-benzisothiazole derivatives from the reaction of bis(2-cyanophenyl)disulphide derivatives with metal amides followed by treatment with an oxidizing agent.
SUMMARY OF THE INVENTION
The present invention relates to a compound of the formula ##STR2## wherein R.sup.1 is ##STR3##
The present invention also relates to a process for preparing a compound of the formula ##STR4## comprising reacting a compound of the formula ##STR5## wherein R.sup.1 is ##STR6## with piperazine at a temperature from about 80.degree. C. to about 170.degree. C. Preferably, R.sup.1 is a group of the formula "c". Preferably, the amount of piperazine is about 2 mole equivalents to about 15 mole equivalents relative to the amount of the compound of formula II. Most preferably, the amount of piperazine is about 10 mole equivalents relative to the amount of a compound of formula II.
A preferred embodiment o the present invention relates to a process for converting a compound of formula II into a compound of formula I in the presence of a piperazine clearing agent. Suitable piperazine clearing agents are isopropanol, pyridine or t-butanol, preferably isopropanol. Preferably about 1.2 volumes (a relative proportion (mL/gm) to the weight of the compound of formula II) of the piperazine clearing agent is used.
A preferred embodiment of the present invention also relates to a process for converting a compound of formula II wherein R.sup.1 is ##STR7## into a compound of formula I, further comprising reacting said compound of the formula II with piperazine in the presence of a thiol oxidizing agent. Suitable thiol oxidizing agents are dimethyl sulfoxide, air, copper(II) salts, bisulfite, metabisulfite or hydrogen peroxide, preferably dimethyl sulfoxide. Preferably, the amount of said thiol oxidizing agent, dimethyl sulfoxide, is 2-4 mole equivalents relative to the compound of formula II.
The most preferred embodiment of the present invention relates to a process for converting a compound of formula II, wherein R.sup.1 is the group "c", into a compound of the formula I, comprising reacting said compound of the formula II with piperazine, a piperazine clearing agent (most preferably isopropanol), and a thiol oxidizing agent (most preferably dimethyl sulfoxide).
"Piperazine clearing agent," when used herein, refers to a solvent that when refluxing is capable of diss
REFERENCES:
patent: 5679827 (1997-10-01), Goda et al.
patent: 5756806 (1998-05-01), Goda et al.
patent: 5861511 (1999-01-01), Goda et al.
Yevich et al, J. Med. Chem. vol. 29, p. 359-369, 1986.
Saji et al, Chemical Abstracts, vol. 122, No. 31512K (Abstract for JP 06 220030 Aug. 9, 1994) 1995.
Fox Darrell E.
Lambert John F.
Sinay Terry G.
Walinsky Stanley W.
Benson Gregg C.
Bernhardt Emily
Creagan B. Timothy
Pfizer Inc.
Richardson Peter C.
LandOfFree
Processes and intermediates for preparing 3-(1-piperazinyl)-1,2- does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Processes and intermediates for preparing 3-(1-piperazinyl)-1,2-, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Processes and intermediates for preparing 3-(1-piperazinyl)-1,2- will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1251388