Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1997-08-18
2000-02-08
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C07D23910
Patent
active
060229683
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to novel processes for preparing the pharmaceutically active compound 5-(3-[(2S)-exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)3,4,5,6 tetrahydropyrimidin-2(1H)-one and its corresponding 2R enantiomer and for preparing certain intermediates used in the synthesis of these compounds. It also relates to novel intermediates used in the synthesis of such pharmaceutically active compounds and to other novel compounds that are related to such intermediates.
International Patent Application WO 87/06576, which was published on Nov. 5, 1987, refers to 5-(3-[(2-exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)-3,4,5,6tetrahydr opyrimidin-2(1H)-one, and states that it is useful as an antidepressant. International Patent Application WO 91/07178, which was published on May 30, 1991, refers to the utility of this compound in the treatment of asthma, inflammatory airway diseases and skin diseases.
U.S. Pat. No. 5,270,206, which issued on Dec. 14, 1993, refers to a process for preparing (+)-(2R)-endo-norbomeol (also referred to as (2R)-endo-bicyclo[2.2.1]heptan-2-ol or (1S, 2R, 4R)-bicyclo[2.2.1]heptan-2-ol) and (-)-(2S)-endo-norborneol (also referred to as (2S)-endo-bicyclo[2.2.1]heptan-2-ol or (1R, 2S, 4S)-bicyclo[2.2.1]heptan-2-ol), and to their further conversion into the pharmaceutically active agents 5-(3-[(2S)-exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)-3,4,5,6-tetrah ydropyrimidin-2(1H)-one, depicted below, ##STR1## and 5-(3-[(2R-exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)-3,4,5,6-tetrahy dropyrimidin-2(1H)-one, depicted below, ##STR2##
All documents cited herein, including the foregoing, are incorporated herein by reference in their entireties.
SUMMARY OF THE INVENTION
This invention relates to a compound having the formula ##STR3## wherein X and Y are the same and are selected from --CN, --CO.sub.2 (C.sub.1 -C.sub.6)alkyl, --CONH.sub.2 and --CONHOH, or X and Y, taken together, form a group of the formula ##STR4##
This invention also relates to a compound having the formula ##STR5## wherein R.sup.1 and R.sup.2 are independently selected from (C.sub.1 -C.sub.6)alkyl and hydrogen.
This invention also relates to compounds of the formulae ##STR6## wherein each R.sup.2 is independently selected from (C.sub.1 -C.sub.6) akyl.
This invention also relates to a process for preparing a compound of the formula ##STR7## wherein X and Y are the same and are selected from --CN, --CO.sub.2 (C.sub.1 -C.sub.6)alkyl, --CONH.sub.2 and --CONHOH, or X and Y, taken together, form a group of the formula ##STR8## comprising: (1) reacting 3-hydroxy-4-methoxybenzaldehyde with a compound of the formula XCH.sub.2 CO.sub.2 H, wherein X is defined as above, in the presence of a base, preferably a tertiary amine, to yield a compound of the formula II wherein X and Y are both --CN, --CO.sub.2 (C.sub.1 -C.sub.6)alkyl, --CONH.sub.2 or --CONHOH; or (2) (a) reacting a compound of the formula II wherein X and Y are both --CN with hydrogen peroxide, preferably basic aqueous hydrogen peroxide, to form the corresponding bis-amide in which both --CN groups are replaced by --CONH.sub.2; (b) subjecting the bis-amide formed in step (a) to a Hoffman rearrangement using an oxidizing agent (e.g., bis(acetoxy)iodobenzene, bis(trifluorocetoxy)iodobenzene, NaOCl, NaOBr or lead tetraacetate) to form the corresponding biscarbamate; and (c) reacting the biscarbamate formed in step (b) with a base (e.g., an alkali metal alkoxide containing from one to six carbon atoms or an alkali metal hydroxide), to form a cyclic urea wherein X and Y, taken together, form a group of the formula "a", as depicted above.
This invention also relates to a process for preparing a compound of the formula ##STR9## wherein X and Y are defined as for formula II above, comprising reacting a compound of formula II, as defined above, with, respectively, R-(+)-endo-norbomeol or S-(-)-endo-norbomeol, a triaryl or trialkyl phosphine and an azo dicarboxylate.
This invention also relates to a process for preparing a compound of the for
REFERENCES:
patent: 5270206 (1993-12-01), Saccomano et al.
V. Askam et al., "Compounds Having Antitremorine Activity, Bicarbamate Derivatives of 1,3-Diamino-2-Phenylpropanes," Chemical Abstracts, vol. 92, No. 13, Abstract No. 110633r (1980).
V. Askam et al., "Compounds Having Antitremorine Activity; Biscarbamate Derivatives," J. Chem. Research (S), vol. 7, p. 234 (1979).
H. Rompp, Rompps Chemie-Lexicon, 9th Ed., vol. 3, p. 1825 (1990).
Muller et al., Methoden der Organischen Chemie, 4th Ed., vol. E4, pp. 183-187, 372-373 (Houben-Weyl 1952-).
LaCour Thomas G.
Murtiashaw, III Charles William
Ginsburg Paul H.
Pfizer Inc
Raymond Richard L.
Richardson Peter C.
Waldron Roy F.
LandOfFree
Processes for the synthesis of 5-(3-[exo-bicyclo[2.2.1]hept-2-yl 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 for the synthesis of 5-(3-[exo-bicyclo[2.2.1]hept-2-yl, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Processes for the synthesis of 5-(3-[exo-bicyclo[2.2.1]hept-2-yl will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1682283