Preparation of cyclohexene carboxylate derivatives

Details Preparation of cyclohexene carboxylate derivatives Preparation of cyclohexene carboxylate derivatives

2001-09-27

2003-02-11

Lambkin, Deborah C. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S437000, C549S513000, C560S126000

Reexamination Certificate

active

06518438

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to methods of preparing carbocyclic compounds and intermediates therefore.
2. Brief Description of Related Art
U.S. patent application Ser. No. 08/702,308, filed Aug. 23, 1996, which was a continuation-in-part application of U.S. patent application Ser. No. 08/653,034, filed Mar. 24, 1996, which was a continuation-in-part application of U.S. patent application Ser. No. 08/606,624, filed Feb. 26, 1996, which was a continuation-in-part application of U.S. patent application Ser. No. 08/580,567, filed Dec. 29, 1995, which was a continuation-in-part application of U.S. patent application Ser. No. 08/476,946, filed Jun. 6, 1995, which was a continuation-in-part application of U.S. patent application Ser. No. 08/395,245, filed Feb. 27, 1995, all of which are incorporated herein by reference in their entirety, describe, inter alia, neuraminadase inhibitors and intermediates in the synthesis of neuraminidase inhibitor. The present invention provides processes useful in the preparation of these compositions.
OBJECTS OF THE INVENTION
Selected embodiments of the invention are directed to one or more of the following objects:
A principal object of the invention is to provide new synthetic methods and compositions.
An additional object of the invention is to provide new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors.
An additional object of the invention is to provide compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors.
An additional object of the invention is to provide compositions useful as neuraminidase inhibitors.
SUMMARY OF THE INVENTION
One aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
1
is a cyclic hydroxy protecting group;
R
2
is a carboxylic acid protecting group;
R
3
is a hydroxy protecting group; and
each R
20
is independently H or an alkyl of 1 to 12 carbon atoms;
which process comprises reaction of a compound of the formula:
with a dehydrating reagent.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
each of R
2
, R
3
and R
20
are as defined above;
R
4
is —C(R
30
)
3
;
each R
5
is independently H or R
3
;
each R
7
is independently H or an amino protecting group;
each R
8
is independently H or R
2
;
each R
9
is independently H or a thiol protecting group;
each R
21
is independently R
20
, Br, Cl, F, I, CN, NO
2
or N
3
;
each R
22
is independently F, Cl, Br, I, —CN, N
3
, —NO
2
, —OR
5
, —OR
20
, —N(R
20
)
2
, —N(R
20
)(R
7
), —N(R
7
)
2
, —SR
20
, —SR
9
, —S(O)R
20
, —S(O)
2
R
20
, —S(O)OR
8
, —S(O)
2
OR
20
, —S(O)
2
OR
8
, —C(O)OR
20
, —C(O)OR
8
, —OC(O)R
20
, —N(R
20
)(C(O)R
20
), —N(R
7
)(C(O)R
20
), —N(R
20
)(C(O)OR
20
), —N(R
7
)(C(O)OR
20
), —C(O)N(R
20
)
2
, —C(O)N(R
7
)(R
20
), —C(O)N(R
7
)
2
, —C(NR
20
)(N(R
20
)
2
), —C(N(R
7
))(N(R
20
)
2
), —C(N(R
20
))(N(R
20
)(R
7
)), —C(N(R
7
))(N(R
20
)(R
7
)), —C(N(R
20
))(N(R
7
)
2
), —C(N(R
7
))(N(R
7
)
2
), —N(R
20
)C(N(R
20
))(N(R
20
)
2
), —N(R
20
)C(N(R
20
))(N(R
20
)(R
7
)), —N(R
20
)C(N(R
7
))(N(R
20
)
2
), —N(R
7
)C(N(R
20
))(N(R
20
)
2
), —N(R
7
)C(N(R
7
))(N(R
20
)
2
), —N(R
7
)C(N(R
20
))(N(R
20
)(R
7
)), —N(R
20
)C(N(R
7
)(N(R
20
)(R
7
)), —N(R
20
)C(N(R
20
))(N(R
7
)
2
), —N(R
7
)C(N(R
7
))(N(R
20
)(R
7
)), —N(R
7
)C(N(R
20
))(N(R
7
)
2
), —N(R
20
)C(N(R
7
))(N(R
7
)
2
), —N(R
7
)C(N(R
7
))(N(R
7
)
2
), ═O, ═S, ═N(R
20
), ═N(R
7
) or W;
each R
23
is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
each R
24
is independently R
23
wherein each R
23
is substituted with 0 to 3 R
22
groups;
each R
24a
is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R
22
groups;
each R
28
is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
each R
29
is independently R
22
or R
28
wherein each R
28
is substituted with 0 to 3 R
22
groups;
each R
30
is independently H, R
24
, W or —R
24a
W; and
each W is independently carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R
29
groups;
which process comprises reaction of a compound of the formula:
wherein R
31
is a ketal or acetal, with a lewis acid reagent; provided-that R
4
, taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R
29
groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R
22
groups.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
2
, R
4
, R
7
, R
20
and R
21
are as defined above.
which process comprises reaction of a compound of the formula:
with a reducing reagent.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
2
, R
4
, R
5
, R
20
and R
21
are as described above; and
Y
1
is a mono-, di- or unsubstituted amino group;
which process comprises reaction of a compound of the formula:
with an amine reagent.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
2
, R
4
, R
20
, R
21
and Y
1
are as described above;
which process comprises reaction of a compound of the formula:
with an oxidizing reagent.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
2
, R
4
, R
20
, R
21
and Y
1
are as described above;
which process comprises reaction of a compound of the formula:
with a base.
Another aspect of the present invention is directed to processes for the preparation of compounds of the formula:
wherein:
R
2
, R
4
, R
7
, R
20
, R
21
and Y
1
are as described above;
which process comprises reaction of a compound of the formula:
with a reductive amination reagent.
DETAILED DESCRIPTION
General
The present invention is directed to methods of making the compositions described herein. Even though the compositions of the invention are prepared by any of the applicable techniques of organic synthesis, the present invention provides advantageous methods for accomplishing the preparations.
Many conventional techniques are well known in the art and will not be elaborated here. However, many of the known techniques are elaborated in “Compendium of Organic Synthetic Methods” (John Wiley & Sons, New York), Vol. 1, Ian T. Harrison and Shuyen Harrison, 1971; Vol. 2, Ian T. Harrison and Shuyen Harrison, 1974; Vol. 3, Louis S. Hegedus and Leroy Wade, 1977; Vol. 4, Leroy G. Wade, jr., 1980; Vol. 5, Leroy G. Wade, Jr., 1984; and Vol. 6, Michael B. Smith; as well as March, J., “Advanced Organic Chemistry, Third Edition”, (John Wiley & Sons, New York, 1985), “Comprehensive Organic Synthesis. Selectivity, Strategy & Efficiency in Modern Organic Chemistry. In 9 Volumes”, Barry M. Trost, Editor-in-Chief (Pergamon Press, New York, 1993 printing).
Generally, the reaction conditions such as temperature, reaction time, solvents, workup procedures, and the like, will be those common in the art for the particular reaction to be performed. The cited reference material, together with material cited therein, contains detailed descriptions of such conditions.
The terms “treated”, “treating”, “treatment”, and the like, mean contacting, mixing, reacting, allowing to react, bringing into contact, and other terms common in the art for indicating that one or more chemical entities is treated in such a manner as to convert it to one or more other chemical entities. This means that “treating compound one with compound two” is synonymous with “allowing compound one to react with compound two”, “contacting compound one with compound two”, “reacting compound one with compound t

Affiliated with

Also associated with

Rating

Preparation of cyclohexene carboxylate derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Preparation of cyclohexene carboxylate derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preparation of cyclohexene carboxylate derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3119141