Rearrangement process and tricyclic and tetracyclic compounds

Details Rearrangement process and tricyclic and tetracyclic compounds Rearrangement process and tricyclic and tetracyclic compounds

2000-07-06

2001-07-31

Lambkin, Deborah C. (Department: 1626)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06268510

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention was discovered during the process development work on efavirenz (1), a non-nucleoside reverse transcriptase inhibitor currently being sold under the trademarks Stocrin ™ (registered trademark of Merck & Co., Inc.) and Sustiva™ (registered trademark of DuPont Pharmaceuticals Company). A practical synthesis of efavirenz has been developed, based upon asymmetric alkynylation chemistry, which has been implemented for large scale manufacture [a) M. E. Pierce, R. L. Parsons, Jr., L. A. Radesca. Y. S. Lo, S. Silverman, J. R. Moore, Q. Islam, A. Choudhury, J. M. D. Fortunak, D. Nguyen, C. Luo, S. J. Morgan, W. P. Davis, P. N. Confalone, C. Chen, R. D. Tillyer, L. Frey, L. Tan, F. Xu, D. Zhao, A. S. Thompson, E. G. Corley, E. J. J. Grabowski, R. Reamer, P. J. Reider,
J. Org. Chem.,
1998, 63, 8536-8543. b) Recently, an efficient, protection free process was reported: L. Tan, C. Chen, R. D. Tillyer, E. J. J. Grabowski, P. J. Reider,
Angew. Chem. Int. Ed.,
1999, 38, 711-713.].
In defining the synthesis of 1, two options were evaluated for conversion of protected propargyl alcohols 2
a
/2
b
into the final 1,4-dihydro-2H-3,1-benzoxazin-2-one product. The first involved deprotection of the amino alcohols 2
a
/2
b
to give 3, which was reacted with phosgene or with p-nitrophenylchloroformate to give 1. The alternative approach involved ring closure to give the N-protected carbamates 4
a
or 4
b
, followed by deprotection. While one of the first routes (p-methoxybenzyl [PMB] protection) was developed into the manufacturing process, investigation of the ring closure reaction of trityl protected propargyl alcohol 2
a
[M. E. Pierce, et al.,
J. Org. Chem.,
1998, 63, 8536-8543.]uncovered this novel rearrangement chemistry and ring systems.
SUMMARY OF THE INVENTION
The present invention provides for the preparation of a compound of Formula I:
which comprises the steps of:
a) reacting a compound of Formula II
with carbonyl diimidazole in an aprotic solvent, or alternatively with acetic anhydride in a solvent to produce a protected alcohol of Formula III:
b) heating the protected alcohol of Formula III in a solvent at a temperature of about 50° C. to about 80° C. to produce the compound of Formula I.
Also within the scope of the invention is the process as recited above wherein step (a) is omitted. Additionally, the scope of the invention includes the compounds of Formula I and IV, which is shown below:


REFERENCES:
Vice, Susan F., et al., Tetrahedron Lett., vol. 26(2), pp. 165-168, 1985.*
Dobbs, Adrian P., et al. Tetrahedron, vol. 54, pp. 2149-2160, 1998.*
Eisch, J.J., et al., J. Org. Chem., vol. 36(22), pp. 3376-3381, 1971.
Rathjen, H-J, et al., J. Am. Chem. Soc., vol. 113, pp. 3904-3909, 1991.
von E. Doering, W., et al., J. Am. Chem. Soc., vol. 72, pp. 2305-2306, 1950.
Taber, D.F., et al., J. Am. Chem. Soc., vol. 108, pp. 7686-7693, 1986.
Russell, G.A., et al., J. Org. Chem., vol. 28, pp. 1933-1934, 1963.
Johnson, R.P., Chem. Rev., vol. 89, pp. 1111-1124, 1989.
Burrell, R.C., et al., J. Am. Chem. Soc., vol. 118, pp. 4218-4219, 1996.
Hopf, H, et al., Angew. Chem. Int. Ed. Engl., vol. 36(11), pp. 1187-1190, 1997.
Wiebe, J.M., et al., Tetrahedron, vol. 52(36), pp. 11705-11724, 1996.
Gupta, Y.N., et al., J. Am. Chem. Soc., vol. 104, pp. 7336-7338, 1982.
Verboom, W, et al., Tet. Lett., vol. 24(36), pp. 3923-3926, 1983.
Vanderzande, D.J., et al., J. Org. Chem., vol. 48, pp. 2188-2193, 1983.
Khasanova, T., et al., J. Am. Chem. Soc., vol. 122, pp. 8585-8586, 2000.

Affiliated with

Also associated with

Rating

Rearrangement process and tricyclic and tetracyclic compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Rearrangement process and tricyclic and tetracyclic compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Rearrangement process and tricyclic and tetracyclic compounds will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2439796