.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 9,102,627

« Back to Dashboard

Details for Patent: 9,102,627

Title:Processes for preparing 3-benzazepines
Abstract: The present invention provides processes and intermediates for the preparation of 3-benzazepines and salts thereof which can be useful as serotonin (5-HT) receptor agonists for the treatment of, for example, central nervous system disorders such as obesity.
Inventor(s): Wolgast; Beverly L. (San Diego, CA), Gilson, III; Charles A. (San Diego, CA), Aytes; Shelley (San Diego, CA), Estrada; Scott A. (La Jolla, CA), Sengupta; Dipanjan (San Diego, CA), Smith; Brian (San Diego, CA), Rey; Max (Wallisellen, CH), Weigl; Ulrich (Hilzingen, DE)
Assignee: Arena Pharmaceuticals, Inc. (San Diego, unknown)
Filing Date:Sep 14, 2012
Application Number:13/619,788
Claims:1. A process for preparing a compound of Formula V: ##STR00059## or salt thereof, wherein: R.sup.1 is H or C.sub.1-C.sub.8 alkyl; R.sup.2 is C.sub.1-C.sub.8 alkyl, --CH.sub.2--O--(C.sub.1-C.sub.8 alkyl), C(O)O--(C.sub.1-C.sub.8 alkyl), --C(O)NH--(C.sub.1-C.sub.8 alkyl), or C.sub.1-C.sub.4 haloalkyl; R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each, independently, H, halo, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.8 haloalkyl, hydroxy, OR.sup.9, alkoxyalkyl, C(O)-alkyl, C(O)O-alkyl, C(O)NH-alkyl, hydroxyalkyl, NR.sup.10R.sup.11, CN, NO.sub.2, heterocycloalkyl, aryl, or heteroaryl, wherein said aryl and heteroaryl can be substituted with one or more substituents selected from C.sub.1-C.sub.8 alkyl, halo, C.sub.1-C.sub.8 haloalkyl, and alkoxy; or R.sup.4 and R.sup.5 together with the atoms to which they are attached form a 5- or 6-member heterocyclic ring having one O atom; R.sup.8a and R.sup.8b are each, independently, H, halo, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.8 haloalkyl, alkoxyalkyl, hydroxy, C(O)-alkyl, C(O)O-alkyl, C(O)NH-alkyl, or hydroxyalkyl, or R.sup.8a and R.sup.8b together with the carbon atom to which they are attached form a C.sub.3-C.sub.7 cycloalkyl group; R.sup.9 is H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.8 haloalkyl, aralkyl, aryl, heteroaryl, heteroarylalkyl, or allyl; and R.sup.10 and R.sup.11 are each, independently, H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.8 haloalkyl, aralkyl, aryl, heteroaryl, heteroarylalkyl, or allyl, or R.sup.10 and R.sup.11 together with the N atom to which they are attached form a heterocyclic ring; comprising the step of reacting a compound of Formula IX: ##STR00060## or salt thereof, wherein X.sup.2 is halo or SO.sub.2R''; and R'' is C.sub.1-C.sub.8 alkyl, aryl, or heteroaryl each optionally substituted by one or more halo, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy, or C.sub.1-C.sub.4 haloalkoxy, with a cyclizing reagent for a time and under conditions suitable for forming said compound of Formula V.

2. A process according to claim 1, wherein said cyclizing reagent is AlCl.sub.3.

3. A process according to claim 1, wherein the reaction of said compound of Formula IX with said cyclizing reagent is carried out in the presence of 1,2-dichlorobenzene.

4. A process according to claim 1, wherein the reaction of said compound of Formula IX with said cyclizing reagent is carried out at a temperature between 100 and 150.degree. C.

5. A process according to claim 1, wherein X.sup.2 is Cl.

6. A process according to claim 1, wherein X.sup.2 is Br.

7. A process according to claim 1, wherein R.sup.1 is H, R.sup.2 is Me, R.sup.3 is H, R.sup.4 is Cl, R.sup.5 is H, R.sup.6 is H, R.sup.8a is H, and R.sup.8b is H.

8. A process according to claim 1, said process further comprising the step of forming said compound of Formula IX or salt thereof by reacting a compound of Formula X: ##STR00061## or salt thereof; with a halogenating/sulfonating reagent for a time and under conditions suitable for forming said compound of Formula IX or salt thereof.

9. A process according to claim 8, wherein said halogenating/sulfonating reagent is SOBr.sub.2 or SOCl.sub.2.

10. A process according to claim 8, wherein the reaction of said compound of Formula X with said halogenating/sulfonating reagent is carried out in the presence of solvent.

11. A process according to claim 10, wherein the reaction of said compound of Formula X with said halogenating/sulfonating reagent is carried out in the presence of solvent comprising dimethylformamide or toluene.

12. A process according to claim 8, said process further comprising the step of reacting a compound of Formula XI: ##STR00062## wherein X.sup.1 is a leaving group, with a compound of the following formula: ##STR00063## or salt thereof, for a time and under conditions suitable for forming said compound of Formula X or salt thereof.

13. A process according to claim 12, wherein X.sup.1 is Br.

14. A process according to claim 12, wherein the reaction of said compound of Formula XI to give said compound of Formula X is carried out at a temperature from about 80 to about 110.degree. C.

15. A process according to claim 8, said process further comprising the step of reacting a compound of Formula XII: ##STR00064## with a further halogenating/sulfonating reagent for a time and under conditions suitable for forming said compound of Formula XI.

16. A process according to claim 15, wherein said further halogenating/sulfonating reagent is PBr.sub.3 or PCl.sub.3.

17. A process according to claim 12, wherein X.sup.1 is Cl.

18. A process according to claim 1, wherein: R.sup.1 is H, R.sup.2 is Me, R.sup.3 is H, R.sup.4 is Cl, R.sup.5 is H, R.sup.6 is H, R.sup.8a is H, and R.sup.8b is H; said cyclizing reagent is AlCl.sub.3; the reaction of said compound of Formula IX with said cyclizing reagent is carried out in the presence of 1,2-dichlorobenzene; the reaction of said compound of Formula IX with said cyclizing reagent is carried out at a temperature between 100 and 150.degree. C.; and X.sup.2 is Cl.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc