.

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: 9,365,587

« Back to Dashboard

Details for Patent: 9,365,587

Title:Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates
Abstract: The invention is a process for the preparation of a compound of the following formula (I): ##STR00001## wherein R is --CHO, --CH(OH).sub.2 or --CH(OH)(OR.sup.4); P.sup.1 is H or a hydroxyl protecting group; P.sup.3 is H or a carboxy protecting group; R.sup.3 is H, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, etc.; R.sup.x is H, halogen or R.sup.2--X--NR.sup.1--C(O)--; etc. as defined in the specification. The compounds are useful as intermediates in synthesizing compounds having HIV integrase inhibitory activity.
Inventor(s): Yoshida; Hiroshi (Osaka, JP), Taoda; Yoshiyuki (Osaka, JP), Johns; Brian Alvin (Research Triangle Park, NC), Kawasuji; Takashi (Osaka, JP), Nagamatsu; Daiki (Osaka, JP)
Assignee: SHIONOGI & CO., LTD. (Osaka, JP) ViiV HEALTHCARE COMPANY (Research Triangle Park, NC)
Filing Date:Nov 10, 2015
Application Number:14/936,987
Claims:1. A process for the preparation of a compound of the following formula (I): ##STR00038## wherein R is --CHO, --CH(OH).sub.2 or --CH(OH)(OR.sup.4); P.sup.1 is H or a hydroxyl protecting group; P.sup.3 is H or a carboxy protecting group; R.sup.3 is H, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted lower alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy and optionally substituted amino; R.sup.4 is lower alkyl; R.sup.x is H, halogen or R.sup.2--X--NR.sup.1--C(O)--; R.sup.2 is optionally substituted aryl; X is a single bond, a heteroatom group selected from the group consisting of O, S, SO, SO.sub.2, and NH or a lower alkylene or a lower alkenylene wherein each may be intervened by the heteroatom; and R.sup.1 is H or lower alkyl, which comprises the steps of: i) reacting a compound of formula (II): ##STR00039## wherein P.sup.1, P.sup.3, R.sup.x and R.sup.3 are defined above; with an amine of formula (III) or (IV): ##STR00040## wherein R.sup.5 and R.sup.6 are independently lower alkyl or R.sup.5 and R.sup.6 can be alkyl and joined to form a 5-, 6-, or 7-membered ring, to produce an intermediate of formula (V) or (VI), respectively: ##STR00041## wherein P.sup.1, P.sup.3, R.sup.x, R.sup.3, R.sup.5 and R.sup.6 are defined above; and ii) refunctionalizing the intermediate of formula (V) or (VI) to produce the compound of formula (I).

2. The process according to claim 1, wherein in the compound of formula (I), R.sup.x is H or Br.

3. The process according to claim 1, wherein in the compound of formula (I), P.sup.1 is H or Bn.

4. The process according to claim 1, wherein in the compound of formula (I), R.sup.3 is H.

5. The process according to claim 1, wherein in the compound of formula (I), P.sup.3 is H or Me.

6. The process according to claim 1, wherein the compound of formula (II) is ##STR00042##

7. The process according to claim 1, wherein the compound of formula (VI) is ##STR00043##

8. The process according to claim 1, wherein the compound of formula (VI) is ##STR00044##

9. The process according to claim 1, wherein the compound of formula (I) is ##STR00045##

10. The process according to claim 1, wherein the amine is H.sub.2NCH.sub.2CH.sub.2CH.sub.2OH.

11. The process according to claim 1, wherein R.sup.x is p-F-phenyl-CH.sub.2--NH--C(O)--, R.sup.3 is H, P.sup.1 is Bn and P.sup.3 is a carboxy protecting group.

12. The process according to claim 1, wherein step i) is carried out in EtOH, THF or DMF at a temperature of about 50-150.degree. C.

13. The process according to claim 1, wherein step ii) is carried out using the intermediate of formula (VI) with an oxidizing agent selected from the group consisting of NaIO.sub.4, RuO.sub.4 and Pb(OAc).sub.4 in a solvent selected from the group consisting of H.sub.2O, MeOH and CH.sub.3CN.

14. The process according to claim 1, wherein step ii) is carried out using the intermediate of formula (V) with an acid selected from the group consisting of HCl, CF.sub.3COOH and HCOH.

15. The process according to claim 1, wherein step ii) includes refunctionalization of R.sup.x from R.sup.x=H to R.sup.x=Br.

16. The process according to claim 1, wherein step ii) includes refunctionalization of R.sup.x to R.sup.x=R.sup.2--X--NR.sup.1--C(O)--.

17. The process according to claim 1, wherein step ii) includes refunctionalization of P.sup.3 from P.sup.3=H to P.sup.3=Me.
« 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