Patent
Process for the preparation of 4,4-dimethyl-6-ethynylthiochroman
| العنوان: | Process for the preparation of 4,4-dimethyl-6-ethynylthiochroman |
|---|---|
| Patent Number: | 7,414,143 |
| تاريخ النشر: | August 19, 2008 |
| Appl. No: | 11/158856 |
| Application Filed: | June 22, 2005 |
| مستخلص: | An improved process for the preparation of key intermediates for tazarotene, 4,4-dimethyl-6-ethynylthiochroman, is provided comprising (a) reacting 4,4-dimethyl-6-acetylthiochroman of the formula [chemical expression included] with an acid chloride and an amido-group containing compound of the general formula [chemical expression included] wherein R is hydrogen or a hydrocarbyl of from 1 to 15 carbon atoms and R1 and R2 can be the same or different and are hydrocarbyls of from 1 to 15 carbon atoms or R1 and R2 together with the nitrogen atom to which they are bonded are joined together to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms, or one of R1 and R2 together with the nitrogen atom to which it bonded are joined together with the carbonyl radical to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms to form a β-chloro vinyl carbonyl compound intermediate of the general formula [chemical expression included] wherein R has the aforestated meanings; and (b) reacting the β-chloro vinyl carbonyl compound intermediate with an alkali metal to provide the 4,4-dimethyl-6-ethynylthiochroman. |
| Inventors: | Kumar, Bobba Venkata Siva (Mumbai, IN); Patil, Vishvas Dattatraya (Ahmedabad, IN); Raut, Changdev Namdev (Navi Mumbai, IN); Bhirud, Shekhar Bhaskar (Navi Mumbai, IN); Chandrasekhar, Batchu (Navi Mumbai, IN) |
| Assignees: | Glenmark Pharmaceuticals Limited (Mumbai, IN) |
| Claim: | 1. A β-chloro vinyl carbonyl compound of the general formula: [chemical expression included] wherein R is hydrogen or a hydrocarbyl of from 1 to about 15 carbon atoms. |
| Claim: | 2. The β-chloro vinyl carbonyl compound of claim 1 , wherein R is hydrogen. |
| Claim: | 3. The β-chloro vinyl carbonyl compound of claim 1 , wherein R is a hydrocarbyl group of 1 to about 15 carbon atoms. |
| Claim: | 4. The β-chloro vinyl carbonyl compound of claim 1 , wherein R is an alkyl group of 1 to 6 carbon atoms. |
| Claim: | 5. The β-chloro vinyl carbonyl compound of claim 1 , wherein R is a phenyl group. |
| Claim: | 6. The β-chloro vinyl carbonyl compound of claim 1 , having a purity of about 98%. |
| Claim: | 7. A process for the preparation of a β-chloro vinyl carbonyl compound of the general formula I: [chemical expression included] wherein R is hydrogen or a hydrocarbyl of from 1 to about 15 carbon atoms, the process comprising reacting a 4,4-dimethyl-6-acetylthiochroman of the formula II [chemical expression included] with an acid chloride and an amido-group containing compound of the general formula III [chemical expression included] wherein R has the aforestated meanings and R 1 and R 2 can be the same or different and are hydrocarbyls of from 1 to about 15 carbon atoms or R 1 and R 2 together with the nitrogen atom to which they are bonded are joined together to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms, or one of R 1 and R 2 together with the nitrogen atom to which it is bonded are joined together with the carbonyl radical to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms to provide the β-chloro vinyl carbonyl compound of formula I. |
| Claim: | 8. The process of claim 7 , wherein the acid chloride is selected from the group consisting of phosphorous oxychloride, thionyl chloride, phosgene, oxalyl chloride and mixtures thereof. |
| Claim: | 9. The process of claim 7 , wherein the acid chloride is phosphorous oxychloride. |
| Claim: | 10. The process of claim 7 , wherein R is hydrogen and R 1 and R 2 each are hydrocarbyl groups of 1 to about 15 carbon atoms. |
| Claim: | 11. The process of claim 7 , wherein R is hydrogen and R 1 and R 2 each are hydrocarbyl groups of 1 to about 12 carbon atoms. |
| Claim: | 12. The process of claim 7 , wherein R is hydrogen and R 1 and R 2 each are hydrocarbyl groups of 1 to 6 carbon atoms. |
| Claim: | 13. The process of claim 7 , wherein R is hydrogen and R 1 and R 2 together with the nitrogen atom to which they are bonded are joined together to form a heterocyclic group. |
| Claim: | 14. The process of claim 7 , wherein R is a hydrocarbyl group of from 1 to about 15 carbon atoms and R 1 and R 2 are independently hydrocarbyl groups of from 1 to about 15 carbon atoms. |
| Claim: | 15. The process of claim 7 , wherein R is a hydrocarbyl of from 1 to about 15 carbon atoms and R 1 and R 2 together with the nitrogen atom to which they are bonded are joined together to form a heterocyclic group. |
| Claim: | 16. The process of claim 7 , wherein the amido-group containing compound is selected from the group consisting of dimethyl formamide, N -methyl formanilide, N-formyl piperidine, N-formyl morpholine, dimethyl acetamide, N -methyl pyrrolidone, N,N-dimethyl benzamide and mixtures thereof. |
| Claim: | 17. The process of claim 7 , wherein the amido-group containing compound is present in an amount of about 45 to about 90 weight percent, based on the total weight of the reaction mixture. |
| Claim: | 18. The process of claim 7 , wherein the amido-group containing compound is present in an amount of about 55 to about 75 weight percent, based on the total weight of the reaction mixture. |
| Claim: | 19. The process of claim 7 , wherein the acid chloride is present in a ratio of about 1:3 (w/v) to about 1:5 (w/v) with respect to the 4,4-dimethyl-6-acetylthiochroman. |
| Claim: | 20. The process of claim 7 , wherein the acid chloride is phosphorous oxychloride and the amido-group containing compound is dimethyl formamide. |
| Current U.S. Class: | 549/23 |
| Patent References Cited: | 5717094 February 1998 Chandraratna 5917082 June 1999 Vuligonda et al. 0 290 130 November 1988 0 419 132 March 1991 WO 93/16068 August 1993 WO 96/11686 April 1996 |
| Other References: | Johnson et al. “Synthesis and Biological Activity of High-Affinity Retinoic Acid Receptor Antagonists”, Bioorganic & Medicinal Chemistry, Elsevier Science Ltd., (7):1321-1338, Jul. 1999. cited by other |
| Assistant Examiner: | Havlin, Robert |
| Primary Examiner: | Anderson, Rebecca L |
| Attorney, Agent or Firm: | M. Carmen & Associates, PLLC |
| رقم الانضمام: | edspgr.07414143 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |