Claims
- 1. A process useful for preparing an antipicornaviral agents of formula IA:
- 2. A process useful for preparing a compound of formula IIA:
- 3. The process according to claim 2, wherein Porcine Pancrease Lipase is used as an enzyme in the enzymatic hydrolyzing step.
- 4. The process according to claim 2, wherein the compound of formula XIII is Z-Valine.
- 5. The process according to claim 2, wherein the compound of formula XVI is:
- 6. The process according to claim 2, wherein the β-ketoester of formula XIV is first reacted with an alkali-metal hydride before reacting the β-ketoester with the compound of formula XVI.
- 7. The process according to claim 2, wherein the alkali-metal hydride is sodium hydride.
- 8. The process according to claim 2, wherein step (c) comprises a palladium hydrogenolysis.
- 9. The process according to claim 8, wherein the palladium hydrogenolysis is carried out under pressure.
- 10. The process according to claim 2, wherein diisopropylethyl amine is used as a reagent in the acylation step (d).
- 11. The process according to claim 2, wherein the compound of formula IIA is:
- 12. A process useful for preparing a compound of formula IIA:
- 13. The process according to claim 12, wherein the compound of formula XIX is:
- 14. The process according to claim 12, wherein the compound of formula XX is:
- 15. The process according to claim 12, wherein the compound of formula XXI is:
- 16. The process according to claim 12, wherein the compound of formula XXII is:
- 17. The process according to claim 12, wherein the compound of formula XXIII is :
- 18. A process useful for preparing a compound of formula I comprising the steps of:
- 19. The process according to claim 18, wherein the compound of formula I is:
- 20. The process according to claim 18, wherein the compound of formula II is:
- 21. The process according to claim 18, wherein the compound of formula IIIA is:
- 22. The process according to claim 18, wherein the compound of formula Lv-X is chlorodimethyltriazine.
- 23. The process according to claim 18, wherein the compound of formula IIIA is prepared by a process comprising the step of reacting a compound of formula IIIB with trifluoroacetic acid, wherein the compound of formula IIIB is:
- 24. A process useful for preparing a compound of formula XVIA:
- 25. The process according to claim 24, wherein the reduction reaction of step B is catalyzed by formate dehydrogenase and lactate dehydrogenase.
- 26. The process according to claim 24, wherein the reduction reaction of step B uses membrane-enclosed enzymatic catalysis.
- 27. The process according to claim 24, wherein the reduction reaction of step B uses coimmobilization enzymatic catalysis.
- 28. The process according to claim 27, wherein the coimmobilization enzymatic catalysis uses PAN 500 as a suitable copolymer.
- 29. The process according to claim 25, wherein the lactate dehydrogenase is D-lactate dehydrogenase.
- 30. The process according to claim 25, wherein the lactate dehydrogenase is L-lactate dehydrogenase.
- 31. The process according to claim 24, wherein the esterification step C is performed at about room temperature in the presence of hydrochloric acid and dioxane.
- 32. The process according to claim 24, wherein the catalyst used in step (a) is primary or secondary amine.
- 33. The process according to claim 32, wherein the catalyst is 1-amino-2-propanol.
- 34. A process for preparing a compound of formula XVIA:
- 35. The process according to claim 34, wherein the serine is L-serine.
- 36. The process according to claim 34, wherein the serine is D-serine.
- 37. The process according to claim 34, wherein Q is —MgBr.
- 38. The process according to claim 34, wherein R10 is F in the para-possition of the phenyl ring.
- 39. The process according to claim 34, wherein the esterification step B′ is performed at about room temperature in the presence of hydrochloric acid and dioxane.
- 40. The process according to claim 34, wherein the potassium glycidate formed from step A′ (a) is converted to a glycidic acid before the regioselective epoxide ring-opening reaction of step A′ (b) is performed.
- 41. A process for preparing a compound of formula XVIB:
- 42. The process according to claim 41, wherein the asymmetric dihydroxylation is a Sharpless asymmetric dihydroxylation.
- 43. The process according to claim 41, wherein step (b) is performed at about 80° C.
- 44. The process according to claim 41, wherein the palladium-mediated reduction step is done in the presence of formic acid at about room temperature.
- 45. A compound of formula IVA:
- 46. The compound according to claim 45, wherein R10 is F.
- 47. The compound according to claim 46, wherein F is substituted at the para position of the phenyl ring.
- 48. The compound according to claim 45, wherein X is OH.
- 49. The compound according to claim 45, wherein R′ is methyl.
- 50. A compound of t he following formula:
- 51. A compound of the following formula:
- 52. A compound of the following formula:
- 53. A compound of the following formula:
- 54. A process for preparing a compound of formula VII:
- 55. A process for preparing a compound of formula VII
- 56. The process according to claim 55, wherein the potassium glycidate formed from step (a) is converted to a glycidic acid before the regioselective epoxide ring-opening reaction of step (b) is performed.
- 57. A process for performing a large-catalyst catalyzed reaction comprising:
(a) placing a reagent and a large catalyst in a continuous membrane reactor having a reactor volume; (b) allowing the large catalyst catalyzed reaction to occur in the continuous membrane reactor; and (c) collecting a product from the continuous membrane reactor, wherein the continuous membrane reactor comprises a tangential flow filter unit, a reactor loop to circulate the reagent and the large-catalyst through the tangential flow filter unit, and a substrate feed pump for feeding the reagent into the reactor loop, wherein the reactor loop has a reactor loop volume and comprises:
(i) a tube; and (ii) a circulation pump.
- 58. The process as claimed in claim 57, wherein the large-catalyst is an enzyme.
- 59. The process as claimed in claim 57, wherein the large-catalyst is an anchored catalyst.
- 60. The process as claimed in claim 57, wherein the large-catalyst has a molecular volume larger than the molecular volume of the product.
- 61. The process as claimed in claim 57, wherein the reactor loop volume is at least 50% of the reactor volume.
- 62. The process as claimed in claim 57, wherein the reactor loop volume is at least 80% of the reactor volume.
- 63. The process as claimed in claim 57, wherein the reactor loop volume is at least 95% of the reactor volume.
RELATED APPLICATION DATA
[0001] This application relates to U.S. Provisional Patent Application Serial No. 60/150,365, filed on Aug. 24, 1999.
[0002] This application also relates to a U.S. Provisional Patent Application No. 60/150,358 (Attorney Docket No.: 0125.0028) entitled “Efficient Synthetic Routes For The Preparation Of Rhinovirus Protease Inhibitors And Key Intermediates” having named as inventors: Q. Tian, N. Nayyar, S. Babu, J. Tao, T. Moran, R. Dagnino, Jr., T. Remarchuk, M. Melnick, L. Mitchell, Jr., and S. Bender. This aforementioned application also relates to synthetic routes for the preparation of rhinovirus protease inhibitors and key intermediates for use therein.
[0003] The above-referenced applications are relied upon and are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60150365 |
Aug 1999 |
US |
|
60150358 |
Aug 1999 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09643865 |
Aug 2000 |
US |
Child |
10201944 |
Jul 2002 |
US |