Claims
- 1. A method of synthesizing a compound of Formula (I) comprising
- 2. The method of claim 1, wherein the compound of Formula (I) is derived from a GABA analog of Formula (IV):
- 3. The method of claim 1 wherein the compound of Formula (I) is a compound of Formulae (V) or (VI):
- 4. The method of claim 3, wherein R1 is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl or 3-pyridyl, R2 is hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclohexyl or phenyl, and R3 is hydrogen.
- 5. The method of claim 3, wherein R1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl or 3-pyridyl, R2 is methyl and R3 is methyl.
- 6. The method of claim 3, wherein R1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl or 3-pyridyl, R2 is methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl or cyclohexyloxycarbonyl and R3 is methyl.
- 7. The method of claim 3, wherein, R1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl or 3-pyridyl and R2 and R3 together with the atom to which they are attached form a cyclohexyl ring.
- 8. The method of claim 3, wherein R2 is methyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl or cyclohexyloxycarbonyl and R3 is methyl.
- 9. The method of claim 3, wherein R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl or cyclohexyl and R10 is hydrogen, allyl, benzyl or trimethylsilyl.
- 10. The method of claim 3, wherein R2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl and R3 is hydrogen.
- 11. The method of claim 3, wherein R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, cyclobutyl, cyclopentyl or cyclohexyl, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is hydrogen, methyl, ethyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl and R3 is hydrogen.
- 12. The method of claim 3, wherein R1 is ethyl or isopropyl, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is methyl, n-propyl or isopropyl and R3 is hydrogen.
- 13. The method of claim 3, wherein R1 is isopropyl, R10 is benzyl, R2 is methyl and R3 is hydrogen.
- 14. The method of claim 3, wherein R1 is ethyl or isopropyl, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is methyl, n-propyl or isopropyl, R3 is hydrogen and X is chloro.
- 15. The method of claim 3, wherein R1 is isopropyl, R10 is benzyl, R2 is methyl, R3 is hydrogen and X is chloro.
- 16. The method of claim 1, wherein the ratio of the compound of Formula (II) to the compound of Formula (III) is between about 1:1 and about 1:20.
- 17. The method of claim 1 further comprising contacting the compound of Formula (II) and the compound of Formula (III) and at least one equivalent of a metal salt or an organic base or a combination thereof with an organic solvent.
- 18. The method of claim 17, wherein the solvent is dichloromethane, dichloroethane, chloroform, toluene, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethyl sulfoxide, pyridine, ethyl acetate, acetonitrile, acetone, 2-butanone, methyl tert-butyl ether, methanol, ethanol, isopropanol, tert-butanol, water, hexamethylphosphoramide or combinations thereof.
- 19. The method of claim 1, wherein the metal salt is a Ag, Hg, Na, K, Li, Cs, Ca, Mg or Zn salt.
- 20. The method of claim 1, wherein the organic base is triethylamine, tributylamine, diisopropylethylamine, dimethylisopropylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, pyridine, 2-methylpyridine, 2,6-dimethylpyridine, 4-dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]undec-7-ene or combinations thereof.
- 21. The method of claim 1 wherein the compound of Formula (III) is a liquid.
- 22. The method of claim 21, wherein the compound of Formula (III) is acetic acid, methoxyacetic acid, ethoxyacetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, valeric acid, isovaleric acid, 2-methylbutyric acid, cyclobutanecarboxylic acid, cyclopentanecarboxylic acid or cyclohexanecarboxylic acid.
- 23. The method of claim 22, wherein the compound of Formula (III) is isobutyric acid.
- 24. The method of claim 1, further comprising contacting the compound of Formula (II), the compound of Formula (III) and the metal salt or the organic base or a combination thereof at a temperature between about −25° C. and about 120° C.
- 25. The method of claim 24, wherein, the temperature is between about 0° C. and about 25° C.
- 26. The method of claim 1 further comprising contacting the compound of Formula (II), the compound of Formula (III) and the metal salt or the organic base or a combination thereof with a catalytic amount of an iodide salt.
- 27. The method of claim 26, wherein the iodide salt is sodium iodide, potassium iodide, tetramethylammonium iodide, tetraethylammonium iodide or tetrabutylammonium iodide.
- 28. A compound of Formula (II)
- 29. The compound of claim 28 derived from a GABA analog of Formula (IV):
- 30. The compound of claim 28, wherein the compound of Formula (II) is a compound of Formulae (VII) or (VIII):
- 31. The compound of claim 30, wherein X is chloro, bromo or iodo, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclohexyl or phenyl and R3 is hydrogen.
- 32. The compound of claim 30, wherein X is chloro, bromo or iodo, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is methyl and R3 is methyl.
- 33. The compound of claim 32, wherein X is chloro, bromo or iodo, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl or cyclohexyloxycarbonyl and R3 is methyl.
- 34. The compound of claim 30, wherein X is chloro, bromo or iodo, R10 is hydrogen, allyl, benzyl or trimethylsilyl, and R2 and R3 together with the atom to which they are attached form a cyclohexyl ring.
- 35. The compound of claim 30, wherein X is chloro, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl and R3 is hydrogen.
- 36. The compound of claim 30, wherein X is chloro, R10 is hydrogen, allyl, benzyl or trimethylsilyl, R2 is methyl, n-propyl or isopropyl, and R3 is hydrogen.
- 37. The compound of claim 30, wherein X is chloro, R10 is hydrogen, R2 is methyl, and R3 is hydrogen.
- 38. The compound of claim 30, wherein X is chloro, R10 is allyl, R2 is methyl, and R3 is hydrogen.
- 39. The compound of claim 30, wherein X is chloro, R10 is benzyl, R2 is methyl, and R3 is hydrogen.
- 40. The compound of claim 30, wherein X is chloro, R10 is trimethylsilyl, R2 is methyl, and R3 is hydrogen.
Parent Case Info
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10/171,485, filed Jun. 11, 2002, which claimed the benefit under 35 U.S.C. §119(e) from U.S. Provisional Application Serial No. 60/297,521, filed Jun. 11, 2001; U.S. Provisional Application Serial No. 60/298,514 filed Jun. 14, 2001; and U.S. Provisional Application Serial No. 60/366,090 filed Mar. 19, 2002. The above applications are herein incorporated by reference in their entirety.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60297521 |
Jun 2001 |
US |
|
60298514 |
Jun 2001 |
US |
|
60366090 |
Mar 2002 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
10171485 |
Jun 2002 |
US |
Child |
10460091 |
Jun 2003 |
US |