Process or making N-hydroxy-3[4-[[[2-(2methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide and starting materials therefor
N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide and starting materials therefore are prepared by new synthetic methods.
1. A method of making N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide comprising:
(a) combining 2-methyltryptamine and (E)-3-(4-formyl-phenyl)-acrylic acid methyl ester to form an admixture;
(b) stirring the admixture;
(c) cooling the admixture;
(d) reducing the admixture;
(e) adding hydrochloric acid to the admixture to form the (E)-3-(4-{[2-(2-methyl-1H-indol-3-yl)-ethylamino]-methyl]-phenyl)-acrylic acid methyl ester hydrochloride salt;
(f) combining sodium hydroxide and (E)-3-(4-{[2-(2-methyl-1H-indol-3-yl)-ethylamino]-methyl]-phenyl)-acrylic acid methyl ester hydrochloride salt to form an admixture at a temperature of less than about −10° C.; and subsequently
(g) adding hydroxylamine to the admixture to form the N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide.
2. The method of claim 1 , wherein the (b) stirring occurs at a temperature range of from about 20° C. to about 25° C.
3. The method of claim 1 , wherein the admixture is cooled in (c) to a temperature of about −15° C.
4. The method of claim 1 , wherein reducing (d) is by the addition of sodium borohydride to the admixture.
5. The method of claim 4 , wherein the sodium borohydride is added while the temperature is maintained at a range from about −15° C. to about −10° C.
6. The method of claim 1 , wherein the temperature of (f) is less than about −15° C.
7. The method of claim 1 , wherein the hydroxylamine is used in an amount ranging from about 4 to about 13 equivalents.