Processes and intermediates for making sweet taste enhancers

Patent metadata

Field	Value
Publication number	US-9732052-B2
Application number	US-201615184894-A
Country	US
Kind code	B2
Filing date	Jun 16, 2016
Priority date	Jul 31, 2008
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

The present invention includes methods/processes and intermediates for preparing compounds having structural Formula (I):

wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

First claim

What is claimed is:

1. A compound having structural Formula (II)

wherein
R 1 is —CN, —C(O)OR 2 , or —C(O)NH 2 ;
X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl; and
R 2 is hydrogen or C 1 -C 12 alkyl.

2. A process of preparing a compound having structural Formula (IIIa):

comprising
i) reducing a compound having structural Formula (IV) where R 4 is nitro to provide the compound having structural Formula (IIIa), or
ii) treating a compound having structural Formula (IV) where R 4 is halo with ammonia to provide the compound having structural Formula (IIIa),

wherein
R 4 is nitro or halo; and
X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

3. The process of claim 2 , comprising reducing the compound having structural Formula (IV) to provide the compound of Formula (IIIa), where R 4 is nitro.

4. The process of claim 2 , comprising treating the compound having structural Formula (IV) with ammonia to provide the compound of Formula (IIIa), where R 4 is halo.

5. A process of preparing a compound having structural Formula (IIc):

comprising reacting a compound having structural Formula (IX)

with R 8 —NH 2 , in the presence of an activating reagent;
wherein
R 1 is —CN or —C(O)NH 2 ;
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene;
R 8 is C 1 -C 12 alkyl; and
R 9 is hydrogen or C 1 -C 12 alkyl.

6. A process of preparing a compound having structural Formula (IIc1):

comprising:
adding a solution of a compound having structural Formula (IIIc1)

in a mixed solvent of methylene chloride and dimethylacetamide to a solution of Cl—S(O) 2 —NH 2 in methylene chloride and optionally an additional solvent to form a mixture;
maintaining the mixture at about room temperature for about 6 to about 18 hours; and
extracting the mixture with an aqueous solution of a hydroxide or alkoxide base to form an extracted basic solution wherein the compound having structural formula (IIc1) is stabilized,
wherein:
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 8 is C 1 -C 12 alkyl.

7. The process of claim 6 , wherein the solution is Cl—S(O) 2 —NH 2 in methylene chloride and acetonitrile.

8. A process of preparing a compound having structural Formula (IIc1):

comprising:
adding a solution of a compound having structural Formula (IIIc1)

in a mixed solvent of methylene chloride and dimethylacetamide to a solution of Cl—S(O) 2 —NH 2 in methylene chloride and optionally an additional solvent to form a first mixture;
maintaining the first mixture at about room temperature for about 6 to about 18 hours;
mixing an aqueous solution of NaHCO 3 with the first mixture to form a second mixture, wherein the second mixture is maintained at a temperature of about 45° C. or below during the addition of the aqueous solution of NaHCO 3 ; and
extracting the second mixture with an aqueous solution of a hydroxide or alkoxide base to form an extracted basic solution wherein the compound having structural formula (IIc1) is stabilized,
wherein:
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 8 is C 1 -C 12 alkyl.

9. A process of preparing a compound having structural Formula (IIIc1):

comprising
reacting HO—Y—C(O)—NHR 8 with

in the presence of a base to form a first mixture solution,
concentrating the first mixture solution to form a concentrated first mixture solution, wherein the volume of the concentrated first mixture solution is equivalent to or less than about 50% of the volume of the first mixture solution,
diluting the concentrated first mixture solution with an ether to form a second mixture solution and optionally washing the second mixture solution with water or an aqueous solution,
concentrating the second mixture solution to form a concentrated second mixture solution, wherein the volume of the concentrated second mixture solution is equivalent to or less than about 50% of the volume of the second mixture solution,
diluting the concentrated second mixture solution with ethyl acetate to form a third mixture solution, and
concentrating the third mixture solution to form a concentrated third mixture solution, wherein the compound having structural Formula (IIIc1) precipitates as a solid and optionally diluting the concentrated third mixture solution with an alkane hydrocarbon solvent;
wherein
Y is C 1 -C 12 alkylene; and
R 8 is C 1 -C 12 alkyl.

10. The process of claim 9 comprising diluting the concentrated third mixture solution with an alkane hydrocarbon solvent.

11. The process of claim 9 comprising washing the second mixture solution with water or an aqueous solution.

Assignees

• Senomyx Inc

Inventors

• Tachdjian Catherine
• Karanewsky Donald S
• Tang Xiao-Qing
• Chen Qing
• Leeming Peter
• Rashid Tayyab
• Levin Daniel

Classifications

• C01B21/096

  Amidosulfonic acid; Salts thereof · CPC title

• C07C307/10

  having nitrogen atoms of the sulfamide groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07C255/54

  containing cyano groups and etherified hydroxy groups bound to the carbon skeleton · CPC title

• C07C303/40

  by reactions not involving the formation of sulfonamide groups · CPC title

• C07C255/59

  the carbon skeleton being further substituted by singly-bound oxygen atoms · CPC title