Processes and intermediates for making sweet taste enhancers

Patent metadata

Field	Value
Publication number	US-2016289200-A1
Application number	US-201615184894-A
Country	US
Kind code	A1
Filing date	Jun 16, 2016
Priority date	Jul 31, 2008
Publication date	Oct 6, 2016
Grant date	—

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 (I):

comprising
i) reacting a compound having structural Formula (IIIa)

with NH 2 S(O) 2 NH 2 in the presence of a base to provide the compound having structural Formula (I), or
ii) reacting the compound having structural Formula (IIIa) with Cl—S(O) 2 —NH 2 to provide a compound having structural Formula (IIb)

which is further reacted with a base to provide the compound having structural Formula (I),
wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

3 . The process of claim 2 , comprising reacting the compound having structural Formula (IIIa) with NH 2 —S(O) 2 —NH 2 in the presence of a base to provide the compound of Formula (I).

4 . The process of claim 2 , comprising reacting the compound having structural Formula (IIIa) with Cl—S(O) 2 —NH 2 to provide the compound having structural Formula (II) which is further reacted with a base to provide the compound having structural Formula (I).

5 . 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.

6 . The process of claim 5 , comprising reducing the compound having structural Formula (IV) to provide the compound of Formula (IIIa), where R 4 is nitro.

7 . The process of claim 5 , comprising treating the compound having structural Formula (IV) with ammonia to provide the compound of Formula (IIIa), where R 4 is halo.

8 . 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.

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

comprising reacting a compound having structural Formula (I)

with an alkali metal-based inorganic base,
wherein
M is a cation of sodium;
X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl; and
n is 1.

10 . A process of preparing a compound having structural Formula (Ia):

comprising:
reacting a compound having structural Formula (IIc1)

with a hydroxide or alkoxide base in an aqueous solution at a temperature ranging from about 25° C. to about 95° C. to provide a mixture,
combining an alcohol with the mixture to form an aqueous-alcohol mixture having a pH,
combining a hydrochloride solution with the aqueous-alcohol mixture to adjust the pH thereof to a range from about 4 to about 5,
wherein:
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and R 8 is C 1 -C 12 alkyl.

11 . The process of claim 10 , wherein the mixture is washed with an ether prior to combination with the alcohol.

12 . 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.

13 . The process of claim 12 , wherein the solution is Cl—S(O) 2 —NH 2 in methylene chloride and acetonitrile.

14 . 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.

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

comprising
reacting HO—Y—C(O)—NH

Assignees

• Senomyx Inc

Inventors

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

Classifications

• C07C231/02

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title

• C07C237/44

  having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring · CPC title

• C01B21/096

  Amidosulfonic acid; Salts thereof · CPC title

• C07C255/59

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

• C07D285/16 Primary

  Thiadiazines; Hydrogenated thiadiazines · CPC title