Processes and intermediates for making sweet taste enhancers

Patent metadata

Field	Value
Publication number	US-9382196-B2
Application number	US-201314053897-A
Country	US
Kind code	B2
Filing date	Oct 15, 2013
Priority date	Jul 31, 2008
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

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

We claim:

1. A compound having structural Formula (IIIc):

wherein
R 1 is —CN, or —C(O)N(R 2 ) 2 ;
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene;
R 8 is C 1 -C 12 alkyl; and
R 2 is C 1 -C 12 alkyl.

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

comprising reducing a compound having structural Formula (IV), or treating a compound having structural Formula (IV) with ammonia,

wherein
R 4 is nitro or halo; and
X is —Y—C(O)—NHR 2 ,
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 2 is hydrogen or C 1 -C 12 alkyl.

3. A compound having structural Formula (IV):

wherein
R 4 is nitro, —NH 2 , or halo; and
X is —Y—C(O)—NHR 2 ,
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 2 is hydrogen or C 1 -C 12 alkyl.

4. A process of preparing the compound of claim 3 , comprising reacting a compound having structural Formula (V)

with X—OH in the presence of NaH, NaHMDS, KO-t-Bu or K 2 CO 3 ;
wherein
R 4 is nitro, —NH 2 , or halo; and
R 5 is nitro or halo.

5. A process of preparing the compound of claim 3 , comprising reacting a compound having structural Formula (VI)

with X—R 6 in the presence of NaH, NaHMDS, KO-t-Bu or K 2 CO 3 or an activating reagent;
wherein
R 4 is nitro, —NH 2 , or halo; and
R 6 is a leaving group selected from halo, —OMs, —OTs, and —OTf.

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

comprising reacting a compound having structural Formula (X)

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; and
R 8 is C 1 -C 12 alkyl; and
R 9 is hydrogen or C1-C12 alkyl.

7. 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,
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;
wherein
Y is C1-C12 alkylene or C1-C12 alkenylene; and
R 8 is C1-C12 alkyl.

8. The process of claim 5 , wherein X is alkyl or alkenyl.

9. The compound of claim 1 having the formula:

10. The process of claim 2 , wherein the compound of structural Formula (IIIa) has the formula:

comprising reducing a compound having the structural formula:

or treating a compound having the formula:

with ammonia.

11. The compound of claim 3 having the formula:

wherein R 4 is nitro, —NH 2 , or fluoro.

Assignees

• Senomyx Inc

Inventors

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

Classifications

• 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

• C07C231/02

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

• C07C235/20

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C231/14

  by formation of carboxamide groups together with reactions not involving the carboxamide groups · CPC title

• C07C307/10

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