[Problem] To provide a novel means capable of generating highly stereoselective and/or highly efficient amidation reactions in a variety of substrates having a carboxyl group and an amino group, and capable of producing amide compounds.

[Solution] A reaction agent for amide reactions between carboxyl groups and amino groups and including a silane compound indicated by general formula (A) and/or general formula (B).

##STR00001##

(In general formulas (A) and (B), each substituent represents the definition described in the Claims.)

[Problem] To provide a novel means capable of generating highly stereoselective and/or highly efficient amidation reactions in a variety of substrates having a carboxyl group and an amino group, and capable of producing amide compounds.

[Solution] A reaction agent for amide reactions between carboxyl groups and amino groups and including a silane compound indicated by general formula (A) and/or general formula (B).

##STR00001##

(In general formulas (A) and (B), each substituent represents the definition described in the Claims.)

Production of a high efficiency arthropod repellent by chemically transforming a substance used by mosquitoes as an attractant, the lactic acid, as well as lactates, in this case (S)-ethyl lactate, which is an essential attractant for A. aegypti females. The hydroxyl functional group of lactic acid must be transformed into esters, and the carboxylic acid functional group into amides, since esters and amides are functional groups already present in other repellents, such as in the structure of DEET, IR 3535 and dimethyl phthalate. The ester functional group of (S)-ethyl lactate must undergo a reaction in which the acyl functional group is substituted by an amine of interest and the hydroxyl functional group must be acylated. The structure of an attractant, or a derivative thereof, is transformed into a high efficiency repellent.

Production of a high efficiency arthropod repellent by chemically transforming a substance used by mosquitoes as an attractant, the lactic acid, as well as lactates, in this case (S)-ethyl lactate, which is an essential attractant for A. aegypti females. The hydroxyl functional group of lactic acid must be transformed into esters, and the carboxylic acid functional group into amides, since esters and amides are functional groups already present in other repellents, such as in the structure of DEET, IR 3535 and dimethyl phthalate. The ester functional group of (S)-ethyl lactate must undergo a reaction in which the acyl functional group is substituted by an amine of interest and the hydroxyl functional group must be acylated. The structure of an attractant, or a derivative thereof, is transformed into a high efficiency repellent.

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

A method for producing a diglycolamide molecule having the formula:

##STR00001##

wherein R.sup.1 and R.sup.2 are independently selected from alkyl groups (R) and acyl groups (C(O)R) in which the alkyl groups (R) contain 1-30 carbon atoms and optionally contain an ether or thioether linkage between carbon atoms, and R.sup.5 and R.sup.6 are independently selected from hydrogen atom and alkyl groups containing 1-3 carbon atoms; and one or both pairs of R.sup.1 and R.sup.2 are optionally interconnected to form a ring; the method comprising: combining a diglycolic acid molecule (A) and a secondary amine (B) to form a salt intermediate (C), and heating the salt intermediate (C) to a temperature of 100° C. to 300° C. to form the diglycolamide of Formula (1) in a dehydration process, wherein the method is shown schematically as follows:

##STR00002##

A method for producing a diglycolamide molecule having the formula:

##STR00001##

wherein R.sup.1 and R.sup.2 are independently selected from alkyl groups (R) and acyl groups (C(O)R) in which the alkyl groups (R) contain 1-30 carbon atoms and optionally contain an ether or thioether linkage between carbon atoms, and R.sup.5 and R.sup.6 are independently selected from hydrogen atom and alkyl groups containing 1-3 carbon atoms; and one or both pairs of R.sup.1 and R.sup.2 are optionally interconnected to form a ring; the method comprising: combining a diglycolic acid molecule (A) and a secondary amine (B) to form a salt intermediate (C), and heating the salt intermediate (C) to a temperature of 100° C. to 300° C. to form the diglycolamide of Formula (1) in a dehydration process, wherein the method is shown schematically as follows:

##STR00002##

A method for producing a diglycolamide molecule having the formula:

##STR00001##

wherein R.sup.1 and R.sup.2 are independently selected from alkyl groups (R) and acyl groups (C(O)R) in which the alkyl groups (R) contain 1-30 carbon atoms and optionally contain an ether or thioether linkage between carbon atoms, and R.sup.5 and R.sup.6 are independently selected from hydrogen atom and alkyl groups containing 1-3 carbon atoms; and one or both pairs of R.sup.1 and R.sup.2 are optionally interconnected to form a ring; the method comprising: combining a diglycolic acid molecule (A) and a secondary amine (B) to form a salt intermediate (C), and heating the salt intermediate (C) to a temperature of 100° C. to 300° C. to form the diglycolamide of Formula (1) in a dehydration process, wherein the method is shown schematically as follows:

##STR00002##

The present invention provides a process for preparing 2-methyl-N-(2′-methylbutyl)butanamide of the following formula (1):the process comprising: subjecting an α-arylethyl-2-methylbutylamine compound of the following general formula (2): wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, to N-2-methylbutyrylation to form an N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (3): wherein Ar is as defined above, and removing the α-arylethyl group of the resulting compound (3) to form 2-methyl-N-(2′-methylbutyl)butanamide (1).

##STR00001##