This disclosure relates to picolinamides of Formula I and their use as fungicides. ##STR00001##

The present disclosure discloses a water-soluble ynamide coupling reagent and a method for using the water-soluble ynamide coupling reagent in the synthesis of amide, polypeptide, ester and thioester compound. The ynamide coupling reagent has the structure represented by the following formula (I): ##STR00001##
and in the formula (I), R is one selected from the group consisting of methylsulfonyl, benzenesulfonyl, p-toluenesulfonyl, trifluoroacetyl and other electron withdrawing groups.

A 3-(alkylsulfonyl)pyridine-2-carboxylic acid or a salt thereof can be manufactured by comprising: allowing a compound represented by formula (1-N): ##STR00001## wherein X represents a halogen atom, to react with a compound represented by formula (2):
R.sup.2SM.sup.2(2) wherein R.sup.2 represents a C.sub.1-8 straight-chain alkyl group, and M.sup.2 represents a hydrogen atom or an alkali metal, to give a compound represented by formula (3-N): ##STR00002## wherein R.sup.2 and X are as defined above; allowing the compound (3-N) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid; reducing the product in the presence of a base and a heterogeneous transition metal catalyst; and hydrolyzing the product in the presence of a base.

A compound represented by formula (7): ##STR00001## or a salt thereof can be manufactured by the following steps: a step of allowing a compound represented by formula (1-S): ##STR00002## to react with a compound represented by formula (2):
R.sup.2SM.sup.2(2) to give a compound represented by formula (3-S): ##STR00003## a step of allowing the compound represented by formula (3-S) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid to give a compound represented by formula (6-S) or a salt thereof: ##STR00004##
and a step of reducing the compound represented by formula (6-S) or salt thereof in the presence of a base and a heterogeneous transition metal catalyst to give a compound represented by formula (7) or a salt thereof, wherein X, R.sup.1, R.sup.2, and M.sup.2 are defined in the specification.

A compound represented by formula (7): ##STR00001## or a salt thereof can be manufactured by the following steps: a step of allowing a compound represented by formula (1-S): ##STR00002## to react with a compound represented by formula (2):
R.sup.2SM.sup.2(2) to give a compound represented by formula (3-S): ##STR00003## a step of allowing the compound represented by formula (3-S) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid to give a compound represented by formula (6-S) or a salt thereof: ##STR00004##
and a step of reducing the compound represented by formula (6-S) or salt thereof in the presence of a base and a heterogeneous transition metal catalyst to give a compound represented by formula (7) or a salt thereof, wherein X, R.sup.1, R.sup.2, and M.sup.2 are defined in the specification.

Compounds, and methods of using the same, are provided as therapies for the treatment leucine-rich repeat kinase-2 (LRRK2)-related disorders including, but not limited to, neurodegenerative and neuroinflammatory disorders, such as Parkinson's Disease.

Compounds, and methods of using the same, are provided as therapies for the treatment leucine-rich repeat kinase-2 (LRRK2)-related disorders including, but not limited to, neurodegenerative and neuroinflammatory disorders, such as Parkinson's Disease.

A 3-(alkylsulfonyl)pyridine-2-carboxylic acid or a salt thereof can be manufactured by comprising: a step of allowing a compound represented by formula (1-N):

##STR00001## (wherein X represents a halogen atom) to react with a compound represented by formula (2):

R.sup.2SM.sup.2(2) (wherein R.sup.2 represents a C.sub.1-8 straight-chain alkyl group, and M.sup.2 represents a hydrogen atom or an alkali metal) to give a compound represented by formula (3-N):

##STR00002## (wherein R.sup.2 and X are as defined above); a step of allowing the compound represented by formula (3-N) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid to give a compound represented by formula (6-N):

##STR00003## (wherein R.sup.2 and X are as defined above); a step of reducing the compound represented by formula (6-N) in the presence of a base and a heterogeneous transition metal catalyst to give a compound represented by formula (8-N):

##STR00004## (wherein R.sup.2 is as defined above); and a step of hydrolyzing the compound represented by formula (8-N) in the presence of a base to give a compound represented by formula (7) or a salt thereof:

##STR00005## (wherein R.sup.2 is as defined above).

A compound represented by formula (7) or a salt thereof can be manufactured by the following steps: a step of allowing a compound represented by formula (1-S):

##STR00001## (wherein R.sup.1 represents a C.sub.1-8 straight-chain alkyl group, and X represents a halogen atom) to react with a compound represented by formula (2):

R.sup.2SM.sup.2(2) (wherein R.sup.2 represents a C.sub.1-8 straight-chain alkyl group, and M.sup.2 represents a hydrogen atom or an alkali metal) to give a compound represented by formula (3-S):

##STR00002## (wherein R.sup.1, R.sup.2, and X are as defined above); a step of allowing the compound represented by formula (3-S) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid to give a compound represented by formula (6-S) or a salt thereof:

##STR00003## (wherein X and R.sup.2 are as defined above); and a step of reducing the compound represented by formula (6-S) or salt thereof in the presence of a base and a heterogeneous transition metal catalyst to give a compound represented by formula (7) or a salt thereof:

##STR00004## (wherein R.sup.2 is as defined above).

A compound represented by formula (7) or a salt thereof can be manufactured by the following steps: a step of allowing a compound represented by formula (1-S):

##STR00001## (wherein R.sup.1 represents a C.sub.1-8 straight-chain alkyl group, and X represents a halogen atom) to react with a compound represented by formula (2):

R.sup.2SM.sup.2(2) (wherein R.sup.2 represents a C.sub.1-8 straight-chain alkyl group, and M.sup.2 represents a hydrogen atom or an alkali metal) to give a compound represented by formula (3-S):

##STR00002## (wherein R.sup.1, R.sup.2, and X are as defined above); a step of allowing the compound represented by formula (3-S) to react with hydrogen peroxide in the presence of a tungsten catalyst and an acid to give a compound represented by formula (6-S) or a salt thereof:

##STR00003## (wherein X and R.sup.2 are as defined above); and a step of reducing the compound represented by formula (6-S) or salt thereof in the presence of a base and a heterogeneous transition metal catalyst to give a compound represented by formula (7) or a salt thereof:

##STR00004## (wherein R.sup.2 is as defined above).