In one aspect, the disclosure relates to a facile strategy to introduce electron-deficient aryl sulfate diesters to silylated hydroxyl groups of carbohydrates and amino acids, among other substrates, wherein selective hydrolysis and the removal of an electron-deficient aromatic group allows for the efficient generation of sulfated carbohydrates, peptides, and other compounds. The incorporation of electron-deficient aryl sulfate diesters in the early stage of the synthesis of glycans, peptides, and the like, disclosed herein avoids time-consuming protecting group manipulations, simplifies the purification of sulfated products, and improves the overall yield and efficiency. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

In one aspect, the disclosure relates to a facile strategy to introduce electron-deficient aryl sulfate diesters to silylated hydroxyl groups of carbohydrates and amino acids, among other substrates, wherein selective hydrolysis and the removal of an electron-deficient aromatic group allows for the efficient generation of sulfated carbohydrates, peptides, and other compounds. The incorporation of electron-deficient aryl sulfate diesters in the early stage of the synthesis of glycans, peptides, and the like, disclosed herein avoids time-consuming protecting group manipulations, simplifies the purification of sulfated products, and improves the overall yield and efficiency. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared. ##STR00001##

The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared. ##STR00001##

The present invention provides an industrially advantageous production method of (1R,2S)-2-{[((2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.

(1R,2S)-2-{[((2,4-Dimethylpyrimidin-5-yl)oxyl}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (compound [A]) is produced by an industrially advantageous method by a route via a novel compound.

##STR00001##

wherein each symbol is as described in the description.

The present invention provides an industrially advantageous production method of (1R,2S)-2-{[((2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.

(1R,2S)-2-{[((2,4-Dimethylpyrimidin-5-yl)oxyl}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (compound [A]) is produced by an industrially advantageous method by a route via a novel compound.

##STR00001##

wherein each symbol is as described in the description.

The present invention provides an industrially advantageous production method of (1R,2S)-2-{[((2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.

(1R,2S)-2-{[((2,4-Dimethylpyrimidin-5-yl)oxyl}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (compound [A]) is produced by an industrially advantageous method by a route via a novel compound.

##STR00001##

wherein each symbol is as described in the description.

Compositions comprising a sulfonated reaction product or a salt thereof may be prepared from a biphenyl compound that has been alkylated with an olefin of formula R.sup.1R.sup.2CCH.sub.2, wherein R.sup.1 is a C.sub.6-C.sub.24 hydrocarbyl group, and R.sup.2 is H or a C.sub.6-C.sub.24 hydrocarbyl group. Methods for sulfonating an alkylated biphenyl compound prepared from a biphenyl compound that has been alkylated with an olefin of formula R.sup.1R.sup.2CCH.sub.2, wherein R.sup.1 is a C.sub.6-C.sub.24 hydrocarbyl group, and R.sup.2 is H or a C.sub.6-C.sub.24 hydrocarbyl group may comprise contacting the alkylated biphenyl compound with a sulfonating reagent; forming a sulfonated reaction product; and converting the sulfonated reaction product into a sulfonate salt.

Compositions comprising a sulfonated reaction product or a salt thereof may be prepared from a biphenyl compound that has been alkylated with an olefin of formula R.sup.1R.sup.2CCH.sub.2, wherein R.sup.1 is a C.sub.6-C.sub.24 hydrocarbyl group, and R.sup.2 is H or a C.sub.6-C.sub.24 hydrocarbyl group. Methods for sulfonating an alkylated biphenyl compound prepared from a biphenyl compound that has been alkylated with an olefin of formula R.sup.1R.sup.2CCH.sub.2, wherein R.sup.1 is a C.sub.6-C.sub.24 hydrocarbyl group, and R.sup.2 is H or a C.sub.6-C.sub.24 hydrocarbyl group may comprise contacting the alkylated biphenyl compound with a sulfonating reagent; forming a sulfonated reaction product; and converting the sulfonated reaction product into a sulfonate salt.

There is disclosed a cyclic process for producing taurine from monoethanolamine comprising the steps of: (a) reacting monoethanolamine with ammonium sulfate in the recycling mother liquor to yield monoethanolamine sulfate; (b) reacting the monoethanolamine sulfate with sulfuric acid to form 2-aminoethyl hydrogen sulfate ester; (c) subjecting the 2-aminoethyl hydrogen sulfate ester to a sulfonation reaction with ammonium sulfite to yield taurine and ammonium sulfate; (d) separating the taurine and the ammonium sulfate by means of solid-liquid separation; (e) removing the excess ammonium sulfite from the mother liquor to obtain an aqueous solution comprised of ammonium sulfate and (f) returning the aqueous solution to step (a) to complete the cyclic process.