The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

The present invention relates to a process for the preparation of methionine comprising the step of contacting a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile and/or 2-amino-4-(methylthio)butaneamide with water in the presence of a catalyst to give a methionine comprising mixture, wherein the catalyst comprises CeO2 comprising particles, wherein the CeO2 comprising particles have a BET surface area of from 175 to 300+/−10% m2/g measured according to DIN ISO 9277-5 (2003), a mean maximum Feret diameter x.sub.Fmax, mean of from 3+/−10% to 40+/−10% nm and a mean minimum Feret diameter x.sub.Fmin, mean of from 2+/−10% to 30+/−10% nm, both measured according to DIN ISO 9276-6 (2012).

The present invention relates to a process for the preparation of methionine comprising the step of contacting a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile and/or 2-amino-4-(methylthio)butaneamide with water in the presence of a catalyst to give a methionine comprising mixture, wherein the catalyst comprises CeO2 comprising particles, wherein the CeO2 comprising particles have a BET surface area of from 175 to 300+/−10% m2/g measured according to DIN ISO 9277-5 (2003), a mean maximum Feret diameter x.sub.Fmax, mean of from 3+/−10% to 40+/−10% nm and a mean minimum Feret diameter x.sub.Fmin, mean of from 2+/−10% to 30+/−10% nm, both measured according to DIN ISO 9276-6 (2012).

The present invention relates to a process for the preparation of methionine comprising the step of contacting a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile and/or 2-amino-4-(methylthio)butaneamide with water in the presence of a catalyst to give a methionine comprising mixture, wherein the catalyst comprises CeO2 comprising particles, wherein the CeO2 comprising particles have a BET surface area of from 175 to 300+/−10% m2/g measured according to DIN ISO 9277-5 (2003), a mean maximum Feret diameter x.sub.Fmax, mean of from 3+/−10% to 40+/−10% nm and a mean minimum Feret diameter x.sub.Fmin, mean of from 2+/−10% to 30+/−10% nm, both measured according to DIN ISO 9276-6 (2012).

The present disclosure provides, in part, a process for preparing compounds (I) having allosteric effector properties against Hepatitis B virus Cp.

##STR00001##

The present disclosure provides, in part, a process for preparing compounds (I) having allosteric effector properties against Hepatitis B virus Cp.

##STR00001##

A preparation method of a sulfur-containing biphenylsulfur-containing biphenyl compound shown by the general formula (I) has a reaction formula as follows:

##STR00001##

Each substituent in the formula is defined in the description. In the method, halogeno benzene shown by the general formula (II) generates a coupling reaction in a catalytic system composed of a nickel compound and at least one ligand under the combined action of metallic zinc to obtain the sulfur-containing biphenyl compound shown by the general formula (I).

A preparation method of a sulfur-containing biphenylsulfur-containing biphenyl compound shown by the general formula (I) has a reaction formula as follows:

##STR00001##

Each substituent in the formula is defined in the description. In the method, halogeno benzene shown by the general formula (II) generates a coupling reaction in a catalytic system composed of a nickel compound and at least one ligand under the combined action of metallic zinc to obtain the sulfur-containing biphenyl compound shown by the general formula (I).

A preparation method of a sulfur-containing biphenylsulfur-containing biphenyl compound shown by the general formula (I) has a reaction formula as follows:

##STR00001##

Each substituent in the formula is defined in the description. In the method, halogeno benzene shown by the general formula (II) generates a coupling reaction in a catalytic system composed of a nickel compound and at least one ligand under the combined action of metallic zinc to obtain the sulfur-containing biphenyl compound shown by the general formula (I).