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

The present invention relates to a compound of Formula (I)/(II) or pharmaceutically acceptable salts thereof. In Formula (I), Rh, Rg, Rf, m, Re, Rd, Ra, Rb, and Rc are as defined in the description. The present invention further relates to a pharmaceutical composition comprising the compound of Formula (I)/(II) or pharmaceutically acceptable salts thereof, and use of the compound of Formula (I)/(II) or the pharmaceutical composition in the manufacture of a medicament for treating inflammations such as rheumatoid arthritis.

##STR00001##

The present invention relates to a compound of Formula (I)/(II) or pharmaceutically acceptable salts thereof. In Formula (I), Rh, Rg, Rf, m, Re, Rd, Ra, Rb, and Rc are as defined in the description. The present invention further relates to a pharmaceutical composition comprising the compound of Formula (I)/(II) or pharmaceutically acceptable salts thereof, and use of the compound of Formula (I)/(II) or the pharmaceutical composition in the manufacture of a medicament for treating inflammations such as rheumatoid arthritis.

##STR00001##

The present invention relates to a method for purifying N-substituted maleimide. More specifically, the present invention, without performing a water washing process, enables to remove organic-acid-impurities which are difficult to remove through distillation because of having similar boiling points to the N-substituted maleimide compound by utilizing solubility of organic-acid-impurities in an organic solvent used in the preparing process of the maleimide compound, and thereby, without producing washing wastewater, ensuring removal efficiency of the organic-acid-impurities equal to or similar to an N-substituted maleimide compound subjected to a water washing process.

The present invention relates to a method for purifying N-substituted maleimide. More specifically, the present invention, without performing a water washing process, enables to remove organic-acid-impurities which are difficult to remove through distillation because of having similar boiling points to the N-substituted maleimide compound by utilizing solubility of organic-acid-impurities in an organic solvent used in the preparing process of the maleimide compound, and thereby, without producing washing wastewater, ensuring removal efficiency of the organic-acid-impurities equal to or similar to an N-substituted maleimide compound subjected to a water washing process.

An object is to provide a method for easily producing maleimide (MI) in which trace amounts of residual acid components as impurities in a crude MI are efficiently reduced, that is, the acid value is sufficiently reduced. <1> A method for producing purified MI, comprising reducing an acid value of crude MI by 50% or more, by adding carbodiimide (CDI) to a solution comprising the crude MI to react an acid component in the crude MI with the CDI. <2> The method for producing purified MI, comprising adding 0.5% by mass or more and 8% by mass or less of the CDI with respect to a mass of the crude MI for reaction. <3> The method for producing purified MI, wherein the CDI is N,N-diisopropyl carbodiimide (DIC). <4> The method for producing purified MI, comprising removing a urea derivative of the CDI (CDI-U) by-produced when reacting the acid component in the crude MI with the CDI.

An object is to provide a method for easily producing maleimide (MI) in which trace amounts of residual acid components as impurities in a crude MI are efficiently reduced, that is, the acid value is sufficiently reduced. <1> A method for producing purified MI, comprising reducing an acid value of crude MI by 50% or more, by adding carbodiimide (CDI) to a solution comprising the crude MI to react an acid component in the crude MI with the CDI. <2> The method for producing purified MI, comprising adding 0.5% by mass or more and 8% by mass or less of the CDI with respect to a mass of the crude MI for reaction. <3> The method for producing purified MI, wherein the CDI is N,N-diisopropyl carbodiimide (DIC). <4> The method for producing purified MI, comprising removing a urea derivative of the CDI (CDI-U) by-produced when reacting the acid component in the crude MI with the CDI.

A compound represented by the following formula (0).

##STR00001##

(In the above formula (0), R.sup.X represents a 2n.sup.A-valent group having 1 to 70 carbon atoms or a single bond; each R.sup.1A independently represents any of an alkyl group having 1 to 30 carbon atoms and optionally having a substituent, an aryl group having 6 to 30 carbon atoms and optionally having a substituent, a crosslinkable group having 2 to 30 carbon atoms and optionally having a substituent, an alkoxy group having 1 to 30 carbon atoms and optionally having a substituent, a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent, a maleimide group having 4 to 30 carbon atoms and optionally having a substituent, a halogen atom, a nitro group, an amino group having 0 to 30 carbon atoms and optionally having a substituent, a carboxyl group, a thiol group and a hydroxy group, wherein, when R.sup.1A is any of the alkyl group, the aryl group, the crosslinkable group and the alkoxy group, at least one bond selected from the group consisting of an ether bond, a ketone bond and an ester bond is optionally contained, and at least one R.sup.1A is any of a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent and a maleimide group having 4 to 30 carbon atoms and optionally having a substituent; X represents an oxygen atom or a sulfur atom, or is optionally not present; each R independently represents any of a benzene ring, a naphthalene ring and an anthracene ring; each m is independently an integer of 0 to 9, wherein at least one m is an integer of 1 to 9; and n.sup.A is an integer of 1 to 4.)

A compound represented by the following formula (0).

##STR00001##

(In the above formula (0), R.sup.X represents a 2n.sup.A-valent group having 1 to 70 carbon atoms or a single bond; each R.sup.1A independently represents any of an alkyl group having 1 to 30 carbon atoms and optionally having a substituent, an aryl group having 6 to 30 carbon atoms and optionally having a substituent, a crosslinkable group having 2 to 30 carbon atoms and optionally having a substituent, an alkoxy group having 1 to 30 carbon atoms and optionally having a substituent, a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent, a maleimide group having 4 to 30 carbon atoms and optionally having a substituent, a halogen atom, a nitro group, an amino group having 0 to 30 carbon atoms and optionally having a substituent, a carboxyl group, a thiol group and a hydroxy group, wherein, when R.sup.1A is any of the alkyl group, the aryl group, the crosslinkable group and the alkoxy group, at least one bond selected from the group consisting of an ether bond, a ketone bond and an ester bond is optionally contained, and at least one R.sup.1A is any of a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent and a maleimide group having 4 to 30 carbon atoms and optionally having a substituent; X represents an oxygen atom or a sulfur atom, or is optionally not present; each R independently represents any of a benzene ring, a naphthalene ring and an anthracene ring; each m is independently an integer of 0 to 9, wherein at least one m is an integer of 1 to 9; and n.sup.A is an integer of 1 to 4.)

An object is to provide a method for easily producing maleimide (MI) in which trace amounts of residual acid components as impurities in a crude MI are efficiently reduced, that is, the acid value is sufficiently reduced. <1> A method for producing purified MI, comprising reducing an acid value of crude MI by 50% or more, by adding carbodiimide (CDI) to a solution comprising the crude MI to react an acid component in the crude MI with the CDI. <2> The method for producing purified MI, comprising adding 0.5% by mass or more and 8% by mass or less of the CDI with respect to a mass of the crude MI for reaction. <3> The method for producing purified MI, wherein the CDI is N,N-diisopropyl carbodiimide (DIC). <4> The method for producing purified MI, comprising removing a urea derivative of the CDI (CDI-U) by-produced when reacting the acid component in the crude MI with the CDI.