Regioselective reduction of fused pyrrolocarbazoles-5,7-diones

A method for regioselectively reducing a compound of formula (I) into a compound of formula (II):

• wherein:
• ring B, together with the carbon atoms to which it is attached, is selected from:
• (a) a phenylene ring in which from 1 to 3 carbon atoms may be replaced by nitrogen atoms;
• and
• (b) a 5-membered aromatic ring in which either
• (1) one carbon atom may be replaced with an oxygen, nitrogen, or sulfur atom;
• (2) two carbon atoms may be replaced with a sulfur and a nitrogen atom, an oxygen and a nitrogen atom, or two nitrogen atoms;
• or
• (3) three carbon atoms may be replaced with three nitrogen atoms, one oxygen and two nitrogen atoms, or one sulfur and two nitrogen atoms;
• R1 and R2 are each independently selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl, wherein said optional substituents are one to three R10 groups;
• at least one of R3, R4, R5, and R6 is selected from H, (alkylene)xOR13, (CH2)pOR22, O-(alkylene)-R27, OCH[(CH2)pOR20]2, NR11R32, NR11R33, (alkylene)-NR18R19, substituted alkyl, wherein one of the substituents is a spirocycloalkyl group, optionally substituted (alkylene)x-cycloalkyl, and optionally substituted-(alkylene)x-heterocycloalkyl, wherein the heterocycloalkyl does not include unsubstituted N-morpholinyl, N-piperidyl, or N-thiomorpholinyl;
• wherein any said alkylene group may be optionally substituted with one to three R10 groups;
• the other R3, R4, R5, or R6 moieties can be selected independently from H, halogen, R10, OR20, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl, wherein said optional substituents are one to three R10 groups;
• Q is selected from an optionally substituted C1-2 alkylene, wherein said optional substituents are one to three R10 groups;
• R10 is selected from alkyl, aryl, heteroaryl, cycloalkyl, spirocycloalkyl, heterocycloalkyl, arylalkoxy, F, Cl, Br, I, CF3, NR31AR31B, OR30, OCF3, O—Si(R29)3, O-tetrahydropyranyl, ethylene oxide, (CH2)pOR30, OR28, and a monosaccharide wherein each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by H, alkyl, or alkoxy;
• R11 is selected from H and optionally substituted alkyl, wherein said optional substituents are one to three R10 groups;
• R13 is independently selected from optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl, wherein said optional substituents are one to three R10 groups;
• R18 and R19 are each independently selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl, wherein said optional substituents are one to three R10 groups;
• R20 is selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl, wherein said optional substituents are one to three R10 groups;
• R22 is optionally substituted C5-C10 alkyl, wherein said optional substituents are one to three R10 groups;
• R27 is selected from optionally substituted cycloalkyl, wherein said optional substituents are one to three R10 groups;
• R28 is the residue of an amino acid after the removal of the hydroxyl moiety from the carboxyl group thereof;
• R29 is H or alkyl;
• R30 is H, alkyl, aryl, arylalkyl, heteroaryl, cycloalkyl, or heterocycloalkyl;
• R31A and R31B are each independently selected from H, alkyl, and arylalkyl, or together with the nitrogen to which they are attached form a heterocycloalkyl;
• R32 is optionally substituted aryl, wherein said optional substituents are one to three R10 groups;
• R33 is selected from optionally substituted cycloalkyl, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl, wherein said optional substituents are one to three R10 groups;
• p is independently selected from 1, 2, 3, and 4;
• x is 0 or 1;
• or a stereoisomer or salt form thereof,
• said method comprising the steps of:
• i) contacting said compound of formula (I) with a metal hydride together with an activating agent selected from a mineral, organic or Lewis acid in a solvent;
• and optionally
• ii) recovering the obtained compound of formula (II) or a stereoisomer or salt form-thereof.