Methods for producing oxindoles and ortho-substituted anilines and their use as intermediate products for synthesis

摘要

Preparing ortho-substituted aniline compound (I), comprises reacting a mixture comprising substituted aniline compound (II) and thioether derivative (III), in presence of a chlorinating agent and an organic solvent at a reaction temperature of -65[deg] C, preferably -50 to -20[deg] C and obtaining the ortho-substituted aniline compound. Preparing ortho-substituted aniline compound of formula (I), comprises reacting a mixture comprising substituted aniline compound of formula (II) and thioether derivative of formula (R1-S-C(R2)(H)(R3)) (III), in presence of a chlorinating agent and an organic solvent at a reaction temperature of -65[deg] C, preferably -50 to -20[deg] C and obtaining the ortho-substituted aniline compound. R1 : 1-6C alkyl, substituted alkyl, substituted aryl or aryl, preferably 1-4C alkyl; R3 : electron withdrawing- or activating group comprising -CO-R1, -CO-X, SO(n 1)-R1, -CN, -NO 2, aryl or heteroaryl; either R2 : H, 1-6C alkyl, substituted alkyl, substituted aryl or aryl; and R21 : R2 or residue other than R2; or R2R21 : ring; X : OR1, SR1, NR2R21; n 1 : 0-2; R4 : halo, CF 3, CN, NO 2or COY1, preferably 2-F; Y1 : OR1, SR1, NR2R22; R22 : R2 or residue other than R2; n : 1-4, preferably 1; and R5 : R2. Independent claims are also included for: (1) preparing substituted indole compound of formula (IV) and substituted oxindole compound of formula (V), comprising converting (I) in presence of an acid catalyst, with or without the isolation of (I) (optional for (IV) and preferred for (V)), and obtaining (IV) or (V); (2) an intermediate comprising ortho-substituted aniline compound of formula (VI); and (3) end products comprising substituted indole- and substituted oxindole compound of formula (VII) and (VIII). R6 : 1-6C alkyl, substituted alkyl, substituted aryl or aryl, preferably 1-4C alkyl or OH; R7 : 2-6C alkyl, preferably benzyl; R8 : H; R9 : CO 2Ra; Ra : 1-6C alkyl or optionally benzyl ester; R10 : 2-F; and R11 : H, 1-4C alkyl; R12 : 7-F; and R13 : 1-6C alkyl or optionally benzyl or OH. [Image] [Image] [Image].