Process for the preparation of biphenylamines

A process to prepare a compound of formula (IV) or a salt thereof

• wherein
• q is an integer selected from the group consisting of 0, 1, 2, 3 and 4;
• p is an integer selected from the group consisting of 1, 2, 3, 4 and 5;
• R11 is hydrogen or a nitrogen protecting group;
• R12 is hydrogen;
• each R1, if present, is independently selected from the group consisting of the halogens;
• and
• each R3 is independently selected from the group consisting of the halogens;
• the process comprising reacting an ortho-substituted aniline and a phenylboro derivative in the presence of a base and a palladium catalyst, said palladium catalyst comprising a palladium source and a biphenyl phosphine ligand,
• wherein said ortho-substituted aniline is a compound of formula (I), or a salt thereof
• wherein
• q, R1, R11 and R12 are as defined above;
• and
• X1 is a group capable of transmetalation with palladium;
• wherein said phenylboro derivative is a compound of formula (II)
• wherein
• p and R3 are as defined above;
• y is an integer selected from 0 or 1;
• wherein,
• when y is 1, then z is an integer selected from 1, 2 or 3;
• when y is 0, then z is an integer selected from 1, 2, 3 or 4, and the compound of formula (II) forms a borate accompanied by a cation A having a charge a+;
• and
• each R2 is independently selected from the group consisting of hydrogen, halogen, —OH, —OR9, and C1-C10-alkyl, wherein R9 is C1-C10-alkyl or C6-C12-aryl;
• or wherein, z being 1, two R2 groups together form a bridging group —O—(CH2)r—O—, wherein r is 2 or 3, so that said two R2 groups, together with the oxygen atoms and the boron atom, form a 5- or 6-membered ring, where the CH2 groups are optionally substituted by one or two C1-C4-alkyl groups;
• and
• wherein the biphenyl phosphine ligand is a compound of formula (III) or a salt thereof
• wherein
• m is an integer selected from the group consisting of 0, 1, 2 and 3;
• n is an integer selected from the group consisting of 0, 1, 2, 3 and 4;
• each R4 is independently selected from the group consisting of C1-C16-alkyl, C3-C15-cycloalkyl, and C6-C10-aryl;
• each R5 is independently selected from the group consisting of hydrogen, —OR10, —SR10, —N(R10)(R10), C1-C16-alkyl, C3-C10-cycloalkyl, halogen, cyano, and C1-C6-haloalkyl, provided that one R5 is not hydrogen, wherein R10 is selected from the group consisting of C1-C16-alkyl, C3-C10-cycloalkyl, and C1-C6-haloalkyl;
• each R6 is independently selected from the group consisting of halogen, cyano, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alcoxyl and C1-C6-haloalcoxyl;
• each R7 is independently selected from the group consisting of halogen, cyano, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alcoxyl and C1-C6-haloalcoxyl.