US 12,344,586 B2
Process for the preparation of biphenylamines
Xi Zhen, Tianjin (CN); Pingping Tang, Tianjin (CN); Natali Ashush, Bat-Hefer (IL); and Einat Kisin-Finfer, Hod Hasharon (IL)
Assigned to ADAMA MAKHTESHIM LTD., Beer-Sheva (IL)
Appl. No. 17/628,349
Filed by ADAMA MAKHTESHIM LTD., Beer-Sheva (IL)
PCT Filed Jul. 16, 2020, PCT No. PCT/IL2020/050799
§ 371(c)(1), (2) Date Jan. 19, 2022,
PCT Pub. No. WO2021/014437, PCT Pub. Date Jan. 28, 2021.
Claims priority of application No. PCT/CN2019/096684 (WO), filed on Jul. 19, 2019.
Prior Publication US 2022/0380321 A1, Dec. 1, 2022
Int. Cl. C07D 241/24 (2006.01); C07D 213/82 (2006.01); C07D 231/14 (2006.01)
CPC C07D 241/24 (2013.01) [C07D 213/82 (2013.01); C07D 231/14 (2013.01); B01J 2531/824 (2013.01)] 19 Claims
 
1. A process to prepare a compound of formula (IV) or a salt thereof

OG Complex Work Unit Chemistry
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

OG Complex Work Unit Chemistry
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)

OG Complex Work Unit Chemistry
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

OG Complex Work Unit Chemistry
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.