Processes for the facile synthesis of diaryl amines and analogues thereof

A process for producing a diaryl amine compound of the formula (I):

• or a salt thereof,
• said process comprising the steps of
• (1) coupling a compound of formula (II) with an amine of formula (III) in the presence of an alkali metal salt or a transition metal catalyst:
• to form a compound of formula (IV):
• and
• (2) removing radical Y from the compound of formula (IV) in the presence of an acid;
• wherein:
• Ar1 and Ar2 are independently Q;
• wherein each Q is an aryl or heteroaryl ring system optionally fused to a saturated or unsaturated 5–8 membered sing having 0–4 heteroatoms, wherein either Ar1 or Ar2, is a heteroaryl ring;
• wherein Q is optionally substituted at one or more ring atoms with one or more substituents independently selected from halo;
• C1–C6 aliphatic optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2, OC(O)N(R′)2, NR′CO2R′, NR′C(O)R′, SO2N(R′)2, N═CH—N(R′)2, or OPO3H2;
• C1–C6 alkoxy optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2, OC(O)N(R′)2, NR′CO2R′, NR′C(O)R′, SO2N(R′)2, N═CH—N(R′)2, or OPO3H2;
• Ar3;
• CF3;
• OCF3;
• OR′;
• SR′;
• SO2N(R′)2;
• OSO2R′;
• SCF3;
• NO2;
• CN;
• N(R′)2;
• CO2R′;
• CO2N(R′)2;
• C(O)N(R′)2;
• NR′C(O)R′;
• NR′CO2R′;
• NR′C(O)C(O)R′;
• NR′SO2R′;
• OC(O)R′;
• NR′C(O)R2;
• NR′CO2R2;
• NR′C(O)C(O)R2;
• NR′C(O)N(R′)2;
• OC(O)N(R′)2;
• NR′SO2R2;
• NR′R2;
• N(R2)2, OC(O)R2;
• OPO3H2;
• and N═CH—N(R′)2;
• R′ is selected from hydrogen;
• C1–C6 aliphatic;
• or a 5–6 membered carbocyclic or heterocyclic ring system optionally substituted with 1 to 3 substituents independently selected from halo, C1–C6 alkoxy, cyano, nitro, amino, hydroxy, and C1–C6 aliphatic;
• R2 is a C1–C6 aliphatic optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2or SO2N(R′)2;
• or a carbocyclic or heterocyclic ring system optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2or SO2N(R′)2;
• wherein Ar3 is an aryl or heteroaryl ring system optionally fused to a saturated or unsaturated 5–8 membered ring having 0–4 heteroatoms;
• wherein Ar3 is optionally substituted at one or more ring atoms with one or more substituents independently selected from halo;
• C1–C6 aliphatic optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2, OC(O)N(R′)2, NR′CO2R′, NR′C(O)R′, SO2N(R′)2, N═C—N(R′)2, or OPO3H2;
• C1–C6 alkoxy optionally substituted with N(R′)2, OR′, CO2R′, C(O)N(R′)2, OC(O)N(R′)2, SO2N(R′)2, NR′CO2R, NR′C(O)R′, N═C—N(R′)2, or OPO3H2;
• CF3;
• OCF3;
• OR′;
• SR′;
• SO2N(R′)2;
• OSO2R′;
• SCF3;
• NO2;
• CN;
• N(R′)2;
• CO2R′;
• CO2N(R′)2;
• C(O)N(R′)2;
• NR′C(O)R′;
• NR′CO2R′;
• NR′C(O)C(O)R′;
• NR′SO2R′;
• OC(O)R′;
• NR′C(O)R2;
• NR′CO2R2;
• NR′C(O)C(O)R2;
• NR′C(O)N(R′)2;
• OC(O)N(R′)2;
• NR′SO2R2;
• NR′R2;
• N(R2)2;
• OC(O)R2;
• OPO3H2;
• and —N═C—N(R′)2;
• X is a leaving group;
• Y is —C(O)—O-Z;
• and
• Z is C1–C6 aliphatic, benzyl, Fmoc, —SO2R′or Q, provided that Q is not substituted with X or alkyne.