Process of preparing 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-B]pyridin-2-yl)pyridin-2-amine
The present invention is directed to a processes for the synthesis of 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine:
1. A process of preparing 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine, comprising the steps of
Step 3, reacting tert-butyl (1-(4-((3-amino-6-phenylpyridin-2-yl)amino)phenyl)cyclobutyl)carbamate with 2-amino nicotinaldehyde in the presence of an oxidant and an acid in a polar protic solvent to form tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate; and
Step 4, treating tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate with an acid in a polar aprotic solvent to form 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine.
2. The process according to claim 1 , further comprising before Step 3,
Step 2, treating tert-butyl (1-(4-((3-nitro-6-phenylpyridin-2-yl)amino)phenyl)cyclobutyl)carbamate with a reducing agent in a polar aprotic solvent to form tert-butyl (1-(4-((3-amino-6-phenylpyridin-2yl)amino)phenyl)cyclobutyl)carbamate.
3. The process according to claim 2 , further comprising before Step 2,
Step 1, reacting 2-chloro-3-nitro-6-phenylpyridine with tert-butyl (1-(4-aminophenyl)cyclobutyl)carbamate in the presence of a base in a polar aprotic solvent to form tert-butyl (1-(4-((3-nitro-6-phenylpyridin-2-yl)amino)phenyl)cyclobutyl)carbamate.
4. The process according to claim 2 , further comprising before Step 2,
Step 1a, coupling 3-nitro-6-phenylpyridin-2-amine with tert-butyl (1-(4-bromophenyl)cyclobutyl)carbamate in the presence of a palladium catalyst and a phosphorus ligand in a polar aprotic solvent to form tert-butyl (1-(4-((3-nitro-6-phenylpyridin-2-yl)amino)phenyl)cyclobutyl)carbamate.
5. The process according to claim 1 , wherein the oxidant is air.
6. The process according to claim 1 , wherein the oxidant is a metal or non-metal based salt or catalyst.
7. The process according to claim 6 , wherein the oxidant is selected from the group consisting of metal acetate, metal perborate, metal chloride, palladium based catalyst, and hydrates thereof.
8. The process according to claim 7 , wherein the oxidant is selected from the group consisting of Cu(OAc) 2 .H 2 O, NaBO 3 .4H 2 O, FeCl 3 .6H 2 O, and 10% Pd/C, and hydrates thereof.
9. The process according to claim 8 , wherein the oxidant is NaBO 3 .4H 2 O.