Method for preparing aminoalkanoic acid derivative containing biphenyl group

A method for preparing a compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

• 1) 2-amino-N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)butanamide;
• 2) 2-amino-N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)pentanamide;
• 3) 2-amino-N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)hexanamide;
• 4) 2-amino-N-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)pentanamide;
• 5) N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)-2-(methylamino)butanamide;
• 6) N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)-2-(methylamino)pentanamide;
• 7) N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)-2-(methylamino)hexanamide;
• 8) N-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)-2-(dimethylamino)pentanamide;
• 9) 2-amino-N-((3′,4′-dichloro-[1,1′-biphenyl]-4-yl)methyl)pentanamide;
• 10) 2-amino-N-((3′,4′-dichloro-[1,1′-biphenyl]-4-yl)methyl)hexanamide;
• 11) 2-amino-N-((4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)pentanamide;
• 12) 2-amino-N-((4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)hexanamide;
• 13) 2-amino-N-((4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)methyl)pentanamide;
• 14) 2-amino-N-((4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)methyl)hexanamide;
• 15) N-((3′,4′-dichloro-[1,1′-biphenyl]-4-yl)methyl)-2-(methylamino)pentanamide;
• 16) 2-(methylamino)-N-((4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)pentanamide;
• 17) N-((3′,4′-dichloro-[1,1′-biphenyl]-4-yl)methyl)-2-(dimethylamino)pentanamide;
• 18) 2-amino-N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)butanamide;
• 19) 2-amino-N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 20) 2-amino-N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)hexanamide;
• 21) 2-amino-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)butanamide;
• 22) 2-amino-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 23) 2-amino-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)hexanamide;
• 24) 2-amino-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)butanamide;
• 25) 2-amino-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 26) 2-amino-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)hexanamide;
• 27) 2-amino-N-(2-(3′,4′-difluoro-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 28) N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)-2-(methylamino)butanamide;
• 29) N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)-2-(methylamino)pentanamide;
• 30) N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)-2-(methylamino)hexanamide;
• 31) 2-(methylamino)-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)butanamide;
• 32) 2-(methylamino)-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 33) 2-(methylamino)-N-(2-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)hexanamide;
• 34) 2-(methylamino)-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)butanamide;
• 35) 2-(methylamino)-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)pentanamide;
• 36) 2-(methylamino)-N-(2-(4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)ethyl)hexanamide;
• and
• 37) N-(2-(3′,4′-dichloro-[1,1′-biphenyl]-4-yl)ethyl)-2-(dimethylamino)pentanamide,
• the method comprising:
• a first step of forming a peptide bond by reacting an aminoalkanoic acid derivative compound protected by a butoxycarbonyl (Boc) protecting group, which is represented by the following Formula 2, with a biphenyl derivative compound containing a primary amine group, which is represented by the following Formula 3;
• and
• a second step of removing the Boc protecting group by reacting the compound obtained in the first step with an acid:
• in the formulae,
• n is 0, 1, 2, 3, 4 or 5,
• R2 and R3 are each independently the same as or different from each other, and are each independently selected from hydrogen, a C1-7 alkyl, hydroxyl, a halogen, a halogenated C1-7 alkyl, a C1-7 alkyloxy and a halogenated C1-7 alkyloxy, and
• X is m substituents (m is an integer from 1 to 5) which are the same as or different from each other, selected from the group consisting of a halogen group, a halogenated C1-7 alkyl group and a halogenated C1-7 alkoxy group.