Method for Preparing Halogenated Amines

A method for preparing a compound of formula (VII) or a salt thereof:

• wherein:
• each of m and n is, independently, 0 or 1, provided that one of m and n is 1;
• each of RF1, RF2, RF1′, and RF2′ is, independently, optionally substituted C1-C6 fluoroalkyl;
• each of R3, R4, R3′, and R4′ is, independently, hydrogen, C1-C6 alkyl, —C(O)H, or —C(O)ORa, wherein Ra is C7-C20 aralkyl or C1-C6 alkyl, each of which is optionally substituted;
• ring B is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is optionally further substituted with from 1-5 substituents independently selected from halo;
• NRfRg;
• hydroxyl;
• C1-C12 alkyl or C1-C12 haloalkyl, each of which is optionally substituted;
• optionally substituted C1-C12 alkoxy;
• C1-C12 haloalkoxy;
• nitro;
• C6-C10 aryl or heteroaryl including 5-12 atoms, each of which is optionally substituted;
• C6-C10 aryloxy or heteroaryloxy including 5-12 atoms, each of which is optionally substituted;
• heterocyclyl including 3-10 atoms, C3-C10 cycloalkyl, C7-C12 aralkoxy or heteroaralkoxy including 6-12 atoms, each of which is optionally substituted;
• —C(O)ORh;
• —C(O)NRfRg;
• or —NRiC(O)Rj;
• each of Rf, Rg, and Rh, at each occurrence is, independently:
• (i) hydrogen;
• or
• (ii) C1-C12 alkyl or C1-C12 haloalkyl;
• each of which is optionally substituted;
• or
• (iii) C7-C20 aralkyl;
• C3-C16 cycloalkyl;
• heteroaralkyl including 6-20 atoms;
• C3-C16 cycloalkenyl;
• heterocyclyl including 3-16 atoms;
• or heterocycloalkenyl including 3-16 atoms;
• each of which is optionally substituted;
• or
• (iv) C2-C20 alkenyl or C2-C20 alkynyl;
• or
• (v) C6-C16 aryl or heteroaryl including 5-16 atoms, each of which is optionally substituted;
• Rj is Rh;
• ORh;
• or NRfRg;
• W is C1-C4 alkyl;
• and
• ring C is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is optionally further substituted with from 1-5 substituents independently selected from halo;
• C1-C12 alkyl or C1-C12 haloalkyl, each of which is optionally substituted;
• C1-C12 alkoxy;
• C1-C12 haloalkoxy;
• nitro;
• or C6-C10 aryl or heteroaryl including 5-12 atoms, each of which is optionally substituted;
• from a compound of formula (VIII):
• wherein:
• ring B is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is optionally further substituted with from 1-5 substituents independently selected from halo;
• NRfRg;
• hydroxyl;
• C1-C12 alkyl or C1-C12 haloalkyl, each of which is optionally substituted;
• optionally substituted C1-C12 alkoxy;
• C1-C12 haloalkoxy;
• nitro;
• C6-C10 aryl or heteroaryl including 5-12 atoms, each of which is optionally substituted;
• C6-C10 aryloxy or heteroaryloxy including 5-12 atoms, each of which is optionally substituted;
• heterocyclyl including 3-10 atoms, C3-C10 cycloalkyl, C7-C12 aralkoxy or heteroaralkoxy including 6-12 atoms, each of which is optionally substituted;
• —C(O)Re, wherein Re is C1-C6 alkyl;
• —C(O)NRfRg;
• or —NRiC(O)Rj;
• and
• m, n, ring C, and W are as defined above in conjunction with formula (VII);
• the method comprising reacting the compound of formula (VIII) with a fluoroalkylating agent.

A compound selected from the group consisting of:

• 2-(3-{[(2R)-4-{6-[1-amino-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]pyridin-3-yl}-2-methylpiperazin-1-yl]sulfonyl}phenyl)-1,1,1-trifluoropropan-2-ol;
• 2-(3-{[(2R)-4-{4-[1-amino-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethyl)phenyl}-2-methylpiperazin-1-yl]sulfonyl}phenyl)-1,1,1-trifluoropropan-2-ol;
• 2-[4-({(2R)-4-[4-[1-amino-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]-1,1,1-trifluoropropan-2-ol;
• 1,1,1,3,3,3-hexafluoro-2-[4-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]propan-2-amine;
• and
• 1,1,1,3,3,3-hexafluoro-2-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]propan-2-amine;
• or a pharmaceutically acceptable salt thereof.