4-Methylsulfonyl-Substituted Piperidine Urea Compounds

A method for preparing a compound of formula xi:

• or a pharmaceutically acceptable salt thereof,
• the method comprising:
• reacting a compound of formula ix
• or a salt thereof,
• with a compound of formula x
• to produce the compound of formula xi, wherein:
• Ar is aryl;
• Ar1 is a 5- to 6-membered heteroaryl having at least one nitrogen atom ring member, and is optionally substituted with from 1-3 Ra;
• Ar2 is a 5- to 10-membered aryl or heteroaryl, which is optionally substituted with from 1-5 Rb;
• R1 and R2 are each independently a member selected from H, F, C1-C4 alkyl, C1-C4 deuteroalkyl, and C1-C4 haloalkyl;
• or optionally R1 and R2 can be combined to form a C3-C5 carbocyclic ring which is optionally substituted with one or two F;
• each Ra is independently selected from the group consisting of halo, CN, hydroxyl, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, —CORa1, —CO2Ra1, —SO2Ra1, —SO2NRa1Ra2, and —CONRa1Ra2, wherein each Ra1 and Ra2 is independently selected from the group consisting of H and C1-C4 alkyl or optionally Ra1 and Ra2 when attached to a nitrogen atom are combined to form a 4- to 6-membered ring;
• or optionally, two Ra substituents on adjacent ring members are combined to form a 5- or 6-membered ring having 0, 1 or 2 ring members selected from O, N and S;
• each Rb is independently selected from the group consisting of halo, CN, hydroxyl, C1-C4 alkyl, C1-C4 deuteroalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 cycloalkyl, —NRb1Rb2, —CORb1, —CO2Rb1, —SO2Rb1, —SO2NRb1Rb2, and a 5- or 6-membered heteroaryl which is optionally substituted with C1-C4 alkyl, and wherein each Rb1 and Rb2 is independently selected from the group consisting of H and C1-C4 alkyl or optionally Rb1 and Rb2 when attached to a nitrogen atom are combined to form a 4- to 6-membered ring;
• or optionally, two Rb substituents on adjacent ring members are combined to form a 5- or 6-membered ring having 0, 1 or 2 ring members selected from O, N and S.

A method for preparing a compound having the formula:

• or a pharmaceutically acceptable salt thereof,
• the method comprising:
• reacting a compound
• or a salt thereof,
• with a compound
• to produce the compound
• or a pharmaceutically acceptable salt thereof.

A method for preparing a compound having the formula:

• the method comprising:
• reacting a compound
• with sodium periodate to produce a compound
• reacting the compound
• with lithium diisopropylamide (LDA) followed by N-Fluorobenzenesulfonimide (NFSI) to produce a compound
• reacting the compound
• with iodomethane to produce a compound
• and
• reacting the compound
• with n-Butyllithium to produce the compound