Compounds and methods of preparing compounds S1P1 modulators

A process of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, the process comprising:

• contacting a compound of
• with a compound of
• Formula (III) to produce the compound having the formula of
• wherein:
• A, B, and E are each independently N or CR6;
• X and Y are O;
• R1 is selected from the group consisting of H, OH, NH2, NO2, optionally substituted carbocycle, optionally substituted aryl group, optionally substituted heteroaryl group, branched or unbranched alkyl alcohol, halo, branched or unbranched alkyl, amide, cyano, alkoxy, haloalkyl, alkylsulfonyl, nitrite, and alkylsulfanyl;
• and
• R2, R3, R4, R5, and R6 are each independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 hydroxyalkyl, optionally substituted C1-C6 alkoxy, optionally substituted cycloalkyl, and optionally substituted cycloheteroalkyl;
• R2 and R3 are together optionally substituted cycloalkyl, or optionally substituted cycloheteroalkyl;
• or R4 and R5 are together optionally substituted cycloalkyl, or optionally substituted cycloheteroalkyl;
• wherein the compound of Formula (I) is a compound having the formula selected from the group consisting of
• wherein the optional substituent of the carbocycle, aryl, and heteroaryl group at R1 and C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, cycloalkyl, and cycloheteroalkyl at R2, R3, R4, R5, and R6 is each independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C5-C6 aryl, C1-C6 alkoxy, C3-C5 heteroaryl, C3-C6 cycloalkyl, C5-C6 aryloxy, —CN, —OH, oxo, halo, haloalkyl, —NO2, —CO2H, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —NH(C6 aryl), —N(C5-C6 aryl)2, —CHO, —CO(C1-C6 alkyl), —CO((C5-C6) aryl), —CO2((C1-C6) alkyl), and —CO2((C5-C6) aryl).