Compounds and compositions for inhibiting the activity of HIF2-alpha and their methods of use

A process for producing the compound of formula (I)

• or a pharmaceutically acceptable salt thereof,
• comprising cyclizing a compound of formula (II),
• or a salt, solvate, stereoisomer, complex, co-crystal, ester, or oxazoline thereof;
• wherein the compound of formula (II) is produced by a process
• comprising the step of reacting the compound of formula (IV),
• or a salt, solvate, stereoisomer, complex, co-crystal, ester, or oxazoline thereof,
• with a compound of formula (III)
• or a salt, solvate, stereoisomer, complex, co-crystal, ester, or oxazoline thereof,
• wherein
• R1 is F, Cl, Br, OCH3, OCH2F, OCHF2, or OCF3;
• R2 is F, Cl, CF3, or CN;
• X is (CH2)1-2, CHF, CHD, CD2 or CF2;
• Y is (CH2)0-2, CHF, CHD, CD2, O, S, OCH2, or CF2;
• Z is CH2, CD2, CHF, CDF, CF2, CH(OH), CO, CH(CH3), O, or S,
• wherein, when Y is O, OCH2, or S, then Z is CH2;
• wherein, when Z is O, S, or NCH3, then Y is (CH2)0-2, or CF2;
• wherein, when Z is CH(OH), then Y is CHF or CF2;
• J is CRJ;
• wherein RJ is H, F, Cl, Br, CH3, CD3, CF3, CHF2, CDF2, OCH3 or CN;
• E is CRE or N;
• wherein RE is H, F, Cl, Br, I, CN, CH3, CH2CH3, CH(CH3)2, CD3, CHD2, CH2D, CHF2, CDF2, C(CH3)F2, C(CD3)F2, CF3, cyclopropyl, OCH3, OCH2CH2OH, OCF3, SCH3, SCHF2,
• G is CH or N;
• and
• LG is a leaving group selected from F, Cl, or Br;
• and the reaction of compound (III) and compound (IV) occurs in the presence of base,
• to obtain the compound of formula (I) or a pharmaceutically acceptable salt thereof.