Modulators of the integrated stress pathway

A method of making a compound of Formula (1-7):

• or a pharmaceutically acceptable salt thereof, comprising:
• (i) installing a protecting group PG1 to a compound of formula (1-1):
• to make a compound of formula (1-2),
• (ii) contacting the compound of formula (1-2) with a compound of formula (1-3):
• to make a compound of formula (1-4):
• followed by removal of the protecting group PG1 to make a compound formula (1-5):
• (iii) contacting the compound of formula (1-5) with a compound of formula (1-6):
• thereby making the compound of formula (1-7);
• wherein:
• D is selected from the group consisting of
• L1 is CH2O—*, wherein “—*” indicates the attachment point to A;
• R1 and R2 are each independently hydrogen or C1-C6 alkyl;
• A is phenyl, and W is phenyl or 5-6 membered heteroaryl, wherein each phenyl or 5-6-membered heteroaryl is optionally substituted with 1-5 RY;
• each RX is independently selected from the group consisting of C1-C6 alkyl, hydroxy-C1-C6 alkyl, halo-C1-C6 alkyl, amino-C1-C6, alkyl, cyano-C1-C6 alkyl, oxo, halo, cyano, —ORA, —NRBRC, —NRBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, —SRE, —S(O)RD, —S(O)2RD, and G2;
• each RY is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkenyl, hydroxy-C1-C6 alkyl, hydroxy-C1-C6 alkenyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, amino-C1-C6 alkyl, amido-C1-C6, alkyl, cyano-C1-C6 alkyl, siloxy-C1-C6 alkoxy, hydroxyl-C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkoxy-C1-C6 alkenyl, C1-C6 alkoxy-C1-C6 alkoxy, oxo, halo, cyano, —ORA, —NRBRC, —NRBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, —S(RF)m, —S(O)RD, —S(O)2RD, —S(O)NRBRC, —NRBS(O)2RD, —OS(O)RD, —OS(O)2RD, RFS—C1-C6 alkyl, RDC(O)NRB—C1-C6 alkyl, (RB)(RC)N—C1-C6 alkoxy, RDOC(O)NRB—C1-C6 alkyl, G1, G1-C1-C6 alkyl, G1-N(RB), G1-C1-C6 alkenyl, G1-O—, G1C(O)NRB—C1-C6 alkyl, and G1-NRBC(O);
• or 2 RY groups on adjacent atoms, together with the atoms to which they are attached form a fused phenyl, a 3-7-membered fused cycloalkyl ring, a 3-7-membered fused heterocyclyl ring, or a 5-6-membered fused heteroaryl ring, each optionally substituted with 1-5 RX;
• each G1 or G2 is independently 3-7 membered cycloalkyl, 4-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl, wherein each 3-7 membered cycloalkyl, 4-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl is optionally substituted with 1-6 RZ;
• each RZ is independently selected from the group consisting of —ORA, —C(O)RD, halo, halo C1-C6 alkyl, C1-C6 alkyl, —C(O)RD, and —C(O)ORD;
• RA is, at each occurrence, independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, —ORA1, —C(O)NRBRC, —C(O)RD, —C(O)OH, or —C(O)ORD;
• each of RB and RC is independently hydrogen, C1-C6 alkyl, hydroxy-C1-C6, alkyl, G1-C1-C6 alkyl, 3-7 membered cycloalkyl, or 4-7-membered heterocyclyl, wherein each alkyl, cycloalkyl, or heterocyclyl is optionally substituted with 1-6 RZ;
• or
• RB and RC together with the atom to which they are attached form a 3-7-membered cycloalkyl or heterocyclyl ring optionally substituted with 1-6 RZ;
• RD is, at each occurrence, independently C1-C6 alkyl, C1-C6 alkoxy-C1-C6 alkyl, or halo-C1-C6 alkyl;
• each RE is independently hydrogen C1-C6 alkyl, or halo-C1-C6 alkyl;
• each RF is independently hydrogen, C1-C6 alkyl, or halo;
• and
• each RA1 is hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, 3-7 membered cycloalkyl, or 4-7-membered heterocyclyl.