Cyclooctynes for click chemistry

A process of making a compound of formula (II):

• or a pharmaceutically accepted salt thereof,
• wherein:
• R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, optionally wherein the alkyl and alkenyl are substituted with one or more R5 group;
• R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
• R5 is selected from H, —C1-6-alkyl, —CF3;
• —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
• R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3, —C(O)R5, —C(O)OC1-6 alkyl, NO2, —C1-6 alkyl;
• n is 0, 1, or 2;
• p is 0, 1, or 2;
• and
• X is CH or N;
• wherein the process comprises:
• (A) combining a compound of formula (III):
• with a compound of formula (IV):
• and a non-nucleophilic base to provide the compound of formula (V):
• and
• (B) combining the compound of formula (V) with a carbodiimide to provide the compound of formula (II).