Drug delivery and imaging chemical conjugate, formulations and methods of use thereof

A process for preparing a product, comprising the steps:

• coupling a secondary alcohol at carbon position 43 of rapamycin with a bromo-substituted acyl chloride to obtain an intermediate A, wherein R is X-L-Br,
• reacting intermediate A at room temperature in one portion to a solution of a sodium salt of a compound of Formula 1 in dimethylformamide:
• wherein,
• X is carbonyl or a bond;
• Y and Z are each independently selected from the group consisting of bond, oxygen, carbonyl, and amine, and Y having a point of attachment to L;
• L is a linker comprising at least one selected from the group consisting of a bond, an alkyl, a branched alkyl, an aryl, an ester, an ether, and an amide;
• R1, R2, R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, NR6R7, NR6C(═O)R7, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein R6 and R7 are selected from the group consisting of H, and optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• n is 1 or 2;
• under reaction conditions effective to obtain a product of the formula