Pyrrolobenzodiazepines and conjugates thereof
A compound which is either A: or B: and salts and solvates thereof, as well as their conjugates with a cell-binding agent.
1. A method of synthesising compound B:
from:
via the intermediate:
which comprises the steps of:
(i) removing the Alloc
protecting groups; and
(ii) reacting the product of (i) with Mal-(PEG) 8 -acid.
2. The method of claim 1 , wherein removing the Alloc protecting groups is carried out by the use of Tetrakis(triphenylphosphine)palladium (0).
3. The method of claim 2 , wherein removing the Alloc protecting groups by the use of Tetrakis(triphenylphosphine)palladium (0) occurs in the presence of pyrrolidine.
4. The method of claim 1 , wherein removing the Alloc protecting groups is carried out in dichloromethane.
5. The method of claim 1 , wherein reaction with Mal-(PEG)8-acid is carried out in the presence of EDCl (1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide).
6. The method of claim 5 , wherein reaction with Mal-(PEG) 8 -acid is carried out in dichloromethane.