Hi , actually it's need some time for  review lett. about suitable acid and Anime for  derivative for synthesis Methotrexate and by the same way for Alendronic acid sodium ...

 Sure sir. I will wait for your valuable solution.

To prepare easiest reaction their will be occur practical work doing. 

In the glutamic acid component of methotrexate, there are two carboxylate groups that are prime for amide formation with primary amine of alendronate, which could be achieved with well-established coupling procedures of peptide chemistry. It is possible that you guide the selectivity to one of the conjugate products vs the other but that is unclear. Furthermore, it might be challenging to determine which carboxylate (side chain vs C-terminus) you coupled to, as they will likely appear similarly on NMR and MS, though their retention times in HPLC will likely be different. So you might need to prepare standards anyways, for which I would suggest the following preparation of conjugates: you can take something like Fmoc-Glutamate-OtBu (side chain protected) or whatever other protecting strategy is commercially available, couple the adrenoate to the C-terminal COOH using conventional reagents/strategies, then couple this conjugate product to the "pteroyl"-like portion (i.e., methotrexate without glutamic acid), and finally deprotect the methyl ester. In a similar approach of strategic protecting strategies, you can obtain the other conjugation position (the C-terminal carboxylic acid). However, it would be worthwhile to know why you are hoping to conjugate these two compounds as the glutamic acid portion seems to be involved in the binding of methotrexate to the active site, so coupling there might diminish the binding activity and activity.