Synthesis of Aminobisphosphonate

Aminoalkylbis(phosphonates): Their Complexation Properties in Solution and in the Solid State

“…A solution of tetraethyl aminomethylbis(phosphonate) [30] (4.0 g, 13.2 mmol) in dry acetonitrile (50 mL) was added dropwise to a solution of acetyl chloride (3.0 g, 38.2 mmol) and Na 2 CO 3 (5.2 g, 49 mmol) in dry acetonitrile (50 mL) at -40°C. After the addition was finished, the mixture was warmed slowly to room temperature and stirred overnight.…”

“…Ligands H 4 pam, [29] H 4 ale, [29] H 4 meth [30] and H 4 prop [31] were prepared by modification of reported procedures. The ligands were chemically pure (NMR, MS) and composition of the samples was checked by elemental analysis; see the Supporting Information for full experimental and analytical details, and discussion of the synthesis.…”

The development of bisphosphonates for therapeutic uses, and bisphosphonate structure-activity consideration

“…4 Respectively, much work has been reported in the literature on the synthesis and the reactivity of such systems. [49][50][51][52][53][54][55][56][57] NSubstituted aminomethylene bisphosphonic acids could be synthesized by reacting the corresponding amine with equivalent quantities of triethyl-orthoformate and diethyl phosphonate (or triethyl phosphite). 52 According to this method, the substituted-aminomethylene bisphosphonic acid, 38, which has been described as an effective bone resorption inhibitor, useful in treating osteoporosis, could be obtained from 3-azaspiro [5,5]undecane as described in Scheme 13.…”

1-Amino-1,1-bisphosphonates. Fundamental syntheses and new developments

“…This compound is readily obtained from dibenzylamine, triethyl orthoformate and diethyl phosphite followed by debenzylation with cyclohexene or H 2 and Pd/C as the catalyst. 94 Known applications of 64 include the synthesis of the new macrocyclic DOTA-like ligand 66 containing a bis(phosphonic acid) pendant arm 34 and potential bone-targeting reagents 67-69 for bone tumors consisting of melphalan linked to a bisphosphonate moiety through an amide linkage (Scheme 24).…”