Isradipine is a drug used to lower blood pressure but recently it was found by a team from Nortwestern University, that this molecule can also slow the progression of Parkinson's disease, and restore the dopamine neurons (In animals tests). Isradipine is a calcium channel blocker of the 1,4-dihydropyridine class with a benzoxadiazole moiety in position 4.
The synthesis of the 1,4-dihydropyridine ring is quite classic, the first step consists in a Knoevenagel reaction of methyl acetoacetate on the benzoxadiazole 4-carboxaldehyde using piperidine and acetic acid as catalyst and diisopropylether as solvent in a 61% yield (this is the first time I see a Knoevenagel reaction in an ether!!!???? DCM, Toluene OK, but maybe I am wrong). The second step of this synthesis is the condensation of the acrylate obtained with the isopropyl aminocrotonate in ethanol to give the desire 1,4-dihydropyridine Isradipine in 67% yield after recrystallisation.
(WO/2005/005437) An improved Process for the Manufacture of Isradipine (Shasun Chemical & Drugs Limited)
The synthesis of the 1,4-dihydropyridine ring is quite classic, the first step consists in a Knoevenagel reaction of methyl acetoacetate on the benzoxadiazole 4-carboxaldehyde using piperidine and acetic acid as catalyst and diisopropylether as solvent in a 61% yield (this is the first time I see a Knoevenagel reaction in an ether!!!???? DCM, Toluene OK, but maybe I am wrong). The second step of this synthesis is the condensation of the acrylate obtained with the isopropyl aminocrotonate in ethanol to give the desire 1,4-dihydropyridine Isradipine in 67% yield after recrystallisation.
(WO/2005/005437) An improved Process for the Manufacture of Isradipine (Shasun Chemical & Drugs Limited)
