Sodium hydride → 1-(2-Methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine

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The presently preferred method for preparing compounds of the invention is set forth in Scheme VI. An intermediate dihydropyridine diester derivative of formula 16 is prepared by means known in the art, e.g., by following the Hantzch method (Ann. Chim., 215, 1 (1882)), using reactants selected to provide the desired R1, R2, R3, X1, and X2 substitutions. The diester is then N-protected by mixing with a slight molar excess (preferably between 1.1 and 1.3 moles per mole of compound of formula 16) α-alkoxy-ω-chloromethoxyalkane and a slight molar excess (about 1.2 mol/mol 16) of a suitable strong base, preferably NaH, in a polar, aprotic solvent (preferably DMF or DMSO) at -10° to 0° C. for between about 60 and about 100 minutes, followed by warming to about room temperature for between about 50 and 200 minutes (preferably about 60 minutes), to produce an N-protected diester of formula 17. For example, 1 mol 2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine is reacted with 1.2 mol 1-methoxy-2-chloromethoxyethane and 1.2 mol NaH in DMF at -10° C. for 1 hour, then allowed to warm to about 25° C. for 1 hour to produce 1-(2-methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine (17). (Scheme VI, Step 1)

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