Preparation of Phthalazinecarboxylic Esters

Several routes to such esters have been covered already by primary synthesis (Chapter 8), by Reissert or Reissert-like reactions (Section 9.1.3), by esterification of phthalazinecarboxylic acids (Section 14.1.2), by alcoholysis of phthalazinecar-bonyl halides (Section 14.2), or by a variety of passenger introductions (several chapters). Other minor preparative methods are illustrated in the following examples. 

Ethyl (39, R = H) gave 2-dimethylaminoethyl l-hydroxymethyl-4-oxo-3,4-dihy-dro-6-phthalazinecarboxylate (39, R = NMe2) (neat Me2NCH2CH20H, trace solid KOH, 115°C, 6h 25%) analogs likewise.  

Note This route may well be conhned to the use of A-acylated hydrophthala-zines as substrates it is akin to transacylation of an amine. 2-Acetyl-4-p-methoxybenzyl-3-methyl-1,2,3,4,5,6,7,8-octahydrophthalazine (40, R = Me) gave ethyl 4-p-methoxybenzyl-3-methyl-l,2,3,4,5,6,7,8-octahydro-2-phthalazinecarboxylate (40, R = OEt) (substrate HCl, ClC02Et, CH2CI2, 

Note This procedure has been applied to the ring nitrogen of reduced phthalazines, to unionized phthalazines, or to Reissert derivatives of phtha-lazine. 

Conversion of 1,4-diphenylphthalazine into a solution of its dianion (43) (substrate, anhydrous THE, Na, A, 20°C, 8 h) and subsequent treatment with methyl chloroformate gave dimethyl 1,4-diphenyl-1,2-dUiydro-l,2-phthalazi-nedicarboxylate (44) (dianion solution, —78°C synthonj, 20°C, min  

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