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4-Cyano-lH-pyrrole-2-carboxylic acid methyl ester was prepared as described in Can. J. Chem., 59, 2673-76 (1981). lH-Pyrrole-2-carboxylic acid methyl ester (2.00 g, 16.00 mmol) was dissolved in acetonitrile (5 mL) and the solution was cooled to -20 0C. Chlorosulfonylisocyanate (3.40 g, 24.00 mmol) was dissolved in acetonitrile (5 mL) and added dropwise via syringe over a period of 5 min to the above solution. The solution was allowed to warm to 25 0C and was stirred for 20 h. The solution was cooled back to 0 0C, NN-dimethylformamide (2 mL) was added and the solution was heated to 50 0C for 15 min. The reaction mixture was poured into ice and was extracted with chloroform, washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm, 40% ethyl acetate in hexanes) afforded the desired product, 4-cyano-lH-pyrrole-2- carboxylic acid methyl ester (1.09 g, 7.265 mmol, 45.4% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ: 3.91 (3H, s), 7.12 (IH, t, J= 2.0 Hz), 7.40 - 7.41 (IH, m), 9.60 (IH, bs). FT-IR (ATR) vmax (neat): 2228, 1691 cm"1.
Methyl 1H-pyrrole-2-carboxylate (5.78 g, 46.2 mmol) was dissolved in DMSO and cooled to 10° C. NaH was added in two portions over 5 min. The reaction mixture was stirred at 10° C. for 10 min and <strong>[59237-53-5]methyl 6-chloro-5-nitronicotinate</strong> (5 g, 23.09 mmol) in DMSO (10 mL) was added slowly over 3 min. The red reaction mixture was allowed to warm to room temperature and stirred overnight. It was cooled to 0° C. and quenched with water (12 mL) and diluted with brine (50 mL). The mixture was washed with EtOAc (2.x.25 mL) and the aqueous layer was acidified to pH=2 with 4.5 N HCl. It was extracted with EtOAc (1.x.100 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to afford a yellow solid, which was dissolved in MeOH (100 mL) and cooled to 0° C. Thionyl chloride (45 mL, 617 mmol) was added slowly over 5 min. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature overnight. It was concentrated in vacuo and the resulting solid was triturated with ethyl acetate (300 mL). The solid was filtered off and the filtrate was concentrated in vacuo. then washed with ethyl ether to afford methyl 6-(2-(methoxycarbonyl)-1H-pyrrol-1-yl)-5-nitronicotinate (5.04 g, 16.51 mmol, 92percent yield) as a yellow solid, [M+H] calc'd for C13H11N3O6, 306; found, 306.
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