[Cl-].[NH4+:2].[OH-].[NH4+].[CH3:5][O:6][C:7]([C:9]1[NH:10][CH:11]=[C:12]([C:14]#[N:15])[CH:13]=1)=[O:8].[H-].[Na+].NCl>C(OCC)C.CN(C)C=O>[CH3:5][O:6][C:7]([C:9]1[N:10]([NH2:2])[CH:11]=[C:12]([C:14]#[N:15])[CH:13]=1)=[O:8]Solid ammonium chloride (5.8 g, 109.4 mmol) was suspended in diethyl ether (300 mL) and the suspension was cooled to −5° C. To this were added 29.56% aqueous ammonium hydroxide solution (16 mL) and 6.15% aqueous bleach solution (“Chlorox”, 240 mL) over a period of 15 min. The mixture was stirred for 30 min at −5° C. and then the layers were separated. The organic layer was washed with brine, filtered over sodium sulfate and stored over solid calcium chloride at −5° C. 4-Cyano-1H-pyrrole-2-carboxylic acid methyl ester (Example 15a, 1.09 g, 7.265 mmol) was dissolved in N,N-dimethylformamide (30 mL) and a 60% dispersion of sodium hydride in mineral oil (0.378 g, 9.445 mmol) was added. After stirring for 1 h at 25° C., the above ˜0.36 M solution of monochloramine in ether (26 mL, 9.445 mmol) was added and stirred for 2 h at 25° C. The reaction was quenched with saturated aqueous sodium thiosulfate solution followed by water. The layers were separated and the aqueous layer was extracted with diethyl ether. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude desired product, 1-amino-4-cyano-1H-pyrrole-2-carboxylic acid methyl ester, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ: 3.88 (3H, s), 5.67 (2H, bs), 7.07 (1H, d, J=1.7 Hz), 7.37 (1H, d, J=1.7 Hz).
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