4-Amino-1H-pyrrole-2,4-dicarbonitrile synthesis

Yield:937049-26-8 82%

Reaction Conditions:

Stage #1: pyrrole-2,4-dicarbonitrilewith O-(diphenylphosphinyl)hydroxylamine;sodium hydride in N,N-dimethyl-formamide at 20 - 80; for 2.25 h;
Stage #2: at 80; for 2 h;

Steps:

AX.2

To a solution of DMF (100 mL) was added lH-pyrrole-2,4-dicarbonitrile (1.00 g, 8.54 mmol) followed by NaH, 60% dispersion in mineral oil (0.51 g, 12.8 mmol). The solution was stirred at rt for 15 min and then (aminooxy)(diphenyl)ρhosphine oxide (2.99 g, 12.8 mmol) was added, and the solution was heated to 80 ⁰C for 2 h. Upon cooling to rt the solution was filtered washing with CH₂Cl₂. The solution was partially concentrated and a white precipitate formed which was filtered. The mother liquor was then evaporated under vacuum and subsequently purified by MPLC (Isco) 100% CH₂Cl₂ ramping to 9: 1 v/v CH₂Cl₂-EtOAc. The resulting purified fractions were combined and concentrated in vacuo yielding 0.92 g of a white solid (6.98 mmol, yield 82%). ¹H-NMR (DMSO-J₆) δ 7.92 (d, / = 1.8 Hz, IH), 7.39 (d, J = 1.9 Hz, IH), 6.66 (s, 2H); MS [M+H]⁺ = 133.0; LCMS RT = 0.96 min.

References:

WO2007/64883,2007,A2 Location in patent:Page/Page column 235-236