1-{[Benzyl-(2-cyano-ethyl)-amino]-methyl}-5-methyl-1H-pyrazole-3-carboxylic acid methyl ester

The products of aza-type Michael addition, i.e., β-amino carbonyl compounds and their derivatives, are often used as peptide analogs or precursors of optically active amino acids, amino alcohols, diamines, and lactams [1]. Moreover, β-amino carbonyl functionalities are ubiquitous motifs in natural products such as alkaloids and polyketides [2]. Herein, we report the synthesis of new product using aza-type Michael reactions under mild conditions.

A mixture of 3-(benzylamino)propionitrile 1 [3] (1g; 6.25mmol) and 1-Hydroxymethyl-5-methyl-1H-pyrazole-3-carboxylic acid methyl ester 2 [4] (1.062g ; 6.25 mmol) in 20 ml of acetonitrile was stirred at room temperature for four days, then the mixture was dried with Na₂SO₄ and filtered. The solvent was evaporated under reduced pressure. The product 3 has been obtained with a 99% yield as yellow oil.

¹H-NMR (300 MHz, CDCl₃): δ= 7.31 (CHarom, 5H, s) ; 6.56 ( CHpyr,1H, s) ; 4.94 (OCH₃, 3H, s) ; 3.89 ( N-CH₂-N, 2H, s) ; 3.75 (C₆H₅-CH₂ ,2H, s) ; 3.01-3.06 (CH₂-CH₂-CN, 2H, t, J = 7.33 Hz) ; 2.33-2.37 ( N-CH₂ , t, J = 7 Hz) and 2.18 ( CH₃, 3H, s).

¹³C-NMR (CDCl₃, 75 MHz): δ= 163.32 (l); 142.91 (i); 141.56 (g); 137.46 (m); 129.154 (n); 129.03; 129.08 (f); 128.26 (o); 118.97 (a); 109.30 (h); 67.82 (e); 56.79 (d); 52.37 (k); 48.36 (c); 17.46 (b); 11.55 (j).

EI-MS (70 eV, m/z): 173 (16); 171; 119 (22); 91 (100).