Yield:1610596-42-3 71%

Reaction Conditions:

with potassium carbonate in water;acetonitrile at 20; for 6 h;

Steps:

A.1 1 Preparation of the rectional intermediary octahydroimidazol[1,2-a]pyrazine

1
Preparation of the rectional intermediary octahydroimidazol[1,2-a]pyrazine
A solution of chloroacetaldehyde (50% in H₂O, 98.8 g, 0.63 mol) in 500 mL of acetonitrile are added drop by drop at 20° C. to a solution of diethylenetriamine (64.9 g, 0.63 mol) and K₂CO₃ (1.23 mol, 173.9 g, 2 eq) in 1 L of acetonitrile.
The mix is stirred at ambient temperature for 6 h.
After filtration on celite, the solvent is evaporated.
800 mL of diethyl ether are added onto the residual oil, non-soluble impurities are eliminated by filtration.
After evaporation of the solvent, the compound 1 is obtained in the form of a yellow oil (m=56.8 g, yield=71%).
¹H NMR (300 MHz, CDCl₃, 298 K) δ (ppm): 1.60-1.81 (bs, 2H, NH); 1.93-2.04 (m, 2H); 2.23 (dd, 1H, ²J=11.6 Hz, ³J=8.0 Hz, CH₂CH); 2.43-2.45 (m, 2H); 2.56-2.63 (m, 3H); 2.73-2.77 (m, 2H); 2.87 (dd, 1H, ²J=11.6, ³J=2.6 Hz, CH₂CH).
¹³C{¹1-1} NMR (75 MHz, CDCl₃, 298 K) δ(ppm): 42.1; 44.3; 48.4; 50.2 51.6 (CH₂u); 75.7 (CH).

References:

US2014/142298,2014,A1 Location in patent:Paragraph 0271; 0272