Ammonia → trans-Piperazine 2,5-dicarboxamide

HRID 2350869Notes

Reaction equation

HRID 2350869 reaction equation
[N:1]1[CH:6]=[C:5]([C:7](O)=O)[N:4]=[CH:3][C:2]=1[C:10]([OH:12])=O.CC1C=NC(C)=C[N:15]=1.Cl.N1C[C@@H](C([O-])=O)NC[C@@H]1C([O-])=O.[NH3:34].N1C=CC=CC=1.[OH2:41]>[Pd]>[NH:34]1[CH2:7][C@@H:5]([C:6]([NH2:1])=[O:41])[NH:4][CH2:3][C@@H:2]1[C:10]([NH2:15])=[O:12]

Participants

8

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312522,5-DimethylpyrazineHCID 255280Pyrazine-2,5-dicarboxylic acid2×HCID 66926435Pyridine waterHCID 86743415trans-Piperazine-2,5-dicarboxylate

Product 1

HCID 13526546trans-Piperazine 2,5-dicarboxamide

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

The first aspect of this invention is a process for the synthesis of stereoisomeric tricyclic bis(dioxopiperazines), 53 and 54, and their bis(morpholinomethyl) derivatives, 55 and 56, which comprises synthesizing pyrazine-2,5-dicarboxylic acid by oxidation of 2.5-dimethylpyrazine using SeO2 in refluxing pyridine-water. Thereafter hydrogenation of an alkaline solution of pyrazine-2,5-dicarboxylic acid at 50°-60° C. and 40-42 psi H2 pressure using Pd/C catalyst to produce the cis- and trans- piperazine-2,5-dicarboxylic acid, and gradual addition of HCl to the alkaline solution to separate the cis-and trans- isomers of piperazine-2,5-dicarboxylic acid. Thereafter refluxing a solution of either the cis or trans piperazine-2,5-dicarboxylic acid in saturated methanol-HCl to produce either the dimethyl cis- or trans- piperazine-2,5-dicarboxylate compound and reacting either the cis- or trans- compound with liquid ammonia under pressure to produce the compound cis- or trans- piperazine 2,5-dicarboxamide. And, finally, reacting the piperazine-2,5-dicarboxamide compound with ethyl bromoacetate/K2CO3 in dimethylsulfoxide at room temperature to produce the diethyl- cis- or trans- 2,5-bis(carbamoyl)- 1,4-piperazinediacetate and refluxing either the cis- or trans- compound in ethanol-sodium ethoxide to produce either the cis- or trans-tetrahydrodipyrazino [1,2-a:1',2'-d]pyrazine-1,3,7,9(2H,4H,8H,10H) tetraone compound of the present invention.

Workup

  1. customat 50°-60° C.
  2. customto produce
  3. customto separate the cis-and trans- isomers of piperazine-2,5-dicarboxylic acid
  4. temperatureThereafter refluxing a solution of either the cis or trans piperazine-2,5-dicarboxylic acid in saturated methanol-HCl
  5. customto produce

Sources & evidence

ORD record
ord-fec5c9a0efd9438290fe6310bcd2da14
Source dataset
uspto-grants-1989_10
Patent number
US04871736

Reaction notes

Loading…