2,3-Diaminopyridine → 2,3-Bis(4-methylphenyl)pyrido[2,3-b]pyrazine

HRID 517919Notes

Reaction equation

HRID 517919 reaction equation
[C:1]1([CH3:18])[CH:6]=[CH:5][C:4]([C:7](=O)[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=O)=[CH:3][CH:2]=1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[C:20]=1[NH2:26]>CCO.CC(O)=O>[C:1]1([CH3:18])[CH:6]=[CH:5][C:4]([C:7]2[N:25]=[C:21]3[CH:22]=[CH:23][CH:24]=[N:19][C:20]3=[N:26][C:8]=2[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 99562,3-DiaminopyridineHCID 769961,2-Bis(4-methylphenyl)-1,2-ethanedione

Product 1

HCID 45725312,3-Bis(4-methylphenyl)pyrido[2,3-b]pyrazine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 1,2-di-p-tolylethane-1,2-dione (commercially available)(175 g, 733 mmol) and pyridine-2,3-diamine (80 g, 733 mmol) in EtOH (1609 ml) and AcOH (179 ml) was heated to reflux (bath at 85° C.) for 1.5 h. The mixture was allowed to cool and concentrated in vacuo. The crude material was dissolved in DCM (500 ml) and filtered through silica to remove baseline impurities. The silica was washed with EtOAc (2 L). The combined filtrate layers were concentrated in vacuo to give a brown solid. The material was triturated in 1:1 TBME/heptane (300 ml). The solid was removed by filtration and washed with 1:1 TBME/heptane (200 ml) before drying at RT over 2 days to afford the titled compound as an AcOH salt (1 eq).

Workup

  1. temperatureto cool
  2. concentrationconcentrated in vacuo
  3. dissolutionThe crude material was dissolved in DCM (500 ml)
  4. filtrationfiltered through silica
  5. customto remove baseline impurities
  6. washThe silica was washed with EtOAc (2 L)
  7. concentrationThe combined filtrate layers were concentrated in vacuo
  8. customto give a brown solid
  9. customThe material was triturated in 1:1 TBME/heptane (300 ml)
  10. customThe solid was removed by filtration
  11. washwashed with 1:1 TBME/heptane (200 ml)
  12. custombefore drying at RT over 2 days

Sources & evidence

ORD record
ord-e41118a318044a98b5bee03da3ec6d38
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

Loading…