Triethylamine → (R)-Methyl 5-(4-(6-benzyl-4,5-dimethylpyridazin-3-yl)-2-methylpiperazin-1-yl)pyrazine-2-carboxylate

HRID 1479998Notes

Reaction equation

HRID 1479998 reaction equation
[CH2:1]([C:8]1[N:9]=[N:10][C:11]([N:16]2[CH2:21][CH2:20][NH:19][C@H:18]([CH3:22])[CH2:17]2)=[C:12]([CH3:15])[C:13]=1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]([C:27]1[CH:32]=[N:31][C:30](Cl)=[CH:29][N:28]=1)=[O:26].CCN(CC)CC>O1CCOCC1>[CH3:23][O:24][C:25]([C:27]1[N:28]=[CH:29][C:30]([N:19]2[CH2:20][CH2:21][N:16]([C:11]3[N:10]=[N:9][C:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[C:13]([CH3:14])[C:12]=3[CH3:15])[CH2:17][C@H:18]2[CH3:22])=[N:31][CH:32]=1)=[O:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 59191647(R)-3-Benzyl-4,5-dimethyl-6-(3-methylpiperazin-1-yl)pyridazine

Product 1

HCID 59191561(R)-Methyl 5-(4-(6-benzyl-4,5-dimethylpyridazin-3-yl)-2-methylpiperazin-1-yl)pyrazine-2-carboxylateYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of compound 47 (6.0 g, 20.27 mmol), 5-chloropyrazine-2-carboxylic acid methyl ester (5.3 g, 30.30 mmol), Et3N (6.2 g, 60.60 mmol) and dioxane (100 mL) is heated to reflux overnight. Solvent is removed. Saturated NH4Cl solution is added and extracted with EtOAc. The organic layer is concentrated to afford the crude product that is purified by chromatography on silica gel (EtOAc/heptane: 50%˜100%) to give the title compound (6.6 g, 76%) as a yellow solid.

Workup

  1. temperatureis heated
  2. temperatureto reflux overnight
  3. customSolvent is removed
  4. additionSaturated NH4Cl solution is added
  5. extractionextracted with EtOAc
  6. concentrationThe organic layer is concentrated
  7. customto afford the crude product that
  8. customis purified by chromatography on silica gel (EtOAc/heptane: 50%˜100%)

Sources & evidence

ORD record
ord-77f384bffdb143df97a1405d91bc08ae
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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