Biphenyl → 5-(2,4-dichlorophenyl)-3,6-diethyl-N-(1-propyl-1H-imidazol-2-yl)pyrazin-2-amine

HRID 1612316Notes

Reaction equation

HRID 1612316 reaction equation
Br[C:2]1[C:7]([CH2:8][CH3:9])=[N:6][C:5]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])=[C:4]([CH2:18][CH3:19])[N:3]=1.[CH2:20]([N:23]1[CH:27]=[CH:26][N:25]=[C:24]1[NH2:28])[CH2:21][CH3:22].C1(C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(O)=O.[Na+].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:17][C:11]1[CH:12]=[C:13]([Cl:16])[CH:14]=[CH:15][C:10]=1[C:5]1[N:6]=[C:7]([CH2:8][CH3:9])[C:2]([NH:28][C:24]2[N:23]([CH2:20][CH2:21][CH3:22])[CH:27]=[CH:26][N:25]=2)=[N:3][C:4]=1[CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 7095BiphenylHCID 221474372-Bromo-5-(2,4-dichlorophenyl)-3,6-diethylpyrazineHCID 221475261-propyl-1H-imidazol-2-amineHCID 23676156Sodium t-butoxide

Product 1

HCID 103097425-(2,4-dichlorophenyl)-3,6-diethyl-N-(1-propyl-1H-imidazol-2-yl)pyrazin-2-amineYield 27.2%

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-bromo-5-(2,4-dichlorophenyl)-3,6-diethylpyrazine (0.25 g, 0.69 mmol), 1-propyl-1H-imidazol-2-amine (0.15 g, 1.2 mmol), tris(dibenzylideneacetone) dipalladium (0.032 g, 0.032 mmol), 2-dicyclohexylphosphino)biphenyl (0.037 g, 0.12 mmol), and sodium tert-butoxide (0.093 g, 0.97 mmol) in dioxane (2.0 mL) was heated at 110° C. for 21 h. After cooling to rt, the reaction was diluted with saturated aqueous NaHCO3 and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M) with (Biotage, 40S) with heptanes/EtOAc (3:1) to give 0.076 g (27%) of dark yellow oil: 1H NMR (400 MHz, CDCl3) δ 12.86, 7.47, 7.31, 6.70, 6.55, 3.94, 2.97, 2.48, 2.97, 2.48, 1.84, 1.30, 1.21, 0.98; IR (liq.) 2968, 2934, 1599, 1556, 1549, 1509, 1460, 1422, 1402, 1384, 1373, 1302, 1174, 1102, 712 cm−1; HRMS (FAB) calcd for C20H23Cl2N5+H 404.1408, found 404.1416.

Workup

  1. temperatureAfter cooling to rt
  2. extractionextracted with CH2Cl2
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customdecanted
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (Biotage, 40M) with (Biotage, 40S) with heptanes/EtOAc (3:1)

Sources & evidence

ORD record
ord-f8a4a31054d64ccc9b31be0e491e6677
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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