Sodium Carbonate → 2-(3-(3-(4-Chlorophenyl)pyrazin-2-YL)azetidin-1-YL)quinazoline

HRID 1850328Notes

Reaction equation

HRID 1850328 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl[C:8]1[C:9]([CH:14]2[CH2:17][N:16]([C:18]3[N:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH2:15]2)=[N:10][CH:11]=[CH:12][N:13]=1.[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([C:8]2[C:9]([CH:14]3[CH2:17][N:16]([C:18]4[N:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 585467542-(3-(3-Chloropyrazin-2-yl)azetidin-1-yl)quinazoline

Product 1

HCID 585468062-(3-(3-(4-Chlorophenyl)pyrazin-2-YL)azetidin-1-YL)quinazolineYield 64%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

2M aqueous sodium carbonate (0.378 mL, 0.756 mmol, J. T. Baker) was added to a stirred mixture of 2-(3-(3-chloropyrazin-2-yl)azetidin-1-yl)quinazoline (0.075 g, 0.252 mmol, Preparation 1), trans-dichlorobis(triphenylphosphine)palladium (ii) (0.009 g, 0.013 mmol, Strem), and 4-chlorophenylboronic acid (0.047 g, 0.302 mmol, ASDI) in 1,4-dioxane (1 mL) in a sealed tube under an argon atmosphere. The reaction mixture was stirred at 80° C. for 17 h. The reaction mixture was concentrated in vacuo and diluted with DCM. The resulting suspension was filtered, and the filtrate was concentrated in vacuo. The resulting crude material was purified via reverse phase HPLC (Column: Xbridge 19×100 mm, 5 μm, 1771302301) eluting with 0.1% NH4OH in acetonitrile/water to give 0.060 g (64%) of a yellow amorphous solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with DCM
  3. filtrationThe resulting suspension was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe resulting crude material was purified via reverse phase HPLC (Column: Xbridge 19×100 mm, 5 μm, 1771302301)
  6. washeluting with 0.1% NH4OH in acetonitrile/water

Sources & evidence

ORD record
ord-0b2872c9e14c4b98b7a74825f2018e79
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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