Tetrahydrofuran → HCID 68736697, compound

HRID 1628514Notes

Reaction equation

HRID 1628514 reaction equation
[CH2:1]([Mg]Br)[CH3:2].Cl[C:6]1[C:11]([NH2:12])=[C:10](Cl)[N:9]=[C:8]([CH3:14])[N:7]=1.O1CC[CH2:17][CH2:16]1>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:16]([C:6]1[C:11]([NH2:12])=[C:10]([CH2:1][CH3:2])[N:9]=[C:8]([CH3:14])[N:7]=1)[CH3:17]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 7366744,6-Dichloro-2-methylpyrimidin-5-amineHCID 178418443HCID 178418443, compound

Product 1

HCID 68736697HCID 68736697, compound

Reagents, catalysts & solvents 1

HCID 178418745HCID 178418745, compoundCatalyst

Procedure

Ethylmagnesium bromide (3.0 M solution in diethyl ether, 100 mL, 300 mmol) was added to a stirred suspension of 4,6-dichloro-2-methylpyrimidin-5-amine (10.7 g, 60.1 mmol) and [1,3-bis(diphenylphosphino)propane]dichloronickel(II) (3.26 g, 6.01 mmol) in tetrahydrofuran (400 mL) at 0° C., and the mixture was stirred at room temperature for 4 hr. The reaction was quenched by water, acidified by 1N hydrochloric acid and extracted with ethyl acetate. The aqueous layer was neutralized by 1N sodium hydroxide, extracted with ethyl acetate, and the combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a yellow wax (4.22 g, 25.5 mmol, 42%).

Workup

  1. customThe reaction was quenched by water
  2. extractionextracted with ethyl acetate
  3. extractionextracted with ethyl acetate
  4. washthe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-100% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-c42182df4441422e84785674156cc9c0
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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