7H-Pyrrolo(2,3-d)pyrimidine, 4-chloro- → 4-Methyl-7H-pyrrolo(2,3-d)pyrimidine

HRID 1690033Notes

Reaction equation

HRID 1690033 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:11][Mg]Br>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:11][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 178418573HCID 178418573, compound

Product 1

HCID 513419594-Methyl-7H-pyrrolo(2,3-d)pyrimidineYield 15.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

Into a round bottom flask the catalyst PdCl2(dppf), under an atmosphere of nitrogen, was placed with 15 mL of toluene along with a stir bar. A suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 1.47 g, 9.57 mmol) in 15 mL of toluene was added at room temperature. After stirring for 10 minutes, methylmagnesium bromide (17.00 mL, 3.00 M in ether, 51.00 mmol) was added dropwise. The solution turned from orange to yellow, and was slowly heated to 60° C. and stirred for 3 hrs at 60° C. and then overnight at room temperature. The resulting dark orange reaction mixture was quenched with 1 N hydrochloric acid and adjusted to pH ˜5, then extracted with ethyl acetate and water saturated with sodium chloride. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a yellow solid (42, 202 mg). 1H-NMR(dmso-d6) was consistent with the desired compound. MS(ESI) [M+H+]+=134.3.

Workup

  1. additionwas added at room temperature
  2. stirringstirred for 3 hrs at 60° C.
  3. customovernight
  4. customat room temperature
  5. customThe resulting dark orange reaction mixture was quenched with 1 N hydrochloric acid
  6. extractionextracted with ethyl acetate and water saturated with sodium chloride
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated under vacuum
  11. customThe resulting material was purified by silica gel column chromatography
  12. washeluting with ethyl acetate and hexane
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b284754ef80449d2bee021f6b0683b45
Source dataset
uspto-grants-2012_04
Patent number
US08153641B2

Reaction notes

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