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

HRID 1187279Notes

Reaction equation

HRID 1187279 reaction equation
ClCCl.Cl[C:5]1[C:6]2[CH:13]=[CH:12][NH:11][C:7]=2[N:8]=[CH:9][N:10]=1.[CH3:14][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]>[CH3:14][C:5]1[C:6]2[CH:13]=[CH:12][NH:11][C:7]=2[N:8]=[CH:9][N:10]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 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 [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1:1 complex with dichloromethane (70.0 mg, 0.09 mmol), is placed under nitrogen 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 is added at room temperature. After stirring for 10 minutes, methylmagnesium bromide (17.00 mL, 3.00 M in ether, 51.00 mmol) is added dropwise. The solution is slowly heated to 60° C. and stirred for 3 hrs at 60° C., then overnight at room temperature. The resulting dark orange reaction mixture is 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 is washed with water and brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound as a yellow solid (8, 202 mg). 1H-NMR (dmso-d6) is consistent with the desired compound. MS (ESI) [M+H+]+=134.3.

Workup

  1. additionis 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 is quenched with 1 N hydrochloric acid
  6. extractionextracted with ethyl acetate and water saturated with sodium chloride
  7. washThe organic layer is washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated under vacuum
  11. customThe resulting material is purified by silica gel column chromatography
  12. washeluting with ethyl acetate and hexane
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-477f715bce654e58824ae212a34a033e
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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