7H-Pyrrolo(2,3-d)pyrimidine, 4-chloro- → 4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1690040Notes

Reaction equation

HRID 1690040 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.[CH:11]1([Mg]Br)[CH2:13][CH2:12]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].C1(C)C=CC=CC=1>[CH:11]1([C:2]2[C:3]3[CH:10]=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 178418630HCID 178418630, compound

Product 1

HCID 579633004-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidineYield 99.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 0.452 g, 2.94 mmol), cyclopropylmagnesium bromide (43, 31.4 mL, 0.50 M in tetrahydrofuran, 15.7 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.240 g, complex 1:1 with dichloromethane, 0.294 mmol) were mixed with 15.4 mL of toluene. The reaction was heated at 60° C. overnight, then quenched with 1 M aqueous hydrochoric acid to pH 4 and filtered through a bed of celite. The layers of the filtrate were separated and the aqueous layer extracted with ethyl acetate: The combined organic layers were washed with brine, dried over sodium 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 (44, 0.465 g). MS (ESI) [M+H+]+=160.1.

Workup

  1. customquenched with 1 M aqueous hydrochoric acid to pH 4
  2. filtrationfiltered through a bed of celite
  3. customThe layers of the filtrate were separated
  4. extractionthe aqueous layer extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under vacuum
  9. customThe resulting material was purified by silica gel column chromatography
  10. washeluting with ethyl acetate and hexane
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-54f04cdc39c34f5baa80dc7d1ace052e
Source dataset
uspto-grants-2012_04
Patent number
US08153641B2

Reaction notes

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