Dichloromethane → 4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1396139Notes

Reaction equation

HRID 1396139 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.ClCCl>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

6

Reactant 3

HCID 6344DichloromethaneHCID 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 (9, 0.452 g, 2.94 mmol), cyclopropylmagnesium bromide (17, 31.4 mL, 0.50 M in tetrahydrofuran, 15.7 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.240 g, 0.294 mmol) are combined with 15.4 mL of toluene. The reaction is heated at 60° C. overnight, then quenched with 1 M aqueous hydrochloric acid to pH 4 and filtered through a bed of celite. The layers of the filtrate are separated and the aqueous layer extracted with ethyl acetate. The combined organic layers are washed with brine, dried over sodium 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 (18, 0.465 g). MS (ESI) [M+H+]+=160.1. This is reacted similarly to steps 2 and 3 of Scheme 4 to provide the desired compound 19.

Workup

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

Sources & evidence

ORD record
ord-d248b611418743a995af489004d34010
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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