Toluene → 7-Cyclopent-3-en-1-yl-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-7H-pyrrolo[2,3-d]-pyrimidin-4-amine

HRID 222214Notes

Reaction equation

HRID 222214 reaction equation
[C@@H:1]1([NH:10][C:11]2[C:12]3[CH:19]=[CH:18][NH:17][C:13]=3[N:14]=[CH:15][N:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[C:20]1([CH3:26])[CH:25]=[CH:24][CH:23]=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(OC1CC=CC1)(=O)=O>CN(C)C=O>[CH:23]1([N:17]2[C:13]3[N:14]=[CH:15][N:16]=[C:11]([NH:10][C@@H:1]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH2:3][CH2:2]4)[C:12]=3[CH:19]=[CH:18]2)[CH2:24][CH:25]=[CH:20][CH2:26]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 12174535HCID 12174535, compoundHCID 58944690N-[(1S)-2,3-Dihydro-1H-inden-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 589446687-Cyclopent-3-en-1-yl-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-7H-pyrrolo[2,3-d]-pyrimidin-4-amineYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

N-[(1S)-2,3-Dihydro-1H-inden-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1.32 g, 5.29 mmol) was azeotroped with toluene and placed under high vacuum for 30 min. N,N-Dimethylformamide (17.7 mL) was added, followed by cesium carbonate (1.99 g, 6.10 mmol). The mixture was stirred at 70° C. for 10 min. Cyclopent-3-en-1-yl methanesulfonate (0.660 g, 4.07 mmol) in N,N-dimethylformamide (12.6 mL) was added dropwise. The reaction mixture was heated to 110° C. for 1 h. The reaction mixture was cooled, quenched with brine and diluted with H2O. The aqueous layer was extracted with EtOAc (3×), washed with H2O and brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by via silica gel chromatography, eluting with a gradient of 0 to 5% MeOH in DCM followed by 25 to 50% EtOAc in hexanes, to afford the title compound as a pale brown solid (0.684 g, 53%). LC/MS: Rt=1.38 min, ES+ 317 (FA standard).

Workup

  1. temperatureThe reaction mixture was heated to 110° C. for 1 h
  2. temperatureThe reaction mixture was cooled
  3. customquenched with brine
  4. additiondiluted with H2O
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washwashed with H2O and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by via silica gel chromatography
  11. washeluting with a gradient of 0 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-ac4f2d7eacad4e349bccfbfc7e16222b
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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