Cesium carbonate → N-Cyclopropyl-5-iodopyrimidin-4-amine

HRID 1186835Notes

Reaction equation

HRID 1186835 reaction equation
Cl[C:2]1[C:7]([I:8])=[CH:6][N:5]=[CH:4][N:3]=1.[CH:9]1([NH2:12])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl>[CH:9]1([NH:12][C:2]2[C:7]([I:8])=[CH:6][N:5]=[CH:4][N:3]=2)[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 69828CyclopropylamineHCID 112302044-Chloro-5-iodopyrimidine

Product 1

HCID 66341877N-Cyclopropyl-5-iodopyrimidin-4-amineYield 79.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a vial containing a solution of 4-chloro-5-iodopyrimidine (0.400 g, 1.664 mmol) in DMF (Volume: 2.67 ml) was added cyclopropanamine (0.461 ml, 6.65 mmol) followed by cesium carbonate (1.084 g, 3.33 mmol). The vial was sealed with a Teflon cap and heated at 90° C. for 3 h, then allowed to cool to room temperature. The reaction mixture was filtered through a disposable fritted funnel and the filter cake washed with EtOAc. The filtrate was diluted with H2O and the layers were separated. The organic phase was washed with H2O (2×). The combined aqueous phases were back-extracted with EtOAc (3×). All organics were combined, dried over Na2SO4, filtered, and concentrated to afford an orange residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 20-70% EtOAc in hexanes over 19 min, ret. T=13.5 min) gave Intermediate 108A (348 mg, 1.320 mmol, 79% yield) as a yellow solid. MS (ESI): m/z=262.0 [M+H]+ HPLC Peak ret. T=1.47 minutes was product. (HPLC conditions: Column:Luna C18 4.6×30 mm 3 u A:10:90 H2O:ACN NH4OAc/B:10:90 H2O:ACN NH4OAc; 0%-95% B in 2 min; 4 mL/min flow).

Workup

  1. customcap
  2. temperatureto cool to room temperature
  3. filtrationThe reaction mixture was filtered through a disposable fritted funnel
  4. washthe filter cake washed with EtOAc
  5. additionThe filtrate was diluted with H2O
  6. customthe layers were separated
  7. washThe organic phase was washed with H2O (2×)
  8. extractionThe combined aqueous phases were back-extracted with EtOAc (3×)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford an orange residue
  13. customto be chromatographed
  14. customPurification of the crude material by silica gel chromatography
  15. customan ISCO machine (40 g column, 40 mL/min, 20-70% EtOAc in hexanes over 19 min, ret. T=13.5 min)

Sources & evidence

ORD record
ord-269865e620be4630b5f7d05e4091a0d2
Source dataset
uspto-grants-2014_03
Patent number
US08673922B2

Reaction notes

Loading…