Ethylenediamine → HCID 58010198, compound

HRID 1854465Notes

Reaction equation

HRID 1854465 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:26](COCC[Si](C)(C)C)[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:23](=[O:25])[CH3:24])[N:20]=[C:15]2[CH:14]=1.C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CCOC(C)=O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[NH:26][C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:23](=[O:25])[CH3:24])[N:20]=[C:15]2[CH:14]=1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 58010206HCID 58010206, compound

Product 1

HCID 58010198HCID 58010198, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

N-((6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)acetamide (0.200 g, 0.417 mmol) in DMF (10 mL) was treated with ethylenediamine (0.90 mL, 13 mmol) and TBAF (1 M in THF, 1.7 mL, 1.7 mmol). The mixture was heated to about 85° C. for about 90 min then cooled and concentrated under reduced pressure. The material was stirred with water (20 mL) for about 16 h, Et2O (10 mL) was added, and stirring was continued for about 15 min. The slurry was filtered and the solid collected was dried. The filtrate was extracted with EtOAc (2×25 mL) then the combined organic solutions were dried over anhydrous MgSO4, filtered, and concentrated to give material, which was combined with the previously collected solid. The material was triturated with EtOAc (5 mL) and filtered to give a solid. The filtrate was purified by silica gel chromatography eluting with DCM/MeOH (9:1) to give an additional amount of product which was combined with the solid obtained from the EtOAc trituration to give N-((6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)acetamide (0.108 g, 74%): LC/MS (Table 2, Method a) Rt=1.91 min; MS m/z: 350.2 (M+H)—.

Workup

  1. temperaturethen cooled
  2. concentrationconcentrated under reduced pressure
  3. additionEt2O (10 mL) was added
  4. stirringstirring
  5. waitwas continued for about 15 min
  6. filtrationThe slurry was filtered
  7. customthe solid collected
  8. customwas dried
  9. extractionThe filtrate was extracted with EtOAc (2×25 mL)
  10. dry with materialthe combined organic solutions were dried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give material, which
  14. customThe material was triturated with EtOAc (5 mL)
  15. filtrationfiltered
  16. customto give a solid
  17. customThe filtrate was purified by silica gel chromatography
  18. washeluting with DCM/MeOH (9:1)
  19. customto give an additional amount of product which

Sources & evidence

ORD record
ord-273e5e06478c4e728733fd9b0f1d2f16
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…