Ethylenediamine → HCID 58009976, compound

HRID 1854468Notes

Reaction equation

HRID 1854468 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:24](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([CH:21]=[N:22][CH:23]=3)[C:15]=2[CH:14]=1.C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>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:24][C:16]2[N:17]=[CH:18][C:19]3[N:20]([CH:21]=[N:22][CH:23]=3)[C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium Fluoride2×HCID 58010138HCID 58010138, compound

Product 1

HCID 58009976HCID 58009976, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

7-(5-Methoxy-1-methyl-1H-indol-3-yl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.048 g, 0.11 mmol) in DMF (4 mL) was treated with ethylenediamine (0.22 mL, 3.3 mmol) and heated to about 85° C. for about 5 min. The solution was cooled and TBAF (1 M in THF, 0.11 mL, 0.11 mmol) was added. The solution was re-heated to about 85° C. for about 30 min. The mixture was cooled to ambient temperature and another portion of the TBAF (1 M in THF, 0.054 mL, 0.054 mmol) was added and heating was continued for about 1.5 h. The solution was cooled and the material was purified by preparative RP-HPLC (Table 2, Method 1). The product-containing fractions were concentrated to remove MeCN then basified with saturated aqueous NaHCO3 and extracted with EtOAc (2×10 mL). The combined organic solutions were dried over anhydrous MgSO4, filtered, and concentrated. Trituration of the solid with heptane (5 mL) then collection by filtration gave 7-(5-methoxy-1-methyl-1H-indol-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.028 g, 8%): LC/MS (Table 2, Method a) Rt=1.91 min; MS m/z: 318.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6 δ 12.18 (s, 1H), 8.77 (s, 1H), 8.59 (s, 1H), 7.83 (s, 1H), 7.79 (s, 1H), 7.48 (d, J=2.3 Hz, 1H), 7.43 (d, J=8.9 Hz, 1H), 7.20 (d, J=2.3 Hz, 1H), 6.92 (dd, J=8.90, 2.36 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H).

Workup

  1. temperatureThe solution was cooled
  2. temperatureThe solution was re-heated to about 85° C. for about 30 min
  3. temperatureThe mixture was cooled to ambient temperature
  4. temperatureheating
  5. temperatureThe solution was cooled
  6. customthe material was purified by preparative RP-HPLC (Table 2, Method 1)
  7. concentrationThe product-containing fractions were concentrated
  8. customto remove MeCN
  9. extractionextracted with EtOAc (2×10 mL)
  10. dry with materialThe combined organic solutions were dried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customTrituration of the solid with heptane (5 mL) then collection
  14. filtrationby filtration

Sources & evidence

ORD record
ord-fd873d0521294cba91fd3e1d142a39f7
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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