Ethylenediamine → 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

HRID 1854518Notes

Reaction equation

HRID 1854518 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:25](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH3:24])=[N:22][N:23]=3)[C:15]=2[CH:14]=1.CN(C=O)C.C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O>[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:25][C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH3:24])=[N:22][N:23]=3)[C:15]=2[CH:14]=1

Participants

6

Reactant 4

HCID 3301Ethylenediamine2×HCID 6228DimethylformamideHCID 2724141Tetrabutylammonium Fluoride2×HCID 580100647-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazine

Product 1

HCID 1361988607-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazineYield 8.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

To a round bottom flask was added 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.040 g, 0.086 mmol), DMF (0.865 mL), ethylenediamine (0.088 mL, 2.6 mmol) and TBAF (1.0 M in THF, 0.346 mL, 0.173 mmol). The reaction mixture was heated to about 85° C. for about 4 h. To the reaction mixture was added ethylenediamine (0.088 mL, 2.6 mmol) and TBAF (1.0 M in THF, 0.346 mL, 0.173 mmol). The reaction mixture was heated at about 85° C. for about 2 h. The reaction mixture cooled to room temperature and diluted with water (50 mL). The mixture was extracted with EtOAc (50 mL) and the organic layer was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by preparatory RP-HPLC (Table 2, Method u). The material was further purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to give 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.0024 g, 8.4%). LC/MS (Table 1, Method a) Rt=1.84 min; MS m/z: 333 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated at about 85° C. for about 2 h
  2. temperatureThe reaction mixture cooled to room temperature
  3. extractionThe mixture was extracted with EtOAc (50 mL)
  4. dry with materialthe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by preparatory RP-HPLC (Table 2, Method u)
  8. customThe material was further purified by silica gel chromatography
  9. washeluting with a gradient of 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-eb3216dc4bee447b9ba7792f1cffd0b3
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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