Acetaldehyde → 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

HRID 2204669Notes

Reaction equation

HRID 2204669 reaction equation
[NH:1]([C:3]1[N:4]=[C:5]2[CH:11]=[C:10]([C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]([CH3:23])[CH:13]=3)[N:9]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:6]2=[N:7][CH:8]=1)[NH2:2].C(Cl)Cl.[CH:35](=O)[CH3:36].N>[Cu](Cl)Cl.CCOC(C)=O.CN(C=O)C>[CH3:22][O:21][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:23])[CH:13]=[C:12]2[C:10]1[N:9]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:6]2[N:7]=[CH:8][C:3]3[N:4]([C:35]([CH3:36])=[N:2][N:1]=3)[C:5]=2[CH:11]=1

Participants

8

Reactant 4

HCID 177AcetaldehydeHCID 222AmmoniaHCID 6344DichloromethaneHCID 580100332-hydrazinyl-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

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]pyrazineYield 21%

Reagents, catalysts & solvents 3

HCID 24014Cupric ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask were added 2-hydrazinyl-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.181 g, 0.413 mmol), DCM (5 mL) and acetaldehyde (10.0 M in DCM, 0.206 mL, 2.06 mmol). The reaction mixture was stirred at room temperature for about 1 h. The reaction mixture was concentrated under reduced pressure followed by the addition of DMF (8 mL) and copper(II) chloride (0.107 g, 0.796 mmol). The reaction mixture was heated to about 90° C. for about 15 min. The reaction mixture was cooled to room temperature and 10% aqueous ammonia (4.5 mL) and EtOAc (6 mL) were added. The reaction mixture was heated to about 40° C. for about 30 min. The reaction mixture was cooled to ambient temperature and extracted with EtOAc (50 mL). The organic layer was washed with water (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The material was purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in heptane to give 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, 21%): LC/MS (Table 1, Method d) Rt=1.67 min; MS m/z: 463 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. temperatureThe reaction mixture was heated to about 90° C. for about 15 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. temperatureThe reaction mixture was heated to about 40° C. for about 30 min
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. extractionextracted with EtOAc (50 mL)
  7. washThe organic layer was washed with water (50 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe material was purified by silica gel chromatography
  12. washeluting with a gradient of 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-6fc97de2290a41fba09a9025064c2fec
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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