tert-Butyl carbazate → tert-butyl 2-(6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarboxylate

HRID 1854515Notes

Reaction equation

HRID 1854515 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Br[C:32]1[N:33]=[C:34]2[CH:40]=[C:39]([C:41]3[C:49]4[C:44](=[CH:45][CH:46]=[C:47]([O:50][CH3:51])[CH:48]=4)[N:43]([CH3:52])[CH:42]=3)[N:38]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[C:35]2=[N:36][CH:37]=1.[NH:61]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[NH2:62].CC(C)([O-])C.[Na+]>O1CCOCC1>[CH3:51][O:50][C:47]1[CH:48]=[C:49]2[C:44](=[CH:45][CH:46]=1)[N:43]([CH3:52])[CH:42]=[C:41]2[C:39]1[N:38]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[C:35]2=[N:36][CH:37]=[C:32]([NH:62][NH:61][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[N:33]=[C:34]2[CH:40]=1

Participants

6

Reactant 4

HCID 70091tert-Butyl carbazateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 580101552-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 58009978tert-butyl 2-(6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarboxylateYield 70.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A round bottom flask was charged with tris(dibenzylidineacetone)dipalladium(0) (0.066 g, 0.072 mmol) and di-tert-butyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.061 g, 0.14 mmol) in 1,4-dioxane (10 mL) to give a black solution which was degassed via vacuum/nitrogen purge (3 times). The mixture was heated to about 80° C. for about 10 min. To the reaction mixture were added 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.35 g, 0.72 mmol, Example #20, Step D) and tert-butyl hydrazinecarboxylate (0.142 g, 1.08 mmol), followed by sodium tert-butoxide (0.104 g, 1.08 mmol). The mixture was heated at about 80° C. for about 20 min. The reaction mixture was cooled and filtered through Celite®. The filter pad was further rinsed with EtOAc (40 mL). The filtrate was concentrated under reduced pressure and purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in heptane to give tert-butyl 2-(6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarboxylate (0.272 g, 70%): LC/MS (Table 1, Method d) Rt=1.78 min; MS m/z: 539 (M+H)+.

Workup

  1. customto give a black solution which
  2. customwas degassed via vacuum/nitrogen
  3. custompurge (3 times)
  4. temperatureThe mixture was heated at about 80° C. for about 20 min
  5. temperatureThe reaction mixture was cooled
  6. filtrationfiltered through Celite®
  7. washThe filter pad was further rinsed with EtOAc (40 mL)
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. custompurified by silica gel chromatography
  10. washeluting with a gradient of 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-c2e1bbe3a2ef4652b72e8ae354a03f4e
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…