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

HRID 1628038Notes

Reaction equation

HRID 1628038 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.[C:61](=[O:68])([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])[NH2:62].CC([O-])(C)C.[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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][C:61](=[O:68])[O:63][C:64]([CH3:67])([CH3:66])[CH3:65])[N:33]=[C:34]2[CH:40]=1

Participants

8

Reactant 4

HCID 77922tert-Butyl carbamateHCID 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 67216771tert-butyl 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamateYield 42%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a flask was added Pd2(dba)3 (0.094 g, 0.10 mmol) and di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.087 g, 0.21 mmol) in 1,4-dioxane (10 mL). The mixture was heated to about 80° C. for about 10 min. 2-Bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.500 g, 1.03 mmol, Preparation #C.1), tert-butyl carbamate (0.180 g, 1.54 mmol) and NaOt-Bu (0.148 g, 1.54 mmol) were then added and heating was continued for about 45 min. The mixture was cooled to rt and diluted with EtOAc (20 mL), washed with water (15 mL) and dried over MgSO4. The mixture was filtered and concentrated in vacuo and purified by a 12 g silica column eluting with 0 to 30% EtOAc/DCM to provide tert-butyl 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamate (0.224 g, 42%): LC/MS (Table 2, Method g) Rt=1.99 min; MS m/z 524 (M+H)+.

Workup

  1. temperatureheating
  2. temperatureThe mixture was cooled to rt
  3. washwashed with water (15 mL)
  4. dry with materialdried over MgSO4
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated in vacuo
  7. custompurified by a 12 g silica column
  8. washeluting with 0 to 30% EtOAc/DCM

Sources & evidence

ORD record
ord-6c473d0737744f40bcb1c4220d5103df
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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