1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 58115030, compound

HRID 1808696Notes

Reaction equation

HRID 1808696 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.C(C1CCCCN1C)C#C.[CH2:29]1[CH2:39][CH2:38][N:37]2[C:32](=N[CH2:34][CH2:35][CH2:36]2)[CH2:31][CH2:30]1>CC(N(C)C)=O.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:31][CH:32]1[CH2:30][CH2:29][CH2:39][CH2:38][N:37]1[CH2:36][C:35]#[C:34][C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 575165972-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazineHCID 866501572228977-48-6

Product 1

HCID 58115030HCID 58115030, compoundYield 63.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A flask was charged with 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (250 mg, 0.76 mmol), 2-propargyl-1-methyl-piperidine (105 mg, 0.76 mmol), copper iodide (15 mg, 0.076 mmol), dichlorobis-(triphenylphosphine)palladium (II) (11 mg, 0.02 mmol) and DBU (0.34 mL, 2.28 mmol) in dry dimethyl acetamide (3 mL). The mixture was vacuum degassed and heated to 120° C. and stirred for 10 hours. The mixture was cooled to ambient and quenched via the addition of water (45 ml) and ethyl acetate (45 ml). The material was shaken in a separatory funnel, and the ethyl acetate phase was collected. The aqueous phases were back extracted with ethyl acetate (2×40 ml), the organics combined, dried (MgSO4), filtered and stripped. The remainder was purified by preparative TLC using 15% ethyl acetate in hexanes as eluant. The plates were re-developed consecutively with 40% and then 60% ethyl acetate in hexanes. The product band was collected to provide 185 mg of (+/−)-2-[3-(2-methyl-piperidin-1-yl)-prop-1-ynyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a golden yellow oil. MS (M+H)+=385

Workup

  1. customdegassed
  2. temperatureThe mixture was cooled to ambient and
  3. customquenched via the addition of water (45 ml) and ethyl acetate (45 ml)
  4. stirringThe material was shaken in a separatory funnel
  5. customthe ethyl acetate phase was collected
  6. extractionThe aqueous phases were back extracted with ethyl acetate (2×40 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customThe remainder was purified by preparative TLC
  10. customThe product band was collected

Sources & evidence

ORD record
ord-7e43a05ef139474a9bb1e82ed3a2df0e
Source dataset
uspto-grants-2013_01
Patent number
US08361962B2

Reaction notes

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