1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86650160, compound

HRID 1808705Notes

Reaction equation

HRID 1808705 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([CH3:12])[CH:8]([CH2:13][C:14]#[C:15][C:16]2[N:17]=[C:18]3[CH:24]=[CH:23][N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:19]3=[N:20][CH:21]=2)[CH2:7]1)(=[O:5])=[O:4])[CH3:2].C1CCN2C(=NCCC2)CC1>CC(N(C)C)=O.[Cu](I)I>[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][C@@H:9]([CH3:12])[C@H:8]([C:13]2[N:17]3[C:16]([CH:21]=[N:20][C:19]4[N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:23]=[CH:24][C:18]=43)=[CH:15][CH:14]=2)[CH2:7]1)(=[O:5])=[O:4])[CH3:2]

Participants

5

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58115051HCID 58115051, compound

Product 1

HCID 86650160HCID 86650160, compoundYield 5.8%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

To a flask containing (+/−)-2-[3-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-prop-1-ynyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (395 mg, 0.83 mmol) was added copper iodide (79 mg, 0.41 mmol), and DBU (0.57 mL, 3.8 mmol) in dry dimethyl acetamide (4 mL). The mixture was vacuum degassed and the flask was wrapped with tin foil (protect from light) and heated to 130° C. and stirred for 5 hours. Additional copper iodide (110 mg) was added and the mixture was stirred for another 6 hours and then cooled to ambient with over-night stirring. The material was taken up in water (30 mL) and ethyl acetate (30 mL), transferred to a reparatory funnel and shaken. The organic phase was collected and shaken with an equal volume of brine. The aqueous phases were back extracted with ethyl acetate (2×25 ml), the organics combined, dried (MgSO4), filtered and stripped. The remainder was purified by preparative TLC eluting with 45% ethyl acetate in hexanes (develop plates in the dark). A less polar component was collected providing 23 mg of semi-pure trans-(+/−)-8-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-3,4,8a-triaza-as-indacene product. MS (M+H)+=477. Also 17 mg of a more polar cis-(+/−)-8-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-3,4,8a-triaza-as-indacene product was collected. MS (M+H)+=477.

Workup

  1. customdegassed
  2. additionAdditional copper iodide (110 mg) was added
  3. stirringthe mixture was stirred for another 6 hours
  4. temperaturecooled
  5. waitto ambient with over-night
  6. stirringstirring
  7. customethyl acetate (30 mL), transferred to a reparatory funnel
  8. stirringshaken
  9. customThe organic phase was collected
  10. stirringshaken with an equal volume of brine
  11. extractionThe aqueous phases were back extracted with ethyl acetate (2×25 ml)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customThe remainder was purified by preparative TLC
  15. washeluting with 45% ethyl acetate in hexanes (
  16. customA less polar component was collected

Sources & evidence

ORD record
ord-ba7a13d77a3a424ba5ffd48fd1713c27
Source dataset
uspto-grants-2013_01
Patent number
US08361962B2

Reaction notes

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