Methanol → HCID 58557399, compound

HRID 1969689Notes

Reaction equation

HRID 1969689 reaction equation
I[C:2]1[C:10]2[N:9]3[CH:11]=[N:12][N:13]=[C:8]3[CH:7]=[N:6][C:5]=2[N:4]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:3]=1.[CH3:22][OH:23].CN([CH:27]=[O:28])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:19][Si:18]([CH3:21])([CH3:20])[CH2:17][CH2:16][O:15][CH2:14][N:4]1[C:5]2[N:6]=[CH:7][C:8]3[N:9]([CH:11]=[N:12][N:13]=3)[C:10]=2[C:2]([C:22]([O:28][CH3:27])=[O:23])=[CH:3]1

Participants

5

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 58557173HCID 58557173, compound

Product 1

HCID 58557399HCID 58557399, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
100 °C

Procedure

To a solution of 8-iodo-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.050 g, 0.12 mmol, prepared using KK from Preparation #GGG.1.1 and NaH), TEA (0.034 mL, 0.24 mmol), MeOH (0.25 mL, 6.2 mmol), and DMF (0.6 mL) purged with nitrogen was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.0098 g, 0.012 mmol). The mixture was purged with CO and a balloon of CO was attached to the reaction vessel. The mixture was warmed to about 100° C. After about 4.5 h, the solution was allowed to cool to ambient temperature. Water (5 mL) was added and the mixture was extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 25-75% EtOAc/heptane over 30 min to afford methyl 6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carboxylate (0.0311 g, 74%): LC/MS (Table 1, Method n) Rt=0.74 min; MS m/z: 348 (M+H)+.

Workup

  1. customThe mixture was purged with CO
  2. temperatureto cool to ambient temperature
  3. additionWater (5 mL) was added
  4. extractionthe mixture was extracted with EtOAc (2×10 mL)
  5. dry with materialThe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 25-75% EtOAc/heptane over 30 min

Sources & evidence

ORD record
ord-e6c4a121f8e5456d82fe4df0da1f69c3
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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