Ethyl orthoformate → 6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

HRID 1969690Notes

Reaction equation

HRID 1969690 reaction equation
C(O[CH2:9][CH3:10])(OCC)OCC.[NH:11]([C:13]1[N:14]=[C:15]2[CH:21]=[CH:20][N:19]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:16]2=[N:17]C=1)[NH2:12]>CN(C=O)C>[S:22]([N:19]1[C:16]2[N:17]=[CH:9][C:10]3[N:14]([CH:13]=[N:11][N:12]=3)[C:15]=2[CH:21]=[CH:20]1)([C:25]1[CH:26]=[CH:27][C:28]([CH3:29])=[CH:30][CH:31]=1)(=[O:24])=[O:23]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 585574426-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazineYield 73.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Triethyl orthoformate (76.0 mL, 456 mmol) was added to a mixture of 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (13.8 g, 45.4 mmol, Example #1, Step D) and DMF (45 mL) under nitrogen. A reflux condenser was attached and the mixture was warmed to about 100° C. After about 17 h, the solution was allowed to cool to ambient temperature. The volatiles were removed under reduced pressure. The residue was slurried in water (100 mL) and then filtered, rinsing with water. The aqueous phase was extracted with EtOAc (200 mL). The organics were dried over anhydrous Na2SO4, filtered, and concentrated. The material was combined with the precipitate and then purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give 6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (10.4 g, 73%): LC/MS (Table 1, Method n) Rt=0.59 min; MS m/z 314 (M+H)+.

Workup

  1. customA reflux condenser was attached
  2. temperatureto cool to ambient temperature
  3. customThe volatiles were removed under reduced pressure
  4. filtrationfiltered
  5. washrinsing with water
  6. extractionThe aqueous phase was extracted with EtOAc (200 mL)
  7. dry with materialThe organics were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography
  11. washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-12604cfebf0e4b1ab48655e4d38bedcc
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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