Hydrochloric Acid → HCID 67216364, compound

HRID 1969892Notes

Reaction equation

HRID 1969892 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]([NH:10][NH:11][C:12]2[N:13]=[C:14]3[CH:20]=[CH:19][N:18]([S:21]([C:24]4[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[C:15]3=[N:16][CH:17]=2)=O)[CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4]1)[CH3:2].S(Cl)(Cl)=O.Cl.CCOCC>O1CCOCC1>[CH2:1]([C@H:3]1[CH2:4][NH:5][CH2:6][C@H:7]1[C:8]1[N:13]2[C:14]3[CH:20]=[CH:19][N:18]([S:21]([C:24]4[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[C:15]=3[N:16]=[CH:17][C:12]2=[N:11][N:10]=1)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 24386Thionyl ChlorideHCID 131730522HCID 131730522, compound

Product 1

HCID 67216364HCID 67216364, compoundYield 87.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (cis)-tert-butyl 3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)pyrrolidine-1-carboxylate (9.4 g, 16.41 mmol) in 1,4-dioxane (150 mL), TEA (7.00 mL, 50.2 mmol) and thionyl chloride (1.80 mL, 24.6 mmol) were each added sequentially in one portion to the solution. The reaction was heated at about 70° C. for about 18 h. The solvent was removed under reduced pressure. A solution of HCl (4 M in 1,4-dioxane, 41.0 mL, 164 mmol) was added in one portion and the reaction was stirred for about 3 h. Et2O (100 mL) was added and the solid was filtered. The solids were combined with the mother liquor and the solvent was removed under reduced pressure. The solid was partially dissolved in EtOAc (650 mL) and washed with aqueous saturated NaHCO3 (150 mL). An emulsion formed and was fitered through Celite® washing with EtOAc. The solid on top of the Celite® layer was product. The solid was scraped off of the Celite® and dissoved in a solution of 10% MeOH in DCM (150 mL). The organic layer was washed with water (2×30 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate (4×150 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 1-((cis)-4-ethylpyrrolidin-3-yl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (5.88 g, 80%) as a brown foam: LC/MS (Table 1, Method a) Rt=1.55 min; MS m/z: 411 (M+H)+.

Workup

  1. additioneach added sequentially in one portion to the solution
  2. customThe solvent was removed under reduced pressure
  3. filtrationthe solid was filtered
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe solid was partially dissolved in EtOAc (650 mL)
  6. washwashed with aqueous saturated NaHCO3 (150 mL)
  7. customAn emulsion formed
  8. washwashing with EtOAc
  9. washThe organic layer was washed with water (2×30 mL)
  10. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate (4×150 mL)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a280e820b39648919cb1b33e1efc78ff
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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