Hydrochloric Acid → (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride

HRID 1854409Notes

Reaction equation

HRID 1854409 reaction equation
[N:1]([CH2:4][C:5]1[N:6]=[C:7]2[CH:13]=[CH:12][N:11]([S:14]([C:17]3[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[C:8]2=[N:9][CH:10]=1)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[ClH:43].CO>C1COCC1.O>[ClH:43].[S:14]([N:11]1[C:8]2=[N:9][CH:10]=[C:5]([CH2:4][NH2:1])[N:6]=[C:7]2[CH:13]=[CH:12]1)([C:17]1[CH:18]=[CH:19][C:20]([CH3:21])=[CH:22][CH:23]=1)(=[O:15])=[O:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11776TriphenylphosphineHCID 866371832-(azidomethyl)-5-tosyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 67068339(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochlorideYield 95.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 2-(azidomethyl)-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (32.6 g, 99.0 mmol) in THF (100 mL) and water (50 mL) was added Ph3P (31.3 g, 119 mmol). The reaction mixture was heated to about 45° C. for about 16 h. The mixture was allowed to cool to ambient temperature followed by removal of THF under reduced pressure. The mixture was partitioned between EtOAc (500 mL) and brine (250 mL), dried over anhydrous Na2SO4, and filtered. The filtrate was diluted with EtOAc to IL total volume. To the rapidly stirring solution was added drop-wise 4N HCl (4N in dioxane, 30.0 mL, 120 mmol) resulting in formation of a tan precipitate. MeOH (10 mL) was added and the mixture was filtered after about 15 min. The precipitate was triturated with Et2O (1000 mL) for about 10 min, filtered, and washed with Et2O (500 mL) to provide (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (32.0 g, 90%) as a tan solid: LC/MS (Table 2, Method a) Rt=1.44 min; MS m/z: 303 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. customfollowed by removal of THF under reduced pressure
  3. customThe mixture was partitioned between EtOAc (500 mL) and brine (250 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. additionThe filtrate was diluted with EtOAc to IL total volume
  7. customresulting in formation of a tan precipitate
  8. filtrationthe mixture was filtered after about 15 min
  9. customThe precipitate was triturated with Et2O (1000 mL) for about 10 min
  10. filtrationfiltered
  11. washwashed with Et2O (500 mL)

Sources & evidence

ORD record
ord-19804d38cec24ac68cbf735f3f4690c6
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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