Sodium Hydroxide → 5-((1S,3R)-3-(6H-Pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino) pyrazine-2-carbonitrile

HRID 2204591Notes

Reaction equation

HRID 2204591 reaction equation
S([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[CH2:27][CH2:26][C@H:25]([NH:28][C:29]5[N:30]=[CH:31][C:32]([C:35]#[N:36])=[N:33][CH:34]=5)[CH2:24]4)=[N:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+]>O1CCOCC1.O.CCO>[C:20]1([C@@H:23]2[CH2:27][CH2:26][C@H:25]([NH:28][C:29]3[N:30]=[CH:31][C:32]([C:35]#[N:36])=[N:33][CH:34]=3)[CH2:24]2)[N:19]2[C:14]3[CH:13]=[CH:12][NH:11][C:15]=3[N:16]=[CH:17][C:18]2=[N:22][N:21]=1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 580101665-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl-amino)pyrazine-2-carbonitrile

Product 1

HCID 1361988455-((1S,3R)-3-(6H-Pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino) pyrazine-2-carbonitrileYield 67.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)pyrazine-2-carbonitrile (0.426 g, 0.853 mmol) and aqueous NaOH (1 N, 1.71 mL, 1.71 mmol) in 1,4-dioxane (4.4 mL) was heated at about 60° C. for about 80 min. The mixture was cooled to ambient temperature and diluted with water (40 mL). A solid precipitated and was collected by vacuum filtration and washed with water to give an off-white solid. The material was dissolved in hot EtOH and allowed to cool to ambient temperature. The precipitate was collected by filtration and dried under vacuum to give an off-white solid that was dried in a vacuum oven at about 70° C. to give an off-white solid (0.199 g). The material was taken up in EtOAc (10 mL) and heated at about 70° C. for about 1.5 h. The solid was collected by vacuum filtration, while rinsing with EtOAc. This material was dried under vacuum to give 54(1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)pyrazine-2-carbonitrile (0.19 g, 64%) as an off-white solid: LC/MS (Table 2, Method a) Rt=1.55 min; MS m/z: 346 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customA solid precipitated
  3. filtrationwas collected by vacuum filtration
  4. washwashed with water
  5. customto give an off-white solid
  6. temperatureto cool to ambient temperature
  7. filtrationThe precipitate was collected by filtration
  8. customdried under vacuum
  9. customto give an off-white solid
  10. customthat was dried in a vacuum oven at about 70° C.

Sources & evidence

ORD record
ord-86b5494e468140a0ad5ef5165d717c4d
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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