Water → 5-(-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile

HRID 1969628Notes

Reaction equation

HRID 1969628 reaction equation
[CH2:1]([CH:3]1[CH:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17](COCC[Si](C)(C)C)[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][CH:5]([O:28][C:29]2[N:30]=[CH:31][C:32]([C:35]#[N:36])=[N:33][CH:34]=2)[CH2:4]1)[CH3:2].C(O)(C(F)(F)F)=O.[OH-].[NH4+].O>C(Cl)Cl>[CH2:1]([CH:3]1[CH:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][CH:5]([O:28][C:29]2[N:30]=[CH:31][C:32]([C:35]#[N:36])=[N:33][CH:34]=2)[CH2:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 585574165-(3-ethyl-4-(6-((2-(trimethyl silyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile

Product 1

HCID 1360095685-(-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrileYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 5-(3-ethyl-4-(6-((2-(trimethyl silyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile (0.097 g, 0.19 mmol, Preparation #11.1) in DCM (2.5 mL) was added TFA (0.7 mL, 10 mmol). The reaction mixture was stirred at ambient temperature for about 1.5 h. The solvents were removed under reduced pressure and the residue was dissolved in 1,4-dioxane (1.3 mL). Ammonium hydroxide (28-30% aqueous ammonia, 2.5 mL, 24 mmol) was added and the reaction mixture was heated at about 60° C. for about 30 min then cooled to ambient temperature. Water (4 mL) was added and the precipitate was collected by filtration to give 5-(-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile (0.0628 g, 87%): LC/MS (Table 1, Method b) Rt=1.99 min; MS m/z: 375 (M+H)+.

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe residue was dissolved in 1,4-dioxane (1.3 mL)
  3. temperaturethe reaction mixture was heated at about 60° C. for about 30 min
  4. temperaturethen cooled to ambient temperature
  5. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-d2e1799da4ce4c19b0bc5bf0685317eb
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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