Sodium hydride → 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

HRID 1969626Notes

Reaction equation

HRID 1969626 reaction equation
[CH2:1]([CH:3]1[CH:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][CH:5]([OH:28])[CH2:4]1)[CH3:2].[H-].[Na+].Cl[C:32]1[CH:37]=[N:36][C:35]([C:38]#[N:39])=[CH:34][N:33]=1>CN(C=O)C>[CH2:1]([CH:3]1[CH:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:25])[CH3:27])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][CH:5]([O:28][C:32]2[N:33]=[CH:34][C:35]([C:38]#[N:39])=[N:36][CH:37]=2)[CH2:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 122957285-Chloropyrazine-2-carbonitrileHCID 585572033-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol

Product 1

HCID 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-carbonitrileYield 70.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.098 g, 0.24 mmol, prepared using FF from Preparation #KK.1) in DMF (1 mL) was added NaH (0.012 g, 0.29 mmol, 60% dispersion in mineral oil) portionwise. After about 5 min, 2-chloro-5-cyanopyrazine (0.039 g, 0.28 mmol, ArkPharm) was added. The reaction mixture was heated at about 70° C. for about 2 h. After cooling to ambient temperature, ice water (2 mL) was added and the mixture was extracted with DCM (3×5 mL). The organic layers were combined and the solvents were removed under reduced pressure. The residue was purified using silica gel chromatography (12 g) eluting with a gradient of 20-80% EtOAc in DCM to give 5-(3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile (0.085 g, 69%): LC/MS (Table 1, Method b) Rt=2.84 min; MS m/z: 505 (M+H)+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionthe mixture was extracted with DCM (3×5 mL)
  3. customthe solvents were removed under reduced pressure
  4. customThe residue was purified
  5. washeluting with a gradient of 20-80% EtOAc in DCM

Sources & evidence

ORD record
ord-2798fbb27a9147179ade06c635ccca2f
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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