Water → (R)-5-amino-3-((1-(dimethylamino)propan-2-yl)oxy)pyrazine-2-carbonitrile

HRID 1477354Notes

Reaction equation

HRID 1477354 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][C@H:4]([OH:6])[CH3:5].[H-].[Na+].[NH2:10][C:11]1[N:12]=[C:13](Cl)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1.O>O1CCOCC1.C(Cl)Cl>[NH3:2].[NH2:10][C:11]1[N:12]=[C:13]([O:6][C@H:4]([CH3:5])[CH2:3][N:2]([CH3:7])[CH3:1])[C:14]([C:17]#[N:18])=[N:15][CH:16]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 7057913(R)-1-(dimethylamino)propan-2-olHCID 210753925-Amino-3-chloropyrazine-2-carbonitrile

Product 2

HCID 222AmmoniaYield 1%HCID 56926516(R)-5-amino-3-((1-(dimethylamino)propan-2-yl)oxy)pyrazine-2-carbonitrileYield 77.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

(R)-1-(Dimethylamino)propan-2-ol (0.667 g, 6.47 mmol) was added dropwise to a suspension of NaH (60% in oil; 0.388 g, 9.71 mmol) in dioxane (16.2 mL) and stirred for 30 minutes. 5-Amino-3-chloropyrazine-2-carbonitrile (Intermediate I-2) (1.00 g, 6.47 mmol) was added in one portion and the mixture was heated at 90° C. for 14 hours. After cooling, water (200 mL) was added and the solution was extracted with Et2O (4×100 mL), dried over MgSO4, and the volatiles removed under vacuum. Gradient column chromatography eluting with MeOH: 1% NH3 in CH2Cl2, gave (R)-5-amino-3-((1-(dimethylamino)propan-2-yl)oxy)pyrazine-2-carbonitrile (0.558 g, 2.52 mmol, 39% yield) as a yellow solid.

Workup

  1. temperatureAfter cooling
  2. extractionthe solution was extracted with Et2O (4×100 mL)
  3. dry with materialdried over MgSO4
  4. customthe volatiles removed under vacuum
  5. washGradient column chromatography eluting with MeOH

Sources & evidence

ORD record
ord-9fe259f75c474012abcdee9de32d3074
Source dataset
uspto-grants-2016_08
Patent number
US09403797B2

Reaction notes

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