Dimethyl Sulfate → (1H-Pyrrolo[2,3-b]pyridin-3-yl)acetonitrile

HRID 726671Notes

Reaction equation

HRID 726671 reaction equation
COS(OC)(=O)=O.CN(C)C[N:11]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[CH:13]=[CH:12]1.[C-]#[N:22].[K+].[CH2:24]1[CH2:28]OCC1>>[NH:11]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[C:13]([CH2:28][C:24]#[N:22])=[CH:12]1

Participants

5

Reactant 4

HCID 6497Dimethyl SulfateHCID 8028Tetrahydrofuran2×HCID 9032Potassium CyanideHCID 70208500HCID 70208500, compound

Product 1

HCID 21911990(1H-Pyrrolo[2,3-b]pyridin-3-yl)acetonitrileYield 56%

Conditions

Temperature
80 °C

Procedure

A solution of dimethylsulfate (32.7 g; 0.25 mol) in THF (50 mL) was added dropwise while stirring to the solution of dimethyl-(1H-pyrrolo[2,3-b]-pyridinyl-methyl)-amine (42 g; 0.24 mol) in THF (800 mL). After the addition was complete, the mixture was heated at 80° C. for 10 minutes then cooled to ambient temperature. The solvent was decanted and the residual gum was triturated with acetone/methanol (1:1 mixture) while warming. The solid formed was collected by filtration. The solid was then dissolved in water (500 mL). Potassium cyanide (22 g; 0.32 mol) was added. The mixture was stirred at ambient temperature for 15 minutes, heated to reflux for 30 minutes, then cooled to ambient temperature. After 2 hours, the solid was collected by filtration and washed with water then dried to give 21 g (56% yield) of the title compound as an off-white solid, m.p. 141°-142° C. which was used for the reaction described in step 3.

Workup

  1. additionAfter the addition
  2. temperaturethen cooled to ambient temperature
  3. customThe solvent was decanted
  4. customthe residual gum was triturated with acetone/methanol (1:1 mixture)
  5. temperaturewhile warming
  6. customThe solid formed
  7. filtrationwas collected by filtration
  8. dissolutionThe solid was then dissolved in water (500 mL)
  9. temperatureheated
  10. temperatureto reflux for 30 minutes
  11. temperaturecooled to ambient temperature
  12. waitAfter 2 hours
  13. filtrationthe solid was collected by filtration
  14. washwashed with water
  15. customthen dried

Sources & evidence

ORD record
ord-b8b4b2cd8db949fab19d7db90fe785e1
Source dataset
uspto-grants-1998_01
Patent number
US05710164

Reaction notes

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