N,N,N',N'-Tetramethylethylenediamine → 5-(5-Cyanopentyl)-imidazo[1,5-a]pyridine

HRID 326124Notes

Reaction equation

HRID 326124 reaction equation
[CH3:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.CN(C)CCN(C)C.C([Li])CCC.Br[CH2:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30]>O1CCCC1.CCCCCC>[C:29]([CH2:28][CH2:27][CH2:26][CH2:25][CH2:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1)#[N:30]

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 794355-BromopentanenitrileHCID 122109855-Methylimidazo(1,5-a)pyridineHCID 178418339Butyllithium

Product 1

HCID 155864755-(5-Cyanopentyl)-imidazo[1,5-a]pyridine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 5-methylimidazo[1,5-a]pyridine (4.0 g) and tetramethylethylene diamine (4.9 g) in 100 ml of tetrahydrofuran is cooled to 0° under nitrogen and 26.5 ml of 1.6 N n-butyllithium in hexane is added dropwise maintaining the temperature below 2°. After 30 minutes this solution is transferred under nitrogen over 45 minutes to an ice-cold solution of 5-bromovaleronitrile (4.86 g) in 80 ml of tetrahydrofuran. After 15 minutes the solvent is evaporated and the residue is partitioned between water and ethyl acetate. The organic phase is reextracted with 2 N hydrochloric acid (3×15 ml). Basification of the aqueous phase to pH=10 with 50% sodium hydroxide, extraction with ethyl acetate (2×75 ml), drying over magnesium sulfate, evaporation and chromatography (SiO2, ethyl acetate) yields 5-(5-cyanopentyl)-imidazo[1,5-a]pyridine.

Workup

  1. temperaturemaintaining the temperature below 2°
  2. customAfter 15 minutes the solvent is evaporated
  3. customthe residue is partitioned between water and ethyl acetate
  4. extractionBasification of the aqueous phase to pH=10 with 50% sodium hydroxide, extraction with ethyl acetate (2×75 ml)
  5. dry with materialdrying over magnesium sulfate, evaporation and chromatography (SiO2, ethyl acetate)

Sources & evidence

ORD record
ord-b4e45a0ddaa94161b6cbf00361d7a160
Source dataset
uspto-grants-1984_04
Patent number
US04444775

Reaction notes

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