Potassium Cyanide → 2-Ethyl-3-methyl-4-oxo-3,4-dihydro-6-quinazolinecarbonitrile

HRID 238203Notes

Reaction equation

HRID 238203 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH3:13])[N:6]([CH3:14])[C:5]2=[O:15].[C-:16]#[N:17].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH2:12]([C:7]1[N:6]([CH3:14])[C:5](=[O:15])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:16]#[N:17])[CH:3]=2)[N:8]=1)[CH3:13]

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 599932916-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-one

Product 1

HCID 450950792-Ethyl-3-methyl-4-oxo-3,4-dihydro-6-quinazolinecarbonitrileYield 46.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

The substrate of 6-bromo-2-ethyl-3-methyl-3H-quinazolin-4-one (50.0 mg, 0.189 mmol), KCN (23.1 mg, 0.37 mmol), Pd (PPh3)4 (10.0 mg, 0.0094 mmol), and CuI (3.6 mg, 0.019 mmol) was added to a flask, which was flushed with N2. The solvent acetonitrile (2 ml) was added via syringe. The resulting mixture was irradiated at 170° C. for 2 hours in the SmithSynthesizer Microwave Reactor (Personal Chemistry) with vigorous agitation by a magnetic stirrer. The mixture was cooled to room temperature, diluted with ethyl acetate (5 ml), and then filtered through Celite. The filtrate was washed with water and brine, dried over anhydrous MgSO4, and concentrated by rotary evaporation. Purification was accomplished by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase). The product was collected and dried under reduced pressure to give 2-Ethyl-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrile (Yield 16.8 mg, 46.2%). 1H NMR (400 MHz, CDCl3): δ 1.35 (t, 3H, J=7.30 Hz), 2.85 (q, 2H, J=14.62, 7.30 Hz), 3.54 (s, 3H), 7.68 (d, 1H, J=8.58 Hz), 7.83 (dd, 1H, J=8.58, 2.02 Hz), 8.51 (d, 1H, J=2.02 Hz). MS/M/Z calc. 213.2, Found (ESI); 214.0 (M+1)+. Retention time 2.13 minutes.

Workup

  1. customwhich was flushed with N2
  2. additionThe solvent acetonitrile (2 ml) was added via syringe
  3. customThe resulting mixture was irradiated at 170° C. for 2 hours in the SmithSynthesizer Microwave Reactor (Personal Chemistry) with vigorous agitation by a magnetic stirrer
  4. additiondiluted with ethyl acetate (5 ml)
  5. filtrationfiltered through Celite
  6. washThe filtrate was washed with water and brine
  7. dry with materialdried over anhydrous MgSO4
  8. concentrationconcentrated by rotary evaporation
  9. customPurification
  10. customThe product was collected
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-d202fad797794946a3f24ba2c0730c03
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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