Dimethylformamide → HCID 86094278, compound

HRID 2099579Notes

Reaction equation

HRID 2099579 reaction equation
[C:1]([CH:3](N1CCOCC1)[C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[C:7]#[N:8])#[N:2].[H-].[Na+].[Cl:20][C:21]1N=C(Cl)[CH:24]=[CH:23][N:22]=1.CN(C=[O:32])C>>[Cl:20][C:21]1[N:2]=[C:1]([C:3]([C:4]2[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=2)[C:7]#[N:8])=[O:32])[CH:24]=[CH:23][N:22]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydride2×HCID 775312,4-DichloropyrimidineHCID 14493457HCID 14493457, compound

Product 1

HCID 86094278HCID 86094278, compoundYield 56%

Conditions

Temperature
0 °C

Procedure

3-[cyano(morpholin-4-yl)methyl]benzonitrile (5 g, 22.0 mmol) was dissolved in 175 mL dry DMF and cooled to 0° C. Add sodium hydride (Aldrich, 0.58 g, 24.2 mmol) in one portion and stir for 25 minutes at 0° C. Add 2,4-dichloropyrimidine (Aldrich, 9.83 g, 66.0 mmol) in one portion. After 10 minutes, additional sodium hydride (1.16 g, 48.4 mmol) was added in one portion and the bath allowed to warm to room temperature. After 15 h, the reaction was quenched with water and partitioned between ethyl acetate and saturated sodium bicarbonate. The aqueous portion was extracted with ethyl acetate (2×). The combined organic portion was dried over sodium sulfate and concentrated in vacuo. The crude material was taken up in 175 mL of 70% (v/v) acetic acid/water and refluxed for 45 min. The reaction mixture was cooled to room temperature, diluted with water, then extracted with ethyl acetate (2×). The combined organic portion was washed with saturated sodium bicarbonate (1×), dried over sodium sulfate, and concentrated in vacuo. The crude material was purified by silica gel chromatography (3-35% ethyl acetate in hexanes) and the product-containing fractions concentrated in vacuo to give 3-[(2-chloropyrimidin-4-yl)carbonyl]benzonitrile (3.0 g, 56%). LRMS m/z (M+H) Calcd: 244.7, found 244.0.

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 15 h
  3. customthe reaction was quenched with water
  4. custompartitioned between ethyl acetate and saturated sodium bicarbonate
  5. extractionThe aqueous portion was extracted with ethyl acetate (2×)
  6. dry with materialThe combined organic portion was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. temperaturerefluxed for 45 min
  9. temperatureThe reaction mixture was cooled to room temperature
  10. additiondiluted with water
  11. extractionextracted with ethyl acetate (2×)
  12. washThe combined organic portion was washed with saturated sodium bicarbonate (1×)
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated in vacuo
  15. customThe crude material was purified by silica gel chromatography (3-35% ethyl acetate in hexanes)
  16. concentrationthe product-containing fractions concentrated in vacuo

Sources & evidence

ORD record
ord-f26ad749621b4bfda711d49434ceedbd
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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