Sodium hydride → 3-[2-(4-Amino-phenyl)-pyrimidin-4-yl]-benzonitrile

HRID 628822Notes

Reaction equation

HRID 628822 reaction equation
[H-].[Na+].Cl.Cl.[NH2:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([NH2:12])=[NH:11])=[CH:8][CH:7]=1.CN(C)[CH:17]=[CH:18][C:19]([C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[C:24]#[N:25])=O>C(O)C>[NH2:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]2[N:12]=[C:19]([C:21]3[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=3)[C:24]#[N:25])[CH:18]=[CH:17][N:11]=2)=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 756264-Amidinoaniline dihydrochlorideHCID 28062053-[3-(Dimethylamino)prop-2-enoyl]benzonitrile

Product 1

HCID 115725913-[2-(4-Amino-phenyl)-pyrimidin-4-yl]-benzonitrileYield 56%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

Part A. A flask containing absolute ethanol (10 mL) is cooled to 0° C., and sodium hydride (42 mg, 60% w/w with mineral oil, 1.05 mmol) is added. After stirring for 0.5 h., the solution is treated with 4-aminobenzamidine dihydrochloride (104 mg, 0.50 mmol) and the mixture is allowed to stir for 5 min. Then, 3-(3-dimethylamino-acryloyl)-benzonitrile (100 mg, 0.50 mmol) is added, and the resulting mixture is heated to reflux for 3 h. then cooled to ambient temperature and stirred for 60 h. The mixture is evaporated, and the resulting mixture is triturated with diethyl ether and filtered. The filtrate is evaporated to afford a yellow oil, which is separated by column chromatography (1:1 ethyl acetate-hexane) to afford the product, 3-[2-(4-amino-phenyl)-pyrimidin-4-yl]-benzonitrile (76 mg, 56%). 1H NMR (300 MHz, CDCl3): δ 8.75 (1H, d, J=6 Hz), 8.49 (1H, t, J=2 Hz), 8.37-8.31 (3H, m), 7.75 (1H, dt, J=8, 2 Hz), 7.59 (1H, t, J=8 Hz), 7.40 (1H, d, J=6 Hz), 6.76 (2H, d, J=9 Hz), 4.03 (2H, br s). 13C NMR (CDCl3): δ 164.6, 160.8, 158.0, 149.2, 138.2, 133.6, 131.0, 130.7, 129.8 (2C), 129.5, 127.2, 118.5, 114.5 (2C), 113.0, 112.9. MS (ES+): m/e 274 (20), 273 (100).

Workup

  1. stirringto stir for 5 min
  2. temperaturethe resulting mixture is heated
  3. temperatureto reflux for 3 h.
  4. temperaturethen cooled to ambient temperature
  5. stirringstirred for 60 h
  6. customThe mixture is evaporated
  7. customthe resulting mixture is triturated with diethyl ether
  8. filtrationfiltered
  9. customThe filtrate is evaporated
  10. customto afford a yellow oil, which
  11. customis separated by column chromatography (1:1 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-6eaaac6616ae430da83da752a1b9ff64
Source dataset
uspto-grants-2016_04
Patent number
US09315467B2

Reaction notes

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