Hydrochloric Acid → HCID 59363794, compound

HRID 2189149Notes

Reaction equation

HRID 2189149 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][CH:22]([CH3:24])[CH3:23])=O)=[CH:6][C:3]=1[C:4]#[N:5].[NH2:26][C:27]([NH2:29])=[O:28].Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1.ClCCl>[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][CH:22]([CH3:24])[CH3:23])[NH:29][C:27](=[O:28])[N:26]=2)=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 1176Urea2×HCID 516892Sodium BicarbonateHCID 59363800HCID 59363800, compound

Product 1

HCID 59363794HCID 59363794, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
115 °C

Procedure

To a sealed vessel were added 2-fluoro-5-(3-(2-isobutoxyphenyl)-3-oxopropanoyl)benzonitrile (5.9 g, 17.4 mmol), urea (10 g) and a solution of 4 N HCl in dioxane (80 mL). The reaction mixture was heated at 115° C. for 4 h then cooled. More urea (10 g) and 4 N HCl in dioxane (50 mL) were added to the vessel and the reaction was again heated to 115° C. for 4 h. Upon cooling, a precipitate formed and the reaction mixture was filtered in vacuo. The filtrate was determined by LC/MS to contain the desired product and was concentrated in vacuo. The concentrated reaction mixture was dissolved in dichloromethane (100 mL) and was neutralized with a solution of saturated sodium bicarbonate and was then partitioned between dichloromethane and water. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo yielding 1.1 g crude 2-fluoro-5-(6-(2-isobutoxyphenyl)-2-oxo-1,2-dihydropyrimidin-4-yl)benzonitrile and was submitted to the next step with no further purification.

Workup

  1. temperaturethen cooled
  2. temperaturethe reaction was again heated to 115° C. for 4 h
  3. temperatureUpon cooling
  4. customa precipitate formed
  5. filtrationthe reaction mixture was filtered in vacuo
  6. concentrationwas concentrated in vacuo
  7. customThe concentrated reaction mixture
  8. customwas then partitioned between dichloromethane and water
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with dichloromethane
  11. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-673a1db59d314effa8569bb8265feed5
Source dataset
uspto-grants-2012_12
Patent number
US08324231B2

Reaction notes

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