Sodium hydride → HCID 20130605, compound

HRID 845995Notes

Reaction equation

HRID 845995 reaction equation
[H-].[Na+].[NH2:3][CH:4]=[C:5]([C:8]#[N:9])[C:6]#[N:7].[H][H].[Cl:12][C:13]1[CH:24]=[C:23]([F:25])[C:22]([N:26]=[C:27]=[O:28])=[CH:21][C:14]=1[C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16]>CN(C)C=O.C(O)(=O)C.O>[NH2:7][C:6]1[N:26]([C:22]2[C:23]([F:25])=[CH:24][C:13]([Cl:12])=[C:14]([CH:21]=2)[C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[C:27](=[O:28])[N:9]=[CH:8][C:5]=1[C:4]#[N:3]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 69595(Aminomethylene)malononitrileHCID 13519895Isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoateHCID 178418361HCID 178418361, compound

Product 1

HCID 20130605HCID 20130605, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

To 0.71 g of a 55% sodium hydride dispersion in 25 ml of dimethylformamide are introduced 1.52 g of 3-amino-2-cyanoacrylonitril, and the mixture is stirred for 30 minutes at 30° C. After completion of the hydrogen evolution the mixture is treated with 4.20 g of isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoate, during which the temperature rises to 30° C. The reaction mixture is then stirred for a further 2 hours at room temperature and poured into water, and the aqueous mixture is acidified with acetic acid and extracted twice with 100 ml of ethyl acetate. The organic phase is washed with water, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is dissolved in 50 ml of methylene chloride and crystallization induced by addition of diethyl ether and cooling to 0° C. Isopropyl 5-[6-amino-5-cyano-2-oxo-1(2H)-pyrimidinyl]-2-chloro-4-fluorobenzoate, m.p. 212°-213° C., is obtained.

Workup

  1. customrises to 30° C
  2. stirringThe reaction mixture is then stirred for a further 2 hours at room temperature
  3. extractionextracted twice with 100 ml of ethyl acetate
  4. washThe organic phase is washed with water
  5. dry with materialdried over anhydrous sodium sulphate
  6. customevaporated to dryness under reduced pressure
  7. dissolutionThe residue is dissolved in 50 ml of methylene chloride
  8. customcrystallization
  9. additioninduced by addition of diethyl ether
  10. temperaturecooling to 0° C

Sources & evidence

ORD record
ord-129987397f9f403c816cb304a182762e
Source dataset
uspto-grants-1988_07
Patent number
US04760163

Reaction notes

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