Sodium hydride → (E)-3-[1-Butyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidin-6-yl]prop-2-enal

HRID 1461348Notes

Reaction equation

HRID 1461348 reaction equation
C1(NC=CP(=O)(OCC)OCC)CCCCC1.[H-].[Na+].[CH2:20]([N:24]1[C:29]2[N:30]=[C:31]([CH:43]([CH3:45])[CH3:44])[C:32]([CH:41]=O)=[C:33]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[C:28]=2[C:27](=[O:46])[NH:26][C:25]1=[O:47])[CH2:21][CH2:22][CH3:23].O.O.[C:50]([OH:55])(=O)[C:51](O)=O>O1CCCC1.O.C1(C)C=CC=CC=1>[CH2:20]([N:24]1[C:29]2[N:30]=[C:31]([CH:43]([CH3:44])[CH3:45])[C:32](/[CH:41]=[CH:51]/[CH:50]=[O:55])=[C:33]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[C:28]=2[C:27](=[O:46])[NH:26][C:25]1=[O:47])[CH2:21][CH2:22][CH3:23]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 61373Oxalic acid dihydrateHCID 89268Diethyl [2-(cyclohexylamino)vinyl]phosphonateHCID 198796971-Butyl-5-(4-fluorophenyl)-6-formyl-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidine

Product 1

HCID 19980383(E)-3-[1-Butyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidin-6-yl]prop-2-enal

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 1.15 g (4.4 mol) of diethyl 2-(cyclohexylamino)-vinyl-phosphonate in 15 ml of tetrahydrofuran is added dropwise in the course of 10 min at 0°-5° C. under argon to a suspension of 0.25 g (8.4 mmol) of 80% strength sodium hydride in 15 ml of anhydrous tetrahydrofuran. The mixture is stirred at 0° C. for 15 min, a solution of 1.5 g (4 mmol) of the compound from Example 5 in 15 ml of tetrahydrofuran is added dropwise at 0° C. in the course of 20 min, and the mixture is stirred at room temperature for 1 h and under reflux for 20 min. The mixture is cooled, 50 ml of water are added cautiously, the mixture is extracted twice with ethyl acetate, and the combined organic phases are washed with sodium chloride solution and concentrated in vacuo. The residue is heated under reflux with a mixture of 25 ml of toluene, 35 ml of water and 2.6 g (36 mmol) of oxalic acid dihydrate for 1 h. The phases are separated, the aqueous phase is extracted with ethyl acetate, and the combined organic phases are washed with sodium chloride solution, dried over magnesium sulphate and concentrated in vacuo. The residue is crystallized from ether/petroleum ether.

Workup

  1. stirringthe mixture is stirred at room temperature for 1 h
  2. temperatureunder reflux for 20 min
  3. temperatureThe mixture is cooled
  4. extractionthe mixture is extracted twice with ethyl acetate
  5. washthe combined organic phases are washed with sodium chloride solution
  6. concentrationconcentrated in vacuo
  7. temperatureThe residue is heated
  8. customThe phases are separated
  9. extractionthe aqueous phase is extracted with ethyl acetate
  10. washthe combined organic phases are washed with sodium chloride solution
  11. dry with materialdried over magnesium sulphate
  12. concentrationconcentrated in vacuo
  13. customThe residue is crystallized from ether/petroleum ether

Sources & evidence

ORD record
ord-fd8be0825c864541abb1fdf8dcc366f3
Source dataset
uspto-grants-1991_12
Patent number
US05075311

Reaction notes

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