2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → Methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-oxopropyl)benzoate

HRID 326913Notes

Reaction equation

HRID 326913 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([C:20](=[O:22])[CH3:21])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1.I[CH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28].CN1CCCN(C)C1=O.C([N-]C(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([C:20](=[O:22])[CH2:21][CH2:24][C:25]4[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=4[C:27]([O:29][CH3:30])=[O:28])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 18504496Methyl 2-(iodomethyl)benzoateHCID 542214971-(3-(2-(7-Chloro-2-quinolinyl)ethenyl)phenyl)ethanone

Product 1

HCID 53394881Methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-oxopropyl)benzoateYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

To a suspension of the ketone (10.0 g, 32.6 mmol) of Step 1 and the iodide (2.7 g, 47.7 mmol) of Step 2 in THF was added 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (4 mL). The ketone was dissolved by heating and the resulting solution was cooled to -60° C. A solution of 0.35M lithium diisopropylamide (89.7 mL, 30.9 mmol) was then added dropwise. After the addition was completed, the dry ice bath was removed and the reaction was allowed to warm to +10° C. The reaction was quenched by the addition of 25% aq. NH4OAc and the desired product was extracted with EtOAc, dried over Na2SO4 and evaporated under reduced pressure. The resulting mixture was purified by flash chromatography (toluene to 5% EtOAc in toluene) to yield 8 g (55%) of the title product.

Workup

  1. temperatureby heating
  2. additionAfter the addition
  3. customthe dry ice bath was removed
  4. temperatureto warm to +10° C
  5. customThe reaction was quenched by the addition of 25% aq. NH4OAc
  6. extractionthe desired product was extracted with EtOAc
  7. dry with materialdried over Na2SO4
  8. customevaporated under reduced pressure
  9. customThe resulting mixture was purified by flash chromatography (toluene to 5% EtOAc in toluene)

Sources & evidence

ORD record
ord-89492c0b284e493eb72bf7aa6e3ec759
Source dataset
uspto-grants-1993_12
Patent number
US05270324

Reaction notes

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