2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → HCID 59739622, compound

HRID 1192940Notes

Reaction equation

HRID 1192940 reaction equation
CN1CCCN(C)C1=O.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1[CH2:18][S:19]([C:22]1[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][N:23]=1)(=[O:21])=[O:20].C([Li])CCC.[I:34]N1C(=O)CCC1=O>C1COCC1>[F:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[C:12]=1[CH:18]([I:34])[S:19]([C:22]1[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][N:23]=1)(=[O:20])=[O:21]

Participants

6

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 120273N-IodosuccinimideHCID 11571391HCID 11571391, compoundHCID 178418339Butyllithium

Product 1

HCID 59739622HCID 59739622, compoundYield 38.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU) (0.10 ml, 0.83 mmol) and 3-(2,6-difluoro-phenylmethanesulfonyl)-5,5-dimethyl-4,5-dihydro-isoxazole (0.20 g, 0.69 mmol) were dissolved under nitrogen in THF (7 ml) and cooled to −78° C. n-Butyl lithium (2.5M in hexane) (0.33 ml, 0.83 mmol) was added dropwise. After 30 min at −78° C., N-iodosuccinimide (NIS) (187 mg, 0.83 mmol) was added. The mixture was stirred for 1 hour and allowed to warm slowly to room temperature. The reaction was quenched by addition of aqueous ammonium chloride solution. Extraction was carried out several times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by chromatography on silica gel (eluent: ethyl acetate/hexane) and recrystallised from isopropyl alcohol to give the product (Compound No. 1.25 of Table 27) as a white solid (110 mg, 38% yield).

Workup

  1. additionwas added dropwise
  2. customThe reaction was quenched by addition of aqueous ammonium chloride solution
  3. extractionExtraction
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography on silica gel (eluent: ethyl acetate/hexane)
  7. customrecrystallised from isopropyl alcohol

Sources & evidence

ORD record
ord-4acf19d3940d40e1a36949ca430eb2ac
Source dataset
uspto-grants-2014_03
Patent number
US08680290B2

Reaction notes

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