Potassium Iodide → HCID 19801313, compound

HRID 1646742Notes

Reaction equation

HRID 1646742 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH:5]1[C:20](=[O:21])[C:9]2[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])=[N:11][O:12][C:8]=2[CH2:7][CH2:6]1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C.[N:37]1[CH:42]=[CH:41][CH:40]=[N:39][C:38]=1[N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.[I-].[K+]>CN(C=O)C>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:10]1[C:9]2[C:20](=[O:21])[CH:5]([CH2:4][CH2:3][CH2:2][N:46]3[CH2:47][CH2:48][N:43]([C:38]4[N:37]=[CH:42][CH:41]=[CH:40][N:39]=4)[CH2:44][CH2:45]3)[CH2:6][CH2:7][C:8]=2[O:12][N:11]=1

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 887471-(2-Pyrimidinyl)piperazineHCID 19786560HCID 19786560, compound

Product 1

HCID 19801313HCID 19801313, compoundYield 38.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution consisting of 5-(3-chloropropyl)-3-(2-fluorophenyl)-6,7-dihydro-1,2-benzisoxazol-4(5H)-one (7.3 g) and DMF (100 ml) was added anhydrous potassium carbonate (1.6 g), diisopropylethyl amine (6.2 ml), 1-(2-pyrimidyl)piperazine (5.8 g) and potassium iodide (0.4 g) at room temperature with stirring. The flask was flushed with nitrogen and warmed to 80° C. for 16 hours. Upon cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted 3 times with ethyl acetate. The combined organic layers were washed with water twice, then brine and dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 2% triethylamine/ether) afforded 4.0 g of 6,7-dihydro-3-(2-fluorophenyl)-5-[3-(4-(2-pyrimidyl)-1-piperazinyl)-propyl]-1,2-benzisoxazol-4(5H)-one as an oil which solidified upon standing. Recrystallization with ether gave the product as a solid, m.p. 115°-117° C.

Workup

  1. customThe flask was flushed with nitrogen
  2. temperatureUpon cooling to room temperature
  3. additionwater and ethyl acetate were added to the reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted 3 times with ethyl acetate
  6. washThe combined organic layers were washed with water twice
  7. dry with materialbrine and dried (MgSO4)
  8. filtrationFiltration and concentration
  9. customgave the crude product
  10. customPurification via flash column chromatography (silica gel, 2% triethylamine/ether)

Sources & evidence

ORD record
ord-512ed13f71d04be499d55a1339b6f60c
Source dataset
uspto-grants-1993_01
Patent number
US05180834

Reaction notes

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