Cesium carbonate → HCID 57422411, compound

HRID 658657Notes

Reaction equation

HRID 658657 reaction equation
[NH:1]1[CH:5]=[C:4]([N:6]2[C:14](=[O:15])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]2=[O:16])[CH:3]=[N:2]1.Cl[CH2:18][C:19]1[C:20]([CH3:25])=[N:21][O:22][C:23]=1[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH3:25][C:20]1[C:19]([CH2:18][N:1]2[CH:5]=[C:4]([N:6]3[C:14](=[O:15])[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[C:7]3=[O:16])[CH:3]=[N:2]2)=[C:23]([CH3:24])[O:22][N:21]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-HCID 2755705HCID 2755705, compound

Product 1

HCID 57422411HCID 57422411, compoundYield 39.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(1H-pyrazol-4-yl)isoindoline-1,3-dione (example 9-1a) (1.5 g, 7 mmol), 4-(chloromethyl)-3,5-dimethylisoxazole (1.5 g, 10 mmol), and cesium carbonate (3.3 g, 10 mmol) were stirred in DMF (20 mL) at 80° C. for 3 hours. The reaction was cooled, diluted with H2O (150 mL), and extracted with ethyl acetate (3×, 75 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated on the rotovap. The solid product was triturated with ethyl acetate/hexanes (1/9) and re-crystallized from refluxing absolute ethanol (30 mL) to afford 2-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)isoindoline-1,3-dione (900 mg, 38%) as a bright, light yellow solid. 1H NMR (DMSO-d6, 400 MHz) 1.36 (d, 3H, δ J2.16 (s, 3H), 2.41 (s, 3H),=7.2 Hz), 5.22 (s, 2H), 7.81 (s, 1H), 7.91-7.83 (m, 4H), 8.21 (s, 1H). MS M+H calculated 323.11; found 323.1. Melting point: 170-171° C. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.18 μM.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with ethyl acetate (3×, 75 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated on the rotovap
  6. customThe solid product was triturated with ethyl acetate/hexanes (1/9)
  7. customre-crystallized
  8. temperaturefrom refluxing absolute ethanol (30 mL)

Sources & evidence

ORD record
ord-221ab24cfca64129b668f6708330fc9a
Source dataset
uspto-grants-2011_12
Patent number
US08076491B2

Reaction notes

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