Potassium phthalamide → 2-((5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione

HRID 521875Notes

Reaction equation

HRID 521875 reaction equation
CS(O[CH2:6][C:7]1([CH2:22][CH3:23])[CH2:12][O:11][CH:10]([C:13]2[N:17]([CH3:18])[N:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[O:9][CH2:8]1)(=O)=O.[C:24]([NH2:35])(=[O:34])[C:25]1[C:26](=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:27](N)=[O:28].[K]>CS(C)=O.CCOC(C)=O.O>[CH2:22]([C:7]1([CH2:6][N:35]2[C:24](=[O:34])[C:25]3[C:26](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:27]2=[O:28])[CH2:12][O:11][CH:10]([C:13]2[N:17]([CH3:18])[N:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[O:9][CH2:8]1)[CH3:23]

Participants

6

Reactant 2

HCID 53445390Potassium phthalamideHCID 86713822(5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl methanesulfonate2×

Product 1

HCID 867138232-((5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dioneYield 35.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of (5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl methanesulfonate (816 mg, 2.25 mmol, intermediate 74) in dry DMSO (10 mL) was added potassium phthalamide (2.1 g, 11.3 mmol) in a single portion. The reaction mixture was heated at 180° C. for 5 hr, cooled to room temperature and diluted with EtOAc (50 mL) and water (30 mL). The organic layer was washed with water (3×30 mL), 2 N NaOH (2×20 mL) and water (20 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-((5-ethyl-2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione as a colourless solid (317 mg, 35%). 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.93-7.88 (m, 2H), 7.82-7.76 (m, 2H), 6.31 (s, 1H), 4.14 (s, 3H), 4.06 (d, J=11.8 Hz, 2H), 3.85 (d, J=11.8 Hz, 2H), 3.51 (s, 2H), 1.92 (q, J=7.6 Hz, 2H), 1.14 (t, J=7.6 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic layer was washed with water (3×30 mL), 2 N NaOH (2×20 mL) and water (20 mL)
  3. customseparated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-12d02336d7024011896b7b2db57bdbd8
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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