Phthalimide → 2-(1-(2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)ethyl)-1H-isoindole-1,3(2H)-dione

HRID 473400Notes

Reaction equation

HRID 473400 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH:18](O)[CH3:19])=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:40]1(=[O:50])[NH:44][C:43](=[O:45])[C:42]2=[CH:46][CH:47]=[CH:48][CH:49]=[C:41]12.O1CCCC1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH:18]([N:44]3[C:40](=[O:50])[C:41]4[C:42](=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:43]3=[O:45])[CH3:19])=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6809PhthalimideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 583186421-(2-(3-Fluorophenyl)-1,5-naphthyridin-3-yl)ethanol

Product 1

HCID 583186412-(1-(2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)ethyl)-1H-isoindole-1,3(2H)-dione

Conditions

Temperature
0 °C

Procedure

A solution of 1-(2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)ethanol (0.0260 g, 0.0969 mmol), triphenylphosphine (0.0508 g, 0.194 mmol), phthalimide (0.0285 g, 0.194 mmol), and tetrahydrofuran (1.29 mL, 0.0969 mmol) was stirred at room temperature for 5 min to dissolve all reactants. The mixture was then cooled to 0° C. and to the cooled homogenous mixture was added dropwise diisopropyl azodicarboxylate (0.0382 mL, 0.194 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 1.5 h. After 1.5 h, the mixture was concentrated under reduced pressure and partitioned between EtOAc (50 mL) and brine (50 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography on a 12 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 11 min and 100% isocratic of EtOAc for 25 min as eluent to give 2-(1-(2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)ethyl)-1H-isoindole-1,3(2H)-dione as a white solid: LC-MS (ESI) m/z 397.9 [M+H]+.

Workup

  1. dissolutionto dissolve all reactants
  2. temperatureto warm to room temperature
  3. waitAfter 1.5 h
  4. concentrationthe mixture was concentrated under reduced pressure
  5. custompartitioned between EtOAc (50 mL) and brine (50 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography on a 12 g of Redi-Sep™ column
  10. customover 11 min

Sources & evidence

ORD record
ord-11ce75a0f85a411bb6e5ad086381cce2
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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