Phthalimide → (+/-)-2-((1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]hept-6-yl)-1H-isoindole-1,3(2H)-dione

HRID 2233003Notes

Reaction equation

HRID 2233003 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:20][C@H:19]3[C@H:16]([CH2:17][C@H:18]3O)[CH2:15]1)=[N:9][C:8]([O:22][CH3:23])=[CH:7][CH:6]=2.CCOC(/N=N/C(OCC)=O)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:55]1(=[O:65])[NH:59][C:58](=[O:60])[C:57]2=[CH:61][CH:62]=[CH:63][CH:64]=[C:56]12>C1COCC1.C1COCC1.O1CCOCC1>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:20][C@H:19]3[C@H:16]([CH2:17][C@@H:18]3[N:59]3[C:55](=[O:65])[C:56]4[C:57](=[CH:61][CH:62]=[CH:63][CH:64]=4)[C:58]3=[O:60])[CH2:15]1)=[N:9][C:8]([O:22][CH3:23])=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 59295127(+/-)-(1S,5R,6R)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]heptan-6-ol

Product 1

HCID 59295124(+/-)-2-((1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]hept-6-yl)-1H-isoindole-1,3(2H)-dioneYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22018518Dioxane tetrahydrofuranSolvent

Procedure

To a solution of (±)-(1S,5R,6R)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]heptan-6-ol (230 mg, 0.73 mmol) in THF (2 mL) as added DEAD (0.11 mL, 0.76 mmol), followed by dropwise addition of a preformed solution of PPh3 (190 mg, 0.72 mmol) and phthalimide-(107 mg, 0.73 mmol) in THF-dioxane (4 mL, 1:1). The resulting solution was heated at reflux. After 12 h, the solution was concentrated and the residue purified via a column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) yielding the title compound (137 mg, 42%) as a yellow oil: LC/MS (ES) m/e 448 (M+H)+.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux
  3. concentrationthe solution was concentrated
  4. customthe residue purified via a column chromatography (silica, 1% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-027650d8e0444059a96883c64fc2f415
Source dataset
uspto-grants-2010_05
Patent number
US07709472B2

Reaction notes

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