N-Hydroxyphthalimide → 2-[3-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)propoxy]-1H-isoindole-1,3(2H)-dione

HRID 1187397Notes

Reaction equation

HRID 1187397 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH2:15]([C:18]1[N:19]([CH2:31][CH2:32][CH2:33][OH:34])[C:20]2[C:29]3[N:28]=[CH:27][CH:26]=[CH:25][C:24]=3[N:23]=[CH:22][C:21]=2[N:30]=1)[CH2:16][CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[N:55]1[C:59](=[O:60])[C:58]2=[CH:61][CH:62]=[CH:63][CH:64]=[C:57]2[C:56]1=[O:65]>O1CCCC1.C(OCC)(=O)C.ClCCl>[CH2:15]([C:18]1[N:19]([CH2:31][CH2:32][CH2:33][O:34][N:55]2[C:59](=[O:60])[C:58]3[C:57](=[CH:64][CH:63]=[CH:62][CH:61]=3)[C:56]2=[O:65])[C:20]2[C:29]3[N:28]=[CH:27][CH:26]=[CH:25][C:24]=3[N:23]=[CH:22][C:21]=2[N:30]=1)[CH2:16][CH3:17]

Participants

8

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 685386673-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)propan-1-ol

Product 1

HCID 685404202-[3-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)propoxy]-1H-isoindole-1,3(2H)-dioneYield 103.8%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropyl azodicarboxylate (8.10 mL, 48.4 inmol) was added dropwise over ten minutes to a stirred solution of 3-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)propan-1-ol (10.9 g, 40.3 mmol), triphenylphosphine (12.7 g, 48.4 mmol), and N-hydroxyphthalimide (7.89 g, 48.4 mmol) in tetrahydrofuran (160 mL) at 0° C. The reaction was allowed to warm to room temperature and was stirred overnight. The solvent was removed under reduced pressure to afford an oil that was dissolved in ethyl acetate (200 mL) and extracted with 2 M HCl (3×100 mL). The aqueous layers were combined, and the pH was adjusted to 7 with the addition of solid sodium bicarbonate. A precipitate formed, was isolated by filtration, and was dissolved in dichloromethane (300 mL). The solution was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford 17.38 g of 2-[3-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)propoxy]-1H-isoindole-1,3(2H)-dione as a tan solid.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto afford an oil that
  3. extractionextracted with 2 M HCl (3×100 mL)
  4. additionthe pH was adjusted to 7 with the addition of solid sodium bicarbonate
  5. customA precipitate formed
  6. customwas isolated by filtration
  7. dry with materialThe solution was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b0819fbab05f4586b66978e08cc1986a
Source dataset
uspto-grants-2014_03
Patent number
US08673932B2

Reaction notes

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