Phthalimide → HCID 66831385, compound

HRID 405970Notes

Reaction equation

HRID 405970 reaction equation
[Br:1][C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:14](O)[CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:36]1(=[O:46])[NH:40][C:39](=[O:41])[C:38]2=[CH:42][CH:43]=[CH:44][CH:45]=[C:37]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Br:1][C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:14]([N:40]1[C:36](=[O:46])[C:37]2[C:38](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:39]1=[O:41])[CH3:15]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 66831350HCID 66831350, compound

Product 1

HCID 66831385HCID 66831385, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-bromo-7-fluoro-2-(1-hydroxyethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (1.238 g, 4.31 mmol), triphenylphosphine (1.357 g, 5.17 mmol), phthalimide (0.761 g, 5.17 mmol), and THF (28.7 mL) was stirred at rt for 5 min to dissolve all reactants. The mixture was then cooled to 0° C. and to the cooled homogenous mixture was added dropwise over 3 min diisopropyl azodicarboxylate (1.019 mL, 5.17 mmol) at 0° C. After stirring at 0° C. for 30 min, the cooling bath was removed and the mixture was stirred at rt. After 1.5 h, the mixture was partitioned between EtOAc (50 mL) and water (50 mL). The insoluble solid was filtered, washed with water (50 mL) and EtOAc (50 mL), and dried under vacuum to give the desired product 2-(1-(3-bromo-7-fluoro-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethyl)isoindoline-1,3-dione as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.92-9.00 (1 H, m), 8.12 (1 H, ddd, J=9.9, 7.1, 2.9 Hz), 7.82-7.92 (4 H, m), 7.75 (1 H, dd, J=9.8, 5.5 Hz), 5.56-5.66 (1 H, m), 1.85 (3 H, d, J=7.0 Hz); Mass Spectrum (ESI) m/e=416.0 [M+1 (79Br)] and 418.0 [M+1 (81Br)]. To the filtrate was added brine (50 mL) and the organic layer was separated, dried over Na2SO4, filtered and concd under reduced pressure to give the crude material as a yellow solid. The yellow solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and 50% isocratic of EtOAc for 10 min as eluent to give the desired product 2-(1-(3-bromo-7-fluoro-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-ethyl)isoindoline-1,3-dione as a light yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.95 (1 H, td, J=3.1, 1.6 Hz), 8.12 (1 H, ddd, J=9.9, 7.1, 2.9 Hz), 7.83-7.93 (4 H, m), 7.71-7.79 (1 H, m), 5.57-5.65 (1 H, m), 1.85 (3 H, d, J=7.0 Hz); Mass Spectrum (ESI) m/e=416.0 [M+1 (79Br)] and 418.0 [M+1 (81Br)].

Workup

  1. dissolutionto dissolve all reactants
  2. customthe cooling bath was removed
  3. stirringthe mixture was stirred at rt
  4. waitAfter 1.5 h
  5. customthe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  6. filtrationThe insoluble solid was filtered
  7. washwashed with water (50 mL) and EtOAc (50 mL)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-16fd89eaf37d4e11b89ee453af77b1eb
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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