Phthalimide → 2-(1-(3-(3-Fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethyl)isoindoline-1,3-dione

HRID 405963Notes

Reaction equation

HRID 405963 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13](=[O:14])[N:12]3[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:11]3=[N:10][C:9]=2[CH:20](O)[CH3:21])[CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:42]1(=[O:52])[NH:46][C:45](=[O:47])[C:44]2=[CH:48][CH:49]=[CH:50][CH:51]=[C:43]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13](=[O:14])[N:12]3[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:11]3=[N:10][C:9]=2[CH:20]([N:46]2[C:42](=[O:52])[C:43]3[C:44](=[CH:48][CH:49]=[CH:50][CH:51]=3)[C:45]2=[O:47])[CH3:21])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 668313383-(3-fluorophenyl)-2-(1-hydroxyethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 668313752-(1-(3-(3-Fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(3-fluorophenyl)-2-(1-hydroxyethyl)-6-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one (0.6500 g, 2.179 mmol), triphenylphosphine (0.6858 g, 2.615 mmol), phthalimide (0.3847 g, 2.615 mmol), and THF (14.53 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 to diisopropyl azodicarboxylate (0.5148 mL, 2.615 mmol) at 0° C. The reaction mixture was allowed to warm to rt and stirred at rt. After 5 h, the mixture was concd under reduced pressure and partitioned between EtOAc (100 mL) and brine (100 mL). The organic layer was dried over Na2SO4, filtered, and concd under reduced pressure. The residue 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 2-(1-(3-(3-fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethypisoindoline-1,3-dione as a bright yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.75-7.82 (2 H, m), 7.65-7.74 (3 H, m), 7.35-7.42 (1 H, m), 7.13-7.24 (1 H, m), 6.90-7.01 (4 H, m), 5.43 (1 H, q, J=7.0 Hz), 2.89 (3 H, s), 1.62 (3 H, d, J=7.4 Hz); Mass Spectrum (ESI) m/e=427.9 (M+1).

Workup

  1. dissolutionto dissolve all reactants
  2. temperatureto warm to rt
  3. custompartitioned between EtOAc (100 mL) and brine (100 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customThe residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  7. customover 25 min
  8. custom50% isocratic of EtOAc for 10 min as eluent to give 2-(1-(3-(3-fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethypisoindoline-1,3-dione as a bright yellow solid

Sources & evidence

ORD record
ord-42ac5eb86f37453498b73721b5a078c3
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

Loading…