Cesium carbonate → 2-{(3E)-4-[2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]but-3-enyl}-1H-isoindole-1,3(2H)-dione

HRID 244815

Reaction equation

HRID 244815 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([CH2:15][CH2:16][CH2:17][O:18][CH:19]([CH3:21])[CH3:20])[C:13]([CH2:22][O:23][CH2:24][CH3:25])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.[CH2:26]([N:30]1[C:38](=[O:39])[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]1=[O:40])[CH2:27][CH:28]=[CH2:29].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[CH2:24]([O:23][CH2:22][C:13]1[N:14]([CH2:15][CH2:16][CH2:17][O:18][CH:19]([CH3:21])[CH3:20])[C:6]2[C:5]3[CH:4]=[CH:3][C:2](/[CH:29]=[CH:28]/[CH2:27][CH2:26][N:30]4[C:38](=[O:39])[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[C:31]4=[O:40])=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:12]=1)[CH3:25]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 339432N-(3-Buten-1-yl)phthalimideHCID 673819647-Bromo-2-ethoxymethyl-1-(isopropoxypropyl)-1H-imidazo[4,5-c]quinoline

Product 1

HCID 690842002-{(3E)-4-[2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]but-3-enyl}-1H-isoindole-1,3(2H)-dioneYield 77.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinoline (1.9 g, 4.68 mmol), 2-but-3-enyl-1H-isoindole-1,3(2H)-dione (1.04 g, 5.15 mmol), cesium carbonate (3.05 g, 9.36 mmol), triphenylphosphine (0.246 g, 0.94 mmol), palladium(II) acetate (0.105 g, 0.47 mmol), and N,N-dimethylformamide (DMF) (28 mL) were added to a pressure tube. The vessel was sealed with a TEFLON cap and heated at 140° C. for 2.5 hours. The reaction was cooled to ambient temperature. The reaction was diluted with ethyl acetate and washed multiple times with water. The initial water wash was extracted with ethyl acetate. The organic fractions were combined and washed with water once again. The organic fractions were concentrated under reduced pressure and the residue was purified using a HORIZON HPFC system (silica cartridge, eluting with a linear gradient of 2-20% CMA in chloroform) to yield 1.9 g of 2-{(3E)-4-[2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]but-3-enyl}-1H-isoindole-1,3(2H)-dione as a pale yellow oil.

Workup

  1. customcap
  2. temperatureThe reaction was cooled to ambient temperature
  3. washwashed multiple times with water
  4. washThe initial water wash
  5. extractionwas extracted with ethyl acetate
  6. washwashed with water once again
  7. concentrationThe organic fractions were concentrated under reduced pressure
  8. customthe residue was purified
  9. washeluting with a linear gradient of 2-20% CMA in chloroform)

Sources & evidence

ORD record
ord-ee3b73b30ec64502ba910176f53a7759
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Linked notes

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