Benzenamine, 4-(4-morpholinyl)- → 6-Methoxy-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

HRID 1825668Notes

Reaction equation

HRID 1825668 reaction equation
COC1C=CC=CC=1N1CC[N:12]([C:15]([C:17]2[O:18][C:19]3[C:24]([C:25](=[O:27])[CH:26]=2)=[CH:23][CH:22]=[CH:21][C:20]=3[N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[O:16])CC1.CN([C:38]([O:42]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.ON1C2C=CC=CC=2N=N1.[N:67]1([C:73]2[CH:79]=[CH:78][C:76](N)=[CH:75][CH:74]=2)[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1>CN(C)C1C=CN=CC=1.CN(C)C=O.C(N(CC)CC)C>[N:67]1([C:73]2[CH:79]=[CH:78][C:76]([NH:12][C:15]([C:17]3[O:18][C:19]4[C:24]([C:25](=[O:27])[CH:26]=3)=[CH:23][C:22]([O:42][CH3:38])=[CH:21][C:20]=4[N:28]3[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]3)=[O:16])=[CH:75][CH:74]=2)[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1

Participants

8

Reactant 4

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 757711-HydroxybenzotriazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 101396012-{1-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-methanoyl}-8-(4-methyl-piperazin-1-yl)-chromen-4-one

Product 1

HCID 235333236-Methoxy-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

6-Methoxy-8-(4-Methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid hydrochloride (Reference Example 2) (3.0 g, 8.5 mmol), TBTU (5.5 g, 17 mmol), 1-hydroxybenztriazole (2.6 g, 17 mmol), 4-dimethylaminopyridine (0.05 g, catalytic) and commercially available 4-morpholin-4-yl-aniline (1.66 g, 9.3 mmol) were dissolved in dimethylformamide (100 mL). Triethylamine (3.5 mL, 25 mmol was added and this mixture stirred at room temperature for 17 hours. The reaction mixture was concentrated under vacuum and the residue was partitioned between chloroform (400 mL) and saturated aqueous sodium bicarbonate (50 mL). The organic layer was separated, dried (Na2SO4), vacuum-filtered and concentrated under vacuum. The residue was purified by chromatography on silica eluted with 2-5% methanol in chloroform and then triturated with ether to yield a yellow powder. (1.6 g=39%) LCMS−m/z=479.5 mp=234-236° C.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was partitioned between chloroform (400 mL) and saturated aqueous sodium bicarbonate (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationvacuum-filtered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by chromatography on silica
  8. washeluted with 2-5% methanol in chloroform
  9. customtriturated with ether
  10. customto yield a yellow powder

Sources & evidence

ORD record
ord-92dd46b1819048c3bff882bec90530cb
Source dataset
uspto-grants-2006_05
Patent number
US07045514B2

Reaction notes

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