3,5-Difluoroaniline → HCID 58235059, compound

HRID 572809Notes

Reaction equation

HRID 572809 reaction equation
Br[CH:2]([C:4]1[CH:5]=[C:6]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:7]=[C:8]2[C:13]=1[O:12][C:11]([N:14]1[CH2:19][CH2:18][O:17][C@@H:16]([CH3:20])[CH2:15]1)=[CH:10][C:9]2=[O:21])[CH3:3].[F:27][C:28]1[CH:29]=[C:30]([CH:32]=[C:33]([F:35])[CH:34]=1)[NH2:31]>CC(N(C)C)=O.C(OCC)(=O)C>[F:27][C:28]1[CH:29]=[C:30]([NH:31][CH:2]([C:4]2[CH:5]=[C:6]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:7]=[C:8]3[C:13]=2[O:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][C@@H:16]([CH3:20])[CH2:15]2)=[CH:10][C:9]3=[O:21])[CH3:3])[CH:32]=[C:33]([F:35])[CH:34]=1

Participants

5

Reactant 2

HCID 965953,5-DifluoroanilineHCID 58234991HCID 58234991, compound

Product 1

HCID 58235059HCID 58235059, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 8-(1-bromoethyl)-N,N-dimethyl-2-((S)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide (670 mg, 1.42 mmol) and 3,5-difluoroaniline (736 mg, 5.70 mmol) in DMA (4 mL) were stirred at 50° C. for 4 hrs then at rt over the weekend. The reaction mixture was diluted with ethyl acetate, washed with a sat. aq. sol. of sodium hydrogenocarbonate, water brine, dried over magnesium sulfate and concentrated to afford the crude product, which was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in DCM. The solvent was evaporated to dryness and the obtained foam was triturated with diethyl ether to give a white solid which was collected by filtration and dried under vacuum to give 8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((S)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide (400 mg, 60%). Mass Spectrum: M+H+ 472. NMR Spectrum (CDCl3): 1.25 (d, 3H), 1.61 (d partially hidden by H2O, 3H), 2.83 (ddd, 1H), 2.90 (bs, 3H), 3.08 (bs, 3H), 3.18 (dddd, 1H), 3.63-3.82 (m, 4H), 4.02 (ddd, 1H), 4.37 (bs, 1H), 4.88-4.97 (m, 1H), 5.55 (s, 1H), 5.97 (d, 2H), 6.13 (t, 1H), 7.72 (d, 1H), 8.12 (d, 1H).

Workup

  1. customat rt
  2. washwashed with a sat. aq. sol. of sodium hydrogenocarbonate, water brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customto afford the crude product, which
  6. customwas purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in DCM
  7. customThe solvent was evaporated to dryness
  8. customthe obtained foam was triturated with diethyl ether
  9. customto give a white solid which
  10. filtrationwas collected by filtration
  11. customdried under vacuum

Sources & evidence

ORD record
ord-6c09cb8ca8b441dfbba392cf3379fa5b
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

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