Dimethylamine → 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 1947341Notes

Reaction equation

HRID 1947341 reaction equation
[B-](F)(F)(F)F.[CH3:6][N:7](C(ON1C(=O)CCC1=O)=[N+](C)C)[CH3:8].[F:21][C:22]1[CH:23]=[C:24]([N:29]([CH3:52])[CH:30]([C:32]2[CH:33]=[C:34]([C:49](O)=[O:50])[CH:35]=[C:36]3[C:41]=2[O:40][C:39]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[CH:38][C:37]3=[O:48])[CH3:31])[CH:25]=[C:26]([F:28])[CH:27]=1.C(N(C(C)C)C(C)C)C.CNC>C(Cl)Cl.O>[F:28][C:26]1[CH:25]=[C:24]([N:29]([CH3:52])[CH:30]([C:32]2[CH:33]=[C:34]([C:49]([N:7]([CH3:8])[CH3:6])=[O:50])[CH:35]=[C:36]3[C:41]=2[O:40][C:39]([N:42]2[CH2:43][CH2:44][O:45][CH2:46][CH2:47]2)=[CH:38][C:37]3=[O:48])[CH3:31])[CH:23]=[C:22]([F:21])[CH:27]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 582349758-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 582350068-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

2-(2,5-dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (2.134 g, 7.09 mmol), was added in one portion to a stirred solution of 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (2.1 g, 4.73 mmol) and N-ethyl-N-isopropylpropan-2-amine (1.646 mL, 9.45 mmol) in DCM (20 mL) at RT and stirred at RT for 90 mins. Dimethylamine (4.73 mL, 9.45 mmol) was then added and the reaction mixture was stirred at RT for 30 min. Water and DCM were added, the organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with DCM/MeCN (1:1) then 0 to 10% MeOH in DCM. The solvent was evaporated to dryness to afford a foam which crystallised from ethyl acetate (10 mL). Ether (10 mL) was added to complete the crytallisation and the white solid was collected by filtration and dried to give 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (1.65 g, 74%). Mass Spectrum: M+H+ 472. NMR Spectrum (DMSOd6): 1.55 (d, 3H), 2.63 (s, 3H), 2.92 (bs, 3H), 3.01 (bs, 3H), 3.21-3.29 (m, 2H), 3.31-3.39 (m partially hidden by H2O, 2H), 3.41-3.49 (m, 2H), 3.49-3.57 (m, 2H), 5.55 (s, 1H), 5.58 (q, 1H), 6.40 (t, 1H), 6.53 (d, 2H), 7.70 (d, 1H), 7.89 (d, 1H).

Workup

  1. stirringthe reaction mixture was stirred at RT for 30 min
  2. washthe organic phase was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel eluting with DCM/MeCN (1:1)
  6. customThe solvent was evaporated to dryness
  7. customto afford a foam which
  8. customcrystallised from ethyl acetate (10 mL)
  9. additionEther (10 mL) was added
  10. filtrationthe white solid was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-b8cc1e2aecd741bf8e431262b84ac169
Source dataset
uspto-grants-2013_03
Patent number
US08399460B2

Reaction notes

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