4-Fluoro-N-methylaniline → N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 1187187Notes

Reaction equation

HRID 1187187 reaction equation
Br.Br[CH:3]([C:5]1[CH:6]=[C:7]([C:22]([NH:24][CH2:25][CH2:26][N:27]([CH3:29])[CH3:28])=[O:23])[CH:8]=[C:9]2[C:14]=1[O:13][C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[CH:11][C:10]2=[O:21])[CH3:4].[F:30][C:31]1[CH:38]=[CH:37][C:34]([NH:35][CH3:36])=[CH:33][CH:32]=1>CN1C(=O)CCC1>[CH3:28][N:27]([CH3:29])[CH2:26][CH2:25][NH:24][C:22]([C:7]1[CH:8]=[C:9]2[C:14](=[C:5]([CH:3]([N:35]([C:34]3[CH:37]=[CH:38][C:31]([F:30])=[CH:32][CH:33]=3)[CH3:36])[CH3:4])[CH:6]=1)[O:13][C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[CH:11][C:10]2=[O:21])=[O:23]

Participants

4

Reactant 2

HCID 680244-Fluoro-N-methylanilineHCID 671039198-(1-bromoethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide

Product 1

HCID 58235058N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 53.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 8-(1-bromoethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (85 mg, 0.16 mmol) and 4-fluoro-N-methylaniline (0.077 mL, 0.64 mmol) in NMP (1 mL) was stirred at room temperature for 4 h then at 45° C. for 1 h. The reaction mixture was allowed to cool to room temperature and purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 mL/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness. The residue was triturated in diethyl ether, collected by filtration and dried to afford N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide (42.0 mg, 53.1%) as a white solid. Mass Spectrum: M+H+ 497. NMR Spectrum: (CDCl3) 1.66 (d, 3H), 2.33 (s, 6H), 2.33 (bs, 2H), 2.60 (bs, 2H), 2.61 (s, 3H), 3.09-3.24 (m, 4H), 3.44-3.57 (m, 4H), 3.57-3.66 (m, 2H), 5.36 (q, 1H), 5.48 (s, 1H), 6.75 (dd, 2H), 6.77 (dd, 2H), 7.14 (bs, 1H), 8.33 (s, 1H), 8.44 (s, 1H).

Workup

  1. custompurified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness
  4. customThe residue was triturated in diethyl ether
  5. filtrationcollected by filtration
  6. customdried

Sources & evidence

ORD record
ord-727b2ed47cad495585825cc6755fa8c5
Source dataset
uspto-grants-2014_03
Patent number
US08673906B2

Reaction notes

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