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

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).

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

ORDレコード

ord-998f190e420b4e98b48025b410e9dbcf

出典データセット

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09029374B2