Dimethylamine → 8-(1-hydroxyethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide

HRID 572806Notes

Reaction equation

HRID 572806 reaction equation
[B-](F)(F)(F)F.[CH3:6][N:7](C(ON1C(=O)CCC1=O)=[N+](C)C)[CH3:8].[OH:21][CH:22]([C:24]1[CH:25]=[C:26]([C:42]([OH:44])=O)[CH:27]=[C:28]2[C:33]=1[O:32][C:31]([N:34]1[CH2:39][CH2:38][O:37][C@H:36]([CH3:40])[CH2:35]1)=[CH:30][C:29]2=[O:41])[CH3:23].C(N(C(C)C)C(C)C)C.CNC>C(Cl)Cl>[OH:21][CH:22]([C:24]1[CH:25]=[C:26]([C:42]([N:7]([CH3:8])[CH3:6])=[O:44])[CH:27]=[C:28]2[C:33]=1[O:32][C:31]([N:34]1[CH2:39][CH2:38][O:37][C@H:36]([CH3:40])[CH2:35]1)=[CH:30][C:29]2=[O:41])[CH3:23]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 582349828-(1-hydroxyethyl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 582349738-(1-hydroxyethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamideYield 84.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(2,5-dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (2.38 g, 3.96 mmol) was added portionwise to 8-(1-hydroxyethyl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid (0.88 g, 2.64 mmol) and N-ethyl-N-isopropylpropan-2-amine (1.380 mL, 7.92 mmol) suspended in DCM (15 mL) at 10° C. under nitrogen. The resulting mixture was stirred at RT for 2 hrs. Dimethylamine (3.96 mL, 7.92 mmol) was then added at 10° C. and the resulting mixture was stirred at RT overnight. The mixture was poured onto a silica gel column and purified by flash chromatography eluting with 0 to 10% methanolic ammonia (7 N) in DCM. The solvent was evaporated to dryness to afford a foam which crystallised from ethyl acetate, the solid was collected by filtration and dried to a constant weight in a vacuum oven to afford 8-(1-hydroxyethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide (0.800 g, 84%) as a white solid.

Workup

  1. stirringthe resulting mixture was stirred at RT overnight
  2. additionThe mixture was poured onto a silica gel column
  3. custompurified by flash chromatography
  4. washeluting with 0 to 10% methanolic ammonia (7 N) in DCM
  5. customThe solvent was evaporated to dryness
  6. customto afford a foam which
  7. customcrystallised from ethyl acetate
  8. filtrationthe solid was collected by filtration
  9. customdried to a constant weight in a vacuum oven

Sources & evidence

ORD record
ord-f6fa8bd8dd8945dd900d48408fc49ce1
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

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