Sodium Iodide → 6-Methoxy-4-oxo-8-piperazin-1-yl-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

HRID 1795360Notes

Reaction equation

HRID 1795360 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[O:17][C:18]4[C:23]([C:24](=[O:26])[CH:25]=3)=[CH:22][C:21]([O:27][CH3:28])=[CH:20][C:19]=4[N:29]3[CH2:34][CH2:33][N:32](C)[CH2:31][CH2:30]3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.ClC(OC(Cl)C)=O.[I-].[Na+]>ClCCCl>[N:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH:13][C:14]([C:16]3[O:17][C:18]4[C:23]([C:24](=[O:26])[CH:25]=3)=[CH:22][C:21]([O:27][CH3:28])=[CH:20][C:19]=4[N:29]3[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]3)=[O:15])=[CH:11][CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 5213051-Chloroethyl chloroformateHCID 235333236-Methoxy-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

Product 1

HCID 235333256-Methoxy-4-oxo-8-piperazin-1-yl-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amideYield 64%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Into a 50 mL round bottom flask equipped with a reflux condenser, nitrogen inlet and magnetic stirrer is placed 50 mg (0.115 mmol, 1.0 equiv.) of 6-Methoxy-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide (Example 31) and 10 mL of 1,2 dichloroethane. To this solution is then added via syringe 49 mg, 37 μL (0.345 mmol, 3.0 equiv.) of 1-chloroethyl chloroformate. A precipitate forms, indicating formation of an intermediate. The reaction is heated to reflux for 3 days, whereupon an analysis of an aliquot by LC/MS indicates only a trace of product has formed. At this time 52 mg (0.345 mmol, 3.0 equiv.) of sodium iodide are added to the refluxing reaction. LC/MS analyses then progressively show formation of demethylated product over 5 additional days. The reaction is then cooled, concentrated on a rotary evaporator, then dried over K2CO3 as a suspension in methylene chloride containing methanol, removal of solids by filtration, followed by flash chromatography of the solution, using a gradient of 5 to 20% methanol in methylene chloride, gives 34 mg (64%) of the pure product as a reddish solid.

Workup

  1. customInto a 50 mL round bottom flask equipped with a reflux condenser, nitrogen inlet and magnetic stirrer
  2. temperatureThe reaction is heated
  3. temperatureto reflux for 3 days, whereupon an analysis of an aliquot by LC/MS
  4. customhas formed
  5. temperatureThe reaction is then cooled
  6. concentrationconcentrated on a rotary evaporator
  7. dry with materialdried over K2CO3 as a suspension in methylene chloride
  8. additioncontaining
  9. custommethanol, removal of solids
  10. filtrationby filtration

Sources & evidence

ORD record
ord-24cde3f7073b4625be27232c304c4b2a
Source dataset
uspto-grants-2006_04
Patent number
US07026314B2

Reaction notes

Loading…