Diethylcarbamoyl chloride → HCID 19595210, compound

HRID 612485Notes

Reaction equation

HRID 612485 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][N:8]2[CH2:16][C:15]3[C:14]([OH:17])=[CH:13][CH:12]=[CH:11][C:10]=3[CH2:9]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH2:25]([N:27]([CH2:31][CH3:32])[C:28]([Cl:30])=[O:29])[CH3:26].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[ClH:30].[CH2:25]([N:27]([CH2:31][CH3:32])[C:28](=[O:29])[O:17][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH2:16][N:8]([NH:7][C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)[CH2:9]2)[CH3:26]

Participants

6

Reactant 4

HCID 6916Diethylcarbamoyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 9859383HCID 9859383, compound

Product 1

HCID 19595210HCID 19595210, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a mixture of 2,3-dihydro-2-(4-pyridinylamino)-1H-isoindol-4-ol (1.50 g), triethylamine (1.47 g) and chloroform (15 ml), diethylcarbamyl chloride (1.07 g) in chloroform (10 ml) was added dropwise, with stirring at ambient temperature, under nitrogen. The reaction mixture was stirred under reflux for 5 hrs, at ambient temperature overnight, and poured into dilute sodium bicarbonate solution (100 ml). The layers were separated. The aqueous phase was extracted with chloroform, and the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated in vacuo. The residue was flash chromatographed (silica), eluting with 7% methanol-dichloromethane followed by 185:14:1 dichloromethane-methanol-ammonium hydroxide. The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with excess ethereal hydrogen chloride. The precipitate was recrystallized from ethanol-ether to give 1.20 g (50%) of product, mp 213-215° C. (dec).

Workup

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred
  3. temperatureunder reflux for 5 hrs, at ambient temperature overnight
  4. customThe layers were separated
  5. extractionThe aqueous phase was extracted with chloroform
  6. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe filtrate was evaporated in vacuo
  9. customchromatographed (silica)
  10. washeluting with 7% methanol-dichloromethane
  11. customThe appropriate fractions were collected
  12. customevaporated
  13. dissolutionThe residue was dissolved in absolute ethanol
  14. additiontreated with excess ethereal hydrogen chloride
  15. customThe precipitate was recrystallized from ethanol-ether

Sources & evidence

ORD record
ord-7f34f9c3d2d34f34b42098a6783b2810
Source dataset
uspto-grants-1999_12
Patent number
US06004977

Reaction notes

Loading…