Triethylamine → HCID 53751487, compound

HRID 612478Notes

Reaction equation

HRID 612478 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:17])[CH:14]=3)[CH2:9]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH2:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH2:27][N:26]1[NH:35][C:36](Cl)=[O:37].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[CH2:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH2:27][N:26]1[NH:35][C:36](=[O:37])[O:17][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH2:9][N:8]([NH:7][C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)[CH2:16]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 19595244HCID 19595244, compoundHCID 19595254HCID 19595254, compound

Product 1

HCID 53751487HCID 53751487, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a mixture of 2,3-dihydro-2-(4-pyridinylamino)-1H-isoindol-5-ol (1.50 g), triethylamine (1.47 g), and chloroform (15 ml), 1,2,3,4-tetrahydroisoquinolin-2-ylcarbamyl chloride (1.55 g) in chloroform (10 ml) was added dropwise with stirring, under nitrogen, at ambient temperature. The reaction mixture was stirred under reflux for 3 hrs, at ambient temperature overnight and poured into dilute sodium bicarbonate solution. The layers were separated. The aqueous phase was extracted with chloroform, and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated in vacuo. The residue was chromatographed on 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 recrystallized from ethanol-toluene to give 800 mg (31%) of product, mp 162-163° C.

Workup

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred
  3. temperatureunder reflux for 3 hrs, at ambient temperature overnight
  4. customThe layers were separated
  5. extractionThe aqueous phase was extracted with chloroform
  6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customthe filtrate was evaporated in vacuo
  9. customThe residue was chromatographed on silica
  10. washeluting with 7% methanol-dichloromethane
  11. customThe appropriate fractions were collected
  12. customevaporated
  13. customThe residue was recrystallized from ethanol-toluene

Sources & evidence

ORD record
ord-681a1a01b08c45cbaba48252b1593616
Source dataset
uspto-grants-1999_12
Patent number
US06004977

Reaction notes

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