Triethylamine → 2,3-Dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-yl 1,2,3,4-tetrahydroisoquinolin-2-ylcarbamate hydrochloride

HRID 612488

Reaktionsgleichung

Reaktionsgleichung von HRID 612488
Br.[F:2][C:3]1[C:11]([OH:12])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][N:6]([NH:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)[CH2:7]2.C([N:22]([CH2:25]C)CC)C.[CH2:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][N:28]1C([Cl:39])=O.C(=O)(O)[O-:41].[Na+]>C(Cl)(Cl)Cl>[ClH:39].[CH2:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][N:28]1[NH:22][C:25](=[O:41])[O:12][C:11]1[C:3]([F:2])=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([NH:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)[CH2:5]2

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 195952012,3-dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-ol hydrobromideHCID 218905713,4-Dihydroisoquinoline-2(1H)-carbonyl chloride

Produkt 1

HCID 701048932,3-Dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-yl 1,2,3,4-tetrahydroisoquinolin-2-ylcarbamate hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel2×

Versuchsvorschrift

To a mixture of 2,3-dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-ol hydrobromide (655 mg), triethylamine (671 mg), and chloroform (10 ml), 1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyl chloride (471 mg) in chloroform (5 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 sodium 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 to give 800 mg of product. The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and excess ethereal hydrogen chloride was added. Ether was added and the mixture was cooled. The precipitate was collected to give 750 mg (85%) of product, mp >260° C.

Aufarbeitung

  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 sodium sulfate
  7. filtrationfiltered
  8. customthe filtrate was evaporated in vacuo
  9. customchromatographed (silica)
  10. washeluting with 7% methanol-dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-c86a15a137b247f9abcaa787fc423495
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US06004977

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