Triphosgene → (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate

HRID 870170

Reaktionsgleichung

Reaktionsgleichung von HRID 870170
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1.[C:21](=O)(OC(Cl)(Cl)Cl)[O:22]C(Cl)(Cl)Cl.[NH2:33][C@@H:34]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:35]([O:37][CH3:38])=[O:36]>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:22])[NH:33][C@@H:34]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:35]([O:37][CH3:38])=[O:36])=[CH:16][CH:15]=1

Komponenten

6

Edukt 3

HCID 94429TriphosgeneHCID 1112071,4-Dimethyl L-aspartateHCID 99443944-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)aniline2×

Produkt 1

HCID 46843171(2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel2×

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenamine (intermediate 30.7) (200 mg, 0.65 mmol, 1.00 equiv) in dichloromethane (10 mL), triethylamine (1.2 mL). This was followed by the addition of bis(trichloromethyl) carbonate (200 mg, 0.67 mmol, 1.03 equiv) slowly with stirring at 0-5° C. The resulting solution was stirred for 1 h at room temperature. To this was added triethylamine (1 mL) followed by (S)-dimethyl 2-aminosuccinate (200 mg, 1.24 mmol, 1.91 equiv) in several batches. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum and the residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:10-1:5). This resulted in 50 mg (15%) of (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate as yellow oil.

Aufarbeitung

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 1 h at room temperature
  4. stirringThe resulting solution was stirred for 2 h at room temperature
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. washeluted with ethyl acetate/petroleum ether (1:10-1:5)
  7. customThis resulted in 50 mg (15%) of (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate as yellow oil

Quellen und Nachweise

ORD-Eintrag
ord-99e7b88b008a43df8570b359bac278c4
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969377B2

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