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Ammonia → (S)-tert-Butyl (1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate

HRID 1052346
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1052346
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrBr.C(N(CC)CC)C.[CH3:29][C:30]1[CH:34]=[CH:33][N:32]([NH:35][C:36](=O)[C@@H:37]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH3:38])[C:31]=1[C:48](=[O:56])[NH:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.N>ClCCl>[CH3:29][C:30]1[CH:34]=[CH:33][N:32]2[C:31]=1[C:48](=[O:56])[N:49]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:36]([C@@H:37]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH3:38])=[N:35]2
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Komponenten

7

Edukt 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 24408BromineHCID 90200400(S)-tert-Butyl 1-(3-methyl-2-(phenylcarbamoyl)-1H-pyrrol-1-ylamino)-1-oxopropan-2-ylcarbamate

Produkt 1

HCID 131736112
(S)-tert-Butyl (1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate
Ausbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Triphenylphosphine (6.8 g, 25.93 mmol) was dissolved in 50 mL dichloromethane. Bromine (1.33 mL, 25.97 mmol) was added dropwise and the reaction was stirred at room temperature for 30 min. Triethylamine (10.3 mL, 73.9 mmol) and (S)-tert-butyl (1-((3-methyl-2-(phenylcarbamoyl)-1H-pyrrol-1-yl)amino)-1-oxopropan-2-yl)carbamate (7.15 g, 18.5 mmol) suspended in 100 mL dichloromethane was added and the reaction mixture was stirred at 60° C. for 2 h. The mixture was concentrated to dryness and was re-dissolved in a pressure reactor with a solution of ammonia (7M in methanol, 350 mL, 2415 mmol). The mixture was heated at 100° C. for 32 h, then cooled at room temperature and evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, brine and dried over sodium sulphate, filtered and concentrated. The residue was purified using Isolera® Purification System (0% to 50%, hexane-ethyl acetate) to obtain 0.95 g (14% yield) of the title compound as a yellow solid.

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction mixture was stirred at 60° C. for 2 h
  3. concentrationThe mixture was concentrated to dryness
  4. temperatureThe mixture was heated at 100° C. for 32 h
  5. temperaturecooled at room temperature
  6. customevaporated under reduced pressure
  7. customThe residue was partitioned between ethyl acetate and water
  8. washThe organic layer was washed with water, brine
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified
  13. customIsolera® Purification System (0% to 50%, hexane-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-05770dab476f4b88a773667ed327ef02
Quelldatensatz
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09388189B2

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