Hydrochloric Acid → Apalutamide

HRID 1051129Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051129
[N:1]([C:4]1[CH:5]=[C:6]([C:12]([F:15])([F:14])[F:13])[C:7]([C:10]#[N:11])=[N:8][CH:9]=1)=[C:2]=[S:3].[C:16]([C:18]1([NH:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=2)[CH2:21][CH2:20][CH2:19]1)#N.CN(C)C=[O:37].Cl>O.C([O-])(O)=O.[Na+].CO>[C:10]([C:7]1[N:8]=[CH:9][C:4]([N:1]2[C:16](=[O:37])[C:18]3([CH2:21][CH2:20][CH2:19]3)[N:22]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=3)[C:2]2=[S:3])=[CH:5][C:6]=1[C:12]([F:15])([F:13])[F:14])#[N:11]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 250199805-Isothiocyanato-3-(trifluoromethyl)pyridine-2-carbonitrileHCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide

Produkt 1

HCID 24872560Apalutamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Crude 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile 9 (1.390 g, 6.07 mmol) is placed in a 50 mL round-bottomed flask and 4-(1-cyanocyclobutylamino)-2-fluoro-N-methylbenzamide 10 (0.5 g, 2.022 mmol) is added to the flask. The mixture is left under vacuum (using an oil pump) for 1 hour. N,N-dimethylformamide (DMF) (6 ml) is added, the flask sealed under argon with a stopper and heated to 80° C. in a CEM microwave reactor for 20 hours. Methanol (10 ml) and 2N HCl (6 ml) is added and the mixture is refluxed for 2 hours. The mixture is diluted with water (30 ml) and saturated aqueous NaHCO3 (30 ml) is added. The mixture is extracted with ethyl acetate (3×20 ml).

Aufarbeitung

  1. waitThe mixture is left under vacuum (
  2. customfor 1 hour
  3. customthe flask sealed under argon with a stopper
  4. temperaturethe mixture is refluxed for 2 hours
  5. additionis added
  6. extractionThe mixture is extracted with ethyl acetate (3×20 ml)

Quellen und Nachweise

ORD-Eintrag
ord-6e746ff9cb4e440aa415f801badd26a5
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388159B2

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