Propanamide, 3,3,3-trifluoro-N-(4-mercaptophenyl)- → HCID 178428243, Verbindung

HRID 490246Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 490246
[CH:1]1([C:4]2([F:25])[CH2:7][N:6]([C:8]3[N:13]=[C:12]([S:14]([CH3:17])(=O)=O)[N:11]=[C:10]([NH:18][C:19]4[NH:23][N:22]=[C:21]([CH3:24])[CH:20]=4)[CH:9]=3)[CH2:5]2)[CH2:3][CH2:2]1.[F:26][C:27]([F:40])([F:39])[CH2:28][C:29]([NH:31][C:32]1[CH:37]=[CH:36]C(S)=[CH:34][CH:33]=1)=[O:30]>CC#N>[CH3:24][C:21]1[CH:20]=[C:19]([NH:18][C:10]2[CH:9]=[C:8]([N:6]3[CH2:7][C:4]([CH:1]4[CH2:3][CH2:2]4)([F:25])[CH2:5]3)[N:13]=[C:12]([S:14][C:17]3[CH:34]=[CH:33][C:32]([NH:31][C:29](=[O:30])[CH2:28][C:27]([F:40])([F:26])[F:39])=[CH:37][CH:36]=3)[N:11]=2)[NH:23][N:22]=1

Komponenten

4

Edukt 2

HCID 57674932Propanamide, 3,3,3-trifluoro-N-(4-mercaptophenyl)-HCID 1784282456-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine

Produkt 1

HCID 178428243HCID 178428243, VerbindungAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

An slurry of 6-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine (61 g, 170 mmol) and 3,3,3-trifluoro-N-(4-mercaptophenyl)propanamide (41 g, 175 mmol) in CH3CN (1300 mL) was heated to reflux for 1.5 hours. During this time, the slurry transforms from thin and yellowish to thick and brilliant white. The mixture was then cooled to 0° C. and stirred at this temperature for 15 min. Filtered and washed with cold CH3CN (650 mL). The resulting solid was dried for 20 hours at 38° C. under house vacuum. The white solid was charged to a suitable reactor with EtOAc (1300 mL) and NaHCO3 (sat) (1300 mL). The mixture was stirred until no more solid remained. Then, the layers were separated and washed the aqueous with EtOAc (390 mL). The combined organic layers were dried over MgSO4, filtered, washed with EtOAc (130 mL) and concentrated to minimal volume on rotavap. The resulting mixture was re-crystallized out of EtOAc and hexane to give the desired product as a white solid (56.2 g, 72%) 1H NMR (MeOD, 400 MHz): 0.40-0.45 (2H, m), 0.60-0.65 (2H, m), 1.3-1.4 (1H, m), 2.05 (2H, s), 3.25-3.40 (2H, m), 3.85-3.40 (4H, m), 5.40-5.50 (2H, m), 7.50-7.55 (2H, d), 7.65-7.70 (2H, d). ES+ 522.

Aufarbeitung

  1. temperatureto reflux for 1.5 hours
  2. filtrationFiltered
  3. washwashed with cold CH3CN (650 mL)
  4. customThe resulting solid was dried for 20 hours at 38° C. under house vacuum
  5. additionThe white solid was charged to a suitable reactor with EtOAc (1300 mL) and NaHCO3 (sat) (1300 mL)
  6. stirringThe mixture was stirred until no more solid
  7. customThen, the layers were separated
  8. washwashed the aqueous with EtOAc (390 mL)
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. washwashed with EtOAc (130 mL)
  12. concentrationconcentrated to minimal volume on rotavap
  13. customThe resulting mixture was re-crystallized out of EtOAc and hexane

Quellen und Nachweise

ORD-Eintrag
ord-89cf82f15d9146d8becc85099b525d4d
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07528142B2

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