Acetone → 5-(2,6-Dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine hydrochloride hydrate

HRID 709525Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 709525
[N:1]1([C:7]2[N:12]=[C:11]([C:13]3[C:14]([C:20]([F:23])([F:22])[F:21])=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=3)[CH:10]=[C:9]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CC(C)=O.[ClH:34]>O>[ClH:34].[OH2:4].[N:1]1([C:7]2[N:12]=[C:11]([C:13]3[C:14]([C:20]([F:23])([F:21])[F:22])=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=3)[CH:10]=[C:9]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[N:8]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Komponenten

5

Edukt 3

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 16654980Buparlisib

Produkt 1

HCID 668340295-(2,6-Dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine hydrochloride hydrateAusbeute 151,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Charge a nitrogen-flushed 2 L reactor that equipped with an overhead stirrer, condenser, nitrogen inlet/outlet and 500 mL addition funnel with 82.08 g (0.20 mol, 1 eq.) of 5 and 792 g (1.0 L) of acetone. Stir the slurry at 25° C. for 15 minutes. Add a solution of 34.3 mL (0.206 mol, 1.03 eq.) of 6 N hydrogen chloride in water. Add 3 mg of seed. Solids formed. Add 20 mL of water. Heat the batch to reflux (55-56° C.) and maintain at reflux for 15 minutes. Cool to 20° C. over 1.5 h. Cool to 5° C. over 1 h and filter the solids. Wash the filter cake with 80 mL of 5° C. acetone and dry the solids at 40° C., 35 mbar for 16 h to afford 70.4 g (75.7% yield) of the title compound as a yellow, crystalline solid. Following this procedure, the resulting compound is the monohydrate of the monohydrochloride salt (Polymorph Form Ha) of the Compound of Formula A.

Aufarbeitung

  1. additionCharge a nitrogen-
  2. customflushed 2 L reactor
  3. additionAdd 3 mg of seed
  4. customSolids formed
  5. temperatureHeat the batch
  6. temperatureto reflux (55-56° C.)
  7. temperaturemaintain
  8. temperatureat reflux for 15 minutes
  9. temperatureCool to 20° C. over 1.5 h
  10. temperatureCool to 5° C. over 1 h
  11. filtrationfilter the solids
  12. washWash the filter cake with 80 mL of 5° C. acetone
  13. customdry the solids at 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-c3a0cf1a640049b0affd9e114b904594
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181215B2

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