Tetrahydrofuran → 5-(6-Chloro-2-morpholin-4-ylpyrimidin-4-yl)pyridin-2-ylamine

HRID 1043801

Reaktionsgleichung

Reaktionsgleichung von HRID 1043801
C1COCC1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:13]1[CH:18]=[C:17]([Cl:19])[N:16]=[C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:14]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=2)O1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.CCOC(C)=O>[Cl:19][C:17]1[N:16]=[C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:14]=[C:13]([C:34]2[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=2)[CH:18]=1

Komponenten

8

Edukt 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholine

Produkt 1

HCID 595075305-(6-Chloro-2-morpholin-4-ylpyrimidin-4-yl)pyridin-2-ylamineAusbeute 44,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

THF (130 mL) and aq. Na2CO3 (2M, 40 mL, 80 mmol) were added to a glass pressure vessel containing 4,6-dichloro-2-morpholinopyrimidine (prepared as in Method 22; 4.5 g, 19.2 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (4.7 g, 21.2 mmol). The resulting mixture was stirred and sparged with argon for 1-2 minutes. The catalyst, dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (1.26 g, 1.54 mmol), was then added in one portion. After sealing the reaction vessel, the reaction was heated at 85° C. for 1 hour with stirring. Upon cooling to RT, the THF was removed under reduced pressure to leave a viscous residue. EtOAc (450 mL) and water (50 mL) were added. After vigorously stirring for 1-2 minutes, the solids were filtered off and washed with EtOAc (100 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (100 mL). The combined organic layers were washed with saturated NaCl solution (1×50 mL), dried with Na2SO4, filtered and evaporated under reduced pressure. The crude material was further purified by silica gel chromatography to give 5-(6-chloro-2-morpholin-4-yl-pyrimidin-4-yl)-pyridin-2-ylamine (2.48 g, 44%). LC/MS (m/z): 292.1 (MH+), Rt 2.06 minutes.

Aufarbeitung

  1. customsparged with argon for 1-2 minutes
  2. stirringwith stirring
  3. temperatureUpon cooling to RT
  4. customthe THF was removed under reduced pressure
  5. customto leave a viscous residue
  6. stirringAfter vigorously stirring for 1-2 minutes
  7. filtrationthe solids were filtered off
  8. washwashed with EtOAc (100 mL)
  9. customThe organic layer was separated
  10. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  11. washThe combined organic layers were washed with saturated NaCl solution (1×50 mL)
  12. dry with materialdried with Na2SO4
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. customThe crude material was further purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-1b334ca990f84f09b9942467c39315eb
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563549B2

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