Diisopropylethylamine → N2-[(1S)-1-(5-Fluoropyridin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-yl-5-nitropyrimidine-2,4-diamine

HRID 450393

Reaktionsgleichung

Reaktionsgleichung von HRID 450393
[CH3:1][C:2]1[NH:6][N:5]=[C:4]([NH:7][C:8]2[C:13]([N+:14]([O-:16])=[O:15])=[C:12]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:11]=[C:10](SC)[N:9]=2)[CH:3]=1.OOS([O-])=O.[K+].C([O-])(O)=O.[Na+].[F:36][C:37]1[CH:38]=[CH:39][C:40]([C@@H:43]([NH2:45])[CH3:44])=[N:41][CH:42]=1.CCN(C(C)C)C(C)C>CO.C(Cl)Cl.O.CCOC(C)=O>[F:36][C:37]1[CH:38]=[CH:39][C:40]([C@@H:43]([NH:45][C:10]2[N:9]=[C:8]([NH:7][C:4]3[CH:3]=[C:2]([CH3:1])[NH:6][N:5]=3)[C:13]([N+:14]([O-:16])=[O:15])=[C:12]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:11]=2)[CH3:44])=[N:41][CH:42]=1

Komponenten

10

Edukt 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 16097531(S)-1-(5-Fluoropyridin-2-yl)ethanamine2×HCID 23707502Potassium hydroxy sulfiteHCID 68734536N-(5-Methyl-1H-pyrazol-3-yl)-2-(methylthio)-6-morpholin-4-yl-5-nitropyrimidin-4-amine2×

Produkt 1

HCID 68781731N2-[(1S)-1-(5-Fluoropyridin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-yl-5-nitropyrimidine-2,4-diamineAusbeute 147,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of N-(5-methyl-1H-pyrazol-3-yl)-2-(methylthio)-6-morpholin-4-yl-5-nitropyrimidin-4-amine (Intermediate 57, 118 mg) in MeOH (2 ml) and DCM (2 ml) were added Oxone® (302 mg) and NaHCO3 (56 mg) and the resulting mixture was stirred at ambient temperature for 16 hours. [(1S)-1-(5-fluoropyridin-2-yl)ethyl]amine (Intermediate 8, 250 mg) and DIPEA (3 ml) were added and the resulting mixture was stirred at ambient temperature for 3 hours. The mixture was diluted with H2O and EtOAc and the aqueous layer was extracted with EtOAc (4×). The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution, dried and evaporation of the volatiles under reduced pressure gave a colored residue. Purification by column chromatography (60% EtOAc/hexanes) gave the title compound (220 mg). LCMS: 444 [M+1].

Aufarbeitung

  1. stirringthe resulting mixture was stirred at ambient temperature for 3 hours
  2. extractionthe aqueous layer was extracted with EtOAc (4×)
  3. washThe combined organic layers were washed with brine, saturated NaHCO3 (aq) solution
  4. customdried
  5. customevaporation of the volatiles under reduced pressure
  6. customgave a colored residue
  7. customPurification by column chromatography (60% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-75f62d296e20468bbb7cd3537c87a3c8
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486966B2

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