Sodium Carbonate → 2-(2-aminopyrimidin-5-yl)-8-methyl-4-morpholino-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one

HRID 528500Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 528500
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[O:6][CH2:7][C:8](=[O:13])[N:9]([CH3:12])[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][C:31]([NH2:34])=[N:32][CH:33]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:34][C:31]1[N:32]=[CH:33][C:28]([C:2]2[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]3[O:6][CH2:7][C:8](=[O:13])[N:9]([CH3:12])[C:10]=3[N:11]=2)=[CH:29][N:30]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117722-Chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one

Produkt 1

HCID 867117732-(2-aminopyrimidin-5-yl)-8-methyl-4-morpholino-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-oneAusbeute 71,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 2-chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one (100 mg, 0.35 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (116 mg, 0.53 mmol), Pd(PPh3)2Cl2 (25 mg, 0.035 mmol) and sodium carbonate (1.0 mL, 1.0 mmol, 1M aqueous solution) in acetonitrile (4 mL) was degassed then heated at 120° C. for 30 minutes using microwave irradiation. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with methanol and the product eluted with 2M ammonia in methanol. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%) affording 120 as a white solid (86 mg, 71%). LCMS: RT=3.04 min, [M+H]+=344. 1H NMR (400 MHz, CDCl3): δ 9.14 (2H, s), 5.25 (2H, broad s), 4.62 (2H, s), 3.81 (8H, s), 3.49 (3H, s).

Aufarbeitung

  1. customwas degassed
  2. custommicrowave irradiation
  3. washwas washed with methanol
  4. washthe product eluted with 2M ammonia in methanol
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%)

Quellen und Nachweise

ORD-Eintrag
ord-533e8bb4122a46898e1a937555aac64b
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346817B2

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