Sodium Carbonate → 5-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamine

HRID 334179Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 334179
Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[CH:6]=[C:7]3[N:12]([C:13]=2[N:14]=1)[CH2:11][CH2:10][O:9][C:8]3([CH3:16])[CH3:15].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:15][C:8]1([CH3:16])[C:7]2[N:12]([C:13]3[N:14]=[C:2]([C:31]4[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=4)[N:3]=[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]=3[CH:6]=2)[CH2:11][CH2:10][O:9]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 866673893-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene

Produkt 1

HCID 573839575-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamineAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene (75 mg, 0.23 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (115 mg, 0.52 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)-phosphine)dichloropalladium(II) (25 mg, 0.035 mmol) and sodium carbonate (1 mL, 1.0 mmol, 1M aqueous solution) in acetonitrile (3 mL) was degassed and heated at 150° C. for 30 mins in a microwave reactor, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-98%) affording 177 as a off-white solid (13 mg, 15%). LCMS (method B): RT=3.50 min, [M+H]+=382. 1H NMR (400 MHz, CDCl3): δ 9.27 (2H, s), 6.12 (1H, s), 5.27 (2H, broad s), 4.21 (2H, m), 4.14 m), 3.88 (4H, m), 1.62 (6H, s)

Aufarbeitung

  1. customwas degassed
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-92f27845235e4feab6196c8d4a73a22d
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883799B2

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