Sodium Bicarbonate → 1-(4-(5-Isopropyl-6a-methyl-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylurea

HRID 2386231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2386231
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]([CH3:14])[CH3:13])[C:7](=[O:15])[C:6]3([CH3:20])[CH2:16][O:17][CH2:18][CH2:19][N:5]3[C:4]=2[N:3]=1.[CH3:21][NH:22][C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=1)=[O:24].C(=O)(O)[O-].[Na+]>O1CCOCC1.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]>[CH:12]([N:8]1[C:7](=[O:15])[C:6]2([CH3:20])[CH2:16][O:17][CH2:18][CH2:19][N:5]2[C:4]2[N:3]=[C:2]([C:29]3[CH:28]=[CH:27][C:26]([NH:25][C:23]([NH:22][CH3:21])=[O:24])=[CH:31][CH:30]=3)[N:11]=[CH:10][C:9]1=2)([CH3:14])[CH3:13]

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 866515712-chloro-5-isopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Produkt 1

HCID 513520731-(4-(5-Isopropyl-6a-methyl-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylureaAusbeute 22,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

2-Chloro-5-isopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (98 mg, 0.330 mmol) was mixed with PdCl2(dppf) (48.3 mg), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (100 mg, 0.363 mmol) and saturated sodium bicarbonate solution (2 mL, sat.) in 1,4-dioxane (4 mL). The suspension was heated by microwave irradiation at 100° C. for 30 minutes. The suspension was filtered, the solids washed with methanol then DMSO and the filtrate evaporated in vacuo. The resulting solid was purified by mass triggered preparative HPLC eluted with 20-35% of ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column) to give the title compound (30 mg 22% yield) as a pale yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.55 (m, 6H) 1.62 (s, 3H) 2.80 (s, 3H) 3.50 (td, J=12, 4 Hz, 1H) 3.68 (td, J=12, 4 Hz, 1H) 3.79 (d, J=12 Hz, 1H) 4.14 (m, 1H) 4.62 (dd, J=12, 4 Hz, 1H) 4.66 (m, 1 H) 7.62 (d, J=8 Hz, 2H) 8.10 (d, J=8 Hz, 2H) 8.13 (s, 1H). MS [M+H] Found 411.

Aufarbeitung

  1. filtrationThe suspension was filtered
  2. washthe solids washed with methanol
  3. customDMSO and the filtrate evaporated in vacuo
  4. customThe resulting solid was purified by mass
  5. washeluted with 20-35% of ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column)

Quellen und Nachweise

ORD-Eintrag
ord-d4762c80d9864a28a71040ea7cebdc1a
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08268819B2

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