Sodium Carbonate → HCID 68195034, Verbindung

HRID 1631810Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1631810
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([N:15]([CH3:23])[CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])[CH2:7][C@@H:6]3[CH2:24][O:25][CH2:26][CH2:27][N:5]3[C:4]=2[N:3]=1.[NH:28]1[C:36]2[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[C:31]=2[CH:30]=[CH:29]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:28]1[C:36]2[C:31](=[C:32]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([N:15]([CH3:23])[CH2:16][CH:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[O:14])[CH2:7][C@@H:6]5[CH2:24][O:25][CH2:26][CH2:27][N:5]5[C:4]=4[N:3]=3)[CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29]1

Komponenten

8

Edukt 3

HCID 10340Sodium CarbonateHCID 27631731H-Indole-4-boronic acidHCID 86670144HCID 86670144, Verbindung

Produkt 1

HCID 68195034HCID 68195034, VerbindungAusbeute 43,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of (R)-2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x79, 70 mg, 0.177 mmol), indole-4-boronic acid (42.7 mg, 0.265 mmol), tetrakis(triphenylphosphine)palladium(0) (20.43 mg, 0.018 mmol), and sodium carbonate (37.5 mg, 0.354 mmol) in 1,4-dioxane (0.7 mL) and water (0.35 mL) was heated to 120° C. for 1 hour in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica-NH, gradient 0-10% MeOH/CHCl3) to afford the title compound as an off-white solid (36.8 mg, 43.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.61 (m, 4H), 1.78-1.97 (m, 1H), 2.80-3.09 (m, 4H), 3.12-3.38 (m, 7H), 3.58 (t, J=9.98 Hz, 2H), 3.78-4.16 (m, 5H), 4.41-4.60 (m, 2H), 7.11 (t, J=7.71 Hz, 1H), 7.26-7.64 (m, 4H), 7.86-7.95 (m, 1H), 11.11 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C26H32N6O3, 477.26. found 477.3.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica-NH, gradient 0-10% MeOH/CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-92a0bab6de814b6a8f38ef0c6bb23f51
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791107B2

Notizen zur Reaktion

Wird geladen…