Sodium Carbonate → HCID 68195143, Verbindung

HRID 1631812Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1631812
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])[CH2:7][C@@H:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[OH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=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>[OH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:14])[CH2:7][C@@H:6]4[CH2:23][O:24][CH2:25][CH2:26][N:5]4[C:4]=3[N:3]=2)=[CH:31][CH:30]=1

Komponenten

8

Edukt 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 86670145HCID 86670145, Verbindung

Produkt 1

HCID 68195143HCID 68195143, VerbindungAusbeute 32 %

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-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x26, 50 mg, 0.131 mmol), 4-(hydroxymethyl)phenylboronic acid (29.8 mg, 0.196 mmol), tetrakis(triphenylphosphine)palladium(0) (15.13 mg, 0.013 mmol), and sodium carbonate (27.8 mg, 0.262 mmol) in 1,4-dioxane (0.5 mL) and water (0.25 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 a white solid, which was recrystallized from EtOH/EtOAc to give the title compound as an off-white solid (19.0 mg, 32.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.21 (m, 2H), 1.48-1.71 (m, 3H), 2.91-3.02 (m, 3H), 3.12-3.32 (m, 5H), 3.50-3.67 (m, 2H), 3.73-4.08 (m, 6H), 4.49-4.61 (m, 3H), 5.19 (t, J=5.68 Hz, 1H), 7.34 (d, J=8.59 Hz, 2H), 7.47-7.51 (m, 1H), 8.08 (t, J=5.94 Hz, 1H), 8.16 (d, J=8.34 Hz, 2H); ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 454.24. found 454.4.

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)
  7. customto afford a white solid, which
  8. customwas recrystallized from EtOH/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-02c13c8b987549c99628106d67a0dfac
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791107B2

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