1,4-Dioxane → HCID 178461673, Verbindung

HRID 1631797Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1631797
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:13])[C:7](=[O:20])[C@@H:6]3[CH2:21][O:22][CH2:23][CH2:24][N:5]3[C:4]=2[N:3]=1.B1([C:34]2[NH:38][N:37]=[CH:36][CH:35]=2)OC(C)(C)C(C)(C)O1.O1CCOCC1.C([O-])(O)=O.[Na+]>[Pd].Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN(C=O)C>[C:14]1([C@@H:12]([N:8]2[C:7](=[O:20])[CH:6]3[CH2:21][O:22][CH2:23][CH2:24][N:5]3[C:4]3[N:3]=[C:2]([C:36]4[CH:35]=[CH:34][NH:38][N:37]=4)[N:11]=[CH:10][C:9]2=3)[CH3:13])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Komponenten

8

Edukt 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 219315393-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86670120HCID 86670120, Verbindung

Produkt 1

HCID 178461673HCID 178461673, VerbindungAusbeute 17,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a 2 mL microwave vial were added (S)-2-chloro-5-(1-phenylethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x47, 36 mg, 0.104 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxabolone)-pyrrazole (40.5 mg, 0.209 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (4.29 mg, 5.22 μmol). After the vial was sealed, dioxane (0.6 mL) and aqueous saturated NaHCO3 (0.15 mL) were added, and the mixture was degassed by bubbling nitrogen through a syringe needle for 10 minutes. The mixture was then heated in a microwave to 120° C. for 60 minutes. Another 2 equivalents of boronic ester and 0.05 equivalents of palladium catalyst were added, and the mixture was heated in the microwave for another 60 minutes. DMF (1 mL) was added and the mixture was filtered by syringe filter. The crude product was purified by preparatory HPLC, eluting with a gradient of 25-30% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA). Lyophilization of the collected fractions gave a diastereomeric mixture of the title compound (TFA salt) as a white solid (7 mg, 14%). 1H NMR (400 MHz, DMSO-d6) δ 1.68 (d, J=7.1 Hz, 3H), 1.75 (d, J=7.3 Hz, 4H), 2.26 (t, J=1.8 Hz, 1H), 2.60, (t, J=1.8 Hz, 1H), 2.94 (br s, 3H), 3.46-3.73 (m, 11H), 3.90-3.99 (m, 4H), 4.18 (dt, J=11.4, 3.6 Hz, 4H), 4.40-4.66 (m, 7H), 6.13 (d, J=6.8 Hz, 1H), 6.24 (d, J=7.1 Hz, 1H), 6.72 (br s, 3H), 7.17-7.38 (m, 14H), 7.40 (br s, 1H), 7.55 (d, J=18.4 Hz, 4H). ESI-MS m/z [M+H]+ calc'd for C20H20N6O2, 377.16. found 377.4.

Aufarbeitung

  1. customAfter the vial was sealed
  2. customthe mixture was degassed
  3. customby bubbling nitrogen through a syringe needle for 10 minutes
  4. temperaturethe mixture was heated in the microwave for another 60 minutes
  5. filtrationthe mixture was filtered by syringe
  6. filtrationfilter
  7. customThe crude product was purified by preparatory HPLC
  8. washeluting with a gradient of 25-30% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA)
  9. customLyophilization of the collected fractions gave

Quellen und Nachweise

ORD-Eintrag
ord-3172fbdffa5d4c5fb2fa250914476997
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791107B2

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