Sodium hydride → (6S)-6-[(5-Chloro-2-pyrazinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

HRID 1446080Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1446080
[H-].[Na+].[N+:3]([C:6]1[N:7]=[C:8]2[N:13]([CH:14]=1)[CH2:12][C@H:11]([OH:15])[CH2:10][O:9]2)([O-:5])=[O:4].[Cl:16][C:17]1[CH:22]=[N:21][C:20]([CH2:23]I)=[CH:19][N:18]=1>CN(C=O)C>[Cl:16][C:17]1[N:18]=[CH:19][C:20]([CH2:23][O:15][C@@H:11]2[CH2:10][O:9][C:8]3=[N:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:14][N:13]3[CH2:12]2)=[N:21][CH:22]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 10130259(S)-2-nitro-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazin-6-olHCID 866357892-Chloro-5-(iodomethyl)pyrazine

Produkt 1

HCID 49852136(6S)-6-[(5-Chloro-2-pyrazinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazineAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Triethylamine (4.17 mL, 3.0 mmol) and mesyl chloride (1.57 mL, 2.00 mmol) were added to a solution of (5-chloro-2-pyrazinyl)methanol (1.44 g, 10.0 mmol) in anhydrous THF (20 mL) at 0° C. The mixture was stirred at 0° C. for 0.5 h then partitioned between EtOAc/water. The organic fraction was dried (MgSO4) and the solvent was removed under reduced pressure to give the crude mesylate. The mesylate was dissolved in acetone (40 mL), sodium iodide (7.5 g, 50 mmol) was added and the mixture was refluxed for 1 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc/water. The residue was chromatographed on silica gel (DCM) to give 2-chloro-5-(iodomethyl)pyrazine. Sodium hydride (60% w/w, 0.36 g, 9.0 mmol) was added to a solution of (S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxa-zin-6-ol (0.93 g, 5.02 mmol) and 2-chloro-5-(iodomethyl)pyrazine (1.54 g, 6.05 mmol) in DMF (10 mL) at −78° C. The mixture was stirred at 0° C. for 1 h and then quenched with ice. EtOAc (200 mL) was added, the organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with a gradient (0-5%) MeOH/EtOAc to give the title compound (1.015 g, 65%) as a white solid. APCI MS m/z 312.6 (M+H). 1H NMR (400 MHz, (CD3)2SO) δ 8.76 (d, J=1.4 Hz, 1H), 8.50 (d, J=1.4 Hz, 1H), 8.02 (s, 1H), 4.85 (d, J=13.7 Hz, 1H), 4.81 (d, J=13.7 Hz, 1H), 4.70 (td, J=12.1, 2.6 Hz, 1H), 4.49 (bd, J=12.0 Hz, 1H), 4.29-4.38 (m, 2H), 4.25 (dd, J=13.5, 3.3 Hz, 1H).

Aufarbeitung

  1. customquenched with ice
  2. additionEtOAc (200 mL) was added
  3. dry with materialthe organic layer was dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on silica gel
  6. washeluting with a gradient (0-5%) MeOH/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-933b93b416da43f1b24c041e2bb882c4
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07666864B2

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