Cesium carbonate → 3-[(2,3-Dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

HRID 548764Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 548764
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[S:18][N:17]=[C:16]([CH3:19])[N:15]=1)=[O:12].F[C:29]1[CH:41]=[CH:40][C:32]2[C:33](=[O:39])[N:34]([CH3:38])[CH2:35][CH2:36][O:37][C:31]=2[CH:30]=1>CC(N(C)C)=O>[CH3:35][CH:36]1[N:34]([CH3:38])[C:33](=[O:39])[C:32]2[CH:40]=[CH:41][C:29]([O:7][C:8]3[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=3)[C:11]([NH:13][C:14]3[S:18][N:17]=[C:16]([CH3:19])[N:15]=3)=[O:12])=[CH:30][C:31]=2[O:37]1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 576631608-fluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-oneHCID 591271603-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

Produkt 1

HCID 159500393-[(2,3-Dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamideAusbeute 64,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

Cesium carbonate (489 mg, 1.5 mmol) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide (155 mg, 0.5 mmol) and 8-fluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (117 mg, 0.6 mmol) in DMA (5 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 8 hours. The mixture was cooled to RT and pressure, the DMA removed in vacuo, and the residue partitioned between water (25 mL) and ethyl acetate (30 mL). The mixture was adjusted to pH 2, the organic layer washed with brine, dried (MgSO4) and evaporated in vacuo to a residue which was chromatographed on silica, eluting with ethyl acetate, to give desired compound (156 mg). 1H NMR δ (CDCl3): 1.3 (d, 3H), 1.5 (d, 2H), 2.4 (s, 3H), 3.0 (s, 3H), 3.7 (d, 2H), 4.5 (m, 1H), 5.35 (q, 1H), 6.4 (s, 1H), 6.6 (d, 1H), 6.75 (s, 1H), 7.15 (s, 1H), 7.2 (s, 1H), 7.8 (d, 1H); m/z 485 (M+H)+

Aufarbeitung

  1. temperatureThe mixture was cooled to RT
  2. custompressure, the DMA removed in vacuo
  3. customthe residue partitioned between water (25 mL) and ethyl acetate (30 mL)
  4. washthe organic layer washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo to a residue which
  7. customwas chromatographed on silica
  8. washeluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-3d9f88d39d584b38b3dd0aa33e49d68b
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07943607B2

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