Cesium carbonate → HCID 16039605, Verbindung

HRID 1011713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1011713
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:21])[CH2:19][CH3:20])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[N:22]1([C:26]([C:28]2[CH:33]=[CH:32][C:31](Br)=[CH:30][N:29]=2)=[O:27])[CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]Br>[N:22]1([C:26]([C:28]2[N:29]=[CH:30][C:31]([O:1][C:2]3[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:21])[CH2:19][CH3:20])[CH:16]=3)[C:5]([NH:7][C:8]3[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=3)=[O:6])=[CH:32][CH:33]=2)=[O:27])[CH2:25][CH2:24][CH2:23]1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 59127175HCID 59127175, Verbindung

Produkt 1

HCID 16039605HCID 16039605, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11251615Bromotris(triphenylphosphine)copper(I)KatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A mixture of 3-hydroxy-5-{[(1S)-1-methylpropyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.116 g, 0.4 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (116 mg, 0.48 mmol), cesium carbonate (392 mg, 1.2 mmol) and bromotris(triphenylphosphine)copper(I) (38 mg, 0.04 mmol) in DMA (5 mL) was stirred in the microwave reactor at 160° C. for 4 hours. The product was dissolved in ethyl acetate (20 mL) and water (15 mL) and the layers separated. The organic layer was washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a brown oil which was chromatographed on silica, eluting with a gradient of 0-5% methanol in ethyl acetate, and then re-columned on silica, eluting with a gradient of 0-5% methanol in DCM, to give the desired compound as a white foam which crystallised on standing. The material was triturated with 50% ethyl acetate in hexane to give the required product as a white solid (95 mg). 1H NMR δ (CDCl3): 0.90 (t, 3H), 1.23 (d, 3H), 1.51-1.72 (m, 2H), 2.28 (quin, 2H), 3.73 (s, 3H), 4.18 (t, 2H), 4.28 (q, 1H), 4.64 (t, 2H), 6.67 (t, 1H), 6.72 (d, 1H), 6.99 (s, 1H), 7.15 (s, 1H), 7.22 (d, 1H), 7.31 (d, 1H), 8.04 (d, 1H), 8.26 (s, 1H), 8.41 (s, 1H); m/z 450 (M+H)+

Aufarbeitung

  1. customwater (15 mL) and the layers separated
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customto give a brown oil which
  7. customwas chromatographed on silica
  8. washeluting with a gradient of 0-5% methanol in ethyl acetate
  9. washre-columned on silica, eluting with a gradient of 0-5% methanol in DCM

Quellen und Nachweise

ORD-Eintrag
ord-4861208e3665499793d61ec6290aa2e2
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07977328B2

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