Acetic Acid → 3-(1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-1,8-naphthyridin-2-one

HRID 601103Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601103
[CH3:1][CH:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:10]2[N:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])O[C:6]1=[O:16].[O:18]=[S:19]1(=[O:35])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]([CH2:29]C(OCC)=O)=[N:20]1.[H-].[Na+].C(O)(=O)C>C1COCC1.Cl>[O:35]=[S:19]1(=[O:18])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]([C:29]2[C:6](=[O:16])[N:5]([CH2:4][CH2:3][CH:2]([CH3:1])[CH3:17])[C:10]3[C:9]([C:8]=2[OH:15])=[CH:14][CH:13]=[CH:12][N:11]=3)=[N:20]1

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 6588352H-1,2,4-Benzothiadiazine-3-acetic acid ethyl ester 1,1-dioxideHCID 102361501-Isopentyl-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

Produkt 1

HCID 1354945853-(1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-1,8-naphthyridin-2-oneAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

To a solution of the product of Example 12A (0.216 g, 0.92 mmol) and the product of Example 1C (0.247 g, 0.922 mmol) in anhydrous THF (7.5 mL) under nitrogen at 20° C. was added sodium hydride (95%, 0.089 g, 3.7 mmol). The reaction was heated at reflux for 3 hours, cooled to 20° C., and added dropwise glacial acetic acid (2.4 mL). The resulting mixture was heated at reflux for 1 hour, cooled to 25° C., and diluted with aqueous hydrochloric acid (0.5 M, 35 mL). The resulting precipitate was collected by filtration, washed with water and dried. The crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1) to give the title compound as a white solid (0.031 g, 20%). MS (ESI−) m/z 411 (M−H)−. The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 411 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.95 (s, 3H), 0.98 (s, 3H), 1.47 (m, 2H), 1.64 (m, 1H), 4.30 (t, J=7.72 Hz, 2H), 7.13 (dd, J=7.72, 4.78 Hz, 1H), 7.26 (d, J=8.09 Hz, 1H), 7.30 (d, J=7.72 Hz, 1H), 7.55 (t, J=7.72 Hz, 1H), 7.66 (d, J=8.09 Hz, 1H), 8.37 (dd, J=7.72, 1.84 Hz, 1H), 8.53 (dd, J=4.78, 2.21 Hz, 1H), 15.94 (s, 1H).

Aufarbeitung

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 3 hours
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 1 hour
  5. temperaturecooled to 25° C.
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with water
  8. customdried
  9. customThe crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1)

Quellen und Nachweise

ORD-Eintrag
ord-2051f8941d044664896fc03024bde424
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902203B2

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