3-[bis(methylsulfanyl)methylene]-1-isopentyl-2,4(1H,3H)-pyridinedione → 3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-2(1H)-pyridinone

HRID 601421Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601421
CS[C:3](SC)=[C:4]1[C:9](=[O:10])[CH:8]=[CH:7][N:6]([CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:5]1=[O:16].[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26]C(=O)OC(C)(C)C)=[CH:22][C:21]=1[S:34]([NH2:37])(=[O:36])=[O:35]>O1CCOCC1>[NH2:26][C:23]1[CH:24]=[CH:25][C:20]2[NH:19][C:3]([C:4]3[C:5](=[O:16])[N:6]([CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15])[CH:7]=[CH:8][C:9]=3[OH:10])=[N:37][S:34](=[O:36])(=[O:35])[C:21]=2[CH:22]=1

Komponenten

4

Edukt 2

HCID 100395903-[bis(methylsulfanyl)methylene]-1-isopentyl-2,4(1H,3H)-pyridinedioneHCID 59805694(4-Amino-3-sulfamoyl-phenyl)-carbamic acid tert-butyl ester

Produkt 1

HCID 1363519723-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-2(1H)-pyridinone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

The product of Example 457C (2.08 g, 7.29 mmol) was treated with the product of Example 414A (2.00 g, 6.96 mmol) in dioxane (20 mL) at 115° C. for 30 minutes, cooled to 25° C. and concentrated under reduced pressure. A solution of the residue in 4M hydrochloric acid in dioxane (20 mL) was stirred at 25° C. for 18 hours and concentrated under reduced pressure. The residue was triturated with dichloromethane and filtered to give the title compound. The filtrate containing the protected intermediate was concentrated and purified by chromatography on silica gel eluting with 1% methanol in dichloromethane. The protected product was re-subjected to the above deprotection conditions to provide the title compound as its hydrochloride salt (2.02 g, 96%). 1H NMR (300 MHz, DMSO-d6) δ 0.92 (s, 3 H) 0.94 (s, 3 H) 1.58 (m, 3 H) 3.99 (m, 2 H) 6.31 (d, J=7.35 Hz, 1 H) 6.96 (m, 2 H) 7.34 (d, J=8.46 Hz, 1 H) 8.04 (d, J=7.35 Hz, 1 H) 14.04 (s, 1 H) 14.19 (s, 1 H). MS (ESI−) m/z 375 (M−H)−.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was triturated with dichloromethane
  4. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-da8a6508cbcd4108856087f3625c0017
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902203B2

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