4,5-Dichlorothiophene-2-sulfonyl chloride → 4,5-dichloro-N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}thiophene-2-sulfonamide

HRID 601378Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601378
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[Cl:31][C:32]1[S:33][C:34]([S:38](Cl)(=[O:40])=[O:39])=[CH:35][C:36]=1[Cl:37]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:37][C:36]1[CH:35]=[C:34]([S:38]([NH:1][C:2]2[CH:30]=[CH:29][C:5]3[NH:6][C:7]([C:12]4[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]5[C:20]([C:21]=4[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=5)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=3[CH:3]=2)(=[O:40])=[O:39])[S:33][C:32]=1[Cl:31]

Komponenten

5

Edukt 2

HCID 5186224,5-Dichlorothiophene-2-sulfonyl chlorideHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-one

Produkt 1

HCID 1363585024,5-dichloro-N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}thiophene-2-sulfonamideAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To the product of Example 205 (0.020 g, 0.047 mmol) in pyridine (0.2 mL) was added 2,3-dichlorothiophene-5-sulfonyl chloride (0.015 g, 0.056 mmol). The reaction mixture was heated in a microwave reactor at 100° C. for 15 minutes. The reaction was diluted with ethyl acetate (40 mL), washed with 1 N hydrochloric acid, water, and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel eluting with 99:1 dichloromethane:methanol to give the title compound (14.8 mg, 50%). 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.25 Hz, 6 H) 1.56 (m, 2 H) 1.69 (m, 1 H) 4.47 (m, 2 H) 7.50 (m, 2 H) 7.56 (s, 1 H) 7.71 (d, J=8.82 Hz, 1 H) 7.76 (s, 1 H) 8.55 (dd, J=7.91, 2.02 Hz, 1 H) 8.88 (dd, J=4.60, 1.65 Hz, 1 H) 11.28 (s, 1 H) 14.19 (br s, 1 H). MS (ESI−) m/z 640 (M−H)−.

Aufarbeitung

  1. washwashed with 1 N hydrochloric acid, water, and brine
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel eluting with 99:1 dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-b4b8aa4c150642789de4229da30d533e
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902203B2

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