Hydrochloric Acid → 2-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)butanamide

HRID 601353Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601353
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:21]=2[S:20](=[O:30])(=[O:29])[N:19]=1.Cl[CH:32]([CH2:36][CH3:37])[C:33]([NH2:35])=[O:34].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([O:28][CH:32]([CH2:36][CH3:37])[C:33]([NH2:35])=[O:34])=[CH:27][C:21]=2[S:20](=[O:29])(=[O:30])[N:19]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 3449692-ChlorobutyramideHCID 1363584044-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(isobutylamino)quinolin-2(1H)-one

Produkt 1

HCID 1363584952-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)butanamideAusbeute 100,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of the product of Example 321C (20 mg, 0.0467 mmol) in N,N-dimethylformamide (2 mL) was added 2-chlorobutyramide (8.5 mg, 0.070 mmol), tetra-n-butylammonium iodide (1.7 mg, 0.0047 mmol) and cesium carbonate (61 mg, 0.187 mmol). The mixture was stirred at 25° C. for 18 hours, then heated to 80° C. for 3 hours. After cooling to 25° C., 1N aqueous hydrochloric acid (10 mL) was added and the mixture extracted with ethyl acetate (10 mL). The resulting organic layer was separated and dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (24 mg, 100%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 512 (M−Na)−. 1H NMR (300 MHz, DMSO-d6) δ 0.99 (t, J=7.7 Hz, 3H), 1.03 (d, J=6.3 Hz, 6H), 1.83 (m, 3H), 2.50 (m, 1H), 2.75 (m, 1H), 4.46 (m, 1H), 5.94 (m, 1H), 7.08 (m, 2H), 7.17 (m, 1H), 7.23 (m, 1H), 7.32 (s, 1H), 7.58 (m, 2H), 7.64 (s, 1H), 8.07 (d, J=7.8 Hz, 1H), 16.23 (bs, 1H).

Aufarbeitung

  1. temperatureheated to 80° C. for 3 hours
  2. temperatureAfter cooling to 25° C.
  3. extractionthe mixture extracted with ethyl acetate (10 mL)
  4. customThe resulting organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-43a7d4795e4f45c2aa2c3bea24c5cae3
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902203B2

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