Potassium Carbonate → 8-(3-Sulfamoyl-phenylamino)-4,5-dihydro-thiazolo[4,5-h]quinazoline-2-carboxylic acid ethyl ester

HRID 643750

Reaktionsgleichung

Reaktionsgleichung von HRID 643750
[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]2[C:14](=O)[CH2:13][CH2:12][CH2:11][C:9]=2[N:10]=1)=[O:5])[CH3:2].[CH3:16]N(C=O)C.CC(N(C)C)=O.Cl.[NH:28]([C:32]1[CH:33]=[C:34]([S:38]([NH2:41])(=[O:40])=[O:39])[CH:35]=[CH:36][CH:37]=1)[C:29]([NH2:31])=[NH:30].C(=O)([O-])[O-].[K+].[K+]>O>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]2[C:14]3[N:31]=[C:29]([NH:28][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([S:38](=[O:39])(=[O:40])[NH2:41])[CH:33]=4)[N:30]=[CH:16][C:13]=3[CH2:12][CH2:11][C:9]=2[N:10]=1)=[O:5])[CH3:2]

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 14955933Ethyl 7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazole-2-carboxylateHCID 22628260N,N-dimethylformamide N,N-dimethylacetamideHCID 178479386HCID 178479386, Verbindung

Produkt 1

HCID 592628288-(3-Sulfamoyl-phenylamino)-4,5-dihydro-thiazolo[4,5-h]quinazoline-2-carboxylic acid ethyl esterAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To 7-oxo-4,5,6,7-tetrahydro-benzothiazole-2-carboxylic acid ethyl ester (0.1128 g, 0.50 mmol) was added DMF/DMA solution (3 mL) and the mixture was refluxed under nitrogen for 1 hour. The reaction mixture was concentrated in vacuo and the resulting crude product (6-dimethylaminomethylene-7-oxo-4,5,6,7-tetrahydro-benzothiazole-2-carboxylic acid ethyl ester) was taken through to the next step without further purification. The above was dissolved in anhydrous DMA (3 mL) and treated with 3-guanidino-benzenesulfonamide hydrogen chloride (128 mg, 0.51 mmol) and powdered potassium carbonate (35 mg, 0.26 mmol). The mixture was heated to 120° C. with vigorous stirring for 12 hours. The mixture was cooled down to room temperature, and diluted with water. The resulting solid was filtered, rinsed with more water, a little bit of iPrOH and Et2O. The crude solid was purified by silica gel to give the title compound as a brown solid in 24% yield (52mg). MS (ES+) 432, (ES−) 430. δH (d6 DMSO) 1.36 (3H, t), 3.05 (2H, t), 3.17 (2H, t), 4.42 (2H, q), 7.33 (2H, s), 7.41 (1H, d), 7.50 (1H, t), 7.89 (1H, d), 8.43 (1H, t), 8.52 (1H, s), 10.04 (1H, s).

Aufarbeitung

  1. temperaturethe mixture was refluxed under nitrogen for 1 hour
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resulting crude product (6-dimethylaminomethylene-7-oxo-4,5,6,7-tetrahydro-benzothiazole-2-carboxylic acid ethyl ester) was taken through to the next step without further purification
  4. dissolutionThe above was dissolved in anhydrous DMA (3 mL)
  5. temperatureThe mixture was cooled down to room temperature
  6. filtrationThe resulting solid was filtered
  7. washrinsed with more water
  8. customThe crude solid was purified by silica gel

Quellen und Nachweise

ORD-Eintrag
ord-75c65191a20f493098ab8edcfb5c281c
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07700609B2

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