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

HRID 908348

反応式

HRID 908348 の反応式
[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]

参加物

6

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
120 °C

実験手順

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 (52 mg). 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).

後処理

  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

出典と根拠

ORDレコード
ord-39aae3cc59164085bd62a481e934cd97
出典データセット
uspto-grants-2011_09
特許番号
US08017619B2

関連ノート

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