Tetrafluoro-m-phenylenediamine dihydrochloride → n-{4-[1-(6,11-Dihydro-dibenzo [b,e]thiepin-11-yl)-piperidin-4-yl]-butyl}-3-(pyridin-3-yl)-acrylamide

HRID 1294459

反応式

HRID 1294459 の反応式
Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:23])[CH:15]=[CH:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[CH2:5][CH2:4]1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.Cl[CH:39]1[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=2[CH2:43][S:42][C:41]2[CH:50]=[CH:51][CH:52]=[CH:53][C:40]1=2>ClCCl>[CH:53]1[C:40]2[CH:39]([N:3]3[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:23])[CH:15]=[CH:16][C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH2:5][CH2:4]3)[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=3[CH2:43][S:42][C:41]=2[CH:50]=[CH:51][CH:52]=1

参加物

5

反応物 3

HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 1251455711-Chloro-6,11-dihydrodibenz[b,e]thiepinHCID 69451641N-[4-(piperidine-4-yl)butyl]-3-(pyridin-3-yl)-acrylamide Dihydrochloride

生成物 1

HCID 54167607n-{4-[1-(6,11-Dihydro-dibenzo [b,e]thiepin-11-yl)-piperidin-4-yl]-butyl}-3-(pyridin-3-yl)-acrylamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

7.02 g (21.5 mmol) N-[4-(piperidin-4-yl)-butyl]-3-(pyridin-3-yl)-acrylamide dihydrochloride (substance 14 as a dihydrochloride) are suspended in 100 ml abs. dichlormethane and added to 7.08 g (70.0 mmol) TEA. The mixture is cooled to ca 0° C. under moisture exclusion and a solution of 5.30 g (21.5 mmol) 11-chlor-6,11-dihydro-dibenzo[b,e]thiepine in 10 ml abs. dichlormethane is added dropwise. The mixture is stirred for 24 hours at RT without further cooling. Subsequently, the batch is washed with 50 ml 10% sodium hydroxide solution and 30 ml water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum. The red brown residue is chromatographically purified three times over silica gel with CHCl3/CH3OH (100/0, 97/3 and 96/4 to 94/6). Subsequently, a further purification occurs by means of MPLC with CHCl3CH3OH (98/2). Yield: 0.5 g (5%) of a brittle, vitreous solid with a MP of 89–91° C.

後処理

  1. temperatureThe mixture is cooled to ca 0° C. under moisture exclusion
  2. washSubsequently, the batch is washed with 50 ml 10% sodium hydroxide solution and 30 ml water
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. customthe solvent is removed under vacuum
  5. customThe red brown residue is chromatographically purified three times over silica gel with CHCl3/CH3OH (100/0, 97/3 and 96/4 to 94/6)
  6. customSubsequently, a further purification

出典と根拠

ORDレコード
ord-559bfa5d28194cd1aa867d8e48cf2fbd
出典データセット
uspto-grants-2007_07
特許番号
US07241745B2

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