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 1294459노트

반응식

HRID 1294459 반응식
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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-559bfa5d28194cd1aa867d8e48cf2fbd
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07241745B2

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