Piperidine → 2-((Z)-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-((R)-2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one

HRID 2191523노트

반응식

HRID 2191523 반응식
OC(CN1CCOCC1)CN1CCCC2NC(C=O)=C(C)C=2C1=O.[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:30](=[O:35])/[C:29]/2=[CH:36]\[C:37]1[NH:46][C:45]2[CH2:44][CH2:43][CH2:42][N:41]([CH2:47][C@H:48]([OH:56])[CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)[C:40](=[O:57])[C:39]=2[C:38]=1[CH3:58].[F:59][C:60]1[C:65]([F:66])=[CH:64][CH:63]=[CH:62][C:61]=1C1C(F)=CC=C2C=1CC(=O)N2.N1CCCCC1>C(O)C>[F:59][C:60]1[C:65]([F:66])=[CH:64][CH:63]=[CH:62][C:61]=1[C:27]1[C:26]([F:25])=[CH:34][CH:33]=[C:32]2[C:28]=1/[C:29](=[CH:36]/[C:37]1[NH:46][C:45]3[CH2:44][CH2:43][CH2:42][N:41]([CH2:47][C@H:48]([OH:56])[CH2:49][N:50]4[CH2:51][CH2:52][O:53][CH2:54][CH2:55]4)[C:40](=[O:57])[C:39]=3[C:38]=1[CH3:58])/[C:30](=[O:35])[NH:31]2

참가 물질

5

반응물 3

HCID 8082PiperidineHCID 592500644-(2,3-Difluoro-phenyl)-5-fluoro-1,3-dihydro-indol-2-oneHCID 86761721(R,Z)-2-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

생성물 1

HCID 592500832-((Z)-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-((R)-2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one수율 78%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 53f (84 mg, 0.25 mmol) and 4-(2,3-difluoro-phenyl)-5-fluoro-1,3-dihydro-indol-2-one 74 g (60 mg, 0.23 mmol) were dissolved in 2 ml of ethanol, and added with 35 μl of piperidine to the solution at room temperature. Upon completion of the addition, the mixture was heated to reflux for 2 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled to room temperature, and filtered. The filter cake was washed with anhydrous ethanol (3 ml×2) and dried to obtain the title compound 2-((Z)-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-((R)-2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 75 (100 mg, yield 78%) as an orange solid.

후처리

  1. additionUpon completion of the addition
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 2 hours
  4. filtrationfiltered
  5. washThe filter cake was washed with anhydrous ethanol (3 ml×2)
  6. customdried

출처 및 근거

ORD 기록
ord-ec3a2975add24540ab1039c5328afc5e
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329682B2

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