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 2191523ノート

反応式

HRID 2191523 の反応式
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

参加物

5

反応物 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

生成物 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)-one収率 78%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-ec3a2975add24540ab1039c5328afc5e
出典データセット
uspto-grants-2012_12
特許番号
US08329682B2

反応ノート

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