Cesium carbonate → methyl (S)-1-((S)-2-(4-((2R,5R)-5-(4-chloro-3-nitrophenyl)-1-(3,5-difluoro-4-(4-phenylpiperidin-1-yl)phenyl)pyrrolidin-2-yl)-2-nitrophenylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1411421노트

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HRID 1411421 반응식
Cl[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:12][CH2:11][C@H:10]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=3)[N:9]2[C:23]2[CH:28]=[C:27]([F:29])[C:26]([N:30]3[CH2:35][CH2:34][CH:33]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:32][CH2:31]3)=[C:25]([F:42])[CH:24]=2)=[CH:4][C:3]=1[N+:43]([O-:45])=[O:44].[C:46]([C@@H:49]1[CH2:53][CH2:52][CH2:51][N:50]1[C:54](=[O:64])[C@@H:55]([NH:59][C:60](=[O:63])[O:61][CH3:62])[CH:56]([CH3:58])[CH3:57])(=[O:48])[NH2:47].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:10]2[N:9]([C:23]3[CH:24]=[C:25]([F:42])[C:26]([N:30]4[CH2:35][CH2:34][CH:33]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[CH2:32][CH2:31]4)=[C:27]([F:29])[CH:28]=3)[C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:47][C:46]([C@@H:49]4[CH2:53][CH2:52][CH2:51][N:50]4[C:54](=[O:64])[C@@H:55]([NH:59][C:60](=[O:63])[O:61][CH3:62])[CH:56]([CH3:58])[CH3:57])=[O:48])=[C:3]([N+:43]([O-:45])=[O:44])[CH:4]=3)[CH2:12][CH2:11]2)=[CH:14][C:15]=1[N+:20]([O-:22])=[O:21]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582268331-(4-((2R,5R)-2,5-Bis(4-chloro-3-nitrophenyl)pyrrolidin-1-yl)-2,6-difluorophenyl)-4-phenylpiperidineHCID 68574976methyl (S)-1-((S)-2-carbamoylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

생성물 1

HCID 86657192methyl (S)-1-((S)-2-(4-((2R,5R)-5-(4-chloro-3-nitrophenyl)-1-(3,5-difluoro-4-(4-phenylpiperidin-1-yl)phenyl)pyrrolidin-2-yl)-2-nitrophenylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate수율 43.4%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

1-(4-((2R,5R)-2,5-Bis(4-chloro-3-nitrophenyl)pyrrolidin-1-yl)-2,6-difluorophenyl)-4-phenylpiperidine (0.745 g, 1.14 mmol) was dissolved in dioxane (12 mL) in a tube and treated with methyl (S)-1-((S)-2-carbamoylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.309 g, 1.14 mmol), cesium carbonate (0.409 g, 1.25 mmol), Xantphos (0.066 g, 0.11 mmol), and tris(dibenzylideneacetone)dipalladium(0) (0.052 g, 0.057 mmol). Nitrogen was bubbled through this mixture for 15 minutes, then the tube was sealed and heated at 100° C. for 2 hours. The mixture was diluted with water, extracted into dichloromethane, concentrated, and purified by chromatography, eluting with 0-5% methanol in dichloromethane to give 0.44 g (43%) of a dark yellow solid.

후처리

  1. customNitrogen was bubbled through this mixture for 15 minutes
  2. customthe tube was sealed
  3. additionThe mixture was diluted with water
  4. extractionextracted into dichloromethane
  5. concentrationconcentrated
  6. custompurified by chromatography
  7. washeluting with 0-5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-b1b7c52266024af2864a5e2495f913bf
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921514B2

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