Cesium carbonate → (4-(5-(5,6-Dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 592997노트

반응식

HRID 592997 반응식
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:33][CH2:32][N:24]3[C:25]4[CH2:26][CH2:27][CH2:28][CH2:29][C:30]=4[CH:31]=[C:23]3[C:22]2=[O:34])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2].[CH3:35][N:36]1[CH:41]([CH3:42])[CH2:40][N:39]2[N:43]=[C:44]([NH2:46])[CH:45]=[C:38]2[CH2:37]1.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>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].O1CCOCC1>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:33][CH2:32][N:24]3[C:25]4[CH2:26][CH2:27][CH2:28][CH2:29][C:30]=4[CH:31]=[C:23]3[C:22]2=[O:34])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:46][C:44]2[CH:45]=[C:38]3[CH2:37][N:36]([CH3:35])[CH:41]([CH3:42])[CH2:40][N:39]3[N:43]=2)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86684400(4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl AcetateHCID 866844805,6-Dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

생성물 1

HCID 86684481(4-(5-(5,6-Dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate수율 13.1%

시약·촉매·용매 2

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

실험 절차

A 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (4-(5-bromo-1-methyl-6-oxo-1,6-di-hydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate 217a (525 mg, 1.0 mmol), 250e (166 mg, 1.0 mmol), cesium carbonate (652 mg, 2.0 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the suspension for 30 minutes, xantphos (116 mg, 0.20 mmol) and tris(dibenzylideneacetone)dipalladium(0) (92 mg, 0.10 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 250f (80 mg, 13%) as yellow solid. MS-ESI: [M+H]+ 611.4

후처리

  1. customA 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 30 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (2×30 mL)
  8. concentrationthe combined filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel column chromatography
  10. washeluting with dichloromethane/methanol (80:1 to 30:1)

출처 및 근거

ORD 기록
ord-712fff9495914637a6b2b04bf4dc544b
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

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