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Cesium carbonate → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1185243
ノート
印刷プレビュー

反応式

HRID 1185243 の反応式
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[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].[N:37]1[N:38]2[CH2:45][CH2:44][CH2:43][C:39]2=[CH:40][C:41]=1[NH2:42].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[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:42][C:41]2[CH:40]=[C:39]3[CH2:43][CH2:44][CH2:45][N:38]3[N:37]=2)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 675370624H,5H,6H-pyrrolo(1,2-b)pyrazol-2-amineHCID 86684026(4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate

生成物 1

HCID 86684090
(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate
収率 42%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate 142c (166.2 mg, 0.30 mmol), 162c (24.6 mg, 0.20 mmol), cesium carbonate (130 mg, 0.40 mmol), and 1,4-dioxane (4.0 mL). After bubbling nitrogen through the suspension for 10 minutes, Xantphos (23 mg, 0.040 mmol) and tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.020 mmol) were added. The system was subjected to three cycles of vacuum/nitrogen flush and heated at reflux for 2.5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (3×10 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (100:1 to 50:1 to afford 162d (50 mg, 42%) as a yellow solid. MS-ESI: [M+H]+ 598.3

後処理

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 2.5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (3×10 mL)
  8. concentrationThe combined organic layer was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel column chromatography
  10. washeluting with dichloromethane/methanol (100:1 to 50:1

出典と根拠

ORDレコード
ord-06abb4cafe10446c81210102b6a824c0
出典データセット
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08669251B2

反応ノート

読み込み中…

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