Potassium Phosphate, Tribasic → 4-(5-(5-Ethyl-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-hexahydro-pyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 1021947ノート

反応式

HRID 1021947 の反応式
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]2[N:9]=[C:10]([NH:12][C:13]3[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)[CH:11]=[C:5]2[CH2:4]1)[CH3:2].Cl[C:31]1[C:36]([CH:37]=[O:38])=[C:35]([N:39]2[CH2:51][CH2:50][C:49]3[N:48]4[C:43]([CH2:44][CH2:45][CH2:46][CH2:47]4)=[CH:42][C:41]=3[C:40]2=[O:52])[N:34]=[CH:33][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]2[N:9]=[C:10]([NH:12][C:13]3[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=[C:17]([C:31]4[C:36]([CH:37]=[O:38])=[C:35]([N:39]5[CH2:51][CH2:50][C:49]6[N:48]7[C:43]([CH2:44][CH2:45][CH2:46][CH2:47]7)=[CH:42][C:41]=6[C:40]5=[O:52])[N:34]=[CH:33][CH:32]=4)[CH:18]=3)[CH:11]=[C:5]2[CH2:4]1)[CH3:2]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866842464-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehydeHCID 866843903-(5-Ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one

生成物 1

HCID 866843894-(5-(5-Ethyl-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-hexahydro-pyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde収率 56%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 208d (120 mg, 0.30 mmol), 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido-[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 139a (99 mg, 0.30 mmol), PdCl2(dppf) (13 mg, 0.015 mmol), K3PO4 (127 mg, 0.60 mmol), sodium acetate (49 mg, 0.60 mmol), acetonitrile (10 mL), and water (0.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford the 208e (95 mg, 56%) as a yellow solid. MS-ESI: [M+H]+ 567.2.

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-68c1e063587149f2b1c41d1dc0339628
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

読み込み中…