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Dimethylformamide → 4-(1-Methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde

HRID 1021907
ノート
印刷プレビュー

反応式

HRID 1021907 の反応式
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[C:22](=[O:23])[C:14]3=[CH:15][N:16]4[C:21]([CH2:20][CH2:19][CH2:18][CH2:17]4)=[C:13]3[CH:12]=[N:11]2)[N:5]=[CH:4][CH:3]=1.C([CH:26]1[CH2:31][N:30]([CH:32]2[CH2:35][O:34][CH2:33]2)[CH2:29][CH2:28][N:27]1[C:36]1[CH:37]=[CH:38][C:39]([NH:42][C:43]2[C:44](=[O:59])[N:45]([CH3:58])[CH:46]=[C:47](B3OC(C)(C)C(C)(C)O3)[CH:48]=2)=[N:40][CH:41]=1)C.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>O>[CH3:58][N:45]1[C:44](=[O:59])[C:43]([NH:42][C:39]2[CH:38]=[CH:37][C:36]([N:27]3[CH2:28][CH2:29][N:30]([CH:32]4[CH2:33][O:34][CH2:35]4)[CH2:31][CH2:26]3)=[CH:41][N:40]=2)=[CH:48][C:47]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([N:10]3[C:22](=[O:23])[C:14]4=[CH:15][N:16]5[C:21]([CH2:20][CH2:19][CH2:18][CH2:17]5)=[C:13]4[CH:12]=[N:11]3)[N:5]=[CH:4][CH:3]=2)=[CH:46]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 866843003-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridine-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866843524-Chloro-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde

生成物 1

HCID 86684367
4-(1-Methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde
収率 40.8%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

A 50-mL round bottomed flask equipped with a reflux condenser was charged with 4-chloro-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde 192c (118 mg, 0.36 mmol), 1-methyl-3-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 101l (171 mg, 0.36 mmol), Na2CO3 (78 mg, 0.72 mmol), Pd (dppf)Cl2 (30 mg, 0.036 mmol), DMF (10 mL), and water (1 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 50° C. for 10 hours under N2 protection. It was then cooled to room temperature and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 198a (93 mg, 40%) as a brown solid. MS-ESI: [M+H]+ 634.3.

後処理

  1. customA 50-mL round bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. temperatureIt was then cooled to room temperature
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 20:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-d58c62e539ca493d84984cb808fa4e3c
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08716274B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート