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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 592838
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인쇄 미리보기

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HRID 592838 반응식
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
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참가 물질

6

반응물 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

생성물 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
수율 40.8%

시약·촉매·용매 1

HCID 962Water용매

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온도
50 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-cd64a3a251c24253bd9cd158a6c3d993
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09238655B2

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