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Bromobenzene → 2-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide

HRID 2241395
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HRID 2241395 반응식
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16](Cl)=[C:11]3[C:10]([I:18])=[N:9]2)=[CH:5][CH:4]=1.[F:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[N:45]=[CH:44][CH:43]=[CH:42][C:31]=2[C:32]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)=[O:33])[CH:25]=[CH:26][C:27]=1[OH:28].C(=O)([O-])[O-].[Cs+].[Cs+].BrC1C=CC=CC=1>>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:28][C:27]4[CH:26]=[CH:25][C:24]([NH:29][C:30]5[N:45]=[CH:44][CH:43]=[CH:42][C:31]=5[C:32]([NH:34][C:35]5[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=5)=[O:33])=[CH:23][C:22]=4[F:21])=[C:11]3[C:10]([I:18])=[N:9]2)=[CH:5][CH:4]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

5

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HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 672207314-chloro-3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridineHCID 672218842-(3-fluoro-4-hydroxyphenylamino)-N-(4-fluorophenyl)nicotinamide

생성물 1

HCID 672218582-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide수율 79.4%

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온도
160 °C

실험 절차

A 100 mL sealable tube was charged with 1-(4-methoxybenzyl)-4-chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine (0.250 g, 0.626 mmol Example 84, Step D), 2-(3-fluoro-4-hydroxyphenylamino)-N-(4-fluorophenyl)nicotinamide (0.427 g, 1.25 mmol), cesium carbonate (0.408 g, 1.25 mmol), and 1-bromobenzene (6.26 ml, 0.626 mmol). The reaction mixture was heated to 160° C. for 18 hours. The reaction mixture was cooled to ambient temperature and concentrated. The residue was dissolved in EtOAc and washed with brine. The crude material was purified by silica gel (Biotage 40S) eluting with 4:1 Hexane/EtOAc to provide the product (0.35 g, 71%). LRMS M−1 (704.9) observed.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with brine
  5. customThe crude material was purified by silica gel (Biotage 40S)
  6. washeluting with 4:1 Hexane/EtOAc

출처 및 근거

ORD 기록
ord-9d86c0bdc34045ef93743a69daa3cde7
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07723330B2

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