Cesium carbonate → 2-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921869노트

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HRID 921869 반응식
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[NH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])[C:34]=1[Cl:35])[C:30]#[N:31].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.[Fe+2]>[Cl:35][C:34]1[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])=[CH:32][C:29]([C:30]#[N:31])=[CH:28][C:27]=1[NH:26][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 89922410HCID 89922410, 화합물

생성물 1

HCID 899225422-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile수율 97.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (40 mg, 0.113 mmol), 3-amino-4-chloro-5-(4-methyl-2-oxopiperazin-1-yl)benzonitrile (28 mg, 0.106 mmol), palladium(ii) acetate (12 mg, 0.053 mmol), XANTPIIOS (12 mg, 0.021 nmmol), DPPF (12 mg, 0.022 mmol) and cesium carbonate (90 mg, 0.275 mmol) in Dioxane (1.5 mL) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 3 h. LC-MS showed reaction was complete. The reaction mixture was filtered through a pad of Celite, rinsed with EtOAc and the filtrate was concentrated and purification via flash chromatography (0-70% EtOAc in Hexane, 24 g) gave 2-((2-chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (60 mg) as a light oil.

후처리

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. customreaction
  4. filtrationThe reaction mixture was filtered through a pad of Celite
  5. washrinsed with EtOAc
  6. concentrationthe filtrate was concentrated
  7. custompurification via flash chromatography (0-70% EtOAc in Hexane, 24 g)

출처 및 근거

ORD 기록
ord-3c524a5e4e2a497ca5f2f766cd85c278
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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