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Cesium carbonate → tert-Butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate

HRID 921625
ノート
印刷プレビュー

反応式

HRID 921625 の反応式
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[C:28]([Cl:49])=[C:29]([N:35]2[CH2:40][CH2:39][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:37][CH2:36]2)[CH:30]=[C:31]([C:33]#[N:34])[CH:32]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].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].O1CCOCC1>[Cl:49][C:28]1[C:27]([NH:26][C:2]2[N:7]=[C:6]([N:8]([CH:18]3[CH2:20][CH2:19]3)[CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[C:5]3=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]3[N:3]=2)=[CH:32][C:31]([C:33]#[N:34])=[CH:30][C:29]=1[N:35]1[CH2:40][CH2:39][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:37][CH2:36]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

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile2 回HCID 86708478Tert-butyl (1-(3-amino-2-chloro-5-cyanophenyl)piperidin-4-yl)carbamate

生成物 1

HCID 86708476
tert-Butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate
収率 66.3%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

(I12C): 2-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9, 0.912 g, 2.57 mmol), tert-butyl (1-(3-amino-2-chloro-5-cyanophenyl)piperidin-4-yl)carbamate (0.902 g, 2.57 mmol), Pd(OAc)2 (0.173 g, 0.771 mmol), DPPF (0.143 g, 0.257 mmol), Xantphos (0.149 g, 0.257 mmol), and cesium carbonate (1.675 g, 5.14 mmol) were combined in a round bottom flask and dioxane (17.14 ml) was added. The flask was evacuated and backfilled with nitrogen (3×), then heated at 100° C. for 1 h. The reaction mixture was filtered through Celite, rinsing with EtOAc. The organic layer was concentrated and the material was purified by column chromatography on the ISCO Companion (80 g, 0-100% EtOAc/Hex). tert-Butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (1.14 g) was obtained as a yellow foam.

後処理

  1. customThe flask was evacuated
  2. filtrationThe reaction mixture was filtered through Celite
  3. washrinsing with EtOAc
  4. concentrationThe organic layer was concentrated
  5. customthe material was purified by column chromatography on the ISCO Companion (80 g, 0-100% EtOAc/Hex)

出典と根拠

ORDレコード
ord-37f3f9acba9a483181ae8cd80adb84ca
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09273057B2

反応ノート

読み込み中…

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