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Cesium carbonate → (+/-)-tert-butyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-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 1430824
ノート
印刷プレビュー

反応式

HRID 1430824 の反応式
[CH:1]1([N:4]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:5]2[C:10]3=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]3[N:8]=[C:7](S(C)(=O)=O)[N:6]=2)[CH2:3][CH2:2]1.[NH2:29][C:30]1[C:31]([Cl:60])=[C:32]([N:38]2[CH2:43][CH2:42][C@@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[C@H:40]([O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[CH2:39]2)[CH:33]=[C:34]([C:36]#[N:37])[CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Si:53]([O:52][C@H:40]1[C@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:42][CH2:43][N:38]([C:32]2[CH:33]=[C:34]([C:36]#[N:37])[CH:35]=[C:30]([NH:29][C:7]3[N:6]=[C:5]([N:4]([CH:1]4[CH2:3][CH2:2]4)[CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[C:10]4=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]4[N:8]=3)[C:31]=2[Cl:60])[CH2:39]1)([C:56]([CH3:57])([CH3:58])[CH3:59])([CH3:55])[CH3:54]
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 3

HCID 10796Cesium carbonateHCID 86708519HCID 86708519、化合物2 回HCID 131732385(+/-)-tert-butyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethyl silyl)oxy)piperidin-4-yl)carbamate

生成物 1

HCID 131732386(+/-)-tert-butyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-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 72.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

A mixture of 4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylsulfonyl) imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 2, 185 mg, 0.464 mmol), (+/−)-tert-butyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethyl silyl)oxy)piperidin-4-yl)carbamate (223 mg, 0.464 mmol) and cesium carbonate (302 mg, 0.927 mmol) in DMF (5 mL) was heated at 50° C. for 4 h. LCMS showed completion of reaction. The reaction mixture was diluted with ethyl acetate and the solid was filtered off. The filtrate was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10-35% ethyl acetate/hexanes). (+/−)-tert-butyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-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 (270 mg) was obtained as a white solid.

後処理

  1. customcompletion of reaction
  2. filtrationthe solid was filtered off
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe crude product was purified by flash chromatography on silica gel using
  5. washan automated ISCO system (40 g column, eluting with 10-35% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-0868b3dea8c343808b1d5f6afa75a26b
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940736B2

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