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Cesium carbonate → 3-fluoro-4-(3-(5-fluoro-1,3-dioxo-1H-pyrido [1,2-c]pyrimidin-2(3H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide

HRID 523300
ノート
印刷プレビュー

反応式

HRID 523300 の反応式
Br[C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([OH:18])([CH3:17])[CH3:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:19]([NH2:21])=[O:20])=[CH:4][C:3]=1[F:22].[F:23][C:24]1[C:33]2[N:28]([C:29](=[O:51])[N:30]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37](B4OC(C)(C)C(C)(C)O4)[C:36]=3[CH3:50])[C:31](=[O:34])[CH:32]=2)[CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:22][C:3]1[CH:4]=[C:5]([C:19]([NH2:21])=[O:20])[C:6]2[NH:7][C:8]3[C:13]([C:14]=2[C:2]=1[C:37]1[CH:38]=[CH:39][CH:40]=[C:35]([N:30]2[C:31](=[O:34])[CH:32]=[C:33]4[C:24]([F:23])=[CH:25][CH:26]=[CH:27][N:28]4[C:29]2=[O:51])[C:36]=1[CH3:50])=[CH:12][CH:11]=[C:10]([C:15]([OH:18])([CH3:17])[CH3:16])[CH:9]=3
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

7

反応物 3

HCID 10796Cesium carbonateHCID 1177610104-bromo-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide2 回HCID 1237135155-Fluoro-2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione (single enantiomers)2 回

生成物 1

HCID 865824883-fluoro-4-(3-(5-fluoro-1,3-dioxo-1H-pyrido [1,2-c]pyrimidin-2(3H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide
収率 63.8%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

A mixture of 4-bromo-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide [Intermediate 27] (0.200 g, 0.548 mmol), 5-fluoro-2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione [Intermediate 37] (0.260 g, 0.657 mmol) and Cs2CO3 (0.357 g, 1.10 mmol) in dioxane (4 mL) and water (1 mL) was bubbled with nitrogen for 2 min, then was treated with PdCl2(dppf) DCM adduct (0.022 g, 0.027 mmol). Bubbling with nitrogen was continued for 30 sec and the reaction vessel was sealed. The mixture was heated at 60° C. overnight. The cooled mixture was diluted with EtOAc and washed sequentially with water and brine. The combined aqueous layers were extracted with DCM, and combined organic layers were dried and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc-hexanes, to give 3-fluoro-4-(3-(5-fluoro-1,3-dioxo-1H-pyrido[1,2-c]pyrimidin-2(3H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (mixture of four atropisomers) as a yellow solid (0.194 g, 63% yield).

後処理

  1. customwas bubbled with nitrogen for 2 min
  2. customBubbling with nitrogen
  3. customthe reaction vessel was sealed
  4. additionThe cooled mixture was diluted with EtOAc
  5. washwashed sequentially with water and brine
  6. extractionThe combined aqueous layers were extracted with DCM
  7. customwere dried
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with EtOAc-hexanes

出典と根拠

ORDレコード
ord-3566380873e54ffa81e1a3f3335f55de
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09334290B2

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