Cesium carbonate → ethyl 6-(6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-yl)-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate

HRID 1047179ノート

反応式

HRID 1047179 の反応式
[CH2:1]([NH:3][C:4](=[O:26])[NH:5][C:6]1[N:11]=[CH:10][C:9](B(O)O)=[C:8]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:19]=2)[CH:7]=1)[CH3:2].Br[C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][N:37]=1)[N:34]([CH2:38][C:39]1[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=1)[CH:33]=[C:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:31]2=[O:50].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:3][C:4](=[O:26])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:28]2[CH:29]=[C:30]3[C:35](=[CH:36][N:37]=2)[N:34]([CH2:38][C:39]2[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=2)[CH:33]=[C:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:31]3=[O:50])=[C:8]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:19]=2)[CH:7]=1)[CH3:2]

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 672880116-(3-Ethylureido)-4-(4-(1-methyl-1h-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid2 回HCID 86665055ethyl 6-bromo-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate2 回

生成物 1

HCID 68749575ethyl 6-(6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-yl)-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate収率 26.1%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

In a microwave vessel, 6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 98, 0.2 g, 0.54 mmol), ethyl 6-bromo-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (Intermediate 102, 0.21 g, 0.54 mmol) and cesium carbonate (0.229 g, 0.70 mmol) were combined and suspended in a mixture of dioxane and water (5:1; 2.5 mL/0.5 mL). The suspension was degassed and purged with nitrogen. Pd(PPh3)4 (0.05 g, 0.04 mmol) was added and the mixture was degassed and purged a second time. The reaction mixture was heated in the microwave at 90° C. for 90 minutes. The reaction was partitioned between water and ethyl acetate, the layers were separated, and the organic phase was washed with saturated NaHCO3, water and brine, then dried over magnesium sulfate, and concentrated. The resulting solids were filtered, washed with acetonitrile followed by chloroform. Isolation gave 90 mg of the title compound as an off-white solid.

後処理

  1. customThe suspension was degassed
  2. custompurged with nitrogen
  3. customthe mixture was degassed
  4. custompurged a second time
  5. customThe reaction was partitioned between water and ethyl acetate
  6. customthe layers were separated
  7. washthe organic phase was washed with saturated NaHCO3, water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. filtrationThe resulting solids were filtered
  11. washwashed with acetonitrile

出典と根拠

ORDレコード
ord-f09193da7c054338baa9b45faa7ca189
出典データセット
uspto-grants-2013_10
特許番号
US08569484B2

反応ノート

読み込み中…