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Cesium carbonate → N-{6-[2-(2,6-Dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-acetamide

HRID 626749
ノート
印刷プレビュー

反応式

HRID 626749 の反応式
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:30])[CH3:29])[CH:22]=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+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:20][C:21]3[N:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:30])[CH3:29])[CH:22]=3)=[N:3][CH:4]=[C:5]([F:19])[C:6]2=[N:10]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

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3031498N-(6-aminopyrimidin-4-yl)acetamideHCID 866970564-Bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

生成物 1

HCID 69671310N-{6-[2-(2,6-Dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-acetamide
収率 10%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of 4-bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (320 mg, 0.89 mmol), N-(6-aminopyrimidin-4-yl)-acetamide (152 mg, 1.0 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (52 mg, 0.089 mmol) and cesium carbonate (580 mg, 1.78 mmol) in dioxane (10 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 1 h. The resultant mixture was partitioned between ethyl acetate and water and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane) to afford an off-white solid. This was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white solid (31 mg, 10% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.65-10.61 (m, 2H), 9.26 (d, J=2.6 Hz, 1H), 9.08 (d, J=1.1 Hz, 1H), 8.53 (d, J=1.1 Hz, 1H), 7.92 (d, J=3.4 Hz, 1H), 7.83-7.81 (m, 2H), 7.74 (dd, J=9.1, 7.3 Hz, 1H), 2.14 (s, 3H). LCMS (Method B): RT=3.20 min, m/z: 432 [M+H+].

後処理

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. customThe resultant mixture was partitioned between ethyl acetate and water
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane)
  10. customto afford an off-white solid
  11. customThis was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)]

出典と根拠

ORDレコード
ord-05661be5b41b485cb3732df591ccaa77
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09309240B2

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