Cesium carbonate → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

HRID 1926306ノート

反応式

HRID 1926306 の反応式
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[C:5](OS(C(F)(F)F)(=O)=O)[N:6]=[CH:7]2.CC1(C)C(C)(C)OB([C:29]2[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=2)O1.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>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[C:5]([C:29]1[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=1)[N:6]=[CH:7]2

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 438110672-Aminopyridine-3-boronic acid, pinacol esterHCID 86633140Trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester

生成物 1

HCID 675212133-(5-Chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
100 °C

実験手順

A mixture of trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester (9.00 g, 27.4 mmol), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (8.42 g, 38.3 mmol), Pd(PPh3)4 (0.63 g, 2 mol %), and Cs2CO3 (20.5 g, 62.9 mmol) in dioxane/H2O (4:1, 300 mL) were heated under nitrogen at 100° C. for 16 h. Solvents were evaporated in vacuo, water (100 mL) was added to the residue, and the mixture was extracted with EtOAc (3×75 mL). The EtOAc extract was dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. It was purified by column chromatography on silica gel using EtOAc/Hexanes (1:3) to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=6.87 (brs, 2H), 6.81 (dd, J=8.7, 4.8 Hz, 1H), 7.18 (dd, J=9.3, 9.0 Hz, 1H), 7.22 (dd, J=8.1, 4.2 Hz, 1H), 7.99 (dd, J=7.5, 2.1 Hz, 1H), 8.15 (dd, J=6.8, 1.8 Hz, 1H), 8.13 (t, J=1.2 Hz, 1H), 9.56 (d, J=1.2 Hz, 1H).

後処理

  1. customSolvents were evaporated in vacuo, water (100 mL)
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with EtOAc (3×75 mL)
  4. extractionThe EtOAc extract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customIt was purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-0d089d79a93540e1aa0842bb2b817e30
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

反応ノート

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