Sodium Carbonate → 4-(7-chloro-1H-indazol-5-yl)-isoquinoline

HRID 1517047ノート

反応式

HRID 1517047 の反応式
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](B(O)O)=[CH:3][N:2]=1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([Cl:24])[CH:23]=1)[NH:20][N:19]=[CH:18]2.C(=O)([O-])[O-].[Na+].[Na+]>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.C(COC)OC>[Cl:24][C:22]1[CH:23]=[C:15]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=[N:2][CH:3]=2)[CH:16]=[C:17]2[C:21]=1[NH:20][N:19]=[CH:18]2

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 3761204Isoquinoline-4-boronic acidHCID 211021945-Bromo-7-chloro-1H-indazole

生成物 1

HCID 689979964-(7-chloro-1H-indazol-5-yl)-isoquinoline収率 72.1%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

A mixture of isoquinolin-4-ylboronic acid (1.00 g, 5.78 mmol), 5-bromo-7-chloro-1H-indazole (892 mg, 3.85 mmol), 2.0 M sodium carbonate (3.85 mL, 7.71 mmol) and dimethoxyethane was degassed with argon. Tetrakis(triphenylphosphine)palladium(0) (233 mg, 0.193 mmol) was added, the mixture degassed again with argon, then heated to 85° C. for 24 hours. The reaction was cooled and partitioned between ethyl acetate and water, the organic layer washed with and dried with sodium sulfate. The solvent was removed under vacuum and the residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient) to give 4-(7-chloro-1H-indazol-5-yl)-isoquinoline (777 mg, 72%): 1H NMR (300 MHz, CDCl3) δ 10.52 (s, 1H) 9.31 (s, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 8.09 (dd, J=7.4, 1.62 Hz, 1H), 7.28 (dd, J=7.4, 1.2 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.81 (d, J=1.2 Hz, 1H), 7.72-7.64 (m, 2H), 7.57 (d, J=1.3 Hz, 1H).

後処理

  1. customwas degassed with argon
  2. customthe mixture degassed again with argon
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and water
  5. washthe organic layer washed with and
  6. dry with materialdried with sodium sulfate
  7. customThe solvent was removed under vacuum
  8. customthe residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient)

出典と根拠

ORDレコード
ord-9b8c8d66b949499a82f86c19722fa884
出典データセット
uspto-grants-2012_07
特許番号
US08227486B2

反応ノート

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