Potassium Phosphate, Tribasic → 4-Chloro-2-(2,6-dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridine

HRID 2366254ノート

反応式

HRID 2366254 の反応式
[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14](I)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P(C1CCCCC1)(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([CH:20]4[CH2:22][CH2:21]4)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 866689974-Chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine2 回

生成物 1

HCID 867233174-Chloro-2-(2,6-dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridine収率 92.5%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A mixture of 4-chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine (0.20 g, 0.45 mmol), cyclopropyl boronic acid (0.051 g, 0.59 mmol), Pd(OAc)2 (0.005 g, 0.023 mmol), P(Cy)3 (tricyclohexylphosphine) (0.013 g, 0.045 mmol) and potassium phosphate tribasic (0.336 g, 1.58 mmol) in toluene (4 mL) and water (0.2 mL) was degassed with a stream of argon and then heated at 100° C. for 18 hours. After cooling to room temperature, the crude reaction mixture was filtered through Celite® washing with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, then dried (MgSO4) and concentrated under reduced pressure. The resultant residue was combined with the crude reaction mixture (79 mg) obtained by reacting 4-chloro-2-(2,6-dichloro-4-iodophenyl)-thiazolo[5,4-c]pyridine (0.10 g, 0.23 mmol) under the same reaction conditions and purified by column chromatography on silica gel eluting with 0-30% Et2O in petroleum ether (40-60° C.) to afford the title compound as a yellow/orange solid (148 mg, 61%). LCMS (Method D): RT=4.69 min, m/z: 355 [M+H+].

後処理

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. customthe crude reaction mixture
  4. filtrationwas filtered through Celite®
  5. washwashing with EtOAc
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customreaction mixture (79 mg)
  11. customobtained
  12. customunder the same reaction conditions
  13. custompurified by column chromatography on silica gel eluting with 0-30% Et2O in petroleum ether (40-60° C.)

出典と根拠

ORDレコード
ord-124a2d590035451cb4552a8abf4bc059
出典データセット
uspto-grants-2014_04
特許番号
US08697708B2

反応ノート

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