2-Aminothiazole → 1-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473330ノート

反応式

HRID 1473330 の反応式
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1

参加物

5

反応物 3

HCID 21552-AminothiazoleHCID 2733832Lithium HexamethyldisilazideHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonate

生成物 1

HCID 866873831-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A flask containing thiazol-2-amine (0.185 g, 1.843 mmol), perfluorophenyl 1-chloroisoquinoline-6-sulfonate (0.719 g, 1.755 mmol), and THF (0.163 mL) was cooled to 0° C. LHMDS (1.0 M in THF) (3.86 ml, 3.86 mmol) was added dropwise and the reaction was stirred for 5 minutes at 0° C. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was triturated in DCM and loaded onto a silica gel cartridge. The tan solid remaining at the top of the cartridge was scraped into a flask and put aside. The remaining material was purified by silica gel chromatography (40 g column, gradient elution 0 to 100% EtOAc:Heptane with a 10% MeOH:DCM flush). The product fractions were combined with the previously isolated material to afford 1-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a tan solid. m/z (ESI) 326.0 (M+H)+.

後処理

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was triturated in DCM
  9. customwas scraped into a flask
  10. customThe remaining material was purified by silica gel chromatography (
  11. wash40 g column, gradient elution 0 to 100% EtOAc
  12. customHeptane with a 10% MeOH:DCM flush)

出典と根拠

ORDレコード
ord-6bea84c8dd0b4b58a06ee6105e3cd30a
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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