Triethylamine → 8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one

HRID 254433ノート

反応式

HRID 254433 の反応式
CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:11]=[C:10]([C:12]([OH:14])=O)[N:9]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[N:8]=1.C(N(CC)CC)C.[NH2:29][C:30]1[C:38]([Cl:39])=[CH:37][C:36]([I:40])=[CH:35][C:31]=1[C:32](O)=[O:33]>C(#N)C.O>[Cl:39][C:38]1[C:30]2[N:29]=[C:12]([C:10]3[N:9]([C:15]4[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=4)[N:8]=[C:7]([Cl:6])[CH:11]=3)[O:14][C:32](=[O:33])[C:31]=2[CH:35]=[C:36]([I:40])[CH:37]=1

参加物

7

反応物 4

HCID 8471Triethylamine2 回HCID 31297Methanesulfonyl chloride2 回HCID 3029402-Amino-3-chloro-5-iodobenzoic acidHCID 211073323-Chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid2 回

生成物 1

HCID 668577638-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒3 回

反応条件

温度
0 °C

実験手順

To a solution of methanesulfonyl chloride (0.31 mL, 4.07 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the carboxylic acid product of Example 3, Step D) (1.0 g, 3.87 mmol) and triethylamine (0.54 mL, 3.87 mmol) in acetonitrile (5 mL) at 0° C. The reaction mixture was then stirred for 15 minutes at 0° C. Then, 2-amino-3-chloro-5-iodobenzoic acid (i.e. the product from Step A) (1.15 g, 3.87 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (1.08 mL, 7.74 mmol) in acetonitrile (5 mL) was then added dropwise while keeping the temperature below 5° C. The reaction mixture was stirred 40 minutes at 0° C., and then methanesulfonyl chloride (0.31 mL, 4.07 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL), dried (MgSO4) and concentrated under reduced pressure. The residual solid was purified by chromatography on silica gel to afford 575 mg of the title compound as a crude yellow solid.

後処理

  1. stirringstirring
  2. waitwas continued for an additional 5 minutes
  3. customthe temperature below 5° C
  4. stirringThe reaction mixture was stirred 40 minutes at 0° C.
  5. temperatureThe reaction mixture was then warmed to room temperature
  6. stirringstirred overnight
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. washThe combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe residual solid was purified by chromatography on silica gel

出典と根拠

ORDレコード
ord-b4b566a28c8e47eab357234c75dcc4eb
出典データセット
uspto-grants-2011_01
特許番号
US07875634B2

反応ノート

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