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

HRID 444648노트

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HRID 444648 반응식
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

참가 물질

7

반응물 4

HCID 8471Triethylamine2회HCID 31297Methanesulfonyl chloride2회HCID 3029402-Amino-3-chloro-5-iodobenzoic acidHCID 211073323-Chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid2회

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매3회

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e18181eb71b54f078bce9bcb1cda816b
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08475819B2

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