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

HRID 254433Notes

Reaction equation

HRID 254433 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent3×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b4b566a28c8e47eab357234c75dcc4eb
Source dataset
uspto-grants-2011_01
Patent number
US07875634B2

Reaction notes

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