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

HRID 1445539Notes

Reaction equation

HRID 1445539 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[C:8]([N:13]2[C:17]([C:18]([OH:20])=O)=[CH:16][C:15](=[O:21])[NH:14]2)=[N:9][CH:10]=[CH:11][CH:12]=1.C(N(CC)CC)C.[Cl:29][C:30]1[CH:38]=[C:37]([Cl:39])[CH:36]=[C:32]([C:33](O)=[O:34])[C:31]=1[NH2:40]>C(#N)C.O>[Cl:39][C:37]1[CH:38]=[C:30]([Cl:29])[C:31]2[N:40]=[C:18]([C:17]3[N:13]([C:8]4[C:7]([Cl:6])=[CH:12][CH:11]=[CH:10][N:9]=4)[N:14]=[C:15]([O:21][S:2]([CH3:1])(=[O:4])=[O:3])[CH:16]=3)[O:20][C:33](=[O:34])[C:32]=2[CH:36]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 760363,5-Dichloroanthranilic acidHCID 685431821-(3-Chloropyridin-2-yl)-3-hydroxy-1H-pyrazole-5-carboxylic acid

Product 1

HCID 866026636,8-dichloro-2-[1-(3-chloro-2-pyridinyl)-3-[(methylsulfonyl)oxy]-1H-pyrazol-5-yl]-4H-3,1-benzoxazin-4-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of methanesulfonyl chloride (0.14 mL, 1.75 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylic acid (i.e. the product of Step C) (0.4 g, 1.67 mmol) and triethylamine (0.23 mL, 1.67 mmol) in acetonitrile (3 mL) at 0-5° C. The reaction temperature was then maintained at about 0° C. throughout the addition. After stirring for 10 minutes, 3,5-dichloroanthranilic acid (Aldrich, 0.34 g, 1.67 mmol) was added and stirring was continued for an additional 5 minutes. A solution of triethylamine (0.47 mL, 3.33 mmol) in acetonitrile (3 mL) was then added dropwise, and the reaction mixture stirred 40 minutes, followed by the addition of methanesulfonyl chloride (0.14 mL, 1.75 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. Approximately 50 mL of water was then added followed by extraction with ethyl acetate (3×30 mL). The combined ethyl acetate phase was washed with water (1×20 mL) followed by brine (1×20 mL), dried (MgSO4) and concentrated to yield 0.8 g of a crude yellow solid. Chromatography on silica gel using hexanes/ethyl acetate as eluent resulted in isolation of 0.11 g of the title compound as a yellow solid.

Workup

  1. stirringstirring
  2. waitwas continued for an additional 5 minutes
  3. stirringthe reaction mixture stirred 40 minutes
  4. temperatureThe reaction mixture was then warmed to room temperature
  5. stirringstirred overnight
  6. extractionfollowed by extraction with ethyl acetate (3×30 mL)
  7. washThe combined ethyl acetate phase was washed with water (1×20 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto yield 0.8 g of a crude yellow solid

Sources & evidence

ORD record
ord-fd6041c2421f48248660f15d89c02432
Source dataset
uspto-grants-2010_02
Patent number
US07666882B2

Reaction notes

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