反応 #531826

ord-bad644d90fb74bf7831def9e79a985b0

反応方程式

CS(=O)(=O)Cl
methanesulfonyl chloride
O=C(O)c1cc(Br)nn1-c1ncccc1Cl
3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid
O=C(O)c1cc(Br)nn1-c1ncccc1Cl
carboxylic acid
O=C(O)c1cc(Br)nn1-c1ncccc1Cl
3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid
CCN(CC)CC
triethylamine
Cc1cc(I)cc(C(=O)O)c1N
2-amino-3-methyl-5-iodobenzoic acid
CCN(CC)CC
triethylamine
CS(=O)(=O)Cl
methanesulfonyl chloride
Cc1cc(I)cc2c(=O)oc(-c3cc(Br)nn3-c3ncccc3Cl)nc12
title product
Cc1cc(I)cc2c(=O)oc(-c3cc(Br)nn3-c3ncccc3Cl)nc12
2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one

反応条件

温度
0°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.STIRRINGstirring
  2. 2
    workup.WAITwas continued for an additional 5 minutes
  3. 3
    その他the temperature below 5° C
  4. 4
    workup.STIRRINGThe reaction mixture was stirred
  5. 5
    温度The reaction mixture was then warmed to room temperature
  6. 6
    workup.STIRRINGstirred overnight
  7. 7
    抽出extracted with ethyl acetate (3×50 mL)
  8. 8
    洗浄The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 ml) and brine (1×20 mL)
  9. 9
    乾燥dried (MgSO4)
  10. 10
    濃縮concentrated

実験手順

To a solution of methanesulfonyl chloride (0.54 ml, 6.94 mmol) in acetonitrile (15 mL) was added dropwise a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the carboxylic acid product of Step D) (2.0 g, 6.6 mmol) and triethylamine (0.92 ml, 6.6 mmol) in acetonitrile (5 mL) at 0° C. The reaction mixture was then stirred for 15 minutes at 0° C. Then, 2-amino-3-methyl-5-iodobenzoic acid (i.e. the product from Example 1, Step A) (1.8 g, 6.6 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (1.85 mL, 13.2 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 (0.54 ml, 6.94 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 to afford 2.24 g of the title product as a crude yellow solid.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08475819B2uspto-grants-2013_07