반응 #531821

ord-be6d76178cb34b688345984bf45528b3

반응 방정식

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

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.STIRRINGstirring
  2. 2
    workup.WAITwas continued for an additional 5 minutes
  3. 3
    기타the temperature below 5° C
  4. 4
    workup.STIRRINGThe reaction mixture was stirred 40 minutes at 0° C.
  5. 5
    온도The reaction mixture was then warmed to room temperature
  6. 6
    workup.STIRRINGstirred overnight
  7. 7
    추출extracted with ethyl acetate (3×50 mL)
  8. 8
    세척The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL)
  9. 9
    건조dried (MgSO4)
  10. 10
    농축concentrated

실험 절차

To a solution of methanesulfonyl chloride (0.63 mL, 8.13 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 Step D) (2.0 g, 7.75 mmol) and triethylamine (1.08 ml, 7.75 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) (2.14 g, 7.75 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (2.17 mL, 15.15 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 (0.63 mL, 8.13 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 3.18 g of the title product as a crude yellow solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08475819B2uspto-grants-2013_07