반응 #531830

ord-e18181eb71b54f078bce9bcb1cda816b

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
Nc1c(Cl)cc(I)cc1C(=O)O
2-amino-3-chloro-5-iodobenzoic acid
CCN(CC)CC
triethylamine
CS(=O)(=O)Cl
methanesulfonyl chloride
O=c1oc(-c2cc(Cl)nn2-c2ncccc2Cl)nc2c(Cl)cc(I)cc12
title compound
O=c1oc(-c2cc(Cl)nn2-c2ncccc2Cl)nc2c(Cl)cc(I)cc12
8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-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 under reduced pressure
  11. 11
    기타The residual solid was purified by chromatography on silica gel

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.

출처

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