Trifluoroacetic anhydride → 3-fluoro-6-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyridin-2-yl acetate

HRID 2281921노트

반응식

HRID 2281921 반응식
[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]([C:10]2[CH:14]=[CH:13][O:12][N:11]=2)=[CH:8][C:7]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=2)=[N:6]1.OO.NC(N)=O.F[C:33](F)(F)[C:34]([O:36]C(=O)C(F)(F)F)=[O:35]>C(Cl)Cl.C(OC(=O)C)(=O)C>[C:34]([O:36][C:17]1[C:18]([F:21])=[CH:19][CH:20]=[C:15]([C:7]2[CH:8]=[C:9]([C:10]3[CH:14]=[CH:13][O:12][N:11]=3)[N:5]([CH2:4][C:3]3[CH:22]=[CH:23][CH:24]=[CH:25][C:2]=3[F:1])[N:6]=2)[N:16]=1)(=[O:35])[CH3:33]

참가 물질

6

반응물 3

HCID 9845Trifluoroacetic anhydrideHCID 31294Carbamide PeroxideHCID 716222933-(1-(2-fluorobenzyl)-3-(5-fluoropyridin-2-yl)-1H-pyrazol-5-yl)isoxazole

생성물 1

HCID 896573383-fluoro-6-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyridin-2-yl acetate

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 7918Acetic Anhydride용매

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온도
25 °C

실험 절차

To a cold mixture of 3-(1-(2-fluorobenzyl)-3-(5-fluoropyridin-2-yl)-1H-pyrazol-5-yl)isoxazole (1 equiv.) and urea compound with hydrogen peroxide (1:1) (3 equiv.) in DCM (1.7 ml) at 0° C., was added trifluoroacetic anhydride (3 equiv.). The mixture was allowed to warm to 25° C. and stirred for 3 days. The mixture was quenched with saturated solution of sodium bisulfate and extracted with dichloromethane (50 ml×3). The organic layers were combined, filtered and evaporated to give solid. The solid was dissolved in acetic anhydride (1.4 ml) and heated to 145° C. for 4 h. The mixture was cooled to 25° C., diluted with dichloromethane (100 ml) and washed with saturated solution of sodium bicarbonate (50 ml). The organic layer was dried (MgSO4), filtered and evaporated to give an oil. Purification of the oil by column chromatography (0 to 30% ethyl acetate in hexanes) gave 3-fluoro-6-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyridin-2-yl acetate as an yellow oil. The yellow oil was combined with methanol (1.7 ml) and potassium carbonate (1 equiv.). The mixture was heated to 65° C. for 30 min. The mixture was concentrated under vacuum. The resulting residue was diluted with dichloromethane (100 ml) and washed with 1N HCl (30 ml). The organic layer was dried (MgSO4), filtered and evaporated to give a solid. Purification of the solid by column chromatography (0 to 5% methanol in dichloromethane) gave 3-fluoro-6-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyridin-2(1H)-one as a yellow solid (7% overall yield).

후처리

  1. customThe mixture was quenched with saturated solution of sodium bisulfate
  2. extractionextracted with dichloromethane (50 ml×3)
  3. filtrationfiltered
  4. customevaporated
  5. customto give solid
  6. temperatureheated to 145° C. for 4 h
  7. temperatureThe mixture was cooled to 25° C.
  8. washwashed with saturated solution of sodium bicarbonate (50 ml)
  9. dry with materialThe organic layer was dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customto give an oil
  13. customPurification of the oil by column chromatography (0 to 30% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-da730e48a68b40d5a957a890a8fb372f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139564B2

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