Triethylamine → 5-(3-(Cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

HRID 2088637노트

반응식

HRID 2088637 반응식
[CH:1]1([NH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[C:13](I)[C:8]=3[O:7][N:6]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.CC1(C)C(C)(C)OBO1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1.Br[C:59]1[C:64](=[O:65])[N:63]([CH3:66])[C:62]2[N:67]([C:70]3[C:75]([F:76])=[CH:74][CH:73]=[CH:72][C:71]=3[F:77])[N:68]=[CH:69][C:61]=2[CH:60]=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[CH:1]1([NH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[C:13]([C:59]4[C:64](=[O:65])[N:63]([CH3:66])[C:62]5[N:67]([C:70]6[C:75]([F:76])=[CH:74][CH:73]=[CH:72][C:71]=6[F:77])[N:68]=[CH:69][C:61]=5[CH:60]=4)[C:8]=3[O:7][N:6]=2)[CH2:3][CH2:2]1

참가 물질

11

반응물 7

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 461976915-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-oneHCID 58702151N-cyclopropyl-7-iodo-6-methylbenzo[d]isoxazol-3-amine

생성물 1

HCID 250526715-(3-(Cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of N-cyclopropyl-7-iodo-6-methylbenzo[d]isoxazol-3-amine (0.100 g, 0.32 mmol), triethylamine (0.17 ml, 1.25 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.95 ml of 1.0 M in THF solution, 0.95 mmol), 2-(dicyclohexylphosphino)-2′-methylbiphenyl (0.023 g, 0.065 mmol) and palladium acetate (0.0036 g, 0.016 mmol) in 2.0 mL of dioxane in a sealed glass tube was heated in a microwave at 100° C. for 20 min. After cooling to RT, the reaction mixture was transferred to a 50 mL round-bottom flask and treated with 5-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one (0.089 g, 0.26 mmol) and sodium carbonate (1.0 mL of 2.0 M aqueous solution). Tetakis(triphenylphosphine)palladium (0) (9 mg) was added, and the reaction mixture was heated at 110° C. in an oil bath for 5 h. It was cooled to RT, treated with 5 mL of 1 N NaOH and 60 mL of EtOAc. The organic phase was separated, washed with brine, separated from the aqueous layer, then dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on SiO2 (EtOAc/hexane=80/20) to give the title compound as a yellow crystalline solid. MS (ESI, pos.ion) m/z: 448.1 (M+1).

후처리

  1. temperatureAfter cooling to RT
  2. customthe reaction mixture was transferred to a 50 mL round-bottom flask
  3. temperaturethe reaction mixture was heated at 110° C. in an oil bath for 5 h
  4. temperatureIt was cooled to RT
  5. customThe organic phase was separated
  6. washwashed with brine
  7. customseparated from the aqueous layer
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified by flash chromatography on SiO2 (EtOAc/hexane=80/20)

출처 및 근거

ORD 기록
ord-4547ac37434a40c99a68fd6faebd18bf
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08435987B2

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