Bicarbonate Ion → 1-(5-(5-fluoro-1-tosyl-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

HRID 2362695노트

반응식

HRID 2362695 반응식
[F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[CH3:32][O:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41].C(=O)(O)[O-]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:36]3[CH:37]=[C:38]([O:42][CH3:43])[C:39]([O:40][CH3:41])=[C:34]([O:33][CH3:32])[CH:35]=3)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

참가 물질

6

반응물 3

HCID 769Bicarbonate IonHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 670034821-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

생성물 1

HCID 670034831-(5-(5-fluoro-1-tosyl-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

To a stirred ambient solution of 1-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 59A) (200 mg, 0.351 mmol) and 3,4,5-trimethoxy phenylboronic acid (112 mg, 0.527 mmol) in N,N-dimethylformamide (2630 μl) was added saturated aqueous bicarbonate solution (880 μl) followed by bis(triphenylphosphine)palladium dichloride (17.26 mg, 0.025 mmol). The mixture was heated to 70° C. for 4 hours and was quenched by the addition of water and dichloromethane. The layers were separated, and the aqueous layer was extracted with additional dichloromethane. The combined organics were dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give crude product. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 100% ethyl acetate in hexane, to give the title compound. MS ESI(+) m/z 610.2 [M+H]+.

후처리

  1. customwas quenched by the addition of water and dichloromethane
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with additional dichloromethane
  4. dry with materialThe combined organics were dried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give crude product
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 0 to 100% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-a85e1aa70a3646d1a659f055d00baf23
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691810B2

반응 노트

불러오는 중…