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

HRID 2362705
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인쇄 미리보기

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HRID 2362705 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]2[C:40](=[CH:41][CH:42]=1)[N:39]([CH3:43])[CH:38]=[C:37]2B1OC(C)(C)C(C)(C)O1.C(=O)(O)[O-]>CN(C)C=O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=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:37]3[C:36]4[C:40](=[CH:41][CH:42]=[C:34]([O:33][CH3:32])[CH:35]=4)[N:39]([CH3:43])[CH:38]=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
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참가 물질

6

반응물 3

HCID 769Bicarbonate IonHCID 580098415-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 670034821-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

생성물 1

HCID 670035301-(5-(5-fluoro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

시약·촉매·용매 2

HCID 6102075
Dichlorobis(triphenylphosphine)palladium
촉매
HCID 6228Dimethylformamide용매

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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 5-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (Example 106B) (160 mg, 0.557 mmol) in N,N-dimethylformamide (3.21 mL) was added saturated aqueous bicarbonate solution (1.07 mL) followed by bis(triphenylphosphine) palladium dichloride (21.06 mg, 0.030 mmol). The mixture was heated to 70° C. for 2 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. 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. LCMS TFA(+) m/z 602.99 [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. customThe residue was purified by flash chromatography on silica gel
  8. washeluting with a gradient of 0 to 100% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-26b7a0a0a75942799b4952306fe26274
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08691810B2

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