6-chloro-2-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide → 6-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide

HRID 1943953Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943953
[Cl:1][C:2]1[C:7]([C:8]([NH:10][C:11]2[CH:12]=[C:13]3[C:19]([O:20][CH3:21])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)=[O:9])=[C:6]([F:22])[C:5]([NH:23][S:24]([CH2:27][CH2:28][CH2:29][O:30]C2C=CC(OC)=CC=2)(=[O:26])=[O:25])=[CH:4][CH:3]=1>CC#N>[Cl:1][C:2]1[C:7]([C:8]([NH:10][C:11]2[CH:12]=[C:13]3[C:19]([O:20][CH3:21])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)=[O:9])=[C:6]([F:22])[C:5]([NH:23][S:24]([CH2:27][CH2:28][CH2:29][OH:30])(=[O:26])=[O:25])=[CH:4][CH:3]=1

Komponenten

3

Edukt 1

HCID 670890366-chloro-2-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide

Produkt 1

HCID 670889836-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamideAusbeute 83,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A 100 mL, round-bottomed flask was charged with 6-chloro-2-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy) propylsulfonamido)benzamide (30.0 mg, 0.053 mmol), Ce(NH4)2(NO2)6 (72.9 mg, 0.13 mmol) and CH3CN (0.5 mL) The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (overnight). Then the reaction mixture was partitioned between EtOAc (200 mL) and water (100 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×100 mL) The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (EtOAc/hexane from 1/2 to 1/0, v/v) to afford impure 6-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (20.3 mg). Further purification by preparation HPLC afforded pure product (2.1 mg, 8.6%). LRMS (APCI pos): >95% purity, 254 nm, m/e 458.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 8.59 (d, 1H), 8.50 (d, 1H), 7.65 (m, 1H), 7.36 (d, 1H), 4.01 (s, 3H), 3.65 (t, 2H), 3.25 (t, 2H), 2.03 (m, 2H).

Aufarbeitung

  1. customhad been consumed (overnight)
  2. customThen the reaction mixture was partitioned between EtOAc (200 mL) and water (100 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×100 mL) The combined organic layers
  5. dry with materialwere dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude product was purified by silica gel chromatography (EtOAc/hexane from 1/2 to 1/0

Quellen und Nachweise

ORD-Eintrag
ord-4b3674697f7c49ef81cfe6dd02728ecb
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394795B2

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