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 1943953Notes

Reaction equation

HRID 1943953 reaction equation
[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

Participants

3

Reactant 1

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

Product 1

HCID 670889836-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamideYield 83.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4b3674697f7c49ef81cfe6dd02728ecb
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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