Chlorosuccinimide → 3-Chloro-1-(4-fluorophenyl)-4-iodo-1H-pyrazolo[3,4-b]pyridine

HRID 1186828Notes

Reaction equation

HRID 1186828 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([I:17])=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Cl:18]N1C(=O)CCC1=O>CN(C=O)C.C(OCC)(=O)C>[Cl:18][C:10]1[C:11]2[C:12](=[N:13][CH:14]=[CH:15][C:16]=2[I:17])[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 666684371-(4-Fluorophenyl)-4-iodo-1H-pyrazolo[3,4-B]pyridine

Product 1

HCID 680582803-Chloro-1-(4-fluorophenyl)-4-iodo-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Intermediate 2A (33.9 mg, 0.1 mmol) in DMF (Volume: 1 mL) under argon at room temp was added N-chlorosuccinimide (107 mg, 0.800 mmol). The reaction mixture was allowed to stir overnight. The reaction mixture was diluted with ethyl acetate and washed (2×15 mL) with 10% LiCl, once with brine, dried over Na2SO4, filtered and concentrated. The crude product was dissolved in a small amount of dichloromethane and charged to a 4 g silica gel cartridge which was eluted with a 20 min gradient from 0% to 100% of ethyl acetate in dichloromethane. The resulting brown solid (23 mg, 61.6%) was determined to be the desired material by 1HNMR and LCMS. MS (ES): m/z=274.0 [M+H]+. 1H NMR (400 MHz, CCl3D) δ ppm 8.58-8.60 (1 H, m), 8.24 (1 H, s), 8.14-8.20 (2 H, m), 7.18-7.26 (2 H, m).

Workup

  1. washwashed (2×15 mL) with 10% LiCl
  2. dry with materialonce with brine, dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude product was dissolved in a small amount of dichloromethane
  6. additioncharged to a 4 g silica gel cartridge which
  7. washwas eluted with a 20 min gradient from 0% to 100% of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-6e79f23b4f21406ab1950b49188eb6f4
Source dataset
uspto-grants-2014_03
Patent number
US08673922B2

Reaction notes

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