4-Iodo-1H-pyrazolo[3,4-b]pyridine → HCID 59224623, compound

HRID 1898190Notes

Reaction equation

HRID 1898190 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.C([Mg][Cl:15])(C)C.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([N:26]([C:30]2[C:31]([CH:37]=[O:38])=[N:32][CH:33]=[C:34](C)[CH:35]=2)COC)(=[O:25])=[O:24])=[CH:19][C:18]=1[C:39]([F:42])([F:41])[F:40]>C1COCC1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:30]2[C:31]([CH:37]([OH:38])[C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[NH:8][N:9]=[CH:10][C:3]=34)=[N:32][CH:33]=[C:34]([Cl:15])[CH:35]=2)(=[O:25])=[O:24])=[CH:19][C:18]=1[C:39]([F:42])([F:41])[F:40]

Participants

5

Reactant 3

HCID 576428014-Iodo-1H-pyrazolo[3,4-b]pyridineHCID 57942595HCID 57942595, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 59224623HCID 59224623, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-iodo-1H-pyrazolo[3,4-b]pyridine (174.2 mg, 0.71 mmol) in THF (3 mL) under nitrogen atmosphere at 0° C. was added dropwise isopropylmagnesium chloride (2 M solution in THF, 1.06 mL, 2.13 mmol). The resulting yellow suspension was then stirred for 30 min at 0° C. followed by the addition of a solution of 4-chloro-N-(2-formyl-5-methyl-pyridin-3-yl)-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (300 mg, 0.71 mmol) in THF (2 mL) at 0° C. The mixture was stirred at room temperature for 3 hours, quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with EtOAc (2×25 mL). Combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. Obtained residue was column purified (SiO2, 50% EtOAc-hexanes) to obtain 4-chloro-N-{5-chloro-2-[hydroxy-(1H-pyrazolo[3,4-b]pyridin-4-yl)-methyl]-pyridin-3-yl}-3-trifluoromethyl-benzene sulfonamide (192 mg) in 50% yield. ESMS m/z (relative intensity): 542 (M+H)+ (100), 564 (M+Na)+ (10).

Workup

  1. stirringThe mixture was stirred at room temperature for 3 hours
  2. customquenched with saturated aqueous NH4Cl solution (5 mL)
  3. extractionextracted with EtOAc (2×25 mL)
  4. washCombined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL)
  5. dry with materialdried (anhydrous Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified (SiO2, 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-30a130612acd444c9ab711e0202be68c
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

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