2-Fluoro-4-iodoaniline → 4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

HRID 79018Notes

Reaction equation

HRID 79018 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[O:5])[CH3:2].[F:25][C:26]1[CH:32]=[C:31]([I:33])[CH:30]=[CH:29][C:27]=1[NH2:28]>O1CCOCC1.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH:28][C:27]2[CH:29]=[CH:30][C:31]([I:33])=[CH:32][C:26]=2[F:25])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 1856942-Fluoro-4-iodoanilineHCID 53665897Ethyl 4-chloro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

Product 1

HCID 673527014-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl esterYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Chloro-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (1.8 g, 5.2 mmol) and 2-fluoro-4-iodoaniline (1.5 g, 6.3 mmol) were dissolved in dioxane (20 mL) and the resultant mixture stirred at reflux for 16 hours. The reaction mixture was diluted with water (50 mL) and the aqueous layer extracted with dichloromethane (3×20 mL). The combined organic fractions were filtered through a hydrophobic frit and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-30% ethyl acetate in cyclohexane) to yield the title compound as a white solid (1.56 g, 56%). LCMS (Method B): RT=4.78 min, [M+H]+=547.

Workup

  1. temperatureat reflux for 16 hours
  2. extractionthe aqueous layer extracted with dichloromethane (3×20 mL)
  3. filtrationThe combined organic fractions were filtered through a hydrophobic frit
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-55a10149aa2c40b5932c80cedf867b98
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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