Sodium hydride → 7-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine

HRID 1522624Notes

Reaction equation

[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][NH:10][C:3]=12.[H-].[Na+].Cl[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1>CN(C=O)C>[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[C:3]=12.[I:1][C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[N:10]=2)[N:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

7-Iodo-1H-pyrazolo[4,3-b]pyridine (500 mg, 2.041 mmol) and NaH (103 mg, 60% in oil, 4.08 mmol) were combined in DMF (10 mL) at 25° C. After 10 minutes, the mixture was cooled to 0° C. and 1-(chloromethyl)-4-methoxybenzene (0.297 mL, 2.143 mmol) was added and the mixture stirred for a further 15 minutes. The ice bath was removed and the mixture stirred for 1 hour then diluted with water (150 mL) and saturated ammonium chloride solution (50 mL). The product was extracted into EtOAc. The organic layers were combined, dried over magnesium sulfate, filtered and evaporated in vacuo onto silica and subjected to chromatography on silica eluted with EtOAc in hexanes (0-50%) to give 7-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridine and 7-iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine which was used without further purification.

Workup

customThe ice bath was removed
stirringthe mixture stirred for 1 hour
additionthen diluted with water (150 mL) and saturated ammonium chloride solution (50 mL)
extractionThe product was extracted into EtOAc
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated in vacuo onto silica
washeluted with EtOAc in hexanes (0-50%)

Sources & evidence

ORD record: ord-5ff211ea2f444dbc81808e60ef7e45f6
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073918B2

Reaction notes

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