4-Methoxybenzyl bromide → tert-Butyl 6-fluoro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate

HRID 505497Notes

Reaction equation

[F:1][C:2]1[N:7]=[C:6]2[NH:8][N:9]=[C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:5]2=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1>C1COCC1>[F:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:30][C:29]3[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[N:9]=[C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:5]2=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 7.5 °C

Procedure

To a solution of tert-butyl 6-fluoro-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (29.55 g, 125 mmol) in THF (300 mL) cooled in an ice bath was added KOtBu (13.98 g, 125 mmol) at such a rate as to maintain the temperature between 5-10° C., and then 4-methoxybenzyl bromide (18.2 mL, 125 mmol) was added. The resulting mixture was stirred in an ice bath for 1 hour and then stirred at room temperature for 18 hours. The resulting suspension was quenched with saturated aqueous NH4Cl (200 mL) and then extracted with EtOAc (2×300 mL). The combined organic extracts were washed with brine, dried with MgSO4 and the solvent removed in vacuo. The resulting residue was purified on a silica gel (1000 g) column (0-11% EtOAc/hexanes) to give the title compound. LRMS (M+1)=380.1

Workup

stirringstirred at room temperature for 18 hours
customThe resulting suspension was quenched with saturated aqueous NH4Cl (200 mL)
extractionextracted with EtOAc (2×300 mL)
washThe combined organic extracts were washed with brine
dry with materialdried with MgSO4
customthe solvent removed in vacuo
customThe resulting residue was purified on a silica gel (1000 g) column (0-11% EtOAc/hexanes)

Sources & evidence

ORD record: ord-e93adf8281c446c18139049056d9826b
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781454B2

Reaction notes

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