Sodium Cyanide → 3-ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-carbonitrile

HRID 2240175Notes

Reaction equation

[CH2:1]([C:3]1[C:11]2[C:6](=[N:7][C:8](F)=[CH:9][CH:10]=2)[N:5]([CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:4]=1)[CH3:2].[C-:19]#[N:20].[Na+]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CS(C)=O>[CH2:1]([C:3]1[C:11]2[C:6](=[N:7][C:8]([C:19]#[N:20])=[CH:9][CH:10]=2)[N:5]([CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:4]=1)[CH3:2]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 3-ethyl-6-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine (2.92 g, 0.0117 mol), sodium cyanide (3.9 g, 0.079 mol), tetra-N-butylammonium bromide (7.6 g, 0.023 mol) and dimethyl sulfoxide (60 mL) was heated at 150° C. for 2 hours. After cooling, the product was extracted using ethyl acetate (300 mL). The extract was washed with water (5×50 mL) and brine (50 mL), and then concentrated to provide the crude product as a brown solid, which was purified by flash chromatography on silica gel using a 10-50% hexane:ethyl acetate gradient over 15 minutes (flow rate 20 mL/min) to afford 2.22 g (73.9%) of 3-ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-carbonitrile as an off-white solid, which was used without further purification. LC/MS (EI) tR 3.57 (Method E), m/z 257.2 (M++1).

Workup

temperatureAfter cooling
extractionthe product was extracted
washThe extract was washed with water (5×50 mL) and brine (50 mL)
concentrationconcentrated
customto provide the crude product as a brown solid, which
customwas purified by flash chromatography on silica gel using a 10-50% hexane

Sources & evidence

ORD record: ord-58aac154029a4908893fee53005b5218
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723348B2

Reaction notes

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