N,N'-Dimethylethylenediamine → [2-Fluoro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-3-pyridyl]methanol

HRID 57938Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][NH:16][C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1.Br[C:18]1[N:23]=[C:22]([F:24])[C:21]([CH2:25][OH:26])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[F:24][C:22]1[C:21]([CH2:25][OH:26])=[CH:20][CH:19]=[C:18]([N:16]2[C:10]3[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[N:7]=4)[N:13]=[CH:12][C:11]=3[CH:14]=[N:15]2)[N:23]=1

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (2.000 mmol; 422.4 mg), (6-bromo-2-fluoro-3-pyridyl)methanol (2.400 mmol; 494.4 mg), potassium carbonate (4.000 mmol; 552.8 mg), copper(I) iodide (2.000 mmol; 380.9 mg), and N,N′-Dimethylethylenediamine (0.2000 mmol; 17.81 mg; 0.0217 mL) in 1,4-Dioxane (15 mL) was purged with Argon then sealed in a pressure tube and heated at 105° C. overnight. The mixture was cooled to room temperature and filtered through Celite. The filtrate was concentrated and the residue was purified on silica eluted with 0 to 100% EtOAc in Heptane to afford [2-fluoro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-3-pyridyl]methanol (79.5 mg, 12%).

Workup

customwas purged with Argon
customthen sealed in a pressure tube
temperatureThe mixture was cooled to room temperature
filtrationfiltered through Celite
concentrationThe filtrate was concentrated
customthe residue was purified on silica
washeluted with 0 to 100% EtOAc in Heptane

Sources & evidence

ORD record: ord-e7b5c56221d54b3eb30976beb6a48aab
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434725B2

Reaction notes

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