Sodium hydride → 6-[3-Pyridin-2-yl-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinonitrile

HRID 1514727Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([CH2:12][OH:13])=[C:10](/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:9][N:8]=1.Cl[C:23]1[N:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=1.[H-].[Na+]>CN(C=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([CH2:12][O:13][C:23]2[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[CH:27][N:28]=2)=[C:10](/[CH:14]=[CH:15]/[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[O:9][N:8]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of [3-pyridin-2-yl-5([E]-styryl)-isoxazol-4-yl]-methanol (1.5 g, 5 mmol) in DMF (30 mL) was added 6-chloro-3-pyridine-carbonitrile (0.82 g, 6 mmol) and sodium hydride (0.26 g of a 55% dispersion in mineral oil, 6 mmol). The mixture was stirred at 70° C. for 3 h. Then the temperature was raised to 90° C. for 1 h. After evaporation of the solvent the residue was partitioned (ethyl acetate/brine) and the organic phase was dried (Na2SO4) and filtered. Evaporation of the solvent followed by trituration with diisopropylether afforded the title compound (1.8 g, 88%) as a light brown solid. MS: m/e=381.3 [M+H]+.

Workup

temperatureThen the temperature was raised to 90° C. for 1 h
customAfter evaporation of the solvent the residue
customwas partitioned (ethyl acetate/brine)
dry with materialthe organic phase was dried (Na2SO4)
filtrationfiltered
customEvaporation of the solvent

Sources & evidence

ORD record: ord-ed331315294845c48358ce49f70c50ff
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222246B2

Reaction notes

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