Ammonium Chloride → 4-(5-(6-(dibromomethyl)-3-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile

HRID 576784Notes

Reaction equation

CN1C(=O)C(C2N(C3C=CC(C#N)=CC=3)N=CC=2)=C(C)N(C2C=CC=C(C(F)(F)F)C=2)C1=O.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Br:44]N1C(=O)CCC1=O.[Cl-].[NH4+].[Br:54][CH2:55][C:56]1[N:61]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:71])([F:70])[F:69])[CH:63]=2)[C:60](=[O:72])[N:59]([CH3:73])[C:58](=[O:74])[C:57]=1[C:75]1[N:79]([C:80]2[CH:87]=[CH:86][C:83]([C:84]#[N:85])=[CH:82][CH:81]=2)[N:78]=[CH:77][CH:76]=1>O1CCCC1>[Br:54][CH:55]([Br:44])[C:56]1[N:61]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:71])([F:70])[F:69])[CH:63]=2)[C:60](=[O:72])[N:59]([CH3:73])[C:58](=[O:74])[C:57]=1[C:75]1[N:79]([C:80]2[CH:81]=[CH:82][C:83]([C:84]#[N:85])=[CH:86][CH:87]=2)[N:78]=[CH:77][CH:76]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-[5-[3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile (prepared in Example 1) (30.0 mg) in tetrahydrofuran (1.0 ml) was added at 0° C. lithium hexamethyldisilazide (0.1 ml: 1M tetrahydrofuran solution) followed by an addition of N-bromosuccinimide (14.4 mg), and the resulting mixture was stirred at 0° C. for a half hour. To the reaction mixture was added saturated aqueous ammonium chloride solution (5 ml) and the mixture was extracted with ethyl acetate (10 ml×2). The organic layer was washed with saturated saline (10 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 4-[5-(6,6-dibromomethyl)-3-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile (5.4 mg) and 4-[5-(6-bromomethyl)-3-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile (6.9 mg). 4-(5-(6-(Bromomethyl)-3-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile:

Workup

extractionthe mixture was extracted with ethyl acetate (10 ml×2)
washThe organic layer was washed with saturated saline (10 ml)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)
customto afford 4-[5-(6,6-dibromomethyl)-3-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile (5.4 mg) and 4-[5-(6-bromomethyl)-3-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile (6.9 mg)

Sources & evidence

ORD record: ord-66657737863e4c05a4b86bbbdfebac6b
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040516B2

Reaction notes

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