Ethanesulfonamide → N-((5-(3-chloro-4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide

HRID 1897772Notes

Reaction equation

[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([CH:16]=O)[CH:15]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH2:18]([S:20]([NH2:23])(=[O:22])=[O:21])[CH3:19].[CH:24]1([Mg]Br)[CH2:26][CH2:25]1>C1(C)C=CC=CC=1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([CH:16]([CH:24]3[CH2:26][CH2:25]3)[NH:23][S:20]([CH2:18][CH3:19])(=[O:22])=[O:21])[CH:13]=[N:12][CH:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: -40 °C

Procedure

Titanium(IV) isopropoxide (0.365 mL, 1.245 mmol) was added to a mixture of 2-chloro-4-(5-formylpyridin-3-yl)benzonitrile (as prepared in Example 23, step 1; 0.151 g, 0.622 mmol), ethanesulfonamide (0.085 g, 0.778 mmol) in toluene (10 mL) at room temperature. The resulting mixture was heated to reflux for 4 h. After concentration, the residue was dissolved in THF (5 mL), and cooled to −40° C. Cyclopropylmagnesium bromide (3.73 mL, 1.867 mmol) was added dropwise, and the resulting mixture was slowly warmed up to room temperature and stirred overnight. After quenching by saturated NH4Cl solution, the residue was purified by flash column (ethyl acetate-heptane, v/v, 40%-60%) yielded a slightly yellow solid.

Workup

temperatureThe resulting mixture was heated
temperatureto reflux for 4 h
concentrationAfter concentration
dissolutionthe residue was dissolved in THF (5 mL)
temperaturethe resulting mixture was slowly warmed up to room temperature
customAfter quenching by saturated NH4Cl solution
customthe residue was purified by flash column (ethyl acetate-heptane, v/v, 40%-60%)
customyielded a slightly yellow solid

Sources & evidence

ORD record: ord-20d9094c453d48b2ad5a1580a061e8aa
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08519142B2

Reaction notes

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