Ethanesulfonamide → N-(1-(5-(3-chloro-4-cyanophenyl)pyridin-3-yl)-2-methylpropyl)ethanesulfonamide

HRID 391287Notes

Reaction equation

HRID 391287 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].[C:24]([Mg]Br)([CH3:26])=[CH2:25]>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]([NH:23][S:20]([CH2:18][CH3:19])(=[O:22])=[O:21])[CH:24]([CH3:26])[CH3:25])[CH:13]=[N:12][CH:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 73702EthanesulfonamideHCID 595783972-Chloro-4-(5-formyl-pyridin-3-yl)-benzonitrileHCID 178456138HCID 178456138, compound

Product 1

HCID 49819979N-(1-(5-(3-chloro-4-cyanophenyl)pyridin-3-yl)-2-methylpropyl)ethanesulfonamideYield 23.8%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
-40 °C

Procedure

(General Grignard addition reaction procedure): a mixture of 2-Chloro-4-(5-formyl-pyridin-3-yl)-benzonitrile (0.243 g, 1 mmol), titanium(IV) isopropoxide (0.586 mL, 2.000 mmol), ethanesulfonamide (0.109 g, 1.000 mmol) in Toluene (20 mL) was heated to reflux for 4 hr. After concentration, the residue was dissolved in THF (15 mL) and cooled to −40° C. A solution of isopropenylmagnesium bromide (1.500 mL, 3.000 mmol) was added dropwise and the resulting mixture was slowly warmed up to −20° C. and stirred at this temperature for 4 hr. After quenched by NH4Cl solution, filtration, extraction with CH2Cl2, the solution was dried over Na2SO4, and concentrated, the residue was purified by flash column (MeOH—CH2Cl2, v/v, 1%-3%) and yielded a yellow solid (90 mg). Enantiomers were separated by 40% EtOH 60% heptane on a Chiralpak IA column. First peak 14 min (enantiomer 1), second peak 20 min (enantiomer 2). ESI-MS m/z: 378.1 [M+H]+, 1H NMR (400 MHz, CDCl3): δ 0.93 (d, J=6.7 Hz, 3H), 1.06 (d, J=6.7 Hz, 3H), 1.21 (t, J=8.0 Hz, 3H), 2.04-2.11 (m, 1H), 2.76-2.91 (m, 2H), 4.36 (t, J=7.4 Hz, 1H), 4.90 (d, J=7.6 Hz, 1H), 7.58 (d, J=8.2 Hz, 1H), 7.72 (s, 1H), 7.77 (s, 1H), 7.78 (d, J=8.2 Hz, 1H), 8.61 (s, 1H), 8.77 (s, 1H).

Workup

  1. addition(General Grignard addition reaction procedure)
  2. temperaturewas heated
  3. temperatureto reflux for 4 hr
  4. concentrationAfter concentration
  5. dissolutionthe residue was dissolved in THF (15 mL)
  6. temperaturethe resulting mixture was slowly warmed up to −20° C.
  7. customAfter quenched by NH4Cl solution, filtration, extraction with CH2Cl2
  8. dry with materialthe solution was dried over Na2SO4
  9. concentrationconcentrated
  10. customthe residue was purified by flash column (MeOH—CH2Cl2, v/v, 1%-3%)

Sources & evidence

ORD record
ord-c34dadec377147adbd9483ecdd1b5f79
Source dataset
uspto-grants-2013_02
Patent number
US08383827B2

Reaction notes

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