3-(2-Aminoethyl)benzonitrile → 3-{2-[(2-Isopropyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]ethyl}benzonitrile

HRID 2239714Notes

Reaction equation

HRID 2239714 reaction equation
Cl[C:2]1[C:3](=[O:18])[N:4]([CH:15]([CH3:17])[CH3:16])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[C:25]#[N:26]>CN(C=O)C.CCOC(C)=O>[CH:15]([N:4]1[C:3](=[O:18])[C:2]([NH:19][CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[C:25]#[N:26])=[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:5]1(=[O:14])=[O:13])([CH3:17])[CH3:16]

Participants

5

Reactant 2

HCID 118159283-(2-Aminoethyl)benzonitrileHCID 672431604-Chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 672432093-{2-[(2-Isopropyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]ethyl}benzonitrileYield 56.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

4-Chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (150 mg, 0.525 mmol) was dissolved in dry DMF (1 mL) under nitrogen atmosphere. 3-(2-Aminoethyl)benzonitrile (78 mg, 0.530 mmol) was added followed by TEA (53 mg, 0.525 mmol) and the reaction mixture was heated in a microwave reactor for at 120° C. for 20 mins. The mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3-solution, dried over Na2SO4, filtered and evaporated. The crude product was purified on a Biotage Horizon HPFC system using Heptane and EtOAc as eluant affording the title compound (118 mg, 56.3%). 1H NMR (500 MHz, CDCl3): δ 1.59 (d, 6H), 2.60 (t, 2H), 3.17 (q, 2H), 4.37-4.46 (m, 1H), 5.49 (bs, 1H), 6.88 (s, 1H), 7.02 (d, 1H), 7.30-7.34 (m, 1H), 7.47-7.57 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 20.38, 35.75, 44.70, 47.90, 107.72, 113.00, 118.70, 125.17, 129.19, 129.67, 130.36, 130.77, 131.95, 132.20, 133.23, 135.11, 139.03, 158.60; Mass Spectrum: M+H+ 396.1.

Workup

  1. washwashed with saturated aqueous NaHCO3-solution
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified on a Biotage Horizon HPFC system

Sources & evidence

ORD record
ord-c9bbfcce31ba4fee8c9efa47420d5471
Source dataset
uspto-grants-2010_05
Patent number
US07723333B2

Reaction notes

Loading…