Water → 3-{4-[(2-Isopropyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]piperidin-1-yl}propanenitrile

HRID 2239619Notes

Reaction equation

HRID 2239619 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][CH:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][C:28]#[N:29])[CH2:22][CH2:21]1.O>CN(C=O)C>[CH:15]([N:4]1[C:3](=[O:18])[C:2]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][C:28]#[N:29])[CH2:22][CH2:21]2)=[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 3

HCID 962WaterHCID 22562162N-(2-cyanoethyl)-4-aminopiperidineHCID 672431604-Chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 115894583-{4-[(2-Isopropyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]piperidin-1-yl}propanenitrileYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.200 g, 0.700 mmol), TEA (0.283 g, 2.800 mmol) and 3-(4-aminopiperidin-1-yl)propanenitrile (0.161 g, 1.050 mmol) in DMF (3 mL) was heated in a microwave reactor at 120° C. for 10 mins. Water was added and the mixture was extracted with EtOAc. The organic phase was evaporated and the residue was purified by silica gel column chromatography (Horizons Biotage) using a mixture of heptane and EtOAc (20:80) to 100% EtOAc, then a mixture of MeOH and EtOAc (1:99) as eluant, to give the title compound (0.25 g, 89%); 1H NMR (500 MHz, CDCl3): δ 7.54-7.51 (m, 2H), 7.49-7.44 (m, 3H), 5.20 (br d 1H), 4.46-4.38 (m, 1H), 3.01-2.91 (br m, 1H), 2.70-2.65 (br m, 2H), 2.55 (t, 2H), 2.41 (t 2H), 1.74-1.63 (m 4H), 1.60 (d 6H) 1.44-1.35 (m 2H); 13C NMR (125 MHz, CDCl3): δ 158.7, 134.5, 131.8, 130.1, 128.9, 125.3, 118.8, 106.8, 53.3, 51.5, 50.0, 47.8, 32.4, 20.4, 16.4: Mass Spectrum: M−H+ 403.

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. customThe organic phase was evaporated
  3. customthe residue was purified by silica gel column chromatography (Horizons Biotage)
  4. additiona mixture of heptane and EtOAc (20:80) to 100% EtOAc
  5. additiona mixture of MeOH and EtOAc (1:99) as eluant

Sources & evidence

ORD record
ord-f12a0dab549b4b53a6bd2b202f36bb9c
Source dataset
uspto-grants-2010_05
Patent number
US07723333B2

Reaction notes

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