1-(Pyridazin-3-yl)piperidin-4-amine → 2-tert-Butyl-5-phenyl-4-[(1-pyridazin-3-ylpiperidin-4-yl)amino]isothiazol-3(2H)-one 1,1-dioxide

HRID 2422095

Reaction equation

HRID 2422095 reaction equation
[C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N:26]2[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]2)[N:21]=1>CN(C=O)C.O>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:32][CH:29]2[CH2:30][CH2:31][N:26]([C:22]3[N:21]=[N:20][CH:25]=[CH:24][CH:23]=3)[CH2:27][CH2:28]2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 624820041-(Pyridazin-3-yl)piperidin-4-amineHCID 672426272-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 672418232-tert-Butyl-5-phenyl-4-[(1-pyridazin-3-ylpiperidin-4-yl)amino]isothiazol-3(2H)-one 1,1-dioxideYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.240 g, 0.80 mmol), 1-pyridazin-3-ylpiperidin-4-amine (0.257 g, 1.02 mmol) and TEA (0.324 g, 3.2 mmol), was dissolved in dry DMF (10 ml) and heated in a microwave reactor at 120° C. for 30 mins. The reaction mixture was diluted with water (300 ml) and extracted with EtOAc (2×150 ml). The combined organic phases were dried (MgSO4), filtered and evaporated and the residue was purified by silica gel column chromatography using EtOAc as eluant, to give the title compound (0.10 g, 31%). 1H NMR (500 MHz, CDCl3): δ 8.55-8.52 (m, 1H), 7.55-7.50 (m, 2H), 7.47-7.42 (m, 3H), 7.19-7.14 (m, 1H), 6.85-6.82 (m, 1H), 5.21 (d, 1H), 4.17-4.11 (m, 2H), 3.22-3.13 (m, 1H), 2.60-2.52 (m, 2H), 1.80-1.73 (m, 2H), 1.72 (s, 9H), 1.42-1.32 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 159.5, 143.1, 133.8, 131.6, 129.9, 128.7, 127.4, 125, 112.8, 107.2, 61.6, 50.1, 43.6, 31.7, 27.5; Mass Spectrum: M−H+ 442.

Workup

  1. extractionextracted with EtOAc (2×150 ml)
  2. dry with materialThe combined organic phases were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-85896d9ee0c14e5da7fe44b7b052250b
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Linked notes

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