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

HRID 2239692Notes

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].Cl.Cl.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1>CN(C=O)C>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:34][CH:31]2[CH2:32][CH2:33][N:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=3)[CH2:29][CH2:30]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

Conditions

Temperature: 130 °C

Procedure

2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.175 g, 0.58 mmol), 1-pyridin-2-ylpiperidin-4-amine dihydrochloride (0.173 g, 0.69 mmol) and TEA (0.23 g, 2.31 mmol) was dissolved in dry DMF (3 ml) and heated in a microwave reactor at 130° C. for 30 mins. The reaction mixture was purified by preparative HPLC to yield the title compound (0.175 g, 69%). 1H NMR (500 MHz, CDCl3): δ 8.08-8.03 (m, 1H), 7.50-7.44 (m, 2H), 7.41-7.32 (m, 4H), 6.55-6.47 (m, 2H), 5.28-5.20 (m, 1H), 4.02-3.93 (m, 2H), 3.11-3.00 (m, 1H), 2.41-2.30 (m, 2H), 1.73-1.60 (m, 2H), 1.67 (s, 9H), 1.36-1.24 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 159.8, 159.1, 148.0, 137.7, 134.2, 131.9, 130.1, 128.9, 125.4, 113.5, 107.5, 107.0, 61.7, 50.7, 44.1, 41.2, 32.0, 27.8; Mass Spectrum: M−H+ 441.

Workup

customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-84d129c86df24d3782736ee7adbafcc1
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

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