2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide → 2-tert-Butyl-5-phenyl-4-({1-[4-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}amino)isothiazol-3(2H)-one 1,1-dioxide

HRID 2239697Notes

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.[F:22][C:23]([F:38])([F:37])[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([N:30]2[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]2)[CH:25]=1>CN(C=O)C>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:36][CH:33]2[CH2:34][CH2:35][N:30]([C:26]3[CH:25]=[C:24]([C:23]([F:38])([F:37])[F:22])[CH:29]=[CH:28][N:27]=3)[CH2:31][CH2:32]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-[4-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine dihydrochloride (0.220 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 (0.112 g, 38%). 1H NMR (500 MHz, CDCl3): δ 8.28-8.23 (m, 1H), 7.59-7.52 (m, 2H), 7.51-7.44 (m, 3H), 6.79-6.74 (m, 1H), 6.74-6.70 (m, 1H), 5.27-5.17 (m, 1H), 4.17-4.07 (m, 2H), 3.24-3.13 (m, 1H), 2.57-2.48 (m, 2H), 1.83-1.69 (m, 2H), 1.75 (s, 9H), 1.42-1.31 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 159.8, 149.3, 134.1, 131.9, 130.2, 129.0, 125.3, 108.5, 107.4, 102.9, 61.9, 50.5, 43.9, 32.0, 27.8; Mass Spectrum: M−H+ 509.

Workup

customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-2d55eac625f744afba094e02059f976d
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

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