(4,4-Difluorocyclohexyl)amine → 4-[(4,4-Difluorocyclohexyl)amino]-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide

HRID 2239649Notes

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

Participants

Conditions

Temperature: 130 °C

Procedure

4-Chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.155 g, 0.54 mmol), 4,4-difluorocyclohexylamine (0.11 g, 0.81 mmol) and TEA (0.082 g, 0.81 mmol) was dissolved in dry MeCN (3 ml) and heated in a microwave reactor at 130° C. for 10 mins. The reaction mixture was purified by silica gel column chromatography using a 85:15 mixture of hexane and EtOAc as eluant, to give the title compound (0.142 g, 68%); 1H NMR (500 MHz, CDCl3): δ 7.54-7.49 (m, 2H), 7.49-7.42 (m, 3H), 5.23-5.16 (m, 1H), 4.41 (hep, 1H), 3.10-3.00 (m, 1H), 1.97-1.86 (m, 2H), 1.77-1.68 (m, 2H), 1.57 (d, 6H), 1.49-1.37 (m, 2H), 1.37-1.21 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 158.6, 134.5, 131.8, 130.3, 129.0, 125.1, 123.9, 122.0, 120.0, 107.3, 49.9, 47.9, 32.1, 31.9, 31.7, 29.0, 28.9, 20.4; Mass Spectrum: M−H+ 385.

Workup

customThe reaction mixture was purified by silica gel column chromatography
additiona 85:15 mixture of hexane and EtOAc as eluant

Sources & evidence

ORD record: ord-41e70d33ef794e068ec151d9fa79afa1
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

Loading…