3-Hydroxypyridine → 2-tert-Butyl-5-phenyl-4-{[2-(pyridin-3-yloxy)ethyl]amino}isothiazol-3(2H)-one 1,1-dioxide

HRID 2239702Notes

Reaction equation

CC1C=CC(S([O:11][CH2:12][CH2:13][NH:14][C:15]2[C:16](=[O:32])[N:17]([C:28]([CH3:31])([CH3:30])[CH3:29])[S:18](=[O:27])(=[O:26])[C:19]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=O)=O)=CC=1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35](O)[CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[C:28]([N:17]1[C:16](=[O:32])[C:15]([NH:14][CH2:13][CH2:12][O:11][C:35]2[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=2)=[C:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[S:18]1(=[O:27])=[O:26])([CH3:31])([CH3:30])[CH3:29]

Participants

Conditions

Temperature: 120 °C

Procedure

2-[(2-tert-Butyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]ethyl 4-methylbenzenesulfonate (150 mg, 0.313 mmol) was dissolved in dry MeCN (3 mL) under nitrogen atmosphere. Pyridin-3-ol (33 mg, 0.345 mmol) was added followed by potassium carbonate (217 mg, 1.567 mmol). The reaction mixture was heated in a microwave reactor at 120° C. for 15 mins. Potassium carbonate was filtered off and the reaction mixture was evaporated to dryness in a vacuum centrifuge. The crude product was purified by preparative HPLC affording the title compound (46 mg, 35.7%). 1H NMR (CDCl3, 500 MHz): δ 1.74 (s, 9H), 3.30 (q, 2H), 3.92 (t, 2H), 5.64 (t, 1H), 7.12-7.14 (m, 1H), 7.22-7.24 (m, 1H), 7.46-7.48 (m, 3H), 7.53-7.55 (m, 2H), 8.26-8.28 (m, 2H); 13C NMR (CDCl3, 125 MHz): δ 27.84, 43.32, 61.90, 66.37, 108.51, 121.55, 124.15, 125.03, 129.09, 130.10, 131.69, 135.11, 137.90, 143.23, 154.51, 159.64; Mass Spectrum: M+H+ 402.1.

Workup

filtrationPotassium carbonate was filtered off
customthe reaction mixture was evaporated to dryness in a vacuum centrifuge
customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-4089b8515a1a4368a3ef9e73241163da
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

Loading…