Potassium Carbonate → 2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]benzo[d]oxazole

HRID 710185Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=3[F:20])=[N:7][C:6]=2[CH:21]=1.Cl.[CH:23]([C:26]1[N:30]=[C:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[O:28][N:27]=1)([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+].C(CC(=O)C)(=O)C>CN1C(=O)CCC1.Cl[Cu]>[F:20][C:11]1[CH:12]=[C:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:14]=[CH:15][C:10]=1[C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([N:34]3[CH2:33][CH2:32][CH:31]([C:29]4[O:28][N:27]=[C:26]([CH:23]([CH3:25])[CH3:24])[N:30]=4)[CH2:36][CH2:35]3)=[CH:21][C:6]=2[N:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

Intermediate 28 (150 mg, 0.41 mmol), 3-isopropyl-5-(piperidin-4-yl)-1,2,4-oxadiazole hydrochloride (96 mg, 0.5 mmol), K2CO3 (59 mg, 0.43 mmol), CuCl (2 mg, 0.02 mmol), acetyl acetone (5 mg, 0.05 mmol) were dissolved in NMP (1 ml). This reaction mixture was stirred at 130° C. for 16 h under N2 atmosphere. Work up (EtOAc/H2O) followed by purification on combiflash using a gradient mixture of EtOAc and Petether (30:70) as eluent afforded the titled compound (25 mg) as a pale-yellow solid. M. P.: 206-209° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.26 (d, J 8.2, 1H), 7.97 (d, J 1.4, 1H), 7.69 (d, J 1.4, 1H), 7.63 (dd, J 1.5, 8.2, 1H), 7.56-7.48 (m, 2H), 3.49-3.39 (m, 2H), 3.15-3.04 (m, 5H), 3.03-2.93 (m, 2H), 2.25-2.16 (m, 4h), 1.36 (d, J 7, 6H).

Workup

customWork up (EtOAc/H2O) followed by purification on combiflash
additiona gradient mixture of EtOAc and Petether (30:70) as eluent

Sources & evidence

ORD record: ord-16c83d8eeaed415eb577f8855972b3ad
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181214B2

Reaction notes

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