Potassium Carbonate → 5-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

HRID 710187Notes

Reaction equation

HRID 710187 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.[CH2:22]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+].C(CC(=O)C)(=O)C>CN1C(=O)CCC1.Cl[Cu]>[CH2:22]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:3]=[CH:4][C:5]3[O:9][C:8]([C:10]4[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=4[F:20])=[N:7][C:6]=3[CH:21]=2)[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31261AcetylacetoneHCID 759941-BenzylpiperazineHCID 712573645-Bromo-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

Product 1

HCID 712570875-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazoleYield 40.7%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

Intermediate 28 (490 mg, 1.32 mmol), N-Benzylpiprazine (280 mg, 1.6 mmol), K2CO3 (190 mg, 1.4 mmol), CuCl (6.5 mg, 0.05 mmol), acetyl acetone (17 mg, 0.12 mmol) were dissolved in NMP (2 ml). This reaction mixture was stirred at 130° C. for 15 h under N2 atmosphere. Work up (EtOAc/H2O) followed by column purification on 60-120 mesh silica gel using a gradient mixture of EtOAc and Petether (1:1) as eluent afforded 5-(4-benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (250 mg) as a yellow solid. 5-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (130 mg, 0.28 mmol) dissolved in DCM (15 ml) and added isopropylchloro formate (102 mg, 0.84 mmol). This mixture was stirred at reflux for 18 h. Work up (DCM/H2O) followed by purification of the crude by column chromatography on 230-400 mesh silica gel 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.: 231-234° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.28 (d, J 8.7, 1H), 7.96 (d, J 1.6, 1H), 7.68-7.64 (m, 2H), 7.57-7.47 (m, 2H), 4.95 (septet, J 6.2, 1H), 3.71-3.63 (m, 4H), 3.12-3.06 (m, 4H), 1.26 (d, J 6.2, 6H).

Workup

  1. customWork up (EtOAc/H2O) followed by column purification on 60-120 mesh silica gel using
  2. additiona gradient mixture of EtOAc and Petether (1:1) as eluent

Sources & evidence

ORD record
ord-822dccb9c2594164b03868d58c5ea5bb
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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