Potassium Carbonate → 4-(4-chloro-2-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-3-fluoro-N-(pyrimidin-2-yl)benzenesulfonamide

HRID 2203447Notes

Reaction equation

HRID 2203447 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][C:14](=[O:16])[NH:13][C:12]=3[CH:17]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:25][O:26][C:27]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:28]=1[CH2:29][N:30]([C:42]1[N:47]=[CH:46][CH:45]=[CH:44][N:43]=1)[S:31]([C:34]1[CH:39]=[CH:38][C:37](F)=[C:36]([F:41])[CH:35]=1)(=[O:33])=[O:32]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][C:37]2[CH:38]=[CH:39][C:34]([S:31]([N:30]([CH2:29][C:28]3[CH:48]=[CH:49][C:50]([O:52][CH3:53])=[CH:51][C:27]=3[O:26][CH3:25])[C:42]3[N:43]=[CH:44][CH:45]=[CH:46][N:47]=3)(=[O:32])=[O:33])=[CH:35][C:36]=2[F:41])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][C:14](=[O:16])[NH:13][C:12]=3[CH:17]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 895443965-(5-chloro-2-hydroxyphenyl)benzo[d]oxazol-2(3H)-oneHCID 90389104N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide

Product 1

HCID 903890654-(4-chloro-2-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-3-fluoro-N-(pyrimidin-2-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture 5-(5-chloro-2-hydroxyphenyl)benzo[d]oxazol-2(3H)-one (0.068 g, 0.26 mmol) and potassium carbonate (0.054 g, 0.39 mmol) in dimethylsulfoxide (2 mL) was added N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide (0.114 g, 0.27 mmol). The reaction mixture was heated at 70-80° C. for 16 h, allowed to cool to ambient temperature and partitioned between ethyl acetate (100 mL) and water (10 mL). The organic phase was washed with brine (2 5 mL), dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 0-100% gradient of ethyl acetate in hexanes to give 4-(4-chloro-2-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-3-fluoro-N-(pyrimidin-2-yl)benzenesulfonamide as an orange solid which was carried forward without further purification: MS (ES+) m/z: 662.9 (M+1), 664.9 (M+1)

Workup

  1. temperatureto cool to ambient temperature
  2. custompartitioned between ethyl acetate (100 mL) and water (10 mL)
  3. washThe organic phase was washed with brine (2 5 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluting with a 0-100% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-34421d67c2714c43a82623e56ab0ce5e
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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