Hydrochloric Acid → 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 2203425Notes

Reaction equation

HRID 2203425 reaction equation
[S:1]1[CH:5]=[N:4][N:3]=[C:2]1[NH2:6].CC(C)([O-])C.[K+].[Cl:13][C:14]1[CH:39]=[CH:38][C:17]([O:18][C:19]2[C:24]([F:25])=[CH:23][C:22]([S:26](OC3C=CC(Cl)=CC=3)(=[O:28])=[O:27])=[C:21]([F:37])[CH:20]=2)=[C:16]([C:40]2[N:45]3[CH:46]=[CH:47][N:48]=[C:44]3[CH:43]=[CH:42][CH:41]=2)[CH:15]=1.Cl>CS(C)=O.C(OCC)(=O)C.O>[Cl:13][C:14]1[CH:39]=[CH:38][C:17]([O:18][C:19]2[C:24]([F:25])=[CH:23][C:22]([S:26]([NH:6][C:2]3[S:1][CH:5]=[N:4][N:3]=3)(=[O:27])=[O:28])=[C:21]([F:37])[CH:20]=2)=[C:16]([C:40]2[N:45]3[CH:46]=[CH:47][N:48]=[C:44]3[CH:43]=[CH:42][CH:41]=2)[CH:15]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 199091,3,4-Thiadiazol-2-amineHCID 23665647Potassium tert-butoxideHCID 895441914-Chlorophenyl 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluorobenzenesulfonate

Product 1

HCID 895454324-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 42%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1,3,4-thiadiazol-2-amine (0.083 g, 0.8 mmol) in anhydrous dimethylsulfoxide (1.0 mL) at ambient temperature was added potassium tert-butoxide (0.092 g, 0.8 mmol). The mixture was stirred at ambient temperature for 10 minutes and 4-chlorophenyl 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluorobenzenesulfonate (0.15 g, 0.27 mmol) was added. The reaction mixture was stirred for 1 h at ambient temperature and water (6 mL), 1 M hydrochloric acid (0.85 mL) and ethyl acetate (25 mL) were added. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in ethyl acetate to afford 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide as a beige solid in 42% yield (0.060 g): 1H NMR (300 MHz, DMSO-d6) δ8.76 (s, 1H), 7.79 (d, J=2.6 Hz, 1H), 7.71-7.57 (m, 5H), 7.37-7.28 (m, 3H), 7.00 (dd, J=7.0, 0.9 Hz, 1H); MS (ES+) m/z 519.8 (M+1), 521.8 (M+1).

Workup

  1. stirringThe reaction mixture was stirred for 1 h at ambient temperature
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluting with a 0-10% gradient of methanol in ethyl acetate

Sources & evidence

ORD record
ord-1f3e5d9bb79b49cd8e826d6970db5803
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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