Potassium Carbonate → HCID 89555368, compound

HRID 2203412Notes

Reaction equation

HRID 2203412 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]([C:19]1[S:23][N:22]=[CH:21][N:20]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13](F)=[CH:12][C:11]=1[F:18])(=[O:9])=[O:8].C(=O)([O-])[O-].[K+].[K+].[NH2:36][C:37]1[N:42]=[C:41]([C:43]2[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=2[OH:50])[CH:40]=[CH:39][CH:38]=1>CS(C)=O.C(OCC)(=O)C.O>[NH2:36][C:37]1[N:42]=[C:41]([C:43]2[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=2[O:50][C:13]2[C:14]([F:16])=[CH:15][C:10]([S:7]([N:6]([CH2:5][C:4]3[CH:24]=[CH:25][C:26]([O:28][CH3:29])=[CH:27][C:3]=3[O:2][CH3:1])[C:19]3[S:23][N:22]=[CH:21][N:20]=3)(=[O:8])=[O:9])=[C:11]([F:18])[CH:12]=2)[CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 136508802HCID 136508802, compound

Product 1

HCID 89555368HCID 89555368, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.41 g, 0.93 mmol) (prepared according to PCT Published Patent Application No. WO 2010/079443) and potassium carbonate (0.38 g, 2.8 mmol) in dimethylsulfoxide (4 mL) at ambient temperature was added 2-(6-aminopyridin-2-yl)-4-chlorophenol (0.19 g, 0.93 mmol). The mixture was stirred at ambient temperature for 16 h and diluted with ethyl acetate (50 mL) and water (20 mL). The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 20-50% gradient of ethyl acetate in hexanes to afford 4-(2-(6-aminopyridin-2-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide in 83% yield (0.49 g): 1H NMR (300 MHz, CDCl3) δ 8.16 (s, 1H), 7.84 (d, J=2.7 Hz, 1H), 7.51-7.34 (m, 3H), 7.14 (d, J=8.7 Hz, 1H), 7.01 (d, J=8.7 Hz, 1H), 6.97 (d, J=7.5 Hz, 1H), 6.42-6.26 (m, 3H), 6.17 (d, J=2.4 Hz, 1H), 5.25 (s, 2H), 4.39 (s, 2H), 3.75 (s, 3H), 3.63 (s, 3H); MS (ES+) m/z 645.6 (M+1), 647.6 (M+1).

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography
  6. washeluting with a 20-50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e0dc5a0ae10544768efb53ca7830a758
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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