Hydrochloric Acid → 5-Chloro-2-fluoro-4-({3-[2-(piperazin-1-yl)pyridin-4-yl]-4'-(trifluoromethyl)biphenyl-4-yl}oxy)-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide, hydrochloride

HRID 1619614Notes

Reaction equation

HRID 1619614 reaction equation
[Cl:1][C:2]1[CH:43]=[C:42]([S:44](=[O:63])(=[O:62])[N:45](CC2C=CC(OC)=CC=2OC)[C:46]2[S:47][CH:48]=[N:49][N:50]=2)[C:41]([F:64])=[CH:40][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][C:6]=1[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([N:27]2[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]2)[CH:22]=1.Cl>CO.O1CCOCC1>[ClH:1].[Cl:1][C:2]1[C:3]([O:4][C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][CH:12]=3)=[CH:7][C:6]=2[C:21]2[CH:26]=[CH:25][N:24]=[C:23]([N:27]3[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]3)[CH:22]=2)=[CH:40][C:41]([F:64])=[C:42]([S:44]([NH:45][C:46]2[S:47][CH:48]=[N:49][N:50]=2)(=[O:63])=[O:62])[CH:43]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58042246tert-Butyl 4-{4-[4-(2-chloro-4-{[(2,4-dimethoxybenzyl)(1,3,4-thiadiazol-2-yl)amino]sulfonyl}-5-fluorophenoxy)-4'-(trifluoromethyl)biphenyl-3-yl]pyridin-2-yl}piperazine-1-carboxylate

Product 1

HCID 547722405-Chloro-2-fluoro-4-({3-[2-(piperazin-1-yl)pyridin-4-yl]-4'-(trifluoromethyl)biphenyl-4-yl}oxy)-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide, hydrochlorideYield 68.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-(4-(4-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(1,3,4-thiadiazol-2-yl)sulfamoyl)-5-fluorophenoxy)-4′-(trifluoromethyl)biphenyl-3-yl)pyridin-2-yl)piperazine-1-carboxylate (Preparation 113, 340 mg, 0.361 mmol) was dissolved in methanol (1 mL) and a 4M solution of hydrogen chloride in 1,4-dioxane (3 mL) was added. The reaction mixture was stirred at room temperature for 3 hours and then concentrated in vacuo. The resulting residue was purified by reverse phase chromatography using the ISCO™ system and acetonitrile/water 5/95-95/5 with 0.1% formic acid as eluent to afford the title compound (90 mg, 34%) as a white solid.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-98d71e290536417f9b7c7fb208a64151
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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