Hydrochloric Acid → 5-Chloro-4-[(6-chloro-2'-fluoro-4-pyridazin-4-ylbiphenyl-3-yl)oxy]-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 1619618Notes

Reaction equation

HRID 1619618 reaction equation
Cl.O1CCOCC1.[Cl:8][C:9]1[C:10]([O:36][C:37]2[CH:38]=[C:39]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=3[F:56])[C:40]([Cl:49])=[CH:41][C:42]=2[C:43]2[CH:48]=[CH:47][N:46]=[N:45][CH:44]=2)=[CH:11][C:12]([F:35])=[C:13]([S:15]([N:18](CC2C=CC(OC)=CC=2OC)[C:19]2[S:20][CH:21]=[N:22][N:23]=2)(=[O:17])=[O:16])[CH:14]=1>CO>[Cl:8][C:9]1[C:10]([O:36][C:37]2[CH:38]=[C:39]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=3[F:56])[C:40]([Cl:49])=[CH:41][C:42]=2[C:43]2[CH:48]=[CH:47][N:46]=[N:45][CH:44]=2)=[CH:11][C:12]([F:35])=[C:13]([S:15]([NH:18][C:19]2[S:20][CH:21]=[N:22][N:23]=2)(=[O:17])=[O:16])[CH:14]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 580422495-chloro-4-(6-chloro-2'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

Product 1

HCID 566019845-Chloro-4-[(6-chloro-2'-fluoro-4-pyridazin-4-ylbiphenyl-3-yl)oxy]-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 57.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydrogen chloride in dioxane (4M, 1.5 mL, 6.00 mmol) was added to a solution of 5-chloro-4-(6-chloro-2′-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 92, 220 mg, 0.27 mmol) in methanol (1.5 mL) and the reaction stirred at room temperature for 18 hours. The mixture was evaporated to dryness and dissolved in dimethylsulfoxide (4.0 mL) and methanol (2.0 mL). The resulting precipitate was filtered, washed with methanol (2.0 mL) and the filtrate purified by preparative HPLC using a Phenomenex Luna C18 5 u 110 A 21.2×150 mm using acetonitrile:water as eluent to give the title compound (92 mg, 56%) as a beige coloured solid.

Workup

  1. customThe mixture was evaporated to dryness
  2. dissolutiondissolved in dimethylsulfoxide (4.0 mL)
  3. filtrationThe resulting precipitate was filtered
  4. washwashed with methanol (2.0 mL)
  5. customthe filtrate purified by preparative HPLC

Sources & evidence

ORD record
ord-79e441789e53422fb72c789f66e0d7f0
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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