Hydrochloric Acid → 2-(2-((Pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole trihydrochloride

HRID 1487784Notes

Reaction equation

HRID 1487784 reaction equation
[ClH:1].O1CCOCC1.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH:30]2[N:35]([C:36]3[S:37][CH:38]=[CH:39][N:40]=3)[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]2)[CH:23]=1>CO>[ClH:1].[ClH:1].[ClH:1].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH:30]2[CH2:31][NH:32][CH2:33][CH2:34][N:35]2[C:36]2[S:37][CH:38]=[CH:39][N:40]=2)[CH:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131728873tert-butyl 3-((pyridin-3-yloxy)methyl)-4-(thiazol-2-yl)piperazine-1-carboxylate di-TFA salt

Product 1

HCID 667970672-(2-((Pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole trihydrochlorideYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to a solution of tert-butyl 3-((pyridin-3-yloxy)methyl)-4-(thiazol-2-yl)piperazine-1-carboxylate di-TFA salt (130 mg, 0.215 mmol) in MeOH (1 mL). After 1 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient). The desired chromatography fractions were concentrated under reduced pressure, dissolved in MeOH (1 mL), and treated with 4 M HCl in 1,4-dioxane (6 mL). This was concentrated under reduced pressure, yielding 37.9 mg (46%) of the desired product as a white solid. LC-MS: RT=2.64 min, [M+H]+=277.0.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. custompurified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient)
  3. concentrationThe desired chromatography fractions were concentrated under reduced pressure
  4. dissolutiondissolved in MeOH (1 mL)
  5. additiontreated with 4 M HCl in 1,4-dioxane (6 mL)
  6. concentrationThis was concentrated under reduced pressure

Sources & evidence

ORD record
ord-33f3a89e7920418bbd2dfca92c714dd2
Source dataset
uspto-grants-2016_08
Patent number
US09428522B2

Reaction notes

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