Hydrochloric Acid → 4-(4-Methoxyphenyl)-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole hydrochloride

HRID 1487797Notes

Reaction equation

HRID 1487797 reaction equation
[ClH:1].O1CCOCC1.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[N:31]=[C:32]([N:35]3[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH:36]3[CH2:48][O:49][C:50]3[CH:51]=[N:52][CH:53]=[CH:54][CH:55]=3)[S:33][CH:34]=2)=[CH:26][CH:25]=1>CO>[ClH:1].[CH3:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[N:31]=[C:32]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH:36]3[CH2:48][O:49][C:50]3[CH:51]=[N:52][CH:53]=[CH:54][CH:55]=3)[S:33][CH:34]=2)=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131728876HCID 131728876, compound

Product 1

HCID 667973714-(4-Methoxyphenyl)-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole hydrochloride

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 4-(4-(4-methoxyphenyl)thiazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate di-TFA salt (199 mg, 0.280 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 fractions containing the desired product were brought to pH 12 with 1 N NaOH and were extracted with EtOAc (3×). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure, yielding 44.2 mg of the free-base of the desired product. The material was dissolved in MeOH (1 mL) and 4 M HCl in 1,4-dioxane (0.029 mL) was added. This was concentrated under reduced pressure, yielding 48.2 mg (41%) of the desired product as an off-white solid. LC-MS: RT=4.98 min, [M+H]+=383.0.

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. additionThe fractions containing the desired product
  4. extractionwere extracted with EtOAc (3×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-64b6fba51f5f498988e89f940f0b9b27
Source dataset
uspto-grants-2016_08
Patent number
US09428522B2

Reaction notes

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