Acetic Anhydride → 1-(4-(6-Methoxybenzo[d]thiazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazin-1-yl)ethanone dihydrochloride

HRID 549750Notes

Reaction equation

HRID 549750 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[ClH:8].[CH3:9][O:10][C:11]1[CH:33]=[CH:32][C:14]2[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH:19]3[CH2:24][O:25][C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)[S:17][C:13]=2[CH:12]=1>C1COCC1>[ClH:8].[ClH:8].[CH3:9][O:10][C:11]1[CH:33]=[CH:32][C:14]2[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][N:21]([C:1](=[O:3])[CH3:2])[CH2:20][CH:19]3[CH2:24][O:25][C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)[S:17][C:13]=2[CH:12]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 667971466-Methoxy-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)benzo[d]thiazole hydrochloride

Product 1

HCID 667974721-(4-(6-Methoxybenzo[d]thiazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazin-1-yl)ethanone dihydrochlorideYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Acetic anhydride (0.100 mL) was added to a solution of 6-methoxy-2-(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)benzo[d]thiazole hydrochloride (73.2 mg, 0.186 mmol) in THF (2 mL), and the mixture was heated to 70° C. for 2 h. Upon cooling to rt, 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. The material was dissolved in MeOH (1 mL) and treated with 4 M HCl in 1,4-dioxane (6 mL). This was concentrated under reduced pressure, yielding 74.3 mg (85%) of the title compound as a white solid. LC-MS: RT=6.10 min, [M+H]+=399.0.

Workup

  1. temperatureUpon cooling to rt
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. custompurified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient)
  4. additionThe fractions containing the desired product
  5. extractionwere extracted with EtOAc (3×)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe material was dissolved in MeOH (1 mL)
  10. additiontreated with 4 M HCl in 1,4-dioxane (6 mL)
  11. concentrationThis was concentrated under reduced pressure

Sources & evidence

ORD record
ord-85850dd1e9ad43e9b5b1efe45a92654c
Source dataset
uspto-grants-2011_05
Patent number
US07943622B2

Reaction notes

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