Hydrochloric Acid → (5-Bromothiophen-2-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone dihydrochloride

HRID 70166Notes

Reaction equation

HRID 70166 reaction equation
[ClH:1].O1CCOCC1.[Br:8][C:9]1[S:13][C:12]([C:14]([N:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH:17]2[CH2:29][O:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)=[O:15])=[CH:11][CH:10]=1>CO>[ClH:1].[ClH:1].[Br:8][C:9]1[S:13][C:12]([C:14]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH:17]2[CH2:29][O:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)=[O:15])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59671620Tert-butyl 4-(5-bromothiophene-2-carbonyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

Product 1

HCID 66796774(5-Bromothiophen-2-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone dihydrochlorideYield 59%

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-(5-bromothiophene-2-carbonyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (192.6 mg, 0.399 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 108 mg (59%) of the desired product as a white solid. LC-MS: RT=4.16 min, [M+H]+=382.0.

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-1b8031bb49934c018d25f6ddf3fe6157
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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