Hydrochloric Acid → (2-(4-Chlorophenyl)-4-methyloxazol-5-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone trihydrochloride

HRID 70183Notes

Reaction equation

HRID 70183 reaction equation
CN(C(ON1N=[N:16][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15]C1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:31][C:32]([C:36]([OH:38])=O)=[C:33]([CH3:35])[N:34]=2)=[CH:26][CH:25]=1.C([N:41]([CH2:44][CH3:45])[CH2:42][CH3:43])C.[OH-:46].[Na+].[ClH:48].O1CCOCC1.[CH3:55][N:56](C=O)C>CO.O>[ClH:23].[ClH:48].[ClH:23].[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[O:31][C:32]([C:36]([N:41]3[CH2:42][CH2:43][NH:56][CH2:55][CH:44]3[CH2:45][O:46][C:14]3[CH:15]=[N:16][CH:11]=[CH:12][CH:13]=3)=[O:38])=[C:33]([CH3:35])[N:34]=2)=[CH:28][CH:29]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 216665532-(4-Chlorophenyl)-4-methyl-1,3-oxazole-5-carboxylic acid

Product 1

HCID 66797085(2-(4-Chlorophenyl)-4-methyloxazol-5-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone trihydrochlorideYield 24%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

TBTU (141 mg, 0.438 mmol) was added to a solution of Intermediate C (86 mg, 0.29 mmol), 2-(4-chlorophenyl)-4-methyloxazole-5-carboxylic acid (76 mg, 0.32 mmol), and triethylamine (0.123 mL, 0.876 mmol) in DMF (4 mL). After stirring overnight, 1N NaOH (3 mL) was added, and the reaction mixture was stirred for 30 min. Water (15 mL) was added, and the reaction mixture was extracted with EtOAc (3×40 mL). The EtOAc extracts were combined, washed with aqueous NaOH (2×10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient), yielding a yellow oil. The material was dissolved in MeOH (1 mL) and treated with 4 M HCl in 1,4-dioxane (5 mL, 20 mmol). After stirring for 5 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient) to give 37.2 mg (24%) of the title compound as a white solid. LC-MS: RT=4.74 min, [M+H]+=413.6.

Workup

  1. stirringthe reaction mixture was stirred for 30 min
  2. extractionthe reaction mixture was extracted with EtOAc (3×40 mL)
  3. washwashed with aqueous NaOH (2×10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe material was purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient)
  8. customyielding a yellow oil
  9. stirringAfter stirring for 5 h
  10. concentrationthe reaction mixture was concentrated under reduced pressure
  11. custompurified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient)

Sources & evidence

ORD record
ord-91f1d127a75e4ab5a810d341e8741758
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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