Hydrochloric Acid → HCID 66796777, compound

HRID 70185Notes

Reaction equation

HRID 70185 reaction equation
[Cl:1]CCl.Br[C:5]1[CH:6]=[C:7]([CH:31]=[CH:32][CH:33]=1)[C:8]([N:10]1[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH:11]1[CH2:23][O:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1)=[O:9].[F:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+].[ClH:50]>C1(C)C=CC=CC=1.O1CCOCC1.CO.O>[ClH:1].[ClH:50].[F:34][C:35]1[CH:40]=[CH:39][C:38]([C:32]2[CH:33]=[CH:5][CH:6]=[C:7]([C:8]([N:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH:11]3[CH2:23][O:24][C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)=[O:9])[CH:31]=2)=[CH:37][CH:36]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59671502Tert-butyl 4-(3-bromobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

Product 1

HCID 66796777HCID 66796777, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
70 °C

Procedure

[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (11 mg, 0.013 mmol) was added to a mixture of tert-butyl 4-(3-bromobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (126 mg, 0.264 mmol), 4-fluorobenzeneboronic acid (92 mg, 0.66 mmol) and sodium carbonate (56 mg, 0.52 mmol) in toluene (4 mL), 1,4-dioxane (1 mL), and water (1 mL). The reaction mixture was heated to 70° C. overnight. Upon cooling to room temperature, the reaction mixture was filtered through Celite®, concentrated under reduced pressure, and purified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient), yielding a yellow oil. The oil was dissolved in MeOH (1 mL) and 4 M HCl in 1,4-dioxane (5 mL, 20 mmol) was added. After stirring for 4 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). This gave 80.5 mg (68%) of the desired product as a white solid upon conversion to the dihydrochloride salt. LC-MS: RT=4.92 min, [M+H]+=392.7.

Workup

  1. temperatureUpon cooling to room temperature
  2. filtrationthe reaction mixture was filtered through Celite®
  3. concentrationconcentrated under reduced pressure
  4. custompurified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient)
  5. customyielding a yellow oil
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. custompurified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient)

Sources & evidence

ORD record
ord-8012b4d99d0b402fac4f90ce61a9a39f
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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