Dichloromethane → Tert-butyl 4-(2-phenylthiazole-4-carbonyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

HRID 70173Notes

Reaction equation

ClCCl.Cl[C:5]1[S:6][CH:7]=[C:8]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH:13]2[CH2:25][O:26][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)=[O:11])[N:9]=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.O>[C:33]1([C:5]2[S:6][CH:7]=[C:8]([C:10]([N:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH:13]3[CH2:25][O:26][C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)=[O:11])[N:9]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

Conditions

Temperature: 80 °C

Procedure

[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (7 mg, 0.009 mmol) was added to a mixture of tert-butyl 4-(2-chlorothiazole-4-carbonyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (77 mg, 0.18 mmol), benzeneboronic acid (43 mg, 0.35 mmol) and sodium carbonate (37 mg, 0.35 mmol) in toluene (4 mL), 1,4-dioxane (1 mL), and water (1 mL). The reaction mixture was heated to 80° 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). This gave 74.9 mg (72%) of the TFA salt of the desired product. LC-MS: RT=8.74 min, [M+H]+=481.0.

Workup

temperatureUpon cooling to room temperature
filtrationthe reaction mixture was filtered through Celite®
concentrationconcentrated under reduced pressure
custompurified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient)

Sources & evidence

ORD record: ord-36f34a2f2c094e649996679b2e8e0ea3
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822472B2

Reaction notes

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