Dichloromethane → Tert-butyl 4-(6-phenylpicolinoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

HRID 70187Notes

Reaction equation

ClCCl.Cl[C:5]1[N:10]=[C:9]([C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH:14]2[CH2:26][O:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[O:12])[CH:8]=[CH:7][CH:6]=1.[C:34]1(B(O)O)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.O>[C:34]1([C:5]2[N:10]=[C:9]([C:11]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH:14]3[CH2:26][O:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)=[O:12])[CH:8]=[CH:7][CH:6]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

Conditions

Temperature: 80 °C

Procedure

[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (10 mg, 0.012 mmol) was added to a mixture of tert-butyl 4-(6-chloropicolinoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (100 mg, 0.231 mmol), benzeneboronic acid (56 mg, 0.46 mmol) and sodium carbonate (49 mg, 0.46 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 143 mg of the title compound. LC-MS: RT=8.58 min, [M+H]+=475.9.

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-1151f43a685c4fa59297b1aaa409d905
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822472B2

Reaction notes

Loading…