1,4-Dioxane → 1-(5-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-3,4-dihydropyridin-1(2H)-yl)ethanone

HRID 1880143Notes

Reaction equation

[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24](Br)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11].CC1(C)C(C)(C)OB([C:34]2[CH2:35][CH2:36][CH2:37][N:38]([C:40](=[O:42])[CH3:41])[CH:39]=2)O1.C([O-])(=O)C.[K+].O1CCOCC1>O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24]([C:36]3[CH2:35][CH2:34][CH2:39][N:38]([C:40](=[O:42])[CH3:41])[CH:37]=3)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

Conditions

Temperature: 80 °C

Procedure

To a degassed solution of (1H-benzo[d]imidazol-2-yl)(4-(3-bromopyridin-2-yloxy)phenyl)methanone (706 mg, 1.791 mmol), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridin-1(2H)-yl)ethanone (0.5 g, 1.991 mmol), potassium acetate (1.5 g, 15.28 mmol), and dioxane (10 mL) was added A-Phos (140 mg, 0.198 mmol). The solution was stirred at 80° C. After 16 hours, the reaction was allowed to cool to room temperature, diluted with H2O (10 mL), and the aqueous layer extracted with DCM (5 mL). The combined organic layers were concentrated in vacuo and purified by Prep TLC (1:1 hexanes/EtOAc) to give 1-(5-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-3,4-dihydropyridin-1(2H)-yl)ethanone (1.6 mg, 3.65 μmol) as a light yellow film. MS (ESI, pos. ion) m/z: 439.0 (M+1). IC50 (uM) +++++.

Workup

temperatureto cool to room temperature
extractionthe aqueous layer extracted with DCM (5 mL)
concentrationThe combined organic layers were concentrated in vacuo
custompurified by Prep TLC (1:1 hexanes/EtOAc)

Sources & evidence

ORD record: ord-b7ecec2dc3ee42f7ba4004510cd428b7
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318718B2

Reaction notes

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