1,4-Dioxane → 2-(4-((3-(2-Methylpyridin-4-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline

HRID 454928Notes

Reaction equation

Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.C[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][C:31]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:50]1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:50][C:27]1[CH:26]=[C:31]([C:2]2[C:3]([O:8][CH:9]3[CH2:14][CH2:13][N:12]([C:15]4[CH:24]=[CH:23][C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]=4)[CH2:11][CH2:10]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH:30]=[CH:29][N:28]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 2-(4-((3-chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P2.1; 340 mg, 1.0 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (see PREPARATION P12.1; 219 mg, 1.0 mmol) and K3PO4 (424 mg, 2.0 mmol) in 1,4-dioxane (10 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (73 mg, 0.1 mmol) then the reaction mixture was stirred at 110° C. under N2 atmosphere overnight. The reaction mixture was filtered through CELITE® and washed with CH2Cl2 (30 mL). The filtrate was concentrated and the crude product was purified by silica gel column to give 2-(4-((3-(2-methylpyridin-4-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline (200 mg, 0.50 mmol, yield 60%). ESI-MS (M+1): 398 calc. for C24H23N5O 397.

Workup

filtrationThe reaction mixture was filtered through CELITE®
washwashed with CH2Cl2 (30 mL)
concentrationThe filtrate was concentrated
customthe crude product was purified by silica gel column

Sources & evidence

ORD record: ord-8a89b79c29f84842abea64d568ae861c
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497265B2

Reaction notes

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